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ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

Juvenile dermatomyositis (JDM) is a rare systemic autoimmune vasculopathy characterised by weakness in proximal muscles and pathognomonic skin rashes.1 Clinically, some patients are refractory to any available treatments or became steroids dependent.2 The adverse reactions of long-term use of steroids are severe; therefore, more effective and safer medications are urgently needed. JAK inhibitors (JAKi) can reduce interferon (IFN)-induced STAT1 phosphorylation and block the JAK-STAT pathway, demonstrating a therapeutic potential of inflammation control in JDM.3 The successful uses of JAKi were reported in adult dermatomyositis (DM) and two patients with JDM.3–5 Here, we want to share the JAKi using experiences of 25 refractory JDM cases who were diagnosed and classified according to Bohan and Peter’s criteria and treated between November 2017 and May 2019. Written informed consents were obtained from the guardians of all patients before starting the treatment. Among 25 cases, 44% (11/25) patients were female, the mean age of onset was 4.6±3.3 years and the mean age to start add-on JAKi treatment was 7.2±4.0 years. The mean disease course of the 25 JDM patients before JAKi treatment is 21.0 months (range: 14.0–36.5). All cases are refractory JDMs, including 32% (8/25) ineffective patients and 68% (17/25) glucocorticoid-dependent cases. After routine treatment fails, they received …

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a chronic inflammatory disease that severely affects patients’ quality of life. Therapies including tumour necrosis factor inhibitors (TNFi) and bisphosphonates (BPs) yield variable efficacy.1 Tofacitinib, a Janus kinase inhibitor, may suppress osteoclast-mediated joint damage by inhibiting the RANKL pathway.2 A previous study proved the safety and efficacy of tofacitinib in psoriatic arthritis resistant to TNFi over 3 months.3 Additionally, we reported a case where tofacitinib in combination with methotrexate and Tripterygium wilfordii Hook was effective in SAPHO syndrome.4 To further explore tofacitinib efficacy in SAPHO syndrome, we retrospectively reviewed the medical records of patients enrolled from January 2019 to December 2019 in our dynamic cohort of SAPHO syndrome.5 Patients were included if they: (1) received tofacitinib without concomitant TNFi, BPs, or other disease-modifying antirheumatic drugs and (2) had complete clinical data and MRI of SAPHO-related lesions with pain before (within 1 week) and during tofacitinib treatment. The pain visual analogue scale (VAS) score and …

Background:Biologic and target synthetic disease modifying anti-rheumatic drugs (bDMARDs and tcDMARDs) are recommended to control RA disease activity, pain and steroid use. Following randomized clinical trials (RCTs) and their post-hoc analyses, the Janus Kinase Inhibitor tsDMARDs BARI was superior to reference bDMARD Adalimumab in reducing disease activity, pain and functional disability. In addition, BARI monotherapy also determined more significant pain reduction and functional improvement when compared to Tocilizumab monotherapy (3).Objectives:to confirm RCT results in a real-life clinical setting, with focus on disease activity, pain, functional disability and steroid tapering, when comparing BARI to bDMARDs for the treatment of active RA.Methods:RA patients starting BARI or a bDMARD for active RA were retrospectively evaluated from June 2019 to June 2020. Disease activity (DAS28CRP, SDAI, CDAI), pain visual analogic scale (pain_VAS), functional disability (HAQ) assessments and mean prednisone dosage (pred_dose) were collected at baseline (BL), 3 months (3M) and 6 months (6M) after BARI/bDMARD initiation. The changes of the outcome measures were evaluated between BL-3M, 3M-6M and BL-6M, as well as between BARI and bDMARDs groups. Finally, we assessed the variables associated with prednisone tapering in the whole population.Results:90 out of 100 RA patients evaluated (baseline: age 57±12 years, disease duration 131±100 months, DAS28PCR 4.8±1.0, pain_VAS 61±23 mm, prednisone dose 5.5±5.3 mg) were eligible for the study; 49 received BARI and 41 bDMARDs (17 abatacept, 12 TNF inhibitors, 11 tocilizumab, 1 rituximab). At BL, the two groups did not differ statistically in terms of age, sex, disease duration, disease activity, pain_VAS, previous bDMARD failure or ts/bDMARD naive, concomitant conventional synthetic DMARDs treatment, pred_dose. Both BARI and bDMARDs determined a significant reduction in activity scales and HAQ when comparing BL-3M and BL-6M, with only pain_VAS and pred_dose showing a significant decrease in the 3M-6M interval. When comparing the two groups, BARI showed a significantly higher reduction of pred_dose (-3.2±5.1 vs -1.7±3.7 mg at BL-3M, and -4.1±5.3 vs -1.9±4.6 mg at BL-6M), which was not significant after adjusting for BL pred_dose. No other difference was seen when the two groups, including the numerically higher reduction of pain_VAS in the BARI group (-29±28 vs -20±27 mm at BL-3M and -35±25 vs -30±28 mm at BL-6M comparison). The analysis of the predictors for steroid tapering (Δmean_pred) in the two intervals, showed that BL DAS28PCR, DAS28PCR BL-3M change and BL pred_dose were associated with BL-3M Δmean_pred, while 3M pain_VAS and 3M pred_dose were associated with 3M-6M Δmean_pred.Conclusion:Although limited by the small samples and the retrospective nature, our real-life comparison shows similar efficacy of BARI and bDMARDs in terms of disease activity control, functional disability and pain. In addition, the treatment with BARI or bDMARD did not influence the steroid tapering, which was driven mostly by its initial dose, disease activity and pain. Larger real-life multi-center studies are warranted to confirm our results.References:[1]Taylor PC et al. Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis. N Engl J Med. 2017 Feb 16;376(7):652-662.[2]Fautrel B et al. Effect of Baricitinib and Adalimumab in Reducing Pain and Improving Function in Patients with Rheumatoid Arthritis in Low Disease Activity: Exploratory Analyses from RA-BEAM. J Clin Med. 2019 Sep 5;8(9):1394.[3]Fautrel B et al. Comparative effectiveness of improvement in pain and physical function for baricitinib versus adalimumab, tocilizumab and tofacitinib monotherapies in rheumatoid arthritis patients who are naïve to treatment withDisclosure of Interests:Laura Cometi: None declared, Cosimo Bruni Speakers bureau: Actelion, Consultant of: Eli Lilly, Grant/research support from: Fondazione Italiana Ricerca sull’Artrite (FIRA), Gruppo Italiano lotta alla Sclerodermia (GILS), New Horizon Fellowship, European Scleroderma Trials and Research (EUSTAR) group, Foundation for Research in Rheumatology (FOREUM)., Lorenzo Tofani: None declared, Giulia Tesei: None declared, Francesca Nacci: None declared, Ginevra Fiori: None declared, Francesca Bartoli: None declared, Marco Matucci-Cerinic Speakers bureau: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Consultant of: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly, Grant/research support from: Biogen Italia, Actelion, Bayer, Boehringer Ingelheim, CSL Behring, Eli-Lilly

Background:Upadacitinib (UPA), an oral Janus kinase inhibitor, in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), showed significant improvements in clinical and functional measures compared with placebo (PBO) up to 12 weeks (wks), in patients (pts) from China, Brazil, and South Korea with rheumatoid arthritis (RA) and prior inadequate response to csDMARDs (csDMARD-IR).1Objectives:To assess the efficacy and safety of UPA up to 64 wks (long-term extension; LTE) in csDMARD-IR pts with RA from China, Brazil, and South Korea.Methods:Pts were randomized to 12 wks of blinded treatment with UPA 15 mg once daily (QD) or PBO, in combination with csDMARDs. From Wk 12 onward, pts could continue to receive open-label UPA 15 mg QD. Efficacy endpoints were analyzed by original randomized treatment group sequences over 64 wks and included American College of Rheumatology (ACR) responses, and key remission and low disease activity measures. Non-responder imputation was used to handle missing data for binary endpoints. Treatment-emergent adverse events (TEAEs) per 100 patient-years (PY) were summarized for pts receiving ≥1 dose of UPA from baseline through to Wk 64.Results:Of 338 randomized pts who received ≥1 dose of study drug, 310 (91.7%) entered the LTE and 275 (81.4%) completed 64 wks of treatment. Among those initially randomized to UPA, the proportion of pts achieving 20%/50%/70% improvement in ACR criteria, and key remission and low disease activity measures increased over 64 wks of treatment (Figure 1). Improvements from baseline in the Health Assessment Questionnaire-Disability Index and pts’ assessment of pain were observed over 64 wks of UPA treatment (data not shown). By Wk 64, efficacy results for pts who switched from PBO to UPA at Wk 12 followed a similar trajectory to those originally randomized to UPA.The observed rate of serious infections was 8.1 events/100 PY. Herpes zoster events were mostly non-serious, involving only 1 or 2 dermatomes. Most cases of hepatic disorders were Grade 1 or 2 hepatic transaminase elevations. There was 1 case of venous thromboembolic event (VTE; concurrent pulmonary embolism and deep vein thrombosis [DVT] in a patient with a history of DVT) and 3 cases of malignancy. Adjudicated major adverse cardiovascular events (Table 1) occurred in 2 pts (1 with non-fatal myocardial infarction and 1 with non-fatal stroke) who had underlying risk factors for cardiovascular disease. There were no deaths, active tuberculosis, or renal dysfunction.Conclusion:UPA 15 mg was effective in treating the signs and symptoms of RA and in improving physical function over 64 wks with no new safety signals1 in csDMARD-IR pts with RA from China, Brazil, and South Korea.References:[1]Zeng A, et al. Ann Rheum Dis 2020;79(Suppl 1):1016 [abstract SAT0160]Table 1.TEAEs at Wk 64Event (E/100 PY)UPA 15 mg(n=322; PY=334.5)Any AE421.5 (399.8–444.1) Serious AE19.1 (14.7–24.4) AE leading to discontinuation of study drug9.0 (6.1–12.8) Deathsa0AEs of special interest Serious infection8.1 (5.3–11.7) Opportunistic infection0.9 (0.2–2.6) Herpes zoster9.0 (6.1–12.8) Hepatic disorder42.2 (35.5–49.7) Gastrointestinal perforation (adjudicated)0.3 (0.0–1.7) Any malignancy (excluding NMSC)0.6 (0.1–2.2) NMSC0.3 (0.0–1.7) MACE (adjudicated)b0.6 (0.1–2.2) VTE (adjudicated)c0.3 (0.0–1.7) Anemia11.1 (7.8–15.2) Neutropenia11.7 (8.3–15.9) Lymphopenia7.8 (5.1–11.4) CPK elevation11.1 (7.8–15.2)aIncluding non-treatment-emergent deaths. bDefined as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. cIncluding DVT and pulmonary embolism.AE, adverse event; CPK, creatine phosphokinase; E, events; MACE, major adverse cardiovascular event; NMSC, non-melanoma skin cancerAcknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Yanna Song, PhD, of AbbVie provided statistical support. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Xiaofeng Zeng: None declared, Dongbao Zhao: None declared, Sebastiao Radominski: None declared, MAURO KEISERMAN: None declared, Chang-Keun Lee: None declared, Naomi Martin Employee of: AbbVie employee and may own stock or options, Sebastian Meerwein Employee of: AbbVie employee and may own stock or options, Yunxia Sui Employee of: AbbVie employee and may own stock or options, Won Park: None declared

Background:There are currently eleven biologic and targeted synthetic (b/ts)DMARDs acting via five different modes of action available for the treatment of RA in Australia. The cost of b/tsDMARDs is subsidized by government for patients that have active RA despite six months of combination csDMARD therapy. Once a patient is eligible, the clinician can prescribe the b/tsDMARD they deem to be the most clinically appropriate for the patient. In Oct 2015 the first JAK inhibitor (JAKi) became available in Australia (tofacitinib, TOF), baricitinib (BARI) became available in Sept 2018, and upadacitinib (UPA) in May 2020. Each of these oral tsDMARDs possess different selectivity profiles towards different members of the JAK family (JAK1–3 and Tyk2).Objectives:The aim of this analysis was to determine the patterns of JAKi cycling in real-world practice in Australia.Methods:Deidentified clinical data were sourced from the OPAL dataset, which is collected in a custom-built electronic medical record during the routine consultation1. Data from patients >18 years with RA who commenced a b/tsDMARD between Jan-2007 and Dec-2020 were included in the analysis. A visual analytics software program was used to display data on medication initiation and cessation dates, and reasons for stopping tsDMARDs, which is recorded in the medical record at the time of the decision.Results:At Dec 2020, 28% of the 52,190 patients with RA in the OPAL dataset were prescribed b/tsDMARDs. Of these patients, 3,850 (26.3%) were currently prescribed a JAKi with 51.4% receiving TOF, 29.2% BARI and 19.4% UPA. In 2020, JAKi initiations accounted for 48.8% of all initiations and 30.7% of 1st line initiations; an increase of 6.1% and 3.5% from 2019, respectively. The percentage of patients switching from a first line JAKi to a second line JAKi rather than an agent with another mode of action increased from 33.1% in 2019 to 42.6% in 2020. This is despite 26.2% in 2019 and 45.8% in 2020 of the patients switching to another JAKi citing lack of efficacy as the reason for JAKi discontinuation. In the period between May 2020, when a third JAKi (UPA) become available, and Dec 2020, the majority of patients switching from first line TOF or BARI to another JAKI switched to UPA (69.4% and 83.9%, respectively), whilst 30.6% of first line TOF patients switched to BARI (30.6%), and 16.1% of first line BARI patients switched to TOF in second line. The majority of patients switching from second line TOF or BARI to a third line JAKi switched to UPA (73% and 96%, respectively), with 27% of second line TOF patients switching to BARI and a very low number moving from second line BARI to TOF (4%). JAKi choice after a third line TOF or BARI was almost exclusively UPA (86.2% and 95.5%, respectively).Conclusion:There has been significant and sustained uptake of JAKi for the management of RA in Australia and JAKi cycling is increasingly common in routine clinical care. Clinical outcomes and persistence following JAKi cycling requires further investigation.References:[1]Littlejohn GO, Tymms KE, Smith T, Griffiths HT. Using big data from real-world Australian rheumatology encounters to enhance clinical care and research. Clin Exp Rheumatol. Sep-Oct 2020;38(5):874-880.Figure 1.Patterns of JAKi cycling for the management of rheumatoid arthritis in first, second and third line switching.Acknowledgements:The authors acknowledge the members of OPAL Rheumatology Ltd and their patients for providing clinical data for this study, and Software4Specialists Pty Ltd for providing the Audit4 platformDisclosure of Interests:Sabina Ciciriello: None declared, Tegan Smith: None declared, Catherine OSullivan: None declared, Kathleen Tymms: None declared, Peter Youssef: None declared, David Mathers: None declared, Claire Deakin: None declared, Hedley Griffiths Consultant of: AbbVie, Gilead, Novartis and Lilly., Geoff Littlejohn Speakers bureau: Over the last 5 years Geoffrey Littlejohn has received educational grants and consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer, Janssen, Sandoz, Sanofi and Seqirus.

Background:Upadacitinib (UPA) is an oral Janus kinase inhibitor that has demonstrated efficacy and safety among patients with ankylosing spondylitis (AS) in the phase 2/3 SELECT-AXIS 1 study.1 If identified, early predictors of treatment response may inform treat-to-target strategies and optimize patient outcomes in AS.Objectives:To determine whether baseline (BL) characteristics or early responses predict clinical response at 1 year in UPA-treated patients with AS.Methods:In the double-blind, randomized, placebo (PBO)-controlled SELECT-AXIS 1 study, patients received UPA 15 mg once daily or PBO until Week 14.1 At Week 14, PBO-treated patients switched to UPA 15 mg; patients originally randomized to UPA continued UPA therapy. Data from patients in the PBO and UPA arms were combined based on overall exposure to UPA; in the switch arm, exposure was defined as current visit minus 14 weeks (time of switch). The following outcomes were assessed at 1 year: Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS[CRP]) inactive disease (ID; Results:Among 187 patients who received or switched to UPA 15 mg, 70 (37.4%), 134 (71.7%), 73 (39.0%), and 131 (70.1%) achieved ASDAS(CRP) ID, ASDAS(CRP) LDA, ASAS PR, and ASAS40, respectively, following 1 year of UPA treatment. No meaningful predictors of 1-year efficacy outcomes were identified based on BL demographics (including disease duration, gender, and human leukocyte antigen B27 status) or BL disease characteristics (including ASDAS, Bath Ankylosing Spondylitis Disease Activity Index, and CRP levels). In univariable analyses, Week 12 responses based on several disease activity measures and patient-reported outcomes (PROs), including reductions (much better improvement [MBI], ≥30/≥50/≥70% reduction, or improvement) in back pain score, along with lower scores for back pain at Week 12, were associated with the achievement of ASDAS(CRP) ID, ASDAS(CRP) LDA, ASAS PR, and ASAS40 at 1 year (Figure 1). In a multivariable analysis, improvement from BL to Week 12 in back pain score consistently predicted several efficacy outcomes at 1 year.Conclusion:In upadacitinib-treated patients with AS, improvement in PROs and reduction in back pain score at 12 weeks predicted clinical outcomes at 1 year.References:[1]van der Heijde D, et al. Lancet 2019;394:2108–17.Figure 1.Association between Week 12 response or back pain at Week 12 and achievement of efficacy outcomes at 1 year (univariable analysis)All ASDAS scores are calculated using C-reactive proteinASDAS CII: change from BL ≥1.1; ASDAS MI: change from BL ≥2.0; MBI back pain: ≥2-point reduction in absolute score and ≥33% reduction from BL on a 0–10 NRSASAS, Assessment of SpondyloArthritis International Society; ASAS40, ≥40% improvement in ASAS criteria; ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI50, ≥50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index; BL, baseline; CI, confidence interval; CII, clinically important improvement; ID, inactive disease; LDA, low disease activity; MBI, much better improvement; MI, major improvement; NRS, numeric rating scale; OR, odds ratio; PR, partial remissionAcknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Laura Chalmers, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Marina Magrey Consultant of: Consultant for Janssen and Novartis; member of advisory boards for Eli Lilly, Janssen, Novartis, and UCB, Grant/research support from: AbbVie, Sofia Ramiro Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Sanofi, and UCB, Grant/research support from: MSD, Marcelo Pinheiro Consultant of: AbbVie, Eli Lilly, Janssen, and Novartis, Tianming Gao Employee of: AbbVie employee and may own stock or options, Fabiana Ganz Employee of: AbbVie employee and may own stock or options, In-Ho Song Employee of: AbbVie employee and may own stock or options, Ana Biljan Employee of: AbbVie employee and may own stock or options, Nigil Haroon Consultant of: AbbVie, Amgen, Eli Lilly, Janssen, MSD, Novartis, Pfizer, and UCB, Martin Rudwaleit Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer, Roche, and UCB

Objective Tofacitinib is an oral, small-molecule Janus kinase inhibitor that is being investigated for IBD. We evaluated the efficacy and safety of tofacitinib for induction and maintenance treatment in patients with moderate-to-severe Crohn's disease (CD). Design We conducted two randomised, double-blind, placebo-controlled, multicentre phase IIb studies. Adult patients with moderate-to-severe CD were randomised to receive induction treatment with placebo, tofacitinib 5 or 10 mg twice daily for 8 weeks. Those achieving clinical response-100 or remission were re-randomised to maintenance treatment with placebo, tofacitinib 5 or 10 mg twice daily for 26 weeks. Primary endpoints were clinical remission at the end of the induction study, and clinical response-100 or remission at the end of the maintenance study. Results 180/280 patients randomised in the induction study were enrolled in the maintenance study. At week 8 of induction, the proportion of patients with clinical remission was 43.5% and 43.0% with 5 and 10 mg twice daily, respectively, compared with 36.7% in the placebo group (p=0.325 and 0.392 for 5 and 10 mg twice daily vs placebo). At week 26 of maintenance, the proportion of patients with clinical response-100 or remission was 55.8% with tofacitinib 10 mg twice daily compared with 39.5% with tofacitinib 5 mg twice daily and 38.1% with placebo (p=0.130 for 10 mg twice daily vs placebo). Compared with placebo, the change in C-reactive protein from baseline was statistically significant (p

Background:Tofacitinib is an oral Janus Kinase inhibitor for the treatment of rheumatoid arthritis (RA). The survival of remission or low disease activity (LDA) in RA patients, treated with tofacitinib remain unknown.Objectives:To evaluate the survival of DAS28 remission or low disease activity in RA patients treated with tofacitinib.Methods:Data from 102 patients from Russian national register of patients with RA treated with tofacitinib (OREL), achieved DAS28 remission (DAS28Results:Baseline characteristics of the patients are presented in table 1.Table 2.Treatment results in RA patients, received monotherapy of tofacitinib and tofacitinib with mtx, Mean±SD / n (%).ParameterLDA (n=102)Remission (n=92)Male, n (%)19 (18.6)15 (16.3)Age, years (mean ±SD)53.55±13.4652.45±12.56Symptoms duration, month (mean±SD)170±111.92169±110.93Positive rheumatoid factor, n (%)41(40.19)36 (39.13)Erosions of hand joints (X-rays), n (%)43(42.15)41 (44.56)BMI, kg/m2(mean ±SD)25.67 ± 2.2226.87 ± 2.19Smokers (current and in the past), n (%)9 (8.82)9 (9.78)p-value ≥ 0.05 for all the differences.The remission failed in 45 from 92 patients (48.91%), LDA failed in 65 from 102 of patients (63.72%), table 2.Table 1.Time, monthMeStandard error95% Confidential IntervalfromToLDA (n=102)12.0002.0218.03915.961Remission (n=92)10.3126.0000.7964.440Proportions of survival of remission or LDA are presented at figure 1 and figure 2 respectively.Figure 1.Survival proportion in RA patients achieved LDA on tofacitinib (n=102).Figure 2.Survival proportion in RA patients achieved remission on tofacitinib (n=92).In 28 from 45 cases of remission failure (62.22%) and in 34 cases from 65 cases of LDA loss (52.3%) the proposal reasons of treatment effect loss were non-medical (absence of reimbursement, changes in patients accommodation, low treatment compliance, etc.). Medical reasons (side effects, inefficacy, etc.) of decrease in remission or LDA survival rate were registered in 17 from 45 cases of remission loss (37.77%) and in 31 from 65 cases of LDA loss (47.69%).Conclusion:On-year survival of remission or low disease activity achieved in Rheumatoid arthritis patients treated with tofacitinib is 51.1% and 36.3 % respectively. The main reasons of treatment efficacy loss were associated with non-medical.Acknowledgments:PfizerDisclosure of Interests:Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, V Mazurov: None declared, Alexander Lila: None declared, Andrey Baranov Grant/research support from: Bayer, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Aida Babaeva: None declared, Elena Kalinina: None declared, Tatiana Salnikova: None declared, Valentina Sorotskaya: None declared, Ruzana Samigullina: None declared, Diana Chakieva: None declared, Iuliia Grabovetskaya: None declared, Irina Marusenko: None declared, Ekaterina Gaydukova: None declared, Evgeny Nasonov Speakers bureau: Lilly, AbbVie, Pfizer, Biocad, R-Pharm

Background:Current treatments for PsA have proven effective in reducing patient (pt)-reported pain;1,2however, residual pain often remains. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:This descriptive analysis evaluated the effect of tofacitinib, adalimumab and placebo on residual pain in pts with PsA whose inflammation was attenuated after 3 months of therapy.Methods:Data were included from OPAL Broaden (NCT01877668), a randomised, double-blind, placebo-controlled Phase 3 trial of 12 months’ duration in pts with PsA.3Pts were randomised to receive tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks or placebo. This analysis assessed pts with ‘residual pain’ at Month (M)3. Residual pain was considered as pain in pts with complete attenuation of inflammation at M3, defined by a swollen joint count (SJC) of 0 and CRP levels Results:Demographics and baseline disease characteristics have previously been reported in the primary study, and were generally similar between treatment groups.3At M3, 100/422 (23.7%) pts with PsA had achieved SJC of 0 and CRP Conclusion:Changes from baseline in pain and absolute pain at M3 suggest that in pts with PsA whose inflammation has been completely attenuated, tofacitinib might have an effect on residual pain not obviously attributable to inflammation. However, the sample population was small, and there were large standard deviations. To confirm these results and to understand the mechanisms by which tofacitinib may improve residual pain, a meta-analysis will be performed using individual participant data from pts with rheumatic disease who have participated in tofacitinib randomised controlled trials.References:[1]Gladman et al. Ann Rheum Dis 2007;66:163-68.[2]Gladman et al. Arthritis Care Res 2014;66:1085-92.[3]Mease et al. NEJM 2017;377:1537-50.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Mark Bennett of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV, Clifton Bingham Grant/research support from: Bristol-Myers Squibb, Consultant of: Bristol-Myers Squibb, Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Yves Brault Shareholder of: Pfizer France, Employee of: Pfizer France, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Meriem Kessouri Shareholder of: Pfizer France, Employee of: Pfizer France

Background:Treatment effect on pain is a priority for patients (pts) with psoriatic arthritis (PsA) and physicians. As pain is multidimensional, there is growing interest to understand the mechanisms of pain relief during treatment. Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Previous analyses showed that the effect of tofacitinib on pain in pts with PsA was partially mediated through improvement of inflammation as assessed by C-reactive protein (CRP) and Swollen Joint Count (SJC). Additional potential inflammation-associated mediators that might contribute to tofacitinib’s effect on pain include enthesitis and skin disease.Objectives:To describe the interrelationship between pain, tofacitinib treatment and potential inflammatory-associated outcomes, using mediation modelling.Methods:Data from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily (BID) or placebo were used; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Analyses were completed using pooled and individual study data at Months 1 and 3 (using mean scores across visits). Mediation modelling seeks to explain mechanisms underlying observed relationships between independent and dependent variables via other variables (mediators). This initial model included: treatment as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); pain, measured by Patient’s Assessment of Arthritis Pain (VAS, 0–100 mm), as the dependent (outcome) variable; mediators were: pt-reported Itch Severity Index (ISI); CRP; SJC; Psoriasis Area and Severity Index (PASI); and enthesitis, measured by Leeds Enthesitis Index (LEI) or Spondyloarthritis Research Consortium of Canada Enthesitis Index (SPARCC). The final model was revised based on results of the initial model.Results:The initial model (N=329; pooled data) showed that tofacitinib treatment affects pain mainly indirectly via ISI, CRP, SJC, PASI and enthesitis (LEI), with 16.0% (p=0.53) attributable to the direct effect. The indirect effect via SJC (Conclusion:The majority of tofacitinib treatment effect on pain in pts with PsA is collectively mediated by itch, enthesitis and CRP, with itch being the main mediator of treatment effect (~37%), using mediation modelling analyses.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Kurt de Vlam Grant/research support from: Celgene, Eli Lilly, Pfizer Inc, Consultant of: AbbVie, Eli Lilly, Galapagos, Johnson & Johnson, Novartis, Pfizer Inc, UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip J Mease Grant/research support from: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – grant/research support, Consultant of: Abbott, Amgen, Biogen Idec, BMS, Celgene Corporation, Eli Lilly, Novartis, Pfizer, Sun Pharmaceutical, UCB – consultant, Speakers bureau: Abbott, Amgen, Biogen Idec, BMS, Eli Lilly, Genentech, Janssen, Pfizer, UCB – speakers bureau

Background:Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). A recent ad hoc safety analysis (as of August 2019; may be subject to change) from an ongoing, open-label, randomised, post-authorisation safety study, Study A3921133 (NCT02092467), conducted in RA patients (pts) aged ≥50 years with ≥1 cardiovascular risk factor has shown that incidence rates (IRs) of serious infection events (SIEs) were higher with tofacitinib 10 mg BID vs tumour necrosis factor inhibitors (TNFi; adalimumab [ADA] and etanercept) and this difference was more pronounced in pts aged ≥65 years (Pfizer Inc; data on file).Objectives:To assess the IRs of overall infection events and SIEs in pts from Phase (P)2, P3 and P3b/4 tofacitinib RA trials which had a TNFi (ADA) active control or comparator arm.Methods:This is a post hoc analysis of Month 0–12 data pooled from P2 (A3921035;NCT00550446[first 12-week randomised parallel treatment period only]), P3 (ORAL Standard;NCT00853385) and P3b/4 (ORAL Strategy;NCT02187055) studies. Pts randomised to receive tofacitinib 5 mg BID, tofacitinib 10 mg BID, ADA 40 mg subcutaneously every other week and placebo (PBO) were included and assessed overall and by age (Results:Of 2180 pts included in the pooled studies (tofacitinib 5 mg BID: N=1064 [943.4 PY]; tofacitinib 10 mg BID: N=306 [236.6 PY]; ADA: N=643 [554.3 PY]; PBO: N=167 [108.1 PY]), 1841 (84.4%) were aged Conclusion:In this analysis of data pooled from P2, P3 and P3b/4 tofacitinib RA studies which included a TNFi arm (ADA), the risk of SIEs or infections overall was similar for tofacitinib and ADA with the exception of a numerically higher rate of SIEs with tofacitinib 10 mg BID vs ADA in pts aged ≥65 years. In most countries, tofacitinib 10 mg BID is not an approved dose for the treatment of RA. This post hoc comparison is limited by variation in sample size and PY of exposure between treatment and age groups, and a small number of cases of SIEs in the ≥65-year age group resulting in wide 95% CIs; interpretation of results should be made with caution. The findings in the present analysis are consistent with increasing age being a known risk factor for infections.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Christina Viegelmann of CMC Connect and funded by Pfizer Inc.Disclosure of Interests: :Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, David Gold Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dan Henrohn Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrea Shapiro Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Harry Shi Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Gustavo Citera Grant/research support from: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Consultant of: AbbVie, Amgen, Eli Lilly, Gema, Genzyme, Novartis and Pfizer Inc, Hendrik Schulze-Koops Grant/research support from: Pfizer Inc

Background:ABX464 is a small oral molecule with a novel mode of action. It binds the Cap Binding Complex, involved in the biogenesis of RNAs and predominantly upregulates the expression of a microRNA miR-124 in PBMCs and T cells (1). miR-124 has been widely described for its anti-inflammatory properties, with many confirmed targets i.e. monocyte chemoattractant protein 1 (MCP-1, CXCL-1, SERPIN-E1, STAT-3, IL-6 receptor. It post-transcriptionally regulates the expression of MCP-1 in rheumatoid arthritis (RA) synoviocytes and decreases their proliferation (2). While miR-124 is decreased in synoviocytes of RA patients, its injection in joint improved arthritis in rats (3). miR-124 expression in macrophages leads to the induction and maintenance of anti-inflammatory M2 phenotype (4). Its effect in T cells remains controversial.Objectives:(i) To assess the effect of ABX464 on miR-124 expressionin vitroin macrophages andin vivoin patients; (ii) to assess the effect of ABX464 on arthritis in mice and (iii) to decipher the effect of ABX464 on human macrophages and T cells.Methods:miR-124 was measured in human monocyte-derived macrophages (huMDM) treated with ABX464 for 4 days and in patients with ulcerative colitis included in a phase IIa RCT in blood and rectal biopsies at day 56 by TaqMan qPCR. Collagen-induced arthritis (CIA) was induced using usual protocol and ABX464 was given by gavage 2 weeks at 40 mg/kg after the 2ndinjection of collagen and Freund adjuvant. HuMDM were exposed to 5 µM of ABX464 or DMSO (control) for 4 days, during a M1-polarization. Cytokines and chemokines were assessed in supernatants using both Proteome Profiler Array and Luminex. PBMCs were exposed to ABX464 (5 µM) for 6 days. Th1 (IFN-g+), Th17 (CCR6+IL-17+), Th2 (CRTH2+ IL-4+) and Tregs (CD25+CD125-/loFoxP3+) were assessed by flow cytometry. IL-6 receptor was assessed in CD4+ supernatant using ELISA.Results:ABX464 increased miR-124 in vitro by 3.41 folds in huMDM (p=0.001) compared to DMSO. The phase IIa RCT conducted in 32 patients with moderate to severe active ulcerative colitis showed a good safety profile and significant clinical efficacy. A strong increase of miR-124 was observed both in blood and rectal biopsies of patients treated with ABX464 (637 and 7.69 folds respectively, compared to placebo, pConclusion:We demonstrated that ABX464 increases miR-124 bothin vitroand in ulcerative colitis patients.In vitro, ABX464 decreased the expression of miR-124 target genes, that is MCP-1, CXCL-1, SERPIN-E1 in macrophages and decreases the number of Th17 as well as IL-6 soluble receptor in CD4+ T cells. A phase IIa RCT is currently ongoing in patients with rheumatoid arthritis and inadequate response to methotrexate and/or TNF-inhibitors (n=60). Results are expected during 2020 summer.References:[1]Vautrin A et al. Sci Rep. 2019;9:792[2]Nakamachi Y et al. Arthritis Rheum 2009; 60:1294-304[3]Nakamachi Y et al. Ann Rheum Dis 2016; 75:601-8[4]Veremeyko T et al. PLoS ONE 2013; 8:e81774Disclosure of Interests:Christina BEGON-PESCIA: None declared, Julie Mielle: None declared, Noélie Campose Employee of: ABIVAX, Karim Chebli Consultant of: ABIVAX, Laurent Manchon: None declared, Julien Santo Employee of: ABIVAX, Cécile Apolit Employee of: ABIVAX, Kévin Martin Grant/research support from: ABIVAX, Laure Lapasset Employee of: ABIVAX, Audrey Vautrin Employee of: ABIVAX, Didier Scherrer Employee of: ABIVAX, Aude Garcel Employee of: ABIVAX, Jamal Tazi Shareholder of: ABIVAX, Grant/research support from: ABIVAX, Consultant of: ABIVAX, Employee of: ABIVAX, Paid instructor for: ABIVAX, Speakers bureau: ABIVAX, Claire DAIEN Grant/research support from: from Pfizer, Abbvie, Roche-Chugaï, Novartis, Abivax, Sandoz, Consultant of: Abbvie, Abivax, BMS, MSD, Roche-Chugaï, Lilly, Novartis, Speakers bureau: Abbvie, Abivax, BMS, MSD, Roche-Chugaï, Lilly, Novartis

Background:Upadacitinib (UPA), an oral Janus kinase inhibitor (JAKi), has demonstrated efficacy in the phase 3 SELECT clinical program, conducted across a range of patients (pts) with rheumatoid arthritis (RA).1–6 Real-world data for UPA, including in pts previously treated with a JAKi, have not yet been reported since global approvals beginning in 2019.Objectives:To assess the characteristics of US-based pts receiving UPA and its effectiveness in clinical practice at 3 months.Methods:This observational study included US-based pts from the United Rheumatology Normalized Integrated Community Evidence (UR-NICE) database who initiated UPA 15 mg once daily from FDA approval (August 2019) to July 31, 2020 and had ≥6-month pre-baseline data available. Effectiveness was assessed in pts with a reported Clinical Disease Activity Index (CDAI) score at 3 months after UPA initiation and included proportions of pts achieving CDAI remission (≤2.8), CDAI low disease activity (≤10), other disease activity measures, and pt-reported outcomes. A subgroup analysis assessed UPA effectiveness in pts with or without prior tofacitinib (TOFA) treatment.Results:This analysis included 252 pts treated with UPA 15 mg, of whom 98 (38.9%) received UPA monotherapy and 154 (61.1%) received UPA combined with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs). 64.3% of pts were from the Southern region of the USA. 86.1%, 72.2%, and 47.6% of pts had been previously treated with csDMARDs, biologic DMARDs, and JAKis, respectively. Baseline characteristics were largely similar between UPA monotherapy and combination therapy groups and those with or without prior TOFA treatment (Table 1). Pts with prior TOFA treatment had a longer duration of RA since diagnosis and higher steroid use versus those without. UPA 15 mg improved disease activity scores (including CDAI) and pt-reported outcomes (including physical function and pain) after 3 months of treatment (Figure 1). Similar effectiveness was observed with UPA 15 mg in pts with or without prior TOFA treatment.Conclusion:In the UR-NICE real-world database of US-based pts, improvements in clinical and pt-reported outcomes were observed at 3 months in UPA-treated pts with RA, including those with or without prior TOFA treatment, despite the treatment-refractory population included in this dataset.References:[1]Burmester GR, et al. Lancet 2018;391:2503–12.[2]Smolen JS, et al. Lancet 2019;393:2303–11.[3]Fleischmann R, et al. Arthritis Rheumatol 2019;71:1788–800.[4]Genovese MC, et al. Lancet 2018;391:2513–24.[5]van Vollenhoven R, et al. Arthritis Rheumatol 2020;72:1607–20.[6]Rubbert-Roth A, et al. N Engl J Med 2020;383:1511–21.Table 1.Baseline characteristicsn (%), unless otherwise statedFull analysis set(n=252)Pts with prior TOFA treatment(n=113)Pts without prior TOFA treatment (n=139)Mean (SD) exposure, days219.7 (112.1)215.7 (116.7)222.9 (108.5)Female199 (79.0)85 (75.2)114 (82.0)Age ≥65 years75 (29.8)34 (30.1)41 (29.5)Oral steroid use140 (55.6)70 (61.9)70 (50.4)Prior csDMARDs217 (86.1)102 (90.3)115 (82.7)Prior TOFA113 (44.8)113 (100.0)0Prior biologic DMARDs182 (72.2)86 (76.1)96 (69.1)Tumor necrosis factor inhibitor147 (58.3)66 (58.4)81 (58.3)Interleukin-6 receptor inhibitor87 (34.5)47 (41.6)40 (28.8)nMean (SD)nMean (SD)nMean (SD)Duration of RA diagnosis, years1884.0 (3.0)895.1 (2.9)993.1 (2.8)Methotrexate dose, mg/week8817.0 (5.1)2817.8 (5.0)6016.6 (5.2)SJC282394.8 (5.7)1084.5 (5.0)1315.0 (6.2)TJC282376.5 (6.7)1076.5 (6.8)1306.5 (6.6)CDAI22520.4 (13.4)10520.2 (13.5)12020.6 (13.3)Routine assessment of patient index data 31654.2 (2.3)724.2 (2.4)934.3 (2.2)Disease Activity Score in 28 joints based on C-reactive protein1673.9 (1.5)833.9 (1.5)843.9 (1.5)Health Assessment Questionnaire-Disability Index1702.5 (2.1)742.4 (2.2)962.5 (2.1)Pain(0–10)22956.5 (28.5)10456.9 (29.3)12556.1 (28.0)SD, standard deviation; S/TJC, swollen/tender joint countAcknowledgements:AbbVie funded this study; contributed to its design; participated in data collection, analysis, and interpretation of the data; and participated in the writing, review, and approval of the abstract. No honoraria or payments were made for authorship. Medical writing support was provided by Hilary Wong, PhD, of 2 the Nth (Cheshire, UK), and was funded by AbbVie.Disclosure of Interests:Allan Gibofsky Shareholder of: AbbVie, Amgen, Johnson & Johnson, and Pfizer, Consultant of: AbbVie, Celgene, Eli Lilly, Flexion, Pfizer, Relburn Pharma, and Samumed. Paid consultant with investment analysts on behalf of the Gerson Lehrman Group, Bhavna Dhillon Shareholder of: May own stock or options in United Rheumatology, Employee of: United Rheumatology, Mark E. Pearson Shareholder of: May own AbbVie stock or options, Namita Tundia Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Yanna Song Shareholder of: May own stock or options in AbbVie, Employee of: AbbVie, Kendall Dunlap Shareholder of: May own stocks or shares in AbbVie, Employee of: AbbVie, Grace Wright Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Exagen, Myriad Autoimmune, Novartis, Sanofi/Regeneron, UCB, and Vindico, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Exagen, Gilead, Janssen, Myriad Autoimmune, Novartis, Pfizer, Sanofi/Regeneron, and UCB, Employee of: President and Founder of the Association of Women in Rheumatology

Background:In clinical practice, when refractory rheumatoid arthritis (RA) is present, of which the definition implies previous use of at least two biologic disease-modifying antirheumatic drugs (bDMARDs) (generally tumour necrosis factor inhibitors (TNFis)), the next treatment choice often made is a bDMARD of another class (non-TNFis) [1]. However, patients who are inadequately responding to bDMARDs need new treatment options because subsequent bDMARDs treatment reduces their response [2]. Janus Kinase inhibitors (JAKis) are the first targeted synthetic DMARDs (tsDMARD) licensed for the treatment of RA with comparable efficacy to bDMARDs. Unlike the single cytokine targeting approach of bDMARDs, JAKis are specifically designed to inhibit intracellular signalling molecules common to the receptors of multiple inflammatory cytokines implicated in RA pathogenesis. The choice of therapeutic agents for refractory RA is increasing, and its efficacy is expected. On the other hand, it is also true that some patients discontinued JAKis at a rate that cannot be overlooked because of insufficient efficacy. Difficult-to-treat (D2T) RA is defined as refractory to two or more b/ts DMARDs with different mechanisms of action, with active and progressive disease, as published by Eular(3)Objectives:To evaluate real world efficacy of approved JAKis switching in patients with D2T RA who were unable to control their disease activity due to insufficient efficacy despite the sequential use of multiple bDMARDs and JAKis, focusing on the drug retention rate.Methods:In our hospital, RA was diagnosed according to the 1987 or 2010 classification criteria, and when two or more bDMARDs (including both TNFis and non-TNFis) were inadequately effective, it was defined as D2T RA. We retrospectively investigated patients who switched to JAKis for D2T RA. The drug retention rate was investigated by the Kaplan-Meier method, and the difference was tested by the Logrank test.Results:The 1-year retention rate of JAKis for D2T RA was 50.8% in TOF 38 cases [28 women, age average 70.2 years, disease duration average 12.4 years, past bDMARDs use average 3.5 drugs, MTX combination 9 cases, DAS28 ESR average 4.11] and 66.3% in BAR 35 cases [26 cases, 73.0 years old, 14.8 years, 4.17 agents, 9 cases, 3.68], and there was no significant difference (P = 0.30). Among them, there were 17 cases [11 cases, 70.6 years old, 13.5 years, 4.18 drugs, 2 cases, 3.65] of switching between JAKis, all of which were switching from TOF to BAR. The 1-year retention rate was 45.8% [reason for discontinuation: insufficient effect in 3 cases, adverse events in 6 cases], which was not significantly different but tended to be lower than 72.7% [reason for discontinuation: insufficient effect in 1 case, adverse event in 2 cases, patient’s convenience in 1 case] in 16 patients [13 cases, 76.3 years old, 17.1 years, 3.19 drugs, 7 cases, 3.69] who received BAR as the first JAKi for D2T RA patients (P = 0.089).Conclusion:Although the number of cases is small in the retrospective survey, it is suggested that the retention rate of BAR switched to D2T RA may be slightly lower in patients with a history of TOF discontinuation due to insufficient efficacy than in JAKi naive patients. It is expected that the number of new JAKi usage cases will increase in the future, and it is necessary to consider switching between other JAKis in addition to switching from BAR to TOF.References:[1]Smolen JS, Landewe R, Bijlsma J et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update. Ann Rheum Dis 2017;76:960_77.[2]Rendas-Baum R, Wallenstein GV, Koncz T et al. Evaluating the efficacy of sequential biologic therapies for rheumatoid arthritis patients with an inadequate response to tumor necrosis factor-α inhibitors. Arthritis Res Ther 2011;13:R25.[3]Nagy G, et al. EULAR definition of difficult-to-treat rheumatoid arthritis. Ann Rheum Dis 2021;80:31–35. doi:10.1136/annrheumdis-2020-217344.Disclosure of Interests:None declared

Background:Ankylosing spondylitis (AS) can significantly impact quality of life. Tofacitinib is an oral Janus kinase inhibitor under investigation for the treatment of adult patients (pts) with AS. The safety/efficacy (including pt-reported outcomes [PROs]) of tofacitinib in pts with AS was assessed in a Phase 3 trial (NCT03502616).1Objectives:To evaluate the effect of tofacitinib on pt-reported pain, fatigue, overall health and work productivity in pts with active AS enrolled in the Phase 3 trial.Methods:Pts with an inadequate clinical response or intolerance to ≥2 oral NSAIDs were randomised in a double-blind fashion to tofacitinib 5 mg twice daily (BID) or placebo (PBO) for 16 weeks. At Week (W)16, all pts received open-label tofacitinib 5 mg BID up to W48. Least squares (LS) mean changes from baseline (Δ) up to W48 are reported for the following outcomes: pt assessment of nocturnal spinal pain, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Short Form-36 Health Survey version 2 (SF-36v2; W16 and W48 only), and Work Productivity and Activity Impairment Questionnaire (WPAI; W16 and W48 only).Results:At W16, there were greater improvements from baseline in pain (total back pain [previously published1] and nocturnal spinal pain) and fatigue (FACIT-F total score; experience and impact domain scores) with tofacitinib vs PBO (p≤0.05; Table 1); improvements were observed as early as W2. Also, improvements in SF-36v2 physical component summary (PCS) (Table 1), and physical functioning, role-physical, bodily pain, general health and social functioning domains (Figure 1) were greater with tofacitinib vs PBO at W16 (p≤0.05). Similarly, improvements in WPAI scores at W16 were greater with tofacitinib vs PBO (p≤0.05), except for % work time missed (Table 1). Improvements with tofacitinib continued up to W48 (Table 1/Figure 1). Generally, pts receiving PBO who advanced to tofacitinib at W16 reported similar improvements after switching to tofacitinib (Table 1/Figure 1).Table 1.PROs at baseline and Δ at W16 and W48Baseline,mean (SD) [N1]Δ, W16,LS mean (SE)Δ, W48,LS mean (SE)Tofacitinib5 mg BID (N=133)PBO(N=136)Tofacitinib5 mg BIDPBOp valueTofacitinib5 mg BIDPBO→tofacitinib5 mg BIDNocturnalspinal paina6.8 (1.9)6.8 (1.9)-2.67 (0.20)-0.84 (0.20)-3.52 (0.23)-3.01 (0.23)FACIT-Ftotal scorea,b27.2 (10.7)27.4 (9.3)6.54 (0.80)3.12 (0.79)0.00089.54 (0.90)7.35 (0.89)FACIT-F experience domaina8.9 (4.3)8.7 (4.0)2.85 (0.36)1.29 (0.36)0.00074.22 (0.40)3.40 (0.40)FACIT-Fimpactdomaina18.3 (6.9)18.8 (5.9)3.68 (0.49)1.81 (0.49)0.00285.32 (0.54)3.95 (0.54)SF-36v2 PCSb,c33.5 (7.3)33.1 (7.0) [135]6.69 (0.59)3.14 (0.59)8.81 (0.720)7.39 (0.71)SF-36v2 MCSc39.4 (11.1)39.8 (12.7) [135]3.45 (0.91)2.13 (0.92)0.25297.07 (0.93)6.35 (0.92)WPAIc% activity impairment56.5 (23.4)56.0 (21.4)-19.03 (1.97)-5.63 (1.97)-27.37 (2.34)-19.77 (2.31)% work time missed9.9 (22.4) [81]11.5 (24.6) [88]-3.65 (2.66)0.88 (2.62)0.1784-8.10 (2.14)-5.79 (2.05)% impairment while working48.4 (26.3) [79]49.6 (22.2) [85]-19.83 (2.27)-6.94 (2.30)-25.35 (2.77)-23.00 (2.66)% overall work impairment50.8 (27.4) [79]53.5 (23.1) [85]-21.49 (2.51)-7.64 (2.56)-27.63 (3.01)-23.22 (2.90)aMMRMbGlobal type I error-controlled endpointcAnalysis of covariance model for W16 and MMRM for W48MCS, mental component summary; MMRM, Mixed Model for Repeated Measures; N, number of pts in full analysis set; N1, number of pts included in the analysis (if different from N); SD, standard deviation; SE, standard errorConclusion:In pts with active AS, improvements in spinal pain, fatigue, overall health and work productivity were greater with tofacitinib vs PBO at W16; improvements continued up to W48. These PRO findings support the primary efficacy results of this Phase 3 trial,1 and add to the overall understanding of the benefit/risk profile of tofacitinib in patients with AS.References:[1]Deodhar et al. Arthritis Rheumatol 2020; 72 (S10): Abs L11.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Emma Mitchell, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Victoria Navarro-Compán Speakers bureau: AbbVie, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer Inc, UCB, Grant/research support from: AbbVie, Novartis, James Cheng-Chung Wei Speakers bureau: Eli Lilly, Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer Inc, UCB, Filip van den Bosch Shareholder of: AbbVie, Celgene, Eli Lilly, Galapagos, Gilead, Merck, Novartis, Pfizer Inc, UCB, Marina Magrey: None declared, Lisy Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Cunshan Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oluwaseyi Dina Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Vibeke Strand Consultant of: AbbVie, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Corrona, Eli Lilly, Galapagos, Genentech/Roche, Gilead, GSK, Ichnos, Inmedix, Janssen, Kiniksa, Merck, Myriad Genetics, Novartis, Pfizer Inc, Regeneron, Samsung, Sandoz, Sanofi, Scipher, SetPoint Medical, UCB

Background:Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated enzyme with paraoxonase, lactonase and arylesterase activities.1 PON1 contributes to the antioxidant properties of HDL, and is being investigated for its atheroprotective properties.1 Patients (pts) with rheumatoid arthritis (RA) who are homozygous for the RR genotype of the Q192R gene polymorphism on PON1 (rs662) have increased paraoxonase activity, and lower risk of carotid plaques, vs those with QQ or QR genotypes.2 Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA.Objectives:To investigate the relationship between PON1 genotype/activity and risk of major adverse cardiovascular events (MACE) in the tofacitinib RA clinical programme.Methods:In this post hoc analysis, data were pooled from pts enrolled in nine Phase 2/3 studies of tofacitinib in RA. Enzyme activities in pt plasma samples were measured at individual study baseline (BL) and at follow-up visits using three substrates: paraoxon (paraoxonase activity), dihydrocoumarin (lactonase activity) and phenylacetate (arylesterase activity). The effect of the PON1 Q192R genotype (QQ, QR or RR) on BL paraoxonase/lactonase/arylesterase activity was assessed using linear regression for each study, with age and sex as covariates, and then fixed-effect meta-analysis assessed effects across studies. The risk of MACE by enzyme activity was determined using Cox proportional hazards regression stratified by clinical studies. Univariate regression against BL enzyme activity and other risk factors, as well as both minimally and fully adjusted multivariable regressions against time-varying enzyme activity, are presented.Results:The analysis included 1969 pts with RA who received ≥1 dose of tofacitinib and had PON1 activity measures available at BL; 39 pts had ≥1 MACE event. Compared with the QQ genotype, the RR genotype had a highly significant positive association with BL paraoxonase activity, and a highly significant negative association with BL lactonase and arylesterase activity (Table 1). A univariate analysis identified several BL covariates significantly associated with risk of MACE (Figure 1a). Time-varying models found a highly significant association of increased paraoxonase activity over time with lower risk of future MACE, even after controlling for low-density lipoprotein or HDL cholesterol levels, and other traditional cardiovascular (CV) risk factors identified in univariate analysis (Figure 1b), with similar findings for lactonase and arylesterase (data not shown).Table 1.Effect of PON1 genotype (RR vs QQ) on BL enzyme activitynEstimate95% CIp valueCochran’s Q testParaoxonase12291.0350.93, 1.1410.209Lactonase1188-0.375-0.505, -0.2460.025Arylesterase1231-1.016-1.382, -0.6490.251Fixed-effects model; estimate >0 favours RR genotype and BL, baseline; CI, confidence intervalConclusion:Higher activity of the HDL-associated protein PON1 over time was associated with a significantly reduced risk of future MACE in pts with RA receiving tofacitinib, after controlling for traditional CV risk factors and cholesterol levels. Further investigation of PON1 as a novel functional lipid biomarker to assess CV risk in pts with RA is warranted.References:[1]Mackness & Mackness. Gene 2015; 567: 12-21.[2]Charles-Schoeman et al. Arthritis Rheum 2013; 65: 2765-2772.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Jennifer Higginson, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Christina Charles-Schoeman Consultant of: AbbVie, Gilead, Pfizer Inc, Regeneron-Sanofi, Grant/research support from: AbbVie, Bristol-Myers Squibb, Pfizer Inc, Craig Hyde Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shunjie Guan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Neil Parikh: None declared, Jennifer Wang: None declared, Ani Shahbazian: None declared, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Andrews Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

ObjectiveTo evaluate the efficacy, safety and dose response of a novel oral Janus kinase inhibitor, peficitinib (ASP015K), as monotherapy in Japanese patients with moderate to severe rheumatoid arthritis (RA).MethodsIn a 12-week, double-blind study, 281 adult patients with RA with active disease not on concomitant disease-modifying antirheumatic drug therapy were randomised equally to once-daily placebo or peficitinib 25, 50, 100 and 150 mg. The primary endpoint was American College of Rheumatology (ACR) 20 response in the peficitinib treatment groups versus placebo at week 12.ResultsMean age was 53.0 years, 81.1% were female and 25.3% had previously used antitumour necrosis factor therapy. Peficitinib 50, 100 and 150 mg each showed statistically significantly higher ACR20 response rates compared with placebo, and response rates increased up to 150 mg with a statistically significant dose response. The total incidence of treatment-emergent adverse events (TEAEs) was similar between the placebo (64.3%) and peficitinib 25, 50, 100 and 150 mg groups (70.9%, 64.9%, 52.7% and 67.2%, respectively). TEAEs occurring more frequently in the peficitinib group compared with the placebo group included nasopharyngitis, increased blood creatine phosphokinase and diarrhoea. No cases of serious infections were reported. Herpes zoster occurred in four patients (two each in peficitinib 25 and 100 mg).ConclusionsTreatment with peficitinib as monotherapy for 12 weeks in Japanese patients with moderate to severe RA is efficacious and showed acceptable safety profile. These findings support further developments of peficitinib for RA treatment.Trial registration numberNCT01649999; Results.

We read the paper by Rimar et al 1 in your journal with great interest. They reported the case with refractory polyarteritis nodosa treated with tofacitinib, a janus kinase inhibitor, successfully. As shown in their paper, recent advances in the era of biologic agents have improved the management of difficult-to-treat cases dramatically. Considering that tofacitinib blocks interleukin (IL)-6-mediated signalling pathway through inhibiting janus kinase 1, inhibiting IL-6 cascade may also be effective in polyarteritis nodosa. In this regard, tocilizumab, a biologic agent targeting IL-6 receptor, has shown its efficacy in a variety of diseases such as rheumatoid arthritis, adult-onset Still’s disease, large-vessel vasculitis and Behcet’s disease.2–5 Although the precise pathogenesis of polyarteritis nodosa remains unclear, serum IL-6 levels correlate with disease severity, suggesting the involvement of IL-6 in the disease process.6 Therefore, we assume that tocilizumab may benefit polyarteritis nodosa as a therapeutic option. To investigate the effectiveness and safety profile of tocilizumab in patients with polyarteritis nodosa, we performed a systematic literature …

Background:PsA is a disease with multiple manifestations; it has significant impact on physical and emotional aspects of pts’ life. PROs as well as disease activity are an important instrument for assessing treatment response. Tofacitinib (TF) is an oral Janus kinase inhibitor; in RCT TF demonstrated efficacy in active PsA pts concerning PROs [1] but there is currently no evidence from real clinical practice.Objectives:to study the influence of TF on disease activity and PROs in 3/6 months (mo) of therapy in pts with active PsA in clinical practice.Methods:41(M/F=24(58.5%)/17(41.5%) PsA pts fulfilling the CASPAR criteria were included. Mean age 42.4±10.3 years (yrs), median (Me) PsA duration 72 [35;120] mo, pts had inadequate response to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs, mostly Methotrexate)/biological (b) DMARDs (29% of pts). Pts were treated with TF 5 mg twice daily after signing consent participation forms. At baseline (BL) and in 3/6 mo of therapy PsA activity was evaluated by Tender Joint Count (TJC68), Swollen Joint Count (SJC66); PGA, physician global assessment by Visual Analog Scale (VAS), DAPSA. PROs were measured by PtGA VAS, PtPain VAS, BASDAI, HAQ, DLQI, RAPID, FACIT, PsAID12,Patient-AcceptableSymptomState (PASS) of PsAID12≤4. PsAID12 was analyzed as a change above the minimal clinical important difference (MCID) -1.25 points [2]. Higher PsAID12 scores are considered to be worse and correspond to poorer PsA-specific health-related quality of life. M±SD, Me [Q25; Q75], %, t-test, Pierson-χ2, Manna-Whitney tests were performed. All pResults:At BL 87.8% of pts had high PsA activity by DAPSA. By 3/6 mo of therapy significant improvement in all PsA activity indexes and PROs were observed (table 1) (for all pTable 1.Change in all evaluated parameters from BL to 3/6 mo.Parameters,M±SDBL3 mo6 moTJC6818.1 ±9.86.3±6.9*4.9±5.0**SJC6612.8±7.73.7±4.3*2.5±4.0**BASDAI6.0±1.72.2±1.63*1.77±1.42**DAPSA44.2±17.115.2±12.4*11.8±9.4**CRP (mg/l)27.4±29.35.1±7.8*6.2±11.6**PtPain, VAS, mm65 [50; 75]20 [10;30]*18 [5;30]*PtGA, VAS, mm70 [50; 80]23 [14; 35]*20 [10; 30]**ESR (mm/h)32±25.514.8±16,3*13.6±16.3**Total PsAID12 score (over past week, 0-10)5.18±2.142.07±1.65*1.68±1.48**PsAID12 PASS, %25.666.771.8HAQ1 [0.625; 1.5]0.5 [0.125; 0.875]*0.5 [0; 0.875]**DLQI5 [2; 12]2 [0; 6]*2 [0; 4]**FACIT29 [23;38]39.5 [31.5; 48]*38 [32;45]**RAPID16 [13.3; 18.6]6.5 [3.7; 9.1]*5 [2.3; 8.3]***pFigure 1.PsAID12 domains at BL and at 3/6 mo of TF treatment.Conclusion:In real clinical practice TF provides significant and clinically considerable improvement of PsA activity and PROs, including pain, psychological and emotional status.References:[1]Strand V, et al. RMD Open 2019;5:e000806. doi:10.1136/rmdopen-2018-000806.[2]Holland R, et al. Ann Rheum Dis. 2018;77:343-47.Disclosure of Interests:Tatiana Korotaeva Consultant of: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Lyubov Vorobyova: None declared, Elena Loginova Speakers bureau: Janssen, ELENA GUBAR: None declared, Yulia Korsakova: None declared, Svetlana Glukhova: None declared, Polina Karpova: None declared

Background:Obesity is highly prevalent in PsA (~45%)1and is associated with a reduced response to TNF inhibitors.2Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA.Objectives:This post hoc analysis assessed tofacitinib efficacy and safety in patients (pts) with PsA by baseline (BL) body mass index (BMI) category.Methods:Data were pooled from two placebo (PBO)-controlled, double-blind, Phase 3 studies in pts with active PsA and an inadequate response to ≥1 conventional synthetic DMARD (OPAL Broaden [12 months;NCT01877668]) or to ≥1 TNF inhibitor (OPAL Beyond [6 months;NCT01882439]).3,4This analysis included pts randomised to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID or PBO, stratified by BL BMI: 2, ≥25–2, ≥30–2, or ≥35 kg/m2. Efficacy and safety were reported to Month (M)3. M3 efficacy outcomes included ACR20/50/70 and HAQ-DI responses, dactylitis and enthesitis resolution rates and changes from BL in HAQ-DI, Short Form-36 Version 2 (SF-36v2) Physical (PCS) and Mental Component Summary (MCS) scores, and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scores. Safety outcomes included adverse events (AEs), such as cardiovascular (CV) events and changes in lipid levels and liver function tests (LFTs).Results:This analysis included 710 pts; 43.8% were obese (BMI ≥30). At BL, 161 (22.7%) pts had a BMI 2.87 mg/L (49.1% in BMI Conclusion:Regardless of BL BMI, tofacitinib demonstrated greater efficacy than PBO at M3 in pts with PsA. Similar to other advanced therapies,2reduced efficacy was generally observed in tofacitinib and PBO pts with a BL BMI ≥35. Tofacitinib safety appeared consistent across all BL BMI categories.References:[1]Labitigan et al. Arthritis Care Res (Hoboken) 2014;66:600-07.[2]Singh et al. PLoS One 2018;13:e0195123.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.Acknowledgments:Medical writing support was provided by Mark Bennett of CMC Connect, McCann Health Medical Communications, and funded by Pfizer Inc.Disclosure of Interests:Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Alexis Ogdie Shareholder of: Amgen, Novartis, Pfizer Inc, Grant/research support from: Novartis, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Corrona, Eli Lilly, Novartis, Pfizer Inc, Jon T Giles Grant/research support from: Pfizer Inc, Juan Jesus Gomez-Reino Grant/research support from: AbbVie, Novartis, Pfizer Inc, Roche, UCB, Consultant of: Pfizer Inc, Speakers bureau: AbbVie, Bristol-Myers Squibb, Janssen, MSD, Pfizer Inc, Roche, UCB, Philip Helliwell: None declared, Lori Stockert Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Wael Joseph Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Daniela Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, John Woolcott Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ana Belen Romero Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background:Tofacitinib (TF) is an oral Janus kinase inhibitor approved for PsA treatment. It has demonstrated comparable to ADA efficacy in RCT in reducing PsA clinical symptoms1,2. There is currently no data concerning comparative effectiveness of TF and ADA in clinical practice. The Russian PsA RegisTry (RU-PsART) collected data from 43 rheumatology centers of the Russian Federation.Objectives:to study responses to TF or ADA over a period of 6 months (mo) treatment in patients (pts) with active PsA in real clinical practice.Methods:77 (M/F=43/34) PsA pts fulfilling the CASPAR criteria from the RU-PsART cohort were divided into two groups according to the treatment given. 41pts (M/F=24 (58.5%)/17 (41.5%), mean age 42.4±10,3 years (yrs), median (Me) PsA duration 72 [35;120] mo were treated with TF 5 mg twice daily. 36 pts (M/F=19 (52.8%)/17 (47.2%), mean age 44±11.5 yrs, Me PsA duration 59 [22;102] mo were treated with ADA 40 mg/2 weeks, subcutaneous, as a first-line bDMARD. In TF/ADA groups 89%/52.8% pts accordingly were given combination therapy with Methotrexate (MTX). At baseline (BL) and at 6 mo of therapy PsA activity by DAPSA, BASDAI, the number of pts (NPts) with dactylitis, enthesitis by LEI, BSA, HAQ were evaluated in both groups. At 6 mo of therapy the NPts who achieved remission by DAPSA (≤4)/Low activity (LA)≤14) and Minimal disease activity (MDA, 5 of 7) were calculated in both groups. M±SD, Me [Q25; Q75], Min-Max, %, t-test, Pierson-χ2, Manna-Whitney, Wilcoxon tests were performed. All pResults:At BL TF pts had higher PsA activity by DAPSA compared to ADA group: 44.2[37.8; 55.3]/35.8 [21.1; 52] accordingly (p=0.03). At 6 mo of treatment DAPSA significantly decreased in TF/ADA groups - to 11 [4,3; 17,3]/9,1[6; 19,6] (p3% significantly reduced in the TF group: from 20 (51,3%) to 8 (26,7%) pts (pTable 1.MDA, DAPSA LA/Remission in TF/ADA at 6 moTFADAStudyEventsSubjectsEventsSubjectsOR (95% CI)PDAPSA remission abs, % achieved11(26,8%)416(20,8%)291,406(0,453-4,366)0.556DAPSA LA abs, % achieved15(36,6%)4113(44,8%)290,710(0,269-1,872)0.489MDA abs, % achieved16(40%)409(30%)301,556(0,569-4,249)0.389Conclusion:In real clinical practice TF and ADA demonstrated comparable effectiveness in all clinical domains of active PsA and showed equal result in achievement of MDA/LA/Remission according to DAPSA.References:[1]Mease P, Hall S, FitzGerald O, et al. N Engl J Med 2017;377:1537–50.[2]Gladman D, Rigby W, Azevedo VF, et al. N Engl J Med 2017;377:1525–36.Acknowledgments:noDisclosure of Interests:Elena Loginova Speakers bureau: Janssen, Tatiana Korotaeva Consultant of: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, Speakers bureau: Pfizer, MSD, Novartis, AbbVie, Celgene, JSC BIOCAD, Janssen, UCB, Lilly and Novartis-Sandoz, ELENA GUBAR: None declared, Yulia Korsakova: None declared, Svetlana Glukhova: None declared, Elizaveta Vasilenko: None declared, Aleksey Vasilenko: None declared, Natalia Kuznetsova: None declared, Irina Patrikeeva: None declared

Background:PsA is a chronic, systemic inflammatory disease with signs and symptoms across multiple domains, including cutaneous manifestations, which can impact health-related quality of life (HQoL). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. In two Phase 3 randomised studies, patients (pts) with active PsA treated with tofacitinib experienced greater improvements in various dermatologic endpoints, compared with placebo. As pruritus is a bothersome symptom of skin disease in pts with PsA, we sought to determine how tofacitinib affects HQoL via clinical improvements in skin symptoms including itch.Objectives:To determine the relationships between tofacitinib treatment, dermatologic symptoms and pt-reported HQoL related to skin disease in PsA.Methods:Analyses used data (mean scores from Months 1 and 3) from two Phase 3 studies (OPAL Broaden [NCT01877668]; OPAL Beyond [NCT01882439]) of pts with active PsA treated with tofacitinib 5 mg twice daily or placebo; pts were tumour necrosis factor inhibitor (TNFi)-naïve or had previous inadequate response (IR) to ≥1 TNFi. All pts were treated continuously with a single conventional synthetic DMARD. Mediation modelling, a statistical method used to assess mechanisms underlying observed relationships between different variables via other explanatory variables (mediators), was applied. The mediation model included: treatment, as the independent (explanatory) binary variable (tofacitinib 5 mg BID vs placebo); HQoL, measured by Dermatology Life Quality Index (DLQI), as the dependent (outcome) variable; and two mediators, pt-reported Itch Severity Index (ISI) and Physician’s Global Assessment of Psoriasis (PGA-PsO) (a latent variable represented by erythema, induration and scaling). The initial model designated the treatment effect on DLQI mediated via ISI and PGA-PsO as an indirect effect, and treatment effects not attributable to ISI or PGA-PsO as a direct effect (Figure 1).Results:Data were collected from 468 pts, pooled from both studies. In the initial model (pooled data), the effect of tofacitinib treatment on DLQI was largely mediated by itch (measured by ISI) and PGA-PsO (indirect effect) (pConclusion:Dermatology-focused mediation modelling showed that a majority of the effect (~80%) of tofacitinib treatment on DLQI is mediated by improvements in itch, with ~20% mediated via improvements in PGA-PsO.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Peter C. Taylor Grant/research support from: Celgene, Eli Lilly and Company, Galapagos, and Gilead, Consultant of: AbbVie, Biogen, Eli Lilly and Company, Fresenius, Galapagos, Gilead, GlaxoSmithKline, Janssen, Nordic Pharma, Pfizer Roche, and UCB, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rebecca Germino Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Joseph F. Merola Consultant of: Merck, AbbVie, Dermavant, Eli Lilly, Novartis, Janssen, UCB Pharma, Celgene, Sanofi, Regeneron, Arena, Sun Pharma, Biogen, Pfizer, EMD Sorono, Avotres and LEO Pharma, Gil Yosipovitch Grant/research support from: Galderma, Kiniksa, Leo, Menlo, Novartis, Pfizer, Sanofi Regeneron, Consultant of: Eli Lilly, Galderma, Kiniksa, Leo, Menlo Therapeutics, Novartis, Pfizer Inc, Sanofi Regeneron, Trevi, Sienna

Background:Dermatomyositis (DM) is a systemic, autoimmune disease affecting the skin and proximal skeletal muscles. A subset of DM patients present with subclinical or resolved muscle involvement but continue to have skin disease. In these cases, first and second line treatments including glucocorticoids are sometimes insufficient for controlling the disease, necessitating escalation of treatment. Several recent studies have investigated the response of Tofacitinib, an oral Janus Kinase inhibitor approved for the treatment of rheumatoid arthritis, in DM patients and patients with inflammatory skin diseases.Objectives:Due to the reported ability of JAK inhibitors to suppress type 1 interferon (IFN) signaling, which is suspected to be upregulated in DM, we evaluated the efficacy of treatment with Tofacitinib in four refractory DM patients.Methods:Four patients with dermatomyositis without evidence of current muscle involvement began treatment with Tofacitinib 11 mg daily after they had failed or had adverse effects to first and second line immunosuppressive agents. Their medical records were reviewed at 0, 3, and 6 months, with improvement measured using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) activity score. Throughout their treatment they were additionally monitored for improvement in markers of inflammation and the necessity for concomitant treatments. Patients were monitored for adverse effects to Tofacitinib treatment.Results:All four patients within the case series showed significant improvement of their cutaneous disease activity (CDASI scores improved by 8-15 points) over the first 6 months, with three of the four having achieved minimal clinically improved difference of >= 5 point by three months. Based on the CDASI, three of the cases’ disease classification changed from moderate-to-severe disease to mild disease. The last patient initially presented with mild disease. Other outcomes noted included improved pruritus in 3 patients and improvement of calcinosis in 1 patient. One patient was additionally able to stop concomitant treatment with prednisone and IVIG at 3 and 6 months, respectively. This patient had been on daily prednisone for 4 years. Only other patient on prednisone was on low dose of 3mg daily. The patients all had normal muscle exams prior to treatment with Tofacitinib. No worsening muscle involvement or adverse effects were noted with Tofacitinib use.Conclusion:Tofacitinib is believed to play a role in the inhibition of IFN signaling pathways that are overactive in dermatomyositis. All four patients within this retrospective study showed significant improvement of cutaneous disease with Tofacitinib use.References:[1]Moghadam-Kia S.Rheumatology. 2019;58(6):1011-1015.[2]Kurtzman D.JAMA Dermatol. 2016;152(8):944.[3]Paik J.Semin Arthritis Rheum. 2017;46(4):e19.[4]Kurasawa K.Rheumatology. 2018;57(12):2114-2119.[5]Anyanwu CO.Br J Dermatol. 2015; 173(4):969-974.Gender/ Age/ EthnicityDM Subtype /disease durationPrevious TreatmentConcomitant Treatment with TOFCDASI ActivityCDASI Activity 3 monthCDASI Activity 6 monthOther OutcomeM/ 55/ CaucasianAmyopathic DM; 5 yearsAZA, HCQ, IVIG, MTX, MMF, Prednisone, RCI, RTX, TACHCQ1254NoneF/ 37/ CaucasianAmyopathic DM; 7 yearsAZA, HCQ, IVIG, MTX, MMF, Prednisone, RCI, TACPrednisone, IVIG, MTX1585Pruritus and CRP improvedF/ 60/ CaucasianAmyopathic DM; 4 yearsAZA, MTX, PrednisonePrednisone, MTX17155Pruritus improvedF/ 47 African AmericanClassic DM; 5 yearsAZA, colchicine, HCQ, IVIG, MTX, MMF, pamidronate Prednisone, RCI, RTX, TACIVIG, Colchicine2287Pruritus and calcinosis improvedAbbreviations: CDASI, Cutaneous Dermatomyositis Disease Area and Severity Index; AZA, azathioprine; CRP, C-reactive protein; DM, Dermatomyositis, HCQ, hydroxychloroquine; IVIG, intravenous immunoglobulin; MTX, methotrexate; MMF, mycophenolate mofetil; RCI, repository-corticotropin injection; RTX, rituximab; TAC, tacrolimus; TOF, tofacitinib;Disclosure of Interests:Kirsten Riggle: None declared, Aarat Patel Speakers bureau: Abbvie, Mallinckrodt, Celgene, Lilly, Rohit Aggarwal Grant/research support from: Pfizer, Genentech, BMS, Mallinckrodt, Consultant of: Pfizer, Genentech, BMS, Mallinckrodt, Bristol Myers-Squibb, octapharma, CSL Behring, AstraZeneca, Corbus, Kezar, Abbvie

Background:Tofacitinib (TOF) is an orally administered Janus Kinase (JAK) inhibitor and is commonly used in rheumatoid arthritis. There is a heterogeneity among numbers reported from different continents about herpes zoster (HZ) incidence rate (1-3). However, data about HZ risk in our country, which stands like a bridge between Asia and Europe, is lacking.Objectives:To assess the real-life incidence of herpes zoster in RA patients under tofacitinib.Methods:We analyzed all patients who had at least 1 control visit under tofacitinib and registered to HURBIO database. We calculated incidence rate by dividing the number of patients with herpes zoster to total follow-up years, then multiplied by 100 (per 100 patient-years).Results:A total of 204 (174 (85.4%) female) patients were recruited. Mean age was 53.2±12.5 years. Mean disease duration was 11.5±8.1 years. Rheumatoid factor and anti-CCP antibodies were positive in 135/198 (68.1 %) and 115/171 (67.2 %) patients, respectively. Median follow-up while receiving TOF was 11.6 (IQR:5.2-26.2) months. Combination with DMARDs was used in 83.3% of patients. 55.5% of patients was biologic-naive. Eleven (5.3%, incidence rate: 3.9 (2.3-8.5; % 95 CI) per 100 patient-years) patients had zona zoster. Ten of these patients was female, median age was 59 (IQR; 52-69) and 4 of them was older than 65 years-old. Rheumatoid factor was positive in 9 patients. Only 1 of these patients had diabetes. Median follow-up of these patients under TOF was 8.1(IQR: 6-25) months. Ten of these patients had concomitant DMARDs (9 hydroxycholoroquine, 4 methotrexate, 2 leflunomide; according to last follow-up visit) and 9 of them received concomitant steroids (med(IQR); 4 (1-8) mg- at equivalant methyl-prednisolon dose). Eight of them was biologic-naive. Tofacitinib was discontinued in 4 of these patients.Conclusion:In this real-life data from Turkey, we found a HZ incidence rate similar to that reported from USA and global data; however, we found a lower incidence rate that reported from Japan (Figure 1).Figure 1.Reported herpes zoster incidence rates across different countries (numbers in paranthesis indicate reference number)References:[1]Winthrop KL, Curtis JR, Lindsey S, Tanaka Y, Yamaoka K, Valdez H, et al. Herpes Zoster and Tofacitinib: Clinical Outcomes and the Risk of Concomitant Therapy. Arthritis & rheumatology (Hoboken, NJ). 2017;69(10):1960-8.[2]Curtis JR, Xie F, Yun H, Bernatsky S, Winthrop KL. Real-world comparative risks of herpes virus infections in tofacitinib and biologic-treated patients with rheumatoid arthritis. Ann Rheum Dis. 2016;75(10):1843-7.[3]Yamanaka H, Tanaka Y, Takeuchi T, Sugiyama N, Yuasa H, Toyoizumi S, et al. Tofacitinib, an oral Janus kinase inhibitor, as monotherapy or with background methotrexate, in Japanese patients with rheumatoid arthritis: an open-label, long-term extension study. Arthritis Res Ther. 2016;18:34.Disclosure of Interests:Emre Bilgin: None declared, Furkan Ceylan: None declared, Emine Duran: None declared, Ertugrul Cagri Bolek: None declared, Bayram Farisoğullari: None declared, Gözde Kübra Yardimci: None declared, Levent Kiliç: None declared, Ali Akdoğan: None declared, Omer Karadag: None declared, Şule Apraş Bilgen: None declared, Sedat Kiraz: None declared, Ali İhsan Ertenli: None declared, Umut Kalyoncu Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, UCB

Background:Axial involvement in psoriatic arthritis (PsA) is quite common. Tofacitinib (TOFA) is an oral Janus kinase inhibitor. There is no data on the use of TOFA in PsA patients (pts) with axial involvement, nor is there any data on its effect on active MRI sacroiliitis (MRI-SI). There are only preliminary results of a randomized clinical trial on TOFA efficacy on active SI in AS (1).Objectives:To study the effect of TOFA therapy on active MRI-SI in PsA pts.Methods:40 pts (F/M – 23/17) with active PsA fulfilling the CASPAR criteria were examined. No patients with inflammatory back pain (IBP) were specifically selected. Median (Me) age 41.0 [35.0; 50.0] yrs, Me PsA duration 6.0 [3.0; 10.0] yrs. Pts underwent a standard clinical examination of PsA activity: Me tender joint count 19 [12; 24], swollen joint count 11 [8; 16], patient’s global disease activity measured by Visual Analogue Scale (VAS) 70 [50; 80], patient’s pain VAS 65 [50; 75], Me activity indixes: DAPSA 44.2 [37.8; 55.3], BASDAI 6.0 [4.2; 7.0], ASDAS 3.8 [2.8; 4.4]. Me CRP 21.3 [3.2; 72.3] mg/L, ESR 28 [12; 52] mm/h. Enthesitis was observed in 65.9% of pts, dactylitis in 53.7% of pts. Apart from a standard clinical examination, all 40 pts underwent sacroiliac joint (SIJ) MRI on scanner Siemens General Electric 1.5 TESLA. Bone marrow edema/osteitis on MRI (STIR) with one lesion on two consecutive slices or at least two lesions on a single slice, was considered active MRI-SI. MRI results were evaluated by 2 independent readers (radiologist and rheumatologist). TOFA was given in 5 mg tablets bds over a period of 6 months, after which 35 patients underwent SIJ MRI. Me [Q25; Q75], Pierson-χ2tests were performed. All pResults:Prior to TOFA therapy, active MRI-SI was detected in 14 of 40 (35%) pts: bilateral in 9 pts, unilateral in 5 pts. At the end of 6 months therapy, active MRI-SI was detected in 4 of 35 (11.4%) pts observed: in 1 pt with baseline bilateral MRI-SI and in 2 pts with unilateral MRI-SI. 1 pt showed negative dynamics, that is, development of active MRI-SI (absent at baseline). The decrease in number of active MRI-SI patients is statistically significant (p = 0.017; Pearson-χ2). At baseline, inflammatory changes were detected in 23 of 80 (28.8%) SIJs, after 6 months of therapy they were found in 5 of 70 (7.1%) SIJs observed. Decrease in number of SIJs with active inflammation is statistically significant (p = 0.001; Pearson-χ2). At baseline, Me BASDAI 6.0 [4.2; 7.0], Me ASDAS 3.8 [2.8; 4.4]. After 6 months of treatment, Me BASDAI 1.4 [0.6; 3.2], Me ASDAS1.5 [1.0; 2.1] (p = 0.001 for both comparisons).Conclusion:JAK inhibition using TOFA therapy shows high efficacy in reducing active MRI-SI and decreasing activity of axial involvement in PsA. More extensive studies are needed.References:[1]van der Heijde D. et al. Ann. Rheum. Dis. 2017;76:1340–47Disclosure of Interests:ELENA GUBAR: None declared, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Yulia Korsakova: None declared, Elena Loginova Speakers bureau: Janssen, Polina Karpova: None declared

Background:EULAR and ACR guidelines recommend a treat-to-target approach for patients with RA including regular assessments of disease activity. Glucocorticoids are commonly used to control inflammation associated with uncontrolled disease. However, patients using glucocorticoids may develop short- and long-term side effects.Objectives:To examine the real-world use of glucocorticoids among patients with RA who are disease-modifying antirheumatic drug (DMARD)-naïve or failing their first conventional synthetic DMARD (csDMARD) or biologic DMARD (bDMARD).Methods:From a large US health claims database, this study included adults with ≥2 RA claims ≥30 days apart who started (index date [ID], 1/1/2012–3/31/2017) a first DMARD (DMARD-naïve) or patients who newly initiated a csDMARD and then switched to or added another DMARD (csDMARD switchers), and patients who initiated a first bDMARD and then switched to another bDMARD or Janus kinase inhibitor (JAKi; bDMARD switchers). All patients had continuous enrollment 1-year before and ≥1 year after ID and were evaluated for pre- and post-ID use of glucocorticoids (oral or injectable), prednisone equivalent dose (PED), and duration of exposure ≥30 days.Results:The study included 28,201 patients in the DMARD-naïve cohort, 7,816 csDMARD switchers, and 4,656 bDMARD switchers (median age 54 years for all, 73%–78% female).Among DMARD-naïve patients, 66.5% used glucocorticoids during the pre-ID period (Figure 1) and 61.2% had >7.5 mg/day PED, 21.2% had >30 mg/day PED, and 21.2% had ≥30 days of exposure to glucocorticoids (Figure 2). Post-ID, 69.4% of patients used glucocorticoids, while 54.7% had >7.5 mg/day PED, 13.5% had >30 mg/day PED, and 44.9% had ≥30 days of exposure to glucocorticoids.Among csDMARD switchers, 84.5% of patients used glucocorticoids during the pre-ID period (Figure 1), and 73.4% had >7.5 mg/day PED, 16.0% had >30 mg/day PED, and 56.4% had ≥30 days of exposure to glucocorticoids (Figure 2). During the post-ID treatment, 74.1% of patients used glucocorticoids, 56.2% had >7.5 mg/day PED, 14.4% had >30 mg/day PED, and 45.8% had ≥30 days of exposure to glucocorticoids.Among bDMARD switchers, 85.1% of patients used glucocorticoids in the pre-ID period (Figure 1), and 70.2% had >7.5 mg/day PED, 17.4% had >30 mg/day PED, and 55.2% had ≥30 days of exposure to glucocorticoids (Figure 2). During post-ID treatment, 75.4% of patients used glucocorticoids and 59.7% of patients had >7.5 mg/day PED, 16.7% had >30 mg/day PED, and 45.6% had ≥30 days of exposure to glucocorticoids.Conclusion:Real world glucocorticoid use was high in all categories of DMARD-treated RA patients, at baseline and during their next treatment, suggesting ongoing medical needs. Glucocorticoid doses exceeded 7.5 mg/day for most patients. In addition, many patients had ≥30 days exposure to glucocorticoids, posing an additional safety risk.Disclosure of Interests:Robin K Dore Grant/research support from: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Eli Lilly and Co., Gilead Sciences, Inc., GlaxoSmithKline, Myriad, Novartis, Pfizer, Radius, Regeneron, Sanofi, and UCB., Consultant of: AbbVie, Amgen, Biogen, Bristol-Myers Squibb, Eli Lilly and Co., Gilead Sciences, Inc., GlaxoSmithKline, Myriad, Novartis, Pfizer, Radius, Regeneron, Sanofi, and UCB., Jenya Antonova Employee of: Gilead Sciences. Inc., Magdaliz Gorritz Consultant of: Gilead Sciences, Inc., Lawrence Chang Consultant of: Gilead Sciences, Inc., Handing Xie Consultant of: Gilead Sciences, Inc., Mark C. Genovese Grant/research support from: Abbvie, Eli Lilly and Company, EMD Merck Serono, Galapagos, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, Pfizer Inc., RPharm, Sanofi Genzyme, Consultant of: Abbvie, Eli Lilly and Company, EMD Merck Serono, Genentech/Roche, Gilead Sciences, Inc., GSK, Novartis, RPharm, Sanofi Genzyme

Background:With multiple disease domains affected in PsA, clinical and patient-reported outcome (PRO) measures are important to assess disease improvement following treatment. Rapid, meaningful improvements in disease activity are a priority for physicians and patients (pts). Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. Higher proportions of pts achieved responses in PROs and clinical measures when treated with tofacitinib for 3 months vs placebo (PBO).1-5Proportions of responders were also similar between tofacitinib and adalimumab (ADA) after 3, 6 and 12 months.2,3,5Objectives:To determine the time to initial response using responder definitions for selected PROs and clinical endpoints in pts with active PsA treated with tofacitinib, ADA or PBO switching to tofacitinib.Methods:In this post hoc analysis, data were collected from two Phase 3 studies (OPAL Broaden [12 months;NCT01877668]; OPAL Beyond [6 months;NCT01882439]).3,4Pts receiving tofacitinib 5 or 10 mg twice daily (BID), subcutaneous ADA 40 mg once every two weeks (Q2W; OPAL Broaden only), or PBO switching to tofacitinib 5 or 10 mg BID at Month (M)3, were included. Responder definitions included: HAQ-DI ≥0.35-point improvement from baseline (BL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) total score ≥4-point improvement from BL, minimal disease activity (MDA) yes/no composite response (meeting at least 5 of 7 criteria) and PsA Disease Activity Score (PASDAS) post-BL score of ≤3.2 and >1.6-point improvement from BL. First post-BL data were collected at Week 2 (eg for HAQ-DI) or M1. Time-to-event analyses were performed using the Kaplan-Meier (KM) method, with pts censored at the last observed visit. Log-rank tests compared time to initial response across treatment groups.Results:KM analyses show days to initial response (Figure 1, Figure 2). Time to initial HAQ-DI response was significantly different between treatment groups in OPAL Broaden (pConclusion:Times to initial response in functional ability and disease activity were similar in pts treated with either tofacitinib or ADA. Time to initial response prior to first post-BL observation (Week 2 or M1) was not estimable in this analysis. These results may help physicians better understand the time frame for a meaningful response in pts receiving tofacitinib.References:[1]Strand et al. RMD Open 2019;5:e000808.[2]Strand et al. RMD Open 2019;5:e000806.[3]Mease et al. NEJM 2017;377:1537-50.[4]Gladman et al. NEJM 2017;377:1525-36.[5]Helliwell et al. Arthritis Res Ther 2018;20:242.Acknowledgments:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau of CMC Connect and funded by Pfizer Inc.Disclosure of Interests:Dafna D Gladman Grant/research support from: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – grant/research support, Consultant of: AbbVie, Amgen Inc., BMS, Celgene Corporation, Janssen, Novartis, Pfizer, UCB – consultant, Laura C Coates: None declared, Joseph Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Ming-Ann Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Andrew G Bushmakin Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Elizabeth Bacci Employee of: Evidera, Joseph C Cappelleri Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Philip Helliwell: None declared

Background:PsA is an inflammatory arthritis associated with skin and nail PsO. The treatment target of PsA is MDA. In order to achieve MDA it is necessary to significantly improve musculoskeletal (MSK) symptoms, skin symptoms and patient-reported outcomes (PROs). In RCT it has been recently demonstrated that targeting both joint and skin symptoms is very important in achieving optimal improvement in health-related quality of life [1]. However, there is not enough data from clinical practice. Tofacitinib (TF) is an oral Janus kinase inhibitor approved for the treatment of PsA pts.Objectives:to study the influence of joint, enthesitis, skin and nail symptoms on MDA achievement in active PsA (pts) treated with TF for 6 months (mo).Methods:41pts (M/F=24(58.5%)/17(41.5%) with active PsA fulfilling the CASPAR criteria, were included after signing consent participation forms. Mean age 42.4±10.3 years (yrs), median (Me) PsA duration 72 [35;120] mo, PsO duration 192 [98;312] mo, PASI 14.5 [7;23.8], DAPSA 44.2 [37.8;55.3]. Pts were treated with TF 5 mg twice daily. At baseline (BL) and over a period of 6 mo of therapy PsA activity was evaluated by Tender Joint Count (TJC68), Swollen Joint Count (SJC66); PGA, physician global assessment by Visual Analog Scale (VAS), DAPSA. Enthesitis was evaluated by LEI (Leeds Enthesial Index) plus Plantar Facia (PF); PROs were measured by PtGA VAS, PtPain VAS, HAQ. PsO were measured by PASI/BSA (%). The presence/absent of Nail PsO was evaluated. The number of pts (NPts) who reached MDA (5/7: TJC≤1, SJC≤1, PASI≤1/BSA≤3, PtPainGA≤15, PtGA≤20, HAQ≤0,5, enthesitis count≤1) was calculated. M±SD, Me[Q25;Q75], %, Pearson-χ2, OR 95% (CI) were performed. All pResults:At BL mean TJC/SJC/PtPainGA/PtGA/PASI/HAQ were 19[12;24]/11[8;16]/65[50;75]/70[50;80]/14.5[7;23.8]/1[0.625;1.5] accordingly. Enthesitis/Nail PsO were found in 27 pts (65.9%)/in 33 out of 41 pts (80.5%) respectively. BSA>3% was found in 20 out of 41 pts (51.3%). After 6 mo of therapy all MDA parameters as well as DAPSA score decreased significantly (table 1). The NPts with Enthesitis decreased significantly and became 12 out of 41 pts (30.8%). After 6 mo of therapy the NPts with nail PsO didn’t decrease significantly compared with the BL; the dynamics was: from 33 out of 41 pts (80.5%) to 31 (79.5%) accordingly (p=0.991). MDA was found in 15 out of 41 pts (36.58%). After 6 mo of therapy no significant differences were seen between the groups of pts with/without MDA in the NPts with nail PSO: 11 out of 15 pts (73.33%) and 20 out of 24 (83.3%) accordingly (p=0.456). Enthesitis, PASI, nail PsO had a negative impact on achieving MDA, while joint symptoms and PROs were significantly associated with MDA attainment after 6 mo of TF therapy (Fig. 1).Conclusion:In real clinical practice TF treatment improves all MSK symptoms in active PsA pts. The presence of Enthesitis and Skin/Nail PsO severity at BL has a negative impact on MDA attainment in short-term outcomes. These findings should be taken into consideration when choosing treatment.References:[1]Kavanaugh A, Gottlieb A, Morita A, et al. Ann Rheum Dis 2019;0:1–5. doi:10.1136/annrheumdis-2018-215003Research granted by Pfizer.Table 1.Change in all evaluated parameters from BL to 6 mo.Parameters,BLM±SD6 moM±SDTJC6818.1 ±9.84.9±5.0*SJC6612.8±7.72.5±4.0*DAPSA44.2±17.111.8±9.4*PtPain, VAS, mm65 [50; 75]18 [5;30]*PtGA, VAS, mm70 [50; 80]20 [10; 30]*PASI14.5 [7;23.8]5.6 [0;10.4]*LEI+PF1 [0;2]0[0;0]*HAQ1 [0.625; 1.5]0.5 [0; 0.875]** pFig. 1.Forest plot Joint, Enthesitis, PROs, Skin/Nail PsO contribution in MDA attainment at 6 mo of TF therapy.Disclosure of Interests:Maria Chamurlieva: None declared, Elena Loginova Speakers bureau: Janssen, ELENA GUBAR: None declared, Yulia Korsakova: None declared, Svetlana Glukhova: None declared, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB

Background:Psoriatic arthritis (PsA) is a heterogeneous disease with multiple manifestations and choosing among treatments can be a complex decision. Patients (pts) with axial involvement and pts having dactylitis are more likely to develop a severe disease (1, 2). Tofacitinib (TOFA), an oral Janus kinase inhibitor, showed efficacy in treating PsA pts with dactylitis (3). However, its efficacy in treating PsA pts with activesacroiliitis(SI) and dactylitis has not been studied.Objectives:To study the effect of TOFA therapy in PsA pts having active SI on MRI (MRI-SI) and dactylitis.Methods:40 pts (M/F – 23/17) with active PsA fulfilling the CASPAR criteria were examined. Median (Me) age 41.0 [35.0; 50.0] yrs, Me PsA duration 6.0 [3.0; 10.0] yrs. A standard clinical examination of PsA activity was performed: Me tender joint count 19 [12; 24], swollen joint count 11 [8; 16], patient’s global disease activity measured by Visual Analogue Scale (VAS) 70 [50; 80], patient’s pain VAS 65 [50; 75], Me activity indexes: DAPSA 44.2 [37.8; 55.3], BASDAI 6.0 [4.2; 7.0], ASDAS 3.8 [2.8; 4.4]. CRP 21.3 [3.2; 72.3] mg/L, ESR 28 [12; 52] mm/h. Enthesitis was observed in 65.9% of pts with Me LEI index 1 [0; 1], dactylitis in 53.7% of pts, Me digits with dactylitis 1 [0; 2]. Apart from a standard clinical examination, MRI of sacroiliac joints (SIJs) was performed in all 40 pts using MRI scanner Siemens General Electric 1.5 TESLA. Bone marrow edema/osteitis on MRI (STIR) considered active MRI sacroiliitis (MRI-SI), was evaluated by 2 independent readers (radiologist and rheumatologist). TOFA was given in 5 mg tablets bds over a period of 6 months, after which 35 patients underwent SIJ MRI. Me [Q25; Q75], Pierson-χ2tests were performed. All pResults:Prior to TOFA therapy, MRI-SI was detected in 14 of 40 (35.0%) pts. At the end of 6 months therapy, MRI-SI was detected in 4 of 35 (11.4%) pts: in 3 pts with baseline SI; 1 pt showed negative dynamics, that is, development of active SI (absent at baseline). The decrease in number of active MRI-SI pts is statistically significant (p=0.017; Pearson-χ2). Significant differences between baseline symptoms in patients with MRI-SI (n=14) and without it (n=26) were definedby number of digits with dactylitis:2 [0; 4] and 0 [0; 2] (p=0.047),by ESR: 47 [26; 76] and 20 [6; 37] mm/h (p=0.025), and byWPAI overall work impairment due to health index:80 [60; 84]% and 20 [0; 60]% (р=0.033), respectively; these parameters were higher in MRI-SI subgroup. After 6 months of therapy number of digits with dactylitis, ESR and WPAI indexes were significantly lower as compared with the baseline ones (Table 1).After 6 months of TOFA therapy, no differences were found between groups of pts with and without MRI-SI in the number of digits with dactylitis (p=0.47), in ESR (p=0.79) and in WPAI (p=0.93).Conclusion:In PsA pts significant association of active MRI-SI was found with dactylitis, high ESR level and WPAI. Use of TOFA in pts with both active MRI-SI and dactylitis demonstrated its high efficacy in reduction of SI inflammation and dactylitis; it also significantly improved pts’ work productivity. These findings are important for personalized approach to treatment of PsA.References:[1]Brockbank JE et al. Ann Rheum Dis. 2005;64(2):188-90[2]Mease PJ et al. J Rheumatol 2018;45:1389-96[3]Gladman DD et al. N Engl J Med 2017;377:1525-36Disclosure of Interests:ELENA GUBAR: None declared, Tatiana Korotaeva Grant/research support from: Pfizer, Consultant of: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Speakers bureau: Abbvie, BIOCAD, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Merck Sharp & Dohme, Novartis, Novartis-Sandoz, Pfizer, UCB, Yulia Korsakova: None declared, Elena Loginova Speakers bureau: Janssen, Svetlana Glukhova: None declared, Polina Karpova: None declared

Background:Tofacitinib is an oral Janus Kinase inhibitor for the treatment of rheumatoid arthritis (RA).Objectives:To evaluate the three-year effectiveness of tofacitinib in RA conventional synthetic (cs) DMARDs non-responders.Methods:Data from 374 patients from Russian national register OREL of patients with RA treated with tofacitinib not less than 3 years after failure of conventional DMARDs were included in the statistical analysis. Clinical and laboratory data from 4 consecutive visits with an interval of 12 months between the visits (± 28 days) were analyzed. Treatment with any biologics ever was an exclusion criteria. Demographical (age, sex) and disease-related characteristics of RA (symptoms duration, RF- and ACCP positivity, presence of joint erosions, DAS28, CDAI, number of tender and swollen joints (NTJ, NSJ), erythrocytes sedimentation rate (ESR), C-reactive protein (CRP)) collected. Statistical analysis performed with statistical programs SPSS2017 and GraphPadPrizm. p-value < 0.05 considered as significant.Results:Baseline characteristics of RA patients, involved in the analysis are presented in table 1.Table 1.Baseline characteristics of the patients with RA (n=374).ParameterCharacteristicsMale, n (%)92 (24.5)Age, years (mean±SD)53.4±13.38Symptoms duration, month (mean±SD)140±137Positive rheumatoid factor (RF), n (%)123(32.8)Positive antibodies to cyclic citrullinated peptide (ACCP), n (%)329(87.9)Erosions of hand joints (X-rays), n (%)372 (99.4)BMI, kg/m2(mean ±SD)26.8 ± 6.14Smokers (current and in the past), n (%)54 (14.4)Changes in the diseases activity parameters in patients with RA, treated with tofacitinib not less than 3 years after cs DMARD failure are presented in table 2, figure 1, and figure 2.Figure 1.DAS28 of patients with RA, treated with tofacitinib (n=374) – 3-years follow-up (time-points are presented in years ± 28 days).Figure 2.DAS28 of patients with RA, treated with tofacitinib (n=374) – 3-years follow-up (time-points are presented in years ± 28 days).Table 2.Changes in RA parameters in patients treated with tofacitinib, n=374 (M±SE).Disease characteristicsBaselineYear 1#Year 2#Year 3#C-RP, mg/L30.1±35.08.3±12.87.6±10.79.4±13.5ESR, mm/h35.2±21.222.7±17.221.9±17.722.3±17.3NTJ from 2811.2±6.54.6±4.94.8±5.03.9±3.8NTJ from 287.6±5.12.4±3.21.7±3.11.4±2.8*difference with baseline is significant with p#- ±28 daysConclusion:According to the real world data treatment with tofacitinib may provide good response rates in RA patients, refractory to the previous csDMARDs treatment in long-term perspective.Acknowledgments :PfizerDisclosure of Interests: :Inna Gaydukova Grant/research support from: JSC BIOCAD, Speakers bureau: Pfizer, Novartis, AbbVie, JSC BIOCAD, Сelgene, MSD, Sanofi, V Mazurov: None declared, Alexander Lila: None declared, Andrey Baranov Grant/research support from: Bayer, Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Evgeniy Zhilyaev Speakers bureau: Novartis, UCB, Pfizer, Biocad, Abbvie, MSD, Roche, Ekaterina Koltsova: None declared, Evgeniya Shmidt Speakers bureau: MSD, Novartis, Pfizer, Oxana Fomina: None declared, Irina Bondareva: None declared, Olga Anoshenkova: None declared, Aleksey Vasilenko: None declared, Elizaveta Vasilenko: None declared, Natalya Yudina: None declared, Larisa Knyazeva: None declared, Vyacheslav Poncratov: None declared, Ekaterina Gaydukova: None declared, Evgeny Nasonov Speakers bureau: Lilly, AbbVie, Pfizer, Biocad, R-Pharm

ObjectivesTofacitinib is an oral Janus kinase inhibitor for treatment of psoriatic arthritis (PsA). Patient-reported outcomes (PROs) were evaluated in patients with PsA with inadequate responses to tumour necrosis factor inhibitors (TNFi-IR) in a 6-month, phase III randomised controlled trial (OPAL Beyond [NCT01882439]).MethodsPatients (N=394) received tofacitinib 5 or 10 mg twice daily or placebo (advancing to tofacitinib 5 or 10 mg twice daily at month 3). Least squares mean changes from baseline and percentages of patients reporting improvements ≥minimum clinically important differences and scores ≥normative values were determined in Patient Global Assessment of disease activity (PtGA), Pain, Patient Global Joint and Skin Assessment (PGJS), Short Form-36 Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue), EuroQol 5-Dimensions-3-level (EQ-5D-3L), EQ-VAS and Ankylosing Spondylitis Quality of Life (ASQoL). Nominal p values are without multiple comparison adjustments.ResultsAt month 3, PtGA, Pain, PGJS, SF-36v2 Physical Component Summary (PCS), physical functioning (PF), bodily pain (BP), vitality and social functioning (SF) domains, FACIT-Fatigue Total score, EQ-5D-3L pain/discomfort, EQ-VAS and ASQoL scores exceeded placebo with both tofacitinib doses (role physical [RP] with 10 mg twice daily only; p≤0.05). Patients reporting improvements ≥MCID (%) in PtGA, PGJS, Pain, ASQoL and SF-36v2 PCS, PF, RP, BP, SF (both tofacitinib doses) exceeded placebo (p≤0.05).ConclusionTNFi-IR patients with PsA receiving tofacitinib reported statistically and clinically meaningful improvements in PROs versus placebo over 3 months, which were maintained to month 6. Despite lower baseline scores, these improvements were similar to the csDMARD-IR TNFi-naive OPAL Broaden trial.

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives Report the pharmacokinetics (PK), safety and taste acceptability of tofacitinib following multiple oral doses in patients (pts) 2

Background Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). Cytokines involved in lymphocyte development, function and homeostasis are known to signal through JAKs. Objectives To characterise the effects of tofacitinib treatment on absolute lymphocyte counts (ALCs) and lymphocyte subset counts (LSCs) and their reversibility after treatment discontinuation. Methods ALCs were collected as part of safety monitoring procedures throughout the tofacitinib RA clinical programme. Short-term (ST) changes were evaluated in five Phase (P) 2 studies (tofacitinib 1–30 mg twice daily [BID]; treatment duration 6 weeks–6 months). Long-term (LT) changes were assessed in an LT substudy (LSS) of NCT00413699 (study ongoing; database not locked) in which patients (pts) had received tofacitinib 5 or 10 mg BID for up to 8 years. Reversibility of changes in ALCs was evaluated in pts who permanently discontinued tofacitinib due to lymphopenia as defined by a confirmed ALC Results In total, there were 1432 and 4867 pts from P2 and LT extension (LTE) studies, respectively. Approximately 1050 pts from LTE study NCT00413699 were enrolled into the LSS for evaluation of ALCs and LSCs (median tofacitinib exposure of 5 years). Pre-treatment baseline for natural killer (NK) cells, B cells, T cells (CD3+, CD4+ and CD8+) were available for 130, 133, 133, 52 and 52 pts, respectively. Effects of tofacitinib on ALCs and LSCs are summarised in Table 1. Tofacitinib treatment resulted in a transient increase in ALC at Month 1, followed by a gradual decline to stabilise below baseline levels by ∼4 years. Magnitude and time course of changes in CD4+ and CD8+ T cells mirrored those of ALC. CD4+ and CD8+ cell counts were well correlated with ALC. LT treatment showed higher NK cell counts vs baseline, in contrast to decreases seen after ST dosing. B cell counts increased with ST treatment but returned toward baseline with LT treatment. Conclusions Tofacitinib treatment was associated with decreases in ALC. Changes in CD4+ and CD8+ T cell counts were reflected in ALC, while B cell and NK cell counts tended to return to or exceed baseline levels. Reversibility is observed following ST and LT dosing. Acknowledgement This study was sponsored by Pfizer Inc. Editorial support was provided by Claire Cridland of Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest R. van Vollenhoven Grant/research support from: Pfizer Inc, Consultant for: Pfizer Inc, E. Choy Grant/research support from: Amgen, Boehringer Ingelheim, Chugai Pharma, Ferring Pharmaceuticals, Novimmune, Pfizer Inc, Roche, and UCB, Speakers bureau: Amgen, Boehringer Ingelheim, Chugai Pharma, Eli Lilly, Hospira, MSD, Novartis, Pfizer Inc, Regeneron, Roche, Sanofi-Aventis, and UCB, E. B. Lee Consultant for: Pfizer Inc, A. Hazra Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Anisfeld Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, I. Lazariciu Consultant for: Pfizer Inc, Employee of: Quintiles, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Lamba Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Hodge Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. D. Clark Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Krishnaswami Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives The incidence of non-melanoma skin cancer (NMSC) in the tofacitinib RA programme was evaluated using data from randomised Phase (P) 1, 2, 3 and open-label long-term extension (LTE) RA studies (P1P2P3LTE studies). Methods NMSC data (cut-off date: 30 Aug 2013) were pooled from two P1, eight P2, six P3 and two LTE studies; LTE data collection and analyses are ongoing; study databases unlocked. Patients (pts) with RA in P1, P3 and LTE studies received tofacitinib 5 or 10 mg twice daily (BID) either as monotherapy or with background disease-modifying antirheumatic drugs (DMARDs). LTE pts were enrolled from qualifying P1, P2 and P3 studies; pts from P2 studies received tofacitinib 1 to 30 mg BID or 20 mg once daily. Incidence rates (IRs) per 100 pt-years (py) of exposure for first NMSC were calculated for combined doses (all doses) of tofacitinib in the P1P2P3LTE pt population. The overall NMSC IR was analysed as well as IRs for subgroup analyses according to the following conditions: tofacitinib dose (5 mg vs 10 mg BID); tofacitinib monotherapy vs tofacitinib + background DMARDs; prior tumour necrosis factor inhibitors (TNFi); pt age (≥65 vs

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Its effect in pregnant women is of interest, as it has been shown to be foeticidal and teratogenic in both rats and rabbits at exposures 146 times and 13 times, respectively, the maximum recommended human dose. There are no adequate, well-controlled tofacitinib studies in pregnant women; per the RA clinical development programme protocols, all studies exclude pregnant subjects and require use of highly effective contraception by females with child-bearing potential, and study treatment discontinuation if a subject becomes pregnant. Objectives To understand potential effects of tofacitinib, pregnancies in the RA clinical development programme were reviewed. Methods Cases were identified from Pfizer's internal safety database up to 30 April 2014, from interventional (one study is ongoing; database not locked) and non-interventional studies, plus cases from post-marketing reporting. Cases were limited to females administered tofacitinib/placebo/blinded therapy at time of conception and/or foetal subjects exposed to tofacitinib/placebo/blinded therapy through maternal exposure. Potential duplicate cases were eliminated. Remaining cases were reviewed for pregnancy-related outcomes and abnormalities; categorised as healthy newborns, spontaneous abortion, medical termination, still-birth, pending or lost to follow-up. Results 35 cases were identified. In tofacitinib RA clinical studies of 6192 subjects with 16839 patient-years exposure, there were 32 cases of maternal exposure. Subject age ranged from 22 to 40 years. Of the 32 cases, 31 received tofacitinib; 13 received 5 mg BID, 17 received 10 mg BID, and 1 received 15 mg BID. 14 of the 31 cases were also taking methotrexate (MTX). 1 subject received placebo/MTX. Pregnancy outcomes with tofacitinib were: 16 healthy newborns (including 1 low birth weight and 1 pre-term birth), 7 spontaneous abortions, 4 medical terminations, 1 congenital malformation of pulmonary valve stenosis reported in a 32-year-old subject with diabetes and hypertension, 1 ongoing pregnancy and 3 lost to follow-up; the placebo-treated subject experienced a spontaneous abortion. The remaining 3 cases receiving tofacitinib were reported from other data sources: 2 from non-interventional studies, 1 from post-marketing reporting. Foetal subjects had maternal exposure to tofacitinib. Of the 3 cases, 1 had a spontaneous abortion; outcomes were still pending for the other 2 cases. Conclusions Most cases with reported outcomes had healthy newborns. Adverse outcomes including spontaneous abortion and congenital malformation were observed in RA subjects who became pregnant during tofacitinib therapy. Pregnancy outcomes in subjects receiving tofacitinib continue to be monitored through routine pharmacovigilance and via a post-approval safety study within the Organization of Teratology Information Specialists (OTIS) registry. Acknowledgements Previously presented (Marren A et al. Arthritis Rheum 2014; 66(11): S5840 abs 1908) and reproduced with permission from Arthritis and Rheumatism. All aspects of this work were funded by Pfizer Inc. Editorial support, under the guidance of the authors, was provided by Amanda Pedder, of Complete Medical Communications, and funded by Pfizer Inc. Disclosure of Interest A. Marren Shareholder of: Shareholder of Pfizer Inc, Employee of: Employee of Pfizer Inc, Y. Chen Shareholder of: Shareholder of Pfizer Inc, Employee of: Employee of Pfizer Inc, D. Frazier Shareholder of: Shareholder of Pfizer Inc, Employee of: Employee of Pfizer, J. Geier Shareholder of: Shareholder of Pfizer Inc, Employee of: Employee of Pfizer

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). In the global Phase 3 ORAL Sync study ([NCT00856544][1]), tofacitinib improved disease activity in patients (pts) who had active RA despite treatment with nonbiologic disease-modifying antirheumatic drugs (DMARDs).1 Objectives To report a post-hoc analysis of efficacy and safety in a subgroup of Chinese pts. Methods ORAL Sync was a 1-year, double-blind, placebo-controlled, parallel-group study. Pts (N=795) with active RA were randomised 4:4:1:1 to oral tofacitinib 5 or 10 mg twice daily (BID), or placebo advanced to tofacitinib 5 or 10 mg BID at 3 (nonresponders) or 6 (remaining pts) months. All pts remained on ≥1 background nonbiologic DMARD throughout. Co-primary efficacy endpoints were ACR20 response rate at Month 6 (M6), change from baseline in physical function (HAQ-DI) at M3, and proportion of pts achieving DAS28-4(ESR)

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives Here we compare the relationship between clinical measures and patient-reported outcomes (PROs) in patients (pts) with RA treated with tofacitinib or methotrexate (MTX). Methods MTX-naive pts with RA from a double-blind, parallel group, Phase 3 trial (ORAL Start; [NCT01039688][1]) were randomised (2:2:1) and treated with tofacitinib 5 mg twice daily (BID) monotherapy (N=373), tofacitinib 10 mg BID monotherapy (N=397) or MTX titrated from 10 to 20 mg/week (N=186). Clinical measures included: the proportion of pts achieving ACR50 and ACR70 responses, the proportion achieving low disease activity (LDA) measured by Clinical Disease Activity Index (CDAI LDA, CDAI≤10) and Simplified Disease Activity Index (SDAI LDA, SDAI≤11), and the proportion achieving remission (REM) measured by CDAI REM (CDAI≤2.8) and SDAI REM (SDAI≤3.3). PROs included: proportion of pts achieving improvements in physical function measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI, to normative values

Background Rheumatoid arthritis (RA) is a chronic progressive inflammatory condition that is associated with significant economic burden. Tofacitinib is an oral Janus kinase inhibitor indicated in the US for treatment of moderate to severe RA. Given the limited resource and multiplicity of treatment options, economic evaluation of alternate treatment strategies could inform formulary decisions in the US. Objectives The objective of this analysis is to estimate incremental cost effectiveness ratios (ICERs) of tofacitinib after failure of methotrexate (MTX) in a sequence of treatments compared with a similar sequence without tofacitinib from a third-party-payer9s perspective in the US. Methods The model was designed to estimate the costs and outcomes of treating RA with a pre-specified “treatment sequence” (MTX, tofacitinib, adalimumab, abatacept, tocilizumab and rituximab, in that order) vs a “comparator sequence” (MTX, etanercept, adalimumab, abatacept, tocilizumab and rituximab, in that order). Alternative sequences of treatment were also considered but not reported here. Efficacy was measured using Health Assessment Questionnaire (HAQ), and compared using results of a mixed treatment comparison and data from long-term extension trials. Adverse events data were taken from published meta-analyses, trial data on tofacitinib and identified relevant comparators. Patient characteristics were based on averages from tofacitinib clinical trials (NCT00856544, ORAL Sync; NCT00847613, ORAL Scan; NCT00853385, ORAL Standard). Costs related to RA were taken from published data which mapped HAQ onto healthcare resource utilisation in US RA patients. Indirect costs were not considered. Results From the perspective of the US third-party payer, the predicted lifetime cost of “treatment sequence” including tofacitinib had costs of $509,047 vs $546,860 for “comparator sequence” without tofacitinib. The “treatment sequence” with tofacitinib also resulted in an additional 0.11 in quality-adjusted life years (QALYs), vs “comparator sequence” without tofacitinib. Therefore, “treatment sequence” with tofacitinib is dominant vs alternative sequence without tofacitinib. Probabilistic sensitivity analysis suggests that the probability of tofacitinib being cost-effective as a second-line therapy is 64.0% at a threshold of $100,000. Conclusions Our model suggests that inclusion of tofacitinib as second-line therapy following methotrexate failure is a cost-effective alternative vs a “comparator sequence” without tofacitinib. Sensitivity analysis reiterates the robustness of results and cost-effectiveness of a sequence of treatment with tofacitinib. A comparison of alternate sequences of treatment resulted in comparable findings. Acknowledgements This study was funded by Pfizer Inc. Disclosure of Interest L. Claxton Consultant for: Pfizer Inc., M. Taylor Consultant for: Pfizer Inc., D. Moynagh Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., D. Gruben Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., G. Wallenstein Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., A. Singh Shareholder of: Pfizer Inc., Employee of: Pfizer Inc.

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of RA. In Phase 3 ORAL Scan (NCT00847613; MTX-inadequate responders) and ORAL Start (NCT01039688; MTX-naive) 24-month studies, progression in radiographic scores of the protocol-specified primary analysis at the 12-month interim was measured by mean change from baseline (BL) in van der Heijde modified Sharp scores (mTSS) at Month 6. This co-primary endpoint was analysed using Analysis of Covariance (ANCOVA). In ORAL Scan, tofacitinib 10 mg but not 5 mg twice daily (BID) demonstrated statistically significant inhibition of progression in mTSS vs placebo (PBO). In ORAL Start, tofacitinib 5 and 10 mg BID doses showed statistically significant inhibition of progression in mTSS vs MTX. Mean change from BL in mTSS at Month 6 was 0.47 with PBO in ORAL Scan and 0.84 with MTX 20 mg/week in ORAL Start. Objectives To better understand the degree to which radiographic progression was inhibited by tofacitinib in two different patient populations. The goals of these analyses were to demonstrate: 1) the magnitude of tofacitinib efficacy in the presence of predictors of higher risk of structural progression, and 2) whether the results were driven by outliers. The latter was approached by use of a trimmed analysis, whereby extreme values are systematically removed. Methods A literature review was performed for factors predicting higher risk of structural progression. BL data were used to subset the patients by these high-risk factors, tailored to the tofacitinib program, regardless of treatment group assignment. ANCOVA was then applied to each high-risk subset. For trimmed analyses, data were trimmed in 1% increments up to 10% (2% trimming deletes observations >1st and Results High-risk factors for radiographic progression within the tofacitinib program included: anti-CCP+; BL DAS28-4(ESR) >5.1; CRP+ (>7 mg/L); both seropositive (RF+ or anti-CCP+) and BL erosion score ≥3; and, >median BL mTSS. For mTSS, high-risk subsets generally showed greater differentiation, although the degree of differentiation varied by BL risk (Figure). With regard to trimmed analyses, in ORAL Scan, statistical significance (p≤0.05; not corrected for multiple comparisons) was achieved for both tofacitinib doses at 1% trimming, and the significance was maintained with further trimming, with mean values stable at 3%. The trimmed analyses in ORAL Start showed that statistical significance in both doses was maintained, and the upper limit of the confidence intervals remained stable for tofacitinib 5 and 10 mg BID. Conclusions In ORAL Scan and ORAL Start, both tofacitinib 5 and 10 mg BID demonstrated inhibition of structural damage progression vs comparator in high-risk patients, and the trimmed analyses demonstrate that significant inhibition of structural damage was not driven by outliers. These results show that the degree of inhibition of radiographic progression is consistent across the two patient populations. Acknowledgements Study sponsored by Pfizer Inc. Editorial support was provided, under the guidance of the authors, by A Smith, PhD, of CMC, and funded by Pfizer Inc. Disclosure of Interest D. Van der Heijde Consultant for: AbbVie, Amgen, AstraZeneca, Augurex, BMS, Boehringer Ingelheim, Celgene, Centocor, Chugai, Covagen, Daiichi, Eli-Lilly, Galapagos, GSK, Janssen Biologics, Merck, Novartis, Novo-Nordisk, Otsuka, Pfizer Inc, Roche, Sanofi-Aventis, UCB, Vertex, Employee of: Imaging Rheumatology, C. Connell Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Strengholt Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Landewe Grant/research support from: Pfizer Inc, Abbott, Janssen, Merck, Consultant for: Abbott, Amgen, Astra, Bristol-Myers Squibb, Centocor, GlaxoSmithKline, Janssen, Pfizer Inc, UCB, Vertex

Background In the clinical development programme of the novel oral Janus kinase inhibitor tofacitinib for the treatment of rheumatoid arthritis (RA), small mean increases in serum creatinine (SCr) ( 1,2 mean increases in SCr remain small (mean change from baseline Objectives To assess changes in measured glomerular filtration rate (mGFR) with tofacitinib relative to PBO in pts with active RA. Methods In this double-blind, PBO-controlled, Phase 1 study (NCT01484561) RA pts were randomised 2:1 to one of two fixed sequences (Seq): Seq 1 received oral tofacitinib 10 mg BID in Period 1 (P1) then PBO BID in Period 2 (P2); Seq 2 received oral PBO BID in both P1 and P2. P1and P2 were 6-7 and 4-5 weeks in duration, respectively. Each pt underwent mGFR evaluations by iohexol serum clearance at 4 time points (run-in, pre-dose 1 in P1, end of P1, and end of P2); estimated GFR (eGFR) was calculated using the Cockcroft-Gault equation. The primary endpoint was the geometric mean change in mGFR from baseline to end of P1. Secondary endpoints included the geometric mean change in mGFR from baseline to end of P2 and from end of P1 to end of P2; change in eGFR and SCr; RA clinical efficacy and safety. Results 148 pts were randomised to Seq 1 (N=97) and Seq 2 (N=51). Baseline characteristics were similar between groups. In Seq 1, tofacitinib treatment in P1 was associated with a reduction of 8% (90% confidence interval [CI]: 2%, 14%) from baseline in geometric mean mGFR vs Seq 2. The reduction in geometric mean mGFR associated with tofacitinib in P1 reversed on PBO in P2, and there was no difference vs Seq 2 in the adjusted geometric mean fold change of mGFR at the end of the study (Seq 1:Seq 2: 1.04; 90% CI: 0.97, 1.11). However, from P1 to P2 there was a 5% reduction (90% CI: 1%, 10%) in mGFR in Seq 2 (PBO). eGFR and SCr showed similar changes to mGFR in Seq 1 but remained constant in Seq 2 (Table). Clinical efficacy and safety were consistent with prior studies. Conclusions This study suggests that small mean increases in SCr and mean decreases in eGFR in pts with RA treated with tofacitinib occur in parallel with small mean decreases in mGFR, and that changes in these parameters with short term tofacitinib treatment appear reversible after discontinuation. Safety monitoring will continue in ongoing and future clinical trials and routine pharmacovigilance. References Isaacs JD et al. Ann Rheum Dis 2012; 71 (Suppl 3): 672. Wollenhaupt J et al. Arthritis Rheum 2013; 65(Suppl 10): S993. Acknowledgements This study was sponsored by Pfizer Inc. Medical writing support was provided by AM Reid, PhD, of CMC and funded by Pfizer Inc. Disclosure of Interest : J. Kremer Grant/research support: Pfizer Inc, Consultant for: Pfizer Inc, A. Kivitz Grant/research support: Pfizer Inc, Consultant for: Pfizer Inc, Speakers bureau: Pfizer Inc, J. Simon-Campos: None declared, E. Nasanov: None declared, H. Tony: None declared, B. Vlahos Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Hammond Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bukowski Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, H. Li Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Schulman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Raber Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Zuckerman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Isaacs Grant/research support: Pfizer Inc, Consultant for: Pfizer Inc DOI 10.1136/annrheumdis-2014-eular.2492

Background Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis. Phase (P) 3 studies demonstrated tofacitinib is effective and has a manageable safety profile at both 5 and 10 mg twice-daily (BID) doses. Objectives To assess, using post-hoc analyses of P3 data, whether active treatment could affect monthly medical expenditure (MME) compared with placebo. Methods Data from patients with an inadequate response (IR) to methotrexate (MTX) or TNF inhibitors (TNFi) receiving tofacitinib 5 or 10 mg BID, or adalimumab (ORAL Standard only), in combination with methotrexate, were assessed from two randomised P3 studies (ORAL Standard, NCT00853385 [MTX-IR] and ORAL Step, NCT00960440 [TNFi-IR]). Differences across treatment groups in estimated MME were evaluated using a longitudinal model. A total of three models were run for each study, each with one of the following variance–covariance structures: 1) unstructured, 2) auto-regressive of order 1 and 3) compound symmetry. The final variance–covariance structure was selected based on Akaike9s Information Criteria. Results Estimated MME by treatment group for MTX-IR in ORAL Standard is presented in Fig. 1a. By Month 1 mean MME was significantly lower in the active treatment groups when compared with placebo; the MME was decreased −$89 for the tofacitinib 10 mg BID group compared with an increase of $70 in both the tofacitinib 5 mg BID and adalimumab groups. During the placebo-controlled phase of ORAL Step, estimated MME by treatment group for TNFi-IR decreased from baseline to Month 1. Between Month 1 and Month 3 the MME of the placebo group increased but declined further in the two active tofacitinib treatment groups (Fig. 1b). By Month 3 the reduction in MME was over $100 greater in each of the two tofacitinib groups when compared with placebo. Conclusions Tofacitinib is expected to have a positive impact on medical expenditure over time compared with placebo. Acknowledgements Editorial assistance was provided by Mark Walker PhD, of Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest R. Rendas-Baum: None declared, M. Kosinski: None declared, A. Singh Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., C. Mebus Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., B. Wilkinson Shareholder of: Pfizer Inc., Employee of: fizer Inc., R. Riese Shareholder of: Pfizer Inc., Employee of: Pfizer Inc., G. Wallenstein Shareholder of: Pfizer Inc., Employee of: Pfizer Inc. DOI 10.1136/annrheumdis-2014-eular.2476

Background Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Changes in laboratory parameters observed during tofacitinib treatment included mean increases in low (LDL) and high (HDL) density lipoproteins, serum creatinine (SCr) and mean decreases in neutrophils (ANC). It was of interest to understand the inter-relationship between drug and disease effects on these parameters [1]. Objectives To investigate potential explanatory mechanisms for these changes in laboratory parameters. Methods Baseline and Week 12 data from five Phase 3 (P3) nonbiologic or biologic disease-modifying anti-rheumatic drug-inadequate responder trials were pooled for each treatment arm: placebo, tofacitinib 5 mg and 10 mg twice daily (BID), and adalimumab 40 mg every other week (EOW). The defined laboratory parameters were explored with C-reactive protein (CRP) as a marker of inflammation. Mean changes at Week 12 were compared with quartile levels of CRP at baseline and quartiles of change in CRP at Week 12. Results Across the defined laboratory parameters, the smallest mean changes from baseline were observed in the quartile of patients with the smallest reductions in CRP (Figure, 1st quartile) and the greatest changes were observed with the greatest reductions in CRP (Figure, 4th quartile). A similar pattern of association was evident with baseline CRP, where the greatest mean changes in laboratory parameters occurred in patients with highest levels of baseline CRP. Numerical differences in the magnitude of changes across the treatment arms were observed, but no statistical comparisons were performed. Conclusions A consistent pattern of association between mean changes in each of the laboratory parameters and CRP was observed. The precise mechanism behind these laboratory changes is unknown. Based upon these analyses, the lowering of inflammation, as measured by CRP, may partly explain some of the observed mean changes in laboratory parameters during clinical studies. References Genovese MC et al. Arthritis and Rheumatism 2013; 65: S193 Acknowledgements Editorial support was provided by AM Reid, PhD, of CMC and funded by Pfizer Inc. Disclosure of Interest : V. Strand Consultant for: Pfizer Inc, J. Isaacs Consultant for: Pfizer Inc, J. Beal Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Nduaka Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Krishnaswami Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Riese Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, M. Boy Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc DOI 10.1136/annrheumdis-2014-eular.4361

Background Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives To evaluate the malignancies that occurred in Japanese patients in the tofacitinib RA programme from the Phase (P) 2, P3, and long-term extension (LTE) studies up to April 2013. Methods Data were pooled from 2 randomised P2, 1 randomised P3 study and 1 ongoing open-label LTE study (database not locked). Patients (pts) in P3 and LTE studies were treated with tofacitinib 5 or 10 mg twice daily; P2 included additional dosages (LTE pts rolled over from the P2 and P3 studies). Results A total of 556 patients (1479 pt-yr) received tofacitinib in the P2, P3 and LTE studies. Nineteen pts receiving tofacitinib (all doses) reported malignancies; the most common were gastric (5 cases) and breast cancer (3 cases). There were 2 cases of lymphoma. No cases of non-melanoma skin cancer (NMSC) were reported. The overall incidence rate (IR, events per 100 pt-yr) for all malignancies was 1.29 (95% confidence interval [CI]: 0.82, 2.01). The IRs (95% CI) of all malignancies broken down into 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42 and >42 months based on exposure to tofacitinib were 0.39 (0.06, 2.79), 2.13 (0.89, 5.11), 1.82 (0.68, 4.84), 1.45 (0.47, 4.49), 1.55 (0.50, 4.80), 0.60 (0.08, 4.24), 0.98 (0.14, 6.98) and 1.01 (0.14, 7.20), respectively. The cumulative IRs (95% CI) of all malignancies from 0-6, 0-12, 0-18, 0-24, 0-30, 0-36 and 0-42 months were 0.39 (0.06, 2.79), 1.23 (0.55, 2.73), 1.41 (0.76, 2.62), 1.42 (0.82, 2.44), 1.44 (0.88, 2.35), 1.33 (0.83, 2.14) and 1.30 (0.82, 2.07), respectively. The number of cases in each time interval was small, with resultant wide and overlapping 95% CIs. Conclusions Among Japanese patients in the tofacitinib RA clinical development programme the most common malignancies were gastric (5 cases) followed by breast (3 cases) cancer; both malignancies were also common in the general Japanese population [1]. The rate of malignancies was stable over time, but numerically higher in both 6-12 and 12-18 month periods compared with other time intervals. Overall rates appear similar to the global RA tofacitinib programme population [2], published rates for biologic DMARDs, and rates from the tocilizumab Japanese RA clinical trial population [3,4]. Further monitoring within the clinical practice setting is warranted to evaluate the risk of malignancy over time. References Center for Cancer Control and Information Services, National Cancer Center, Japan (http://ganjoho.jp/pro/statistics/en/table_download.html). Mariette X, et al. Arthritis Rheum 2013; 65 (Suppl 10): S340; Abstract 802. Ahadieh S, et al. Arthritis Rheum 2012; 64 (Suppl 10 [supplement]): S726, Abstract 1697. Nishimoto J, et al. Mod Rheumatol 2010; 20: 222-32. Disclosure of Interest : Y. Tanaka Grant/research support: Pfizer Japan Inc, Consultant for: Pfizer Japan Inc, T. Takeuchi Grant/research support: Pfizer Japan Inc, Consultant for: Pfizer Japan Inc, H. Yamanaka Grant/research support: Pfizer Japan Inc, Consultant for: Pfizer Japan Inc, T. Hirose Shareholder of: Pfizer Inc, Employee of: Pfizer Japan Inc, S. Toyoizumi Employee of: Pfizer Japan Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Riese Shareholder of: Pfizer Inc, Employee of: Pfizer Inc DOI 10.1136/annrheumdis-2014-eular.3232

Background Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives An evaluation of malignancies in the tofacitinib RA programme from the Phase (P) 2, P3, and long-term extension (LTE) studies based on data up to April 2013. Methods Data were pooled from 6 P2 and 6 P3 randomised studies and 2 open-label LTE studies (ongoing at time of analysis; databases not locked). Patients (pts) in P3 and LTE studies (LTE pts rolled over from the P2 and P3 studies) were treated with tofacitinib 5 or 10 mg twice daily (BID); P2 included additional doses. Results A total of 5,671 pts (12,664 pt-yrs) received tofacitinib in the P2, P3 and LTE studies. 107 receiving tofacitinib (all doses) reported malignancies (excluding non-melanoma skin cancer [NMSC]); the most common types were lung and breast cancer. There were 10 lymphoma cases. The overall incidence rate (IR, events per 100 pt-yrs) for all malignancies (excluding NMSC) and lymphomas were 0.85 (95% CI: 0.70, 1.02) and 0.08 (0.04, 0.14), respectively. The IRs (95% CI) for all malignancies (excluding NMSC) for P3 were 0.55 (0.27, 1.09) for 5 mg BID and 0.87 (0.50, 1.49) for 10 mg BID. In the LTE the IRs were 1.02 (0.75, 1.39) for 5 mg BID and 0.81 (0.60, 1.10) for 10 mg BID. The IRs (95% CI) for all malignancies (excluding NMSC) broken down into 0–6, 6–12, 12–18, 18–24, 24–30, 30–36, 36–42, and >42 months based on exposure to study drug were 0.70 (0.44, 1.11), 0.66 (0.40, 1.10), 0.94 (0.59, 1.49), 1.04 (0.64, 1.67), 0.83 (0.47, 1.46), 1.00 (0.57, 1.76), 0.79 (0.36, 1.76), and 1.04 (0.54, 2.0), respectively. The standardised incidence ratios (SIRs) (95% CI) (as compared with the US Surveillance Epidemiology and End Result database) for all malignancies (excluding NMSC) and lymphomas were 1.08 (0.89, 1.31) and 2.58 (1.24, 4.74), respectively. The SIRs (95% CI) for lung and breast cancer were 1.91 (1.22, 2.84) and 0.77 (0.46, 1.20), respectively. Overall, 66 pts experienced NMSCs, for an IR of 0.53 (95% CI 0.41, 0.67). The IRs (95% CI) for NMSC in P3 were 0.41 (0.19, 0.92) for 5 mg BID and 0.53 (0.27, 1.07) for 10 mg BID. In the LTE studies the IRs were 0.35 (0.21, 0.59) for 5 mg BID and 0.84 (0.62, 1.13) for 10 mg BID. By comparison, the IR of NMSC in pts treated with anti-TNF was 0.47 in a meta-analysis of randomised controlled trials [1] and ranged from 0.23–0.35 in a meta-analysis of registries [2]. Conclusions The malignancies that occurred in the tofacitinib RA programme, including more than 12,000 pt-yrs of drug exposure, are consistent with the type and distribution of malignancies expected for pts with moderately to severely active RA. The IRs for all malignancies (excluding NMSC), lung cancer, breast cancer, and lymphomas are stable over time and consistent with published estimates in RA pts treated with biologic and non-biologic DMARDs [3–6]. References Askling J, et al. Pharmacoepidemiol Drug Saf 2011; 20: 119-30. Mariette X, et al. Ann Rheum Dis 2011; 70: 1895-904. Carmona L, et al. Semin Arthritis Rheum 2011; 41: 71-80. Pallavicini FB, et al. Autoimmun Rev 2010; 9: 175-80. Simon TA, et al. Ann Rheum Dis 2009; 68: 1819-26. Wolfe F, Michaud K. Arthritis Rheum 2007; 56: 2886-95. Acknowledgements This study was sponsored by Pfizer Inc. Pfizer personnel were involved in protocol development and data analysis. Editorial assistance was provided by Claire Cridland, of Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest : X. Mariette Grant/research support: Pfizer Inc, J. Curtis Grant/research support: Pfizer Inc, Consultant for: Pfizer Inc, E. Lee Consultant for: Pfizer Inc, B. Benda Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, I. Kaplan Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Soma Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kwok Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Geier Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Riese Shareholder of: Pfizer Inc, Employee of: Pfizer Inc DOI 10.1136/annrheumdis-2014-eular.2139

Background Tofacitinib is a novel, oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Objectives To compare the effects of twice daily (BID) tofacitinib 5 mg and 10 mg monotherapy versus methotrexate (MTX) on patient-reported outcomes (PROs) in the 24-month Phase 3, randomised, double-blind, parallel-group ORAL Start study (NCT01039688) in MTX-naive patients. Results from a 12-month interim analysis have been presented previously [1,2] here we present the final analysis at 24 months. Methods MTX-naive patients with moderate-to-severe active RA were randomised 2:2:1 to receive tofacitinib 5 mg (n=373) or 10 mg BID (n=397), or MTX (n=186) titrated from 10 mg per week to 20 mg per week by Week 8. Secondary PRO endpoints included the mean change from baseline in: Patient Global Assessment of arthritis (PtGA; Visual Analogue Scale [VAS]), pain (VAS), physical function (Health Assessment Questionnaire-Disability Index; HAQ-DI), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue Scale; FACIT-F), and health-related quality of life (HR-QoL; Short Form 36 version 2, acute; SF-36). Analyses used a linear mixed-effect model with baseline values as covariates in the full analysis set (all randomised patients who received ≥1 dose of study drug and had ≥1 post-baseline measurement). Least squares (LS) mean changes from baseline (±standard error [SE]) and proportions of patients reporting improvements ≥minimum clinically important differences (MCID; no imputation for missing data) in PROs at Month 24 are presented. P-values presented here are with no correction for type I error inflation. Results A total of 658 patients completed the 24-month study (266, 286, and 106 in the tofacitinib 10 mg and 5 mg and MTX groups, respectively). Over 24 months, significantly (p Conclusions In this Phase 3 trial in MTX-naive patients with RA, tofacitinib 5 and 10 mg BID monotherapy significantly improved multiple PROs over 24 months compared with MTX. References Lee EB et al. Arthritis Rheum 2012; 64 (Suppl 10): S1049. Strand V et al. Ann Rheum Dis 2013; 72: 252-253. Acknowledgements Writing support was provided by Erin Bekes PhD, of Complete Medical Communications and funded by Pfizer Inc. Disclosure of Interest R. Alten Grant/research support: Pfizer Inc, Speakers bureau: Pfizer Inc, V. Strand Consultant for: Pfizer Inc, R. Fleischmann Grant/research support: Pfizer Inc, Consultant for: Pfizer Inc, T. Koncz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, B. Wilkinson Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Krishnaswami Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, G. Wallenstein Shareholder of: Pfizer Inc, Employee of: Pfizer Inc DOI 10.1136/annrheumdis-2014-eular.3168

Background Baricitinib (formerly LY3009104/INCB028050) is a novel, oral inhibitor of JAK1 and JAK2 in the JAK-STAT signalling pathway being investigated as a treatment for rheumatoid arthritis (RA). Objectives To report 52 week safety and efficacy findings of an open label extension of the phase 2b study. Methods Patients (Pts) were initially randomised to placebo (PBO) or 1of 4 once-daily (QD) baricitinib doses (1, 2, 4, or 8 mg) for 12 wks. Pts assigned to 2 mg, 4 mg or 8 mg continued assigned treatment and pts assigned to placebo or 1 mg were reassigned to 4 mg QD or 2 mg BID for an additional 12 weeks of blinded treatment. In the open label portion of the study, patients in 8 mg group continued to receive 8 mg QD and all other patients received 4 mg QD. Doses could be escalated to 8 mg QD at 28 or 32 weeks at the investigator’s discretion when >6 tender and swollen joints were present. Analyses reported here include data through 52 weeks for patients treated in the open-label extension (non-responder imputation used for discontinued patients). Results Of the 212 pts eligible to participate, 201(95%) pts entered the open label extension, 184 patients completed 52 weeks of treatment, 15 pts discontinued, and 2 pts had not yet completed 52 weeks. Among pts who remained on 4 mg (n = 108), TEAEs occurred in 57 (53%), SAEs in 14 (13%), infections in 34 (31%) and serious infections in 4 (4%). Among pts who received 8 mg at any time (n = 93), TEAEs occurred in 59 (63%), SAEs in 8 (9%), infections in 37 (40%) and serious infections in 2 (2%). No opportunistic infections or TB cases were observed. There was one death due to myocardial infarction in the 8 mg group. Among all patients combined in the open label extension, the proportions of pts achieving ACR20, ACR50, ACR70, CDAI Remission, SDAI Remission, DAS28CRP ≤3.2, DAS28CRP Conclusions Among pts completing 52 weeks of a phase 2b study, clinical improvements observed at week 24 were maintained or improved during the open label extension. Safety signals observed over the open label extension were consistent with previously reported results of baricitinib. Reference 1.1. EULAR 2013, Ann Rheum Dis 2013;72 Supplement 3:65, Genovese et al.

Background ASP015K is an oral Janus kinase (JAK) inhibitor with moderate selectivity for JAK3, a key enzyme for interleukin-2 (IL-2) signaling. With IL-2 stimulation, JAK1/3 augments STAT5 phosphorylation (STAT5-P), which is an integral step in the T cell activation pathway. Objectives In two phase1 dose-escalation trials, we evaluated the pharmacodynamics (PD) of ASP015K after single and multiple doses in healthy subjects measuring STAT5-P as a biomarker of JAK1/3 activity. Methods Study A: single doses of ASP015K (3, 10, 30, 60, 120, 200, 300 mg) or placebo (PBO) were given in 9 sequential groups (n=6 active and 2 PBO per group). Study B: 3 groups of men received ASP015K (30, 100, 200 mg twice daily [BID]) or PBO, and 1 group of women received ASP015K (100 mg BID) or PBO (n=9 active and 3 PBO per group) for 13.5 days. PD variables included serial measures of percentage reduction of IL-2–stimulated STAT5-P in T cells; total lymphocyte count and peripheral lymphocyte subtypes pre- and postdose. Results The median peak STAT5-P inhibition occurred at 1–2 hours after a single dose, consistent with the median t max in plasma ASP015K concentrations. ASP015K inhibited STAT5-P in a dose dependent manner, with mean peak percentage inhibitions of 84%, 85%, 92%, and 93% after 60, 120, 200, and 300 mg doses, respectively. The relationship between plasma ASP015K concentration and percentage STAT5-P inhibition was described by an E max model with 50% of maximum effect (EC 50 ) achieved at 48 ng/mL, estimated E max close to 100%, and a shape factor (γ) of ~1.2. With multiple doses on days 1, 7, and 14, median percentage of STAT5-P inhibition peaked at ~2 hours postdose, median peak inhibition ranged from 89%–98% with ASP015K at 100 and 200 mg on all days. The percentage STAT5-P inhibition was similar in men and women after single-dose 30 mg as well as with multiple doses (100 mg BID). After multiple doses, a small decrease in lymphocyte count from baseline was seen with 100 and 200 mg BID doses in men on day 17, with no dose dependency. Dose-dependent decreases in NK cells, a lymphocyte subset, were seen with ASP015K on day 17. Conclusions ASP015K showed dose- and concentration-dependent inhibition of STAT5-P. Total lymphocyte count showed no dose-dependent changes. A dose-dependent reduction in NK cells was seen with multiple doses. These results are consistent with the pharmacologic effect of JAK1/3 inhibition by ASP015K. In a phase 2a study, ASP015K decreased disease severity in psoriasis patients; studies to test safety and efficacy of ASP015K in rheumatoid arthritis patients are underway. Disclosure of Interest T. Zhu Employee of: Astellas Pharma Global Development, U. Valluri Employee of: Astellas Pharma Global Development, M. Lewand Employee of: Astellas Pharma Global Development, Y. Cao Employee of: Astellas Pharma Global Development, K. Cho Employee of: Astellas Pharma Global Development, J. Holman Employee of: Astellas Pharma Global Development, T. Sawamoto Employee of: Astellas Pharma, Inc., J. Keirns Employee of: Astellas Pharma Global Development

Background Tofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor being investigated as a targeted immunomodulator in rheumatoid arthritis. Objectives To assess efficacy of tofacitinib 5 and 10 mg twice-daily (BID) using disease activity scores (DAS) across a wide range of baseline (BL) values. Methods Demographic and BL disease characteristics of patients (pts) in five Phase 3 studies (monotherapy: NCT00814307; background DMARD: NCT00960440, NCT00847613, NCT00856544, NCT00853385) were similar. Data were pooled, and BL DAS values based on 28-joint counts using C-reactive protein (DAS28-3(CRP)) were divided into four groups (≤25th, >25th-50th, >50th-75th, >75th percentiles); for each, mean change from BL, proportion of pts improving by ≥1.2 from BL, and proportions of pts with values ≤3.2 and Results 3072 pts (PBO, 673; 5 mg, 1200; 10 mg, 1199) were divided into groups using BL DAS28-3(CRP) quartiles: ≤4.71 (Q1); >4.71-5.34 (Q2); >5.34-6.01 (Q3); >6.01 (Q4). In each group, both tofacitinib doses demonstrated clinically significant improvements in DAS28-3(CRP)-based analyses compared with PBO. Pts with higher BL values had greater mean reductions in DAS, with correspondingly larger differences from PBO. All BL groups showed numerical benefit of 10 mg BID over 5 mg BID across all DAS28-3(CRP)-based analyses and the proportions of pts achieving various DAS thresholds were 2-13 percentage points greater with 10 mg BID vs 5 mg BID. Data for Q1 and Q4 are shown in Table 1. Conclusions Across a range of BL disease activities, tofacitinib was consistently efficacious at both doses in reducing DAS28-3 (CRP) vs PBO. All groups showed numerical benefit in efficacy of 10 mg BID over 5 mg BID across all measures of DAS28-3 (CRP); the magnitude of benefit of 10 mg BID over 5 mg BID appeared to be independent of BL status. As expected, pts in the lowest quartile were more likely to achieve DAS28-3(CRP) ≤3.2 and Disclosure of Interest R. Fleischmann Grant/Research support from: Pfizer Inc, Consultant for: Pfizer Inc, S. Krishnaswami Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Mebus Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc