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BackgroundA Treat-to-Target approach (T2T) is broadly considered to lead to better clinical outcomes and recommended in patients with RA. However, very few studies have analyzed the effect of T2T on radiographic progression, and any such studies have provided inconsistent results.ObjectivesTo investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice leads to lower radiographic progression in RA.MethodsPatients from the multicenter RA-BIODAM cohort with ≥2 consecutive visits with radiographs available were included. In RA-BIODAM patients were enrolled as they were initiating a new csDMARD/bDMARD treatment were followed-up with the intention to benchmark and intensify treatment. The primary outcome of this analysis was the change in Sharp-van der Heijde score (SvdH, 0-448), assessed every 6 months, using average scores from 2 readers (scores with known chronological order). Following a DAS44-T2T remission strategy, which was defined at each 3-month visit, was the main variable of interest. Patients were categorized based on the proportion of visits in which T2T was followed according to our definition: very low (≤40% of the visits, low (>40%, 75%). Radiographic progression at 2 years was visualized across groups by cumulative probability plots. Per 3-month interval T2T could be followed zero, one or two times (in a total of 2 visits). Associations between the number of visits with T2T in an interval and radiographic progression, both in the same and in the subsequent 6-month interval, were analysed by generalised estimating equations, adjusted for age, gender, disease duration and country.ResultsIn total, 511 patients were included (mean (SD) age: 56 (13) years; 76% female). After 2 years, patients showed on average 2.2 (4.1) units progression (median:1 unit). Mean (SD) 2-year progression was not significantly different across categories of T2T: very low: 2.1 (2.7)-units; low: 2.8 (6.0); high: 2.4 (4.5), very high: 1.6 (2.2) (Figure 1). Meticulously following-up T2T in a 3-month interval neither reduced progression in the same 6-month interval (parameter estimates (for yes vs no): +0.15 units (95%CI: -0.04 to 0.33) for 2 vs 0 visits; and +0.08 units (-0.06;0.22) for 1 vs 0 visits) nor did it reduce progression in the subsequent 6-month interval (Table 1).Table 1.Effect of following DAS44-remission-T2T strategy on 6-month radiographic progression over 2 yearsChange in radiographic damage(regression coefficient (95% CI))N=506T2T during 3 months on radiographic progression in the same 6-month period 2 visits vs 0 followed0.15 (-0.04; 0.33) 1 visit vs 0 followed0.08 (-0.06; 0.22)T2T during 3 months on radiographic progression in the subsequent 6-month period 2 visits vs 0 followed-0.09 (-0.28; 0.10) 1 visit vs 0 followed-0.10 (-0.24; 0.05)Figure 1.Cumulative probability plot with 2-year radiographic progression according to the proportion of 3-monthly visits with T2T followedConclusionIn this daily practice cohort, more meticulously following T2T principles did not result in more reduction of radiographic progression than a somewhat more liberal attitude toward T2T. One possible interpretation of these results is that the intention to apply T2T already suffices and that a more stringent approach does not further improve outcome.AcknowledgementsBIODAM was financially supported by an unrestricted grant from AbbVieDisclosure of InterestsSofia Ramiro Speakers bureau: Eli Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Eli Lilly, MSD, Novartis, Pfizer, UCB, Sanofi, Grant/research support from: AbbVie, Galapagos, Novartis, Pfizer, UCB, Robert B.M. Landewé Speakers bureau: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCB, Consultant of: AbbVie, BMS, Gilead, Galapagos, GSK,Janssen, Lilly, Novartis, Pfizer, UCBDr Landewé owns Rheumatology Consultancy BV, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma. Director of Imaging Rheumatology bv., Alexandre Sepriano Speakers bureau: Novartis, Consultant of: UCB, Oliver FitzGerald Speakers bureau: Biogen, Novartis, AbbVie, BMS, Pfizer, Grant/research support from: BMS, Novartis, UCB, Pfizer, Lilly, Janssen, Mikkel Østergaard Speakers bureau: Abbvie, BMS, Celgene, Eli-Lilly, Galapagos, Gilead, Janssen, Merck, Novartis, Orion, Pfizer, Roche and UCB, Consultant of: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli-Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi and UCB, Grant/research support from: Abbvie, Amgen, BMS, Merck, Celgene and Novartis, Joanne Homik: None declared, Ori Elkayam Speakers bureau: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Consultant of: Pfizer, Lilly, Novartis, Abbvie, BI, Janssen, Grant/research support from: Pfizer, Abbvie, Janssen, Carter Thorne Consultant of: Abbvie, Organon, Pfizer, Sandoz, Maggie Larché Speakers bureau: AbbVie, Actelion, Amgen, BMS, Boehringer-Ingelheim, Fresenius-Kabi, Gilead, Janssen, Mallinckrodt, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi, UCB, Grant/research support from: Abbvie, BMS, Gianfranco Ferraccioli Speakers bureau: SOBI, Consultant of: Abbivie, Marina Backhaus: None declared, Gilles Boire Speakers bureau: Abbvie Canada, BMS Canada, Lilly Canada, Janssen Canada, Merck Canada, Pfizer Canada, Viatris, Consultant of: Abbvie Canada, Amgen Canada, BMS Canada, Celgene, GileadSciences, Janssen Canada, Lilly Canada, Merck Canada, Mylan Canada, Novartis Canada, Pfizer Canada, Roche Canada, Samsung Bioepis, Sanofi Canada, Teva, Grant/research support from: Lilly Canada, BMS Canada, Pfizer, Sandoz Canada, UCB Canada, Merck Canada, Novartis Canada, Roche Canada, Bernard Combe Speakers bureau: Abbvie, BMS,Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Pfizer,Roche-Chugai, Consultant of: Abbvie, Celltrion,Galapgos-Gilead, Janssen, Lilly, MERCK, Roche-Chugai, Grant/research support from: Pfizer, Roche-chugai, Thierry Schaeverbeke: None declared, Alain Saraux Speakers bureau: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, Sanofi, UCB, Consultant of: Abbvie, Lilly, Nordic, Novartis, Pfizer, Roche-Chugai, UCB, Grant/research support from: Novartis, Fresenius, Lilly, Maxime Dougados Consultant of: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Grant/research support from: Pfizer, AbbVie, UCB, Merck, Lilly, Novartis, BMS, Galapagos, Biogen, Roche, Maurizio Rossini Speakers bureau: Amgen, Abbvie, BMS, Eli-Lilly, Galapagos,MSD, Novartis, Pfizer, Sandoz, Theramex, UCB, Marcello Govoni Speakers bureau: Abbvie, Pfizer, Galapagos, BMS, Eli-Lilly, Paid instructor for: Pfizer, Consultant of: Abbvie, BMS, Novartis, Astrazeneca, Pfizer, Luigi Sinigaglia: None declared, Alain Cantagrel Speakers bureau: Abbvie, Amgen, Biogen, BMS, Janssen, Lilly France, Médac, MSD France, Nordic-Pharma, Novartis, Pfizer, Sanofi Aventis, UCB, Consultant of: BMS, Janssen, Lilly France, MSD France, Sandoz, Grant/research support from: MSD France, Novartis, Pfizer, Cornelia Allaart: None declared, Cheryl Barnabe Speakers bureau: Sanofi Genzyme, Pfizer, Fresenius Kabi, Janssen, Consultant of: Gilead, Celltrion Healthcare, Clifton Bingham Consultant of: AbbVie, BMS, Eli Lilly, Janssen, Moderna, Pfizer, Sanofi, Grant/research support from: BMS, Dirkjan van Schaardenburg: None declared, Hilde Berner Hammer Speakers bureau: AbbVie, Novartis, Lilly, Rana Dadashova: None declared, Edna Hutchings: None declared, Joel Paschke: None declared, Walter P Maksymowych Speakers bureau: Abbvie, Janssen, Novartis, Pfizer, UCB, Consultant of: Abbvie, Boehringer Ingelheim, Celgene, Eli-Lilly, Galapagos, Novartis, Pfizer, UCB, Grant/research support from: Abbvie, Novartis, Pfizer

BackgroundDeucravacitinib (DEUC) is a novel, oral, selective TYK2 inhibitor with a unique allosteric mechanism of action that has demonstrated efficacy in patients with psoriasis (PsO)1 and psoriatic arthritis (PsA).2 TYK2 mediates signalling of select immune cytokines, eg, interleukin (IL) 23, IL-12, and Type I interferons, whereas the related Janus kinases (JAK) 1/2/3 mediate signalling of a wider array of cytokines and mediators involved in inflammatory, developmental, metabolic, and hematopoietic pathways. DEUC reduced inflammatory markers associated with skin and joint manifestations but did not result in laboratory abnormalities associated with inhibition of JAK1/2/3 in a PsA trial.3ObjectivesTo identify baseline biomarkers that predict response to DEUC in patients with PsA.MethodsThe double-blind Phase 2 trial (NCT03881059) enrolled 203 patients with PsA randomised 1:1:1 to placebo (PBO), DEUC 6 mg once daily (QD), or 12 mg QD.2 Molecular profiling of baseline serum samples was performed by immunoassays. Clinical response at Week 16 was measured by ≥20% improvement from baseline in American College of Rheumatology Improvement Criteria (ACR 20) and ≥75% improvement from baseline in Psoriasis Area and Severity Index (PASI 75) scores.ResultsBiomarkers of the IL-23/T helper cell type 17 pathway, including IL-17A, IL-17‒induced β-defensin 2 (BD2), and IL-19, were associated with higher PASI but not Psoriatic Arthritis Disease Activity Scores overall at baseline. PASI 75 responders in DEUC-treated groups had higher baseline levels of IL-17A compared with nonresponders. In contrast, PASI 75 responders in PBO-treated patients had lower baseline expression of IL-17A, BD2, and IL-19 compared with nonresponders. In patients treated with DEUC 12 mg QD, greater reductions in BD2 were observed in the PASI 75 responder group compared with nonresponder group. When patients were dichotomised by median baseline biomarker level, higher clinical responses in both PASI 75 and ACR 20 were achieved in those with higher baseline overall biomarker levels in the DEUC-treated groups compared with the PBO group. Higher baseline expression of IL-23 biomarkers IL-17A, IL-19, and BD2 enriched ACR 20 response in patients treated with DEUC compared with PBO (OR=5.64, 6.68, and 4.99, respectively). While greater benefit was observed in high-biomarker groups, the low-biomarker populations still manifested clinical responses although not significant (Figure 1).ConclusionPatients who had higher expression of IL-23 pathway biomarkers were more likely to benefit from DEUC compared with placebo in skin and joint manifestations of PsA. These results reinforce the value of TYK2 inhibition in patients with IL-23‒mediated diseases. The potential value of IL-23-pathway markers in predicting higher responses to DEUC should be further explored in larger trials.References[1]Armstrong A et al. Presented at American Academy of Dermatology Virtual Meeting Experience 2021; April 23-25, 2021.[2]Mease PJ et al. Efficacy and Safety of Selective TYK2 Inhibitor, Deucravacitinib, in a Phase 2 Trial in Psoriatic Arthritis. Ann Rheum Dis. (In Press).[3]FitzGerald O et al. Presented at the 2021 ACR Convergence, American College of Rheumatology; Nov 3-9, 2021.AcknowledgementsThis study was sponsored by Bristol Myers Squibb. Professional medical writing assistance was provided by Julianne Hatfield, PhD at Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Bristol Myers Squibb.Disclosure of InterestsOliver FitzGerald Consultant of: Consulting and/or speaker fees: Biogen, and Novartis., Grant/research support from: Research grants: BMS, Novartis, Pfizer, UCB, Lilly., Dafna D Gladman Consultant of: Consulting fees: AbbVie, Amgen, BMS, Galapagos, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Philip J Mease Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB., Grant/research support from: Research grants: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN Pharma, and UCB, Christopher T. Ritchlin Consultant of: Consultant: AbbVie, Amgen, Janssen, Lily, Novartis, Pfizer, Regeneron, Sun, UCB;, Grant/research support from: Grants / Research Support: AbbVie, Amgen, UCB, Josef S. Smolen Consultant of: Consulting and/or speaker fees: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos-Gilead, Janssen, Merck-Sharp-Dohme, Novartis-Sandoz, Pfizer, Roche-Chugai, Samsung, and UCB., Grant/research support from: Research grants: AbbVie, AstraZeneca, Eli Lilly, Novartis, Lu Gao Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Sarah Hu Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Miroslawa Nowak Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Subhashis Banerjee Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb., Ian Catlett Shareholder of: Bristol Myers Squibb., Employee of: Bristol Myers Squibb.

BackgroundThe Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) has identified a need for biomarkers to predict which patients (pts) with psoriatic arthritis (PsA) are most likely to respond to a specific therapy. Failure to identify effective treatments early on results in sub-optimal PsA disease management. Tofacitinib is an oral JAK inhibitor for the treatment of PsA. The efficacy and safety of tofacitinib 5 and 10 mg twice daily (BID) in pts with PsA have been demonstrated.1,2ObjectivesTo identify protein biomarker candidates, which may identify responders (R) vs non-responders (NR) to treatment of PsA, using mass spectrometry-based proteomics.MethodsBaseline (BL) serum samples from pts with PsA receiving tofacitinib 5 or 10 mg BID, adalimumab or placebo in OPAL Broaden (NCT01877668)1 were analysed. Pts were identified as R and NR based on the Psoriatic Arthritis Disease Activity Score (PASDAS) at Month 3; pts with lowest PASDAS ≤3.2 were defined as R, those with highest PASDAS >3.2 as NR. Two proteomic strategies were employed for analysis of BL serum samples: (1) targeted mass spectrometric multiple reaction monitoring analysis of an in-house panel (‘PAPRICA’) comprising of 206 proteins, originally developed to distinguish between different arthropathies, and (2) unbiased discovery liquid chromatography-tandem mass spectrometry (LC-MS/MS). PAPRICA data were normalised using two methods: normalisation to stable isotopically labelled peptide spike-ins (SIL; corrects for fluctuations in sample injections/mass spectrometry loading amounts), and normalisation to an endogenous peptide panel representing total serum protein abundance (TSPA; corrects for different amounts of total serum protein across samples). Univariate analyses (Student’s t-test) and multivariate machine learning Random Forest (RF) modelling3 were performed. Univariate analysis of the PAPRICA panel of proteins was performed on R vs NR, and within each treatment arm, with no adjustment for multiplicity.Results96 pts were identified as 47 R and 49 NR based on PASDAS scores. Of pts receiving tofacitinib 5 or 10 mg BID (data pooled), adalimumab or placebo, there were 26 R vs 26 NR, 13 R vs 13 NR and 8 R vs 10 NR, respectively. Results from univariate analysis identified 110 differentially expressed PAPRICA peptides between R vs NR (p≤0.05). RF multivariate analysis of all data (n=96) revealed a set of PAPRICA peptide signatures with the ability to differentiate between R and NR. Two RF models generated from the PAPRICA peptide data had training area under curves (AUCs) 0.956 [95% CI 0.93, 0.99] (TSPA) and 0.959 [95% CI 0.94, 0.98] (SIL). In total, 115 PAPRICA peptides representing 87 proteins were identified as potential biomarkers for predicting treatment response. Using unbiased discovery LC-MS/MS, univariate analysis of all data revealed one candidate peptide biomarker (p≤0.05). RF modelling revealed peptides that contributed to two prediction models with training AUCs of 0.903 [95% CI 0.86, 0.96] and 0.928 [95% CI 0.89, 0.96]. In total, from unbiased discovery LC-MS/MS, 66 peptides representing 39 proteins that may act as potential peptide biomarkers were identified in univariate and multivariate analyses.ConclusionUsing two complementary proteomic approaches and a combination of univariate and machine learning models, a total of 181 candidate biomarker peptides corresponding to 106 proteins have been identified that may act as potential biomarkers for predicting response to treatment of PsA. Further study is required to verify and evaluate these candidate biomarkers, and we will report how these proteins map to biological processes, pathways and networks.References[1]Mease et al. N Engl J Med 2017; 377: 1537-1550.[2]Gladman et al. N Engl J Med 2017; 377: 1525-1536.[3]Breiman. Machine Learning 2001; 45: 5-32.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by Lauren Hogarth, CMC Connect, and funded by Pfizer Inc.Disclosure of InterestsJames Waddington Employee of: Atturos, Ruoyi Zhou Employee of: Atturos, Orla Coleman Employee of: Atturos, Bruna Wundervald Employee of: Atturos, Andrew Parnell: None declared, Philip J Mease Speakers bureau: AbbVie, Amgen, Janssen, Novartis, Pfizer Inc and UCB, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, CorEvitas, Eli Lilly, Galapagos, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Novartis, Pfizer Inc, Sun Pharma and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun Pharma and UCB, Vinod Chandran Consultant of: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Lara Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Douglass Chapman Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Remy Pollock Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Shibing Deng Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Oliver FitzGerald Shareholder of: Atturos, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc and UCB, Employee of: University College Dublin, Stephen Pennington Shareholder of: Atturos, Employee of: University College Dublin

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)-Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) working group provided updates at the 2019 GRAPPA annual meeting on its work toward developing a core outcome set for PsA. The working group prioritized 4 domains, including musculoskeletal disease activity (enthesitis and dactylitis), fatigue, physical function, and structural damage. In this report, the working group summarizes its progress in standardizing the core outcome set for these 4 domains.

At the 2019 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members received updates on several ongoing efforts. Among them were updates on research, including the trainee symposium, pilot research grants, and the Collaborative Research Network; GRAPPA's patient research partners; education, including the slide collection; treatment recommendations; and additional work related to advancing the understanding of disease aspects, including the Outcome Measures in Rheumatology (OMERACT)-GRAPPA outcome measure, axial involvement, and ultrasound enthesitis projects; as well as the early psoriatic disease systematic literature review and magnetic resonance imaging.

Background:Dactylitis, a hallmark of psoriatic arthritis (PsA), is a uniformly diffuse and sometimes painful swelling of the fingers and/or toes.1 Up to 50% of patients (pts) with PsA may experience dactylitis;1,2 as such, dactylitis is an accepted domain of PsA that should be considered in treatment decisions.3 In PsA, dactylitis typically involves feet more than hands; dactylitic joints more frequently have erosive damage, compared with non-dactylitic joints.2 There remains a need for effective therapies to treat dactylitis in pts with PsA. Improvements in dactylitis have been associated with tofacitinib, an oral Janus kinase inhibitor for the treatment of PsA.4,5Objectives:To assess the effect of tofacitinib on dactylitis by location (hands/feet) and individual digit involvement in pts with PsA.Methods:These post hoc analyses used data pooled from two Phase 3 studies (12-month OPAL Broaden [NCT01877668];5 6-month OPAL Beyond [NCT01882439]4) in pts with active PsA treated with tofacitinib 5 mg twice daily (BID; approved dose; to Month [M] 6), tofacitinib 10 mg BID (to M6) or placebo (PBO; to M3); pts were treated continuously with a single conventional synthetic disease-modifying antirheumatic drug. Pts were categorised by the presence of dactylitis at baseline (BL) in the hands and/or feet. Endpoints included change from BL in Dactylitis Severity Score (DSS),6 the number of dactylitic digits and the proportion of pts with dactylitis in individual digits at M1, M3 and M6. Descriptive statistics were generated by visit and treatment arm.Results:Data were pooled from 373 pts with DSS >0 at BL. BL characteristics, including gender, age, race, body mass index, PsA duration, BL DSS and dactylitic digits count were similar across dactylitis groups and treatment groups, except for pts with dactylitis in both the hands and feet, who had higher DSS compared to those with dactylitis in the hands or feet only, likely due to having more dactylitic digits (data not shown). Regardless of location, pts treated with tofacitinib had cumulative improvements from BL to M6 in DSS (Figure 1a) and in the number of dactylitic digits (Figure 1b); improvements in DSS were greater at M1 and M3, compared with PBO. Pts treated with tofacitinib 10 mg BID typically had numerically greater improvements in DSS, compared with pts treated with tofacitinib 5 mg BID (Figure 1a). Most pts treated with tofacitinib experienced improvement of dactylitis across all fingers and toes (Figure 1c–f); mean dactylitis presence was ≤15% at M6 in pts treated with tofacitinib for all digits. Generally, at M1 and M3, fewer pts treated with tofacitinib had dactylitis in any digit, compared with PBO (Figure 1c–f).Conclusion:Among pts with pre-existing dactylitis, treatment with tofacitinib resulted in improvements in dactylitis in hands, feet, or both, and in all digits as early as M1, and up to M6.References:[1]Kaeley et al. Semin Arthritis Rheum 2018; 48: 263-273.[2]Brockbank et al. Ann Rheum Dis 2005; 64: 188-190.[3]Coates et al. Arthritis Rheumatol 2016; 68: 1060-1071.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.[5]Mease et al. N Engl J Med 2017; 377: 1537-1550.[6]Helliwell et al. J Rheumatol 2005; 32: 1745-1750.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Ana-Maria Orbai Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Horizon, Janssen, Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Oliver FitzGerald Speakers bureau: AbbVie, Janssen, Pfizer Inc, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Pfizer Inc, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis and Pfizer Inc, Mohammed Bdewi Speakers bureau: AbbVie, Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

Background:Nail disease is an important feature of psoriasis arthritis (PsA), and has been recognised as one of the 6 important clinical domains by GRAPPA. Little is known about how patients with PsA and nail disease compare to patients without nail disease. Nail disease has been found to associate with severe PsA.Objectives:The objective of this study was to examine the association of nail disease with patient demographics and features of active psoriasis and PsA.Methods:For this cross-sectional study, data from 3 PsA cohorts was studied (St Vincent’s University Hospital Dublin, Ireland; University Hospital Kerry, Ireland; and Fatima Memorial Hospital Lahore, Pakistan). Following informed consent, patients underwent detailed skin and rheumatologic assessments including disease activity measures. Since a large number of patients were in clinical remission at the time of assessment, we made 2 documentations of reversible clinical variables (e.g., current skin scores (PASI), current nail disease, current tender and swollen joint counts, current enthesitis, current dactylitis) at the time of study entry and, through extensive medical record review, we identified patient’s maximum skin and joints disease activity scores ever documented, e.g., maximum skin scores (PASI max), TJC max, SJC max, nail disease ever, dactylitis ever, enthesitis ever. Nail disease was stratified by the presence or absence of nail psoriasis.Results:Data on 476 PsA patients was assessed (age 53.8±10.8, PsA duration 13.9±10 years, BMI 29±5; current PASI 2.5±3.2, current TJC 1.8±2.6 years, current SJC 1.4±2.2 years; 37% of the cohort had enthesitis ever, 46% had dactylitis ever, 30.7% had current dactylitis, and 28% with current enthesitis). 63.4% (n=302) of the cohort ever had nail disease, and 45.4% (n=216) had current nail disease at the time of assessment. On univariate analysis, significant or marginally significant statistical association of current nail disease was noted with current PASI (pConclusion:The presence of nail disease among patients with PsA is significantly associated with severity of skin psoriasis with only borderline associations with measures of active musculoskeletal involvement.Disclosure of Interests:Muhammad Haroon Speakers bureau: Roche, Novartis, Grant/research support from: Abbvie, Pfizer, shehla farrukh: None declared., Shabnam Batool: None declared., Sadia Asif: None declared., Oliver FitzGerald Speakers bureau: Abbvie, Janssen, Pfizer, Consultant of: BMS, Celgene, Eli Lilly, Janssen, Pfizer, Grant/research support from: Abbvie, BMS, Eli Lilly, Novartis, Pfizer.

Background:There is a recognised need for a continuous composite measure of disease activity for the assessment of Psoriatic Arthritis (PsA) in routine clinical settings to allow objective assessment of response and implementation of treat to target.1 Longer multidimensional measures are considered less feasible in routine care and a number of shorter measures have been proposed including, the Disease Activity Score for Psoriatic Arthritis (DAPSA), Disease Activity Score 28 (DAS28), the 3 Visual Analogue Scale (VAS) (comprising physician global VAS, patient global VAS and patient skin VAS) or 4 VAS (comprising physician global VAS, patient pain VAS, joint VAS and patient skin VAS). Testing of these measures in clinical trial datasets has been suggested but thresholds of meaning have not been established.2Objectives:To estimate clinically relevant thresholds of disease activity and improvement for composite measures for routine clinical practice in PsA.Methods:Clinical and patient reported outcome measures were assessed in patients fulfilling CASPAR criteria for PsA at three consecutive follow up visits in a UK multicentre observational study. Participants underwent clinical assessment and completed patient reported measures including health anchor questions. Estimates for Minimal Detectible Change (MDC) were derived using 1.96*2*Standard Error of the Mean (SEM). Minimal Clinically Important Difference (MCID) for improvement were derived using the health anchor method and two distribution methods (Table 1). Thresholds for low, moderate and high disease activity were triangulated from established cut-off values for the patient global VAS, PASDAS and DAPSA.Table 1.Minimal Clinically Important Difference (MCID) and Minimal detectable change (MDC)ANCHOR (MEDIAN)DISTRIBUTION#1DISTRIBUTION #2MDCCPDAI0.51.491.54.16GRACE0.260.60.772.18PASDAS1.220.640.761.58DAS280.20.850.621.463VAS1.131.160.913.124VAS1.110.960.942.45DAPSA7.259.0910.4035.63Disease Activity Score for Psoriatic Arthritis (DAPSA); Psoriatic Arthritis Disease Activity Score (PASDAS); Composite Psoriatic Arthritis Disease Activity Index (CPDAI); Disease Activity Score 28 (DAS28).Distribution #1: Baseline standard deviation (sd) * √ 1 – Cronbach’s alphaDistribution #2: 0.5 * baseline sdMinimal detectable change (MDC): 1.96*2*SEM where SEM = baseline sd √1 - ICCResults:139 subjects were recruited (59 male, 80 female, mean (range) age (years) 52.7 (19 – 83), mean (range) duration of psoriasis (years) 21.9 (2 – 71), mean (range) duration of psoriatic arthritis (years) 6.1 (0 – 41). Cut-off values for low, moderate and high disease activity were 1.3, 2.4, and 4.8 for the 3 Vas and 1.6, 2.8 and 5.0 for the 4 VAS (Figure 1). Estimates for the MCID and MDC for the continuous composite measures and are reported in Table 1.Conclusion:We report estimates of clinically relevant improvements for continuous composite measures in PsA and estimates of low, moderate and high disease activity for the 3 and 4 VAS scales. The thresholds of meaning can now be tested in independent observational and clinical trial datasets.References:[1]Coates et al 2018 A&R Mar;70(3):345-355.[2]Tillett W et al 2021 J Rheum In PressAcknowledgements Funding:This report is independent research funded by the National Institute for Health Research, Programme Grants for Applied Research [Early detection to improve outcome in patients with undiagnosed PsA (‘PROMPT’), RP-PG-1212-20007]. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.Disclosure of Interests:William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Janssen, Novartis, Pfizer, and UCB., Julia Day: None declared, Neil McHugh: None declared, Oliver FitzGerald Speakers bureau: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, BMS, Janssen, Novartis, Pfizer, and UCB., Laura C Coates Speakers bureau: AbbVie, Amgen, Biogen, Celgene, Gilead, Eli Lilly, Janssen, Medac, Novartis, Pfizer, and UCB., Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Pfizer, and Novartis, Philip Helliwell: None declared

This chapter will summarize the most important areas of recent progress related to psoriatic arthritis (PsA) as illustrated in the previous chapters. Not all areas of progress will be mentioned but we will endeavour to point out the pivotal developments which have changed the ways by which we diagnose, assess, and treat this complex disease. We will then highlight the key questions which are the focus of ongoing research and in which, in turn, will likely result in further changes to both our understanding of the disease PsA and how it is managed.

Background The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) – Outcome Measures in Rheumatology (OMERACT) Psoriatic Arthritis (PsA) Core Set working group is developing a core instrument set to guide selection of outcome measures (instruments) for PsA randomised controlled trials (RCTs) and longitudinal observational studies (LOS). Candidate instrument measurement properties are being appraised in systematic literature reviews by working group members. Objectives Appraise the content and face validity (domain match) and feasibility of PsA instruments with GRAPPA stakeholders using the OMERACT Filter 2.1 instrument selection process1. Methods The PsA Core set workshop held at the GRAPPA 2017 annual meeting comprised an introductory plenary session and breakout group discussions. Working group members facilitated six breakout groups, with two patient research partners (PRPs) per group, discussing pre-selected domain-instrument pairs. Participants individually reviewed the instrument(s). After group discussion, they completed anonymised paper-based OMERACT questionnaires examining domain match and feasibility, with votes for each aspect of domain match and feasibility centralised by instrument. A final vote (show of hands) on whether the assigned instrument met the requirements for domain match and feasibility using the OMERACT traffic-light scoring system was taken. Consensus was defined as more than 70% agreement, and majority as more than 50% agreement within a group. Consensus represents stronger evidence than majority agreement. Results There were 145 participants across all breakout groups and 116 returned completed questionnaires. Anonymized votes are summarised across groups and instruments in figure 1. More than 70% in the respective breakout groups endorsed the PsA instrument 66 swollen and 68 tender joint count (66/68 SJC/TJC) as a good match with the target domain of arthritis, a subset of MSK disease activity, FACIT-Fatigue as a good match with fatigue, and PsAID12 as a good match with HRQoL. There was consensus or majority agreement for all feasibility questions for the 66/68 SJC/TJC, HAQ-DI and PsAID9 and PsAID12. For the SPARCC enthesitis index only one item in both domain match and feasibility did not reach majority agreement. Conclusions The first two steps of the OMERACT Filter 2.1 instrument selection process for five candidate instruments have been completed. The first set of candidate instruments selected to undergo the next phase of the OMERACT Filter 2.1, construct validity and discrimination appraisal are 66/68 SJC/TJC, SPARCC enthesitis index, PsAID9, PsAID12, HAQ-DI and FACIT-Fatigue. Additional PsA instruments will undergo the OMERACT selection process. Reference [1] Boers M, Kirwan JR, Tugwell P, et al. The OMERACT Handbook. Accessed 8 January 2018. https://www.omeract.org/resources. Disclosure of Interest None declared

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). In a pooled analysis of data from 2 Phase 3 trials in patients (pts) with active PsA, tofacitinib 5 and 10 mg twice daily (BID) significantly improved American College of Rheumatology (ACR) 20 response rates vs placebo (PBO) (50.0, 53.0 vs 28.0%, respectively; p Objectives To compare the efficacy of tofacitinib 5 and 10 mg BID vs PBO in predefined pt subgroups based on differences in BL demographics, disease activity and concomitant medication. Methods This was an analysis of pooled efficacy data from 2 Phase 3, randomised, double-blind, PBO-controlled studies (OPAL Broaden [12 months; NCT01877668] and OPAL Beyond [6 months; NCT01882439]) in pts with active PsA (defined as ≥3 swollen and ≥3 tender joints). Pts in OPAL Broaden were tumour necrosis factor inhibitor (TNFi)-naive with an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Pts in OPAL Beyond had an IR to ≥1 TNFi. Pts were randomised to receive tofacitinib 5 or 10 mg BID, subcutaneous adalimumab 40 mg every 2 weeks (OPAL Broaden; data not included) or PBO. Pts continued to receive a stable dose of a single csDMARD. ACR20 response rates and LSM change from BL in HAQ-DI at Month 3 (primary endpoint data) were evaluated by subgroup category (demographic and disease characteristics at BL or at screening). Analyses were based on the full analysis set (table 1). Results In total, 238, 236 and 236 pts received tofacitinib 5 mg BID, 10 mg BID, or PBO, respectively. Across all subgroups analysed, tofacitinib 5 and 10 mg BID were generally associated with greater improvements at Month 3 in ACR20 and change from BL in HAQ-DI score than PBO (table 1). In pts classified as current smokers, slightly lower ACR20 response rates and similar changes from BL in HAQ-DI score to corresponding PBO at Month 3 were observed relative to never- or ex-smokers; however, the sample size was small. Statistical methods: ACR20 response was defined as achieving a≥20% improvement in ACR criteria components Missing ACR20 response was considered a non-response to treatment LSMs were calculated based on a mixed model for repeated measures without imputation for missing values ACR, American College of Rheumatology; BID, twice daily; BMI, body mass index; BSA, body surface area; CRP, C-reactive protein; csDMARD, conventional synthetic disease-modifying antirheumatic drug; DSS, Dactylitis Severity Score; HAQ-DI, Health Assessment Questionnaire-Disability Index; LEI, Leeds Enthesitis Index; LSM, least squares mean; MTX, methotrexate; N, number of patients in full analysis set (randomised and received ≥1 treatment dose); n, number of responders; N1, number of patients in the full analysis set by category of subgroup and treatment; N2, number of patients included in the repeated measures model by category of subgroup and treatment; NC, analysis not conducted; PASDAS, Psoriatic Arthritis Disease Activity Score; PASI, Psoriasis Area and Severity Index; PsA, psoriatic arthritis; pts, patients; ROW, rest of world (Brazil, Mexico and Taiwan); SPARCC, Spondyloarthritis Research Consortium of Canada (enthesitis index) Conclusions In this analysis of pooled data from 2 Phase 3 studies in pts with active PsA, tofacitinib 5 and 10 mg BID consistently improved efficacy at Month 3 compared with PBO across all predefined subgroups evaluated, with the exception of current smoking; however, as this was not a pre-specified analysis and some subgroups (including smoking status) were small, interpretation should be made with caution. Reference [1] Nash P, et al. Arthritis Rheumatol2017;69(suppl 10):619. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by K Nicholson of CMC and funded by Pfizer Inc. Disclosure of Interest F. Behrens Grant/research support from: AbbVie, Chugai, Novartis, Pfizer Inc, Prophylix, Roche, Consultant for: AbbVie, Biotest, BMS, Celgene, Chugai, Eli Lilly, Genzyme, Janssen, MSD, Novartis, Pfizer Inc, Roche, UCB, Speakers bureau: AbbVie, Biotest, BMS, Celgene, Chugai, Eli Lilly, Genzyme, Janssen, MSD, Novartis, Pfizer Inc, Roche, UCB, J. Gomez-Reino Grant/research support from: AbbVie, MSD, Pfizer Inc and Roche, Consultant for: Pfizer Inc, Speakers bureau: AbbVie, Biogen, Bristol-Myers Squibb, Janssen, MSD, Pfizer Inc and Roche, P. Nash Grant/research support from: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, D. Gladman Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, O. FitzGerald Grant/research support from: AbbVie, BMS, Novartis, Pfizer Inc, Consultant for: Amgen, Celgene, Eli Lilly, Janssen, C. Ritchlin Grant/research support from: AbbVie, Amgen and UCB, Consultant for: AbbVie, Amgen, Celgene, Janssen, Novartis, Pfizer Inc, Sun and UCB, E. Kudlacz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, A. Romero Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Up to 50% of patients with psoriatic arthritis (PsA) have associated spinal involvement similar to ankylosing spondylitis (AS). HLA-B27 positivity is lower in PsA compared to other SpA which may affect the disease phenotype. Objectives Our aim was to compare axial phenotype in PsA patients with and without HLA-B27 with AS patients. Methods A large international collaboration collected BASDAI, CRP, HLA-B27 status and sacroiliac joints (SIJ) and spine radiographs. These were read centrally by two blinded readers using consensus on the modified New York criteria, mSASSS and PASRI. AP spine radiographs were examined for symmetry (score difference ≥2 between sides) and morphology of syndesmophytes (typical marginal vs atypical chunky/non-marginal) were compared. Results Eight sites contributed 244 (25% HLA-B27+) PsA patients and 198 (75% HLA-B27+) AS patients. Mean BASDAI, mSASSS and PASRI were higher in AS. When categorised by diagnosis and HLA-B27 there were significant differences for age, sex, disease duration, mSASSS, PASRI and syndesmophyte symmetry. Regression analysis, with mSASSS and PASRI as dependent variables revealed significant associations with age, sex, duration of disease, and group (HLA-B27 and diagnosis). Binary multivariate logistic regression was used to investigate associations of age, sex, HLA-B27 status, diagnosis (PsA v AS) and concomitant diabetes with radiographic features. Sacroiliac symmetry showed no significant associations, whilst syndesmophyte symmetry was associated with increasing age and HLA-B27 positivity. Typical marginal syndesmophytes were associated with age, HLA-B27 status and disease duration: in the cervical spine significant associations with age, sex and HLA-B27 status; in the lumbar spine with age, HLA-B27 and diagnosis. Atypical chunky syndesmophytes were associated only with increasing age and male sex. Conclusions This analysis suggests less difference in radiographic phenotype between AS and axial PsA than previously thought. HLA-B27 negative PsA patients have less severe disease as measured by mSASSS and PASRI with less typical marginal syndesmophytes and symmetry, whilst HLA-B27 positive PsA appears similar to AS. Disclosure of Interest None declared

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). The efficacy of tofacitinib has been evaluated in 2 Phase 3 studies in patients (pts) with PsA. Objectives To describe the efficacy of tofacitinib by background methotrexate (MTX) dose in pts with PsA. Methods This post-hoc analysis utilised efficacy data pooled from 2 Phase 3, randomised, double-blind, placebo-controlled studies (OPAL Broaden [12 months; NCT01877668] and OPAL Beyond [6 months; NCT01882439]) in pts with a diagnosis (≥6 months) of active PsA (≥3 swollen and ≥3 tender joints). Pts in OPAL Broaden were tumour necrosis factor inhibitor (TNFi)-naive and had an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD). Pts in OPAL Beyond had an IR to ≥1 TNFi. Pts were randomised to tofacitinib 5 or 10 mg twice daily (BID), placebo or adalimumab 40 mg subcutaneous every 2 weeks (OPAL Broaden; adalimumab data not shown). All pts received a stable dose of 1 csDMARD (eg MTX, leflunomide or sulfasalazine) as background therapy. The maximum dose of MTX allowed per protocol was 20 mg/week. Efficacy outcomes for tofacitinib at Month 3 were evaluated by background MTX dose (≤15 vs>15 mg/week) and included: ACR20/50/70 response rates (≥20/50/70% improvement from baseline, respectively), Health Assessment Questionnaire-Disability Index (HAQ-DI) response rate (reduction from baseline ≥0.35 points) and mean change from baseline in HAQ-DI score. Analyses were based on the full analysis set for pts receiving MTX on Day 1; pts with missing data were considered as having a non-response for binary endpoints. No statistical testing was performed. Results In total, data from 556 pts who received tofacitinib plus MTX only or placebo plus MTX only (tofacitinib 5 mg BID, n=186; tofacitinib 10 mg BID, n=178; placebo, n=192) were included in this analysis. Most pts were treated with background MTX at doses≤15 mg/week (n=371, 66.7%; mean [SD] dose, 12.6 [3.1] mg/week) vs >15 mg/week (n=185, 33.3%; mean [SD] dose, 19.8 [0.8] mg/week). Baseline demographics and disease characteristics were generally similar between arms in MTX dose groups (table 1). At Month 3, tofacitinib 5 and 10 mg BID were generally associated with numerically greater ACR and HAQ-DI response rates and greater changes from baseline in HAQ-DI score compared with placebo. The magnitude of tofacitinib effects on efficacy outcomes appeared broadly similar between background MTX dose groups (table 1). Missing values for ACR20/50/70 response rates and HAQ-DI response rate were considered as non-response to treatment LSM were calculated based on a mixed model for repeated measures without imputation for missing values The maximum permitted dose of MTX was 20 mg/week The analyses included all pts who received MTX as background therapy only on Day 1 in the FAS ACR, American College of Rheumatology; BID, twice daily; CRP, C-reactive protein; FAS, full analysis set; HAQ-DI, Health Assessment Questionnaire-Disability Index; LSM, least squares mean; MTX, methotrexate; n, number of pts with response; N, number of pts included in the analysis; N1, number of pts included in the HAQ-DI response analysis; N2, number of pts evaluable for change from baseline in HAQ-DI at Month 3; pts, patients; SD, standard deviation; SE, standard error Conclusions The results of this pooled analysis suggest that the efficacy of tofacitinib in pts with PsA was greater than placebo and does not differ when evaluated by background MTX dose (≤15 vs>15 mg/week), although small pt numbers in some groups may limit the conclusions that can be made. These results are consistent with findings from similar analyses of tofacitinib in pts with rheumatoid arthritis. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by C Viegelmann of CMC and funded by Pfizer Inc. Disclosure of Interest A. Kivitz Consultant for: AbbVie, Celgene, Genentech, Genzyme, Janssen, Merck, Novartis, Pfizer Inc, Sanofi and UCB, Speakers bureau: AbbVie, Celgene, Genentech, Genzyme, Janssen, Merck, Novartis, Pfizer Inc, Sanofi and UCB, O. FitzGerald Grant/research support from: AbbVie, BMS, Novartis, Pfizer Inc, Consultant for: Amgen, Celgene, Eli Lilly, Janssen, P. Nash Grant/research support from: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, S. Pang: None declared, V. Azevedo Grant/research support from: AbbVie, Eli Lilly, Genentech, GSK, Pfizer Inc, UCB, Consultant for: AbbVie, Merck-Serono, Novartis, Pfizer Inc, Speakers bureau: AbbVie, Janssen, Merck-Serono, Novartis, Pfizer Inc, Sanofi, E. Kudlacz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Takiya Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). PsA is a heterogeneous disease and composite endpoints allow assessment of multiple clinical outcomes in one instrument. Objectives To examine the effects of tofacitinib treatment on several composite endpoints in patients (pts) with PsA. Methods In 2 placebo (PBO)-controlled, double-blind, multicentre, global Phase 3 studies, pts had active PsA and either had an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug (csDMARD) and were tumour necrosis factor inhibitor (TNFi)-naive (OPAL Broaden [n=422; 12 months; NCT01877668]), or had an IR to ≥1 TNFi (OPAL Beyond [n=394; 6 months; NCT01882439]). Pts were randomised to receive tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, adalimumab 40 mg subcutaneous injection once every 2 weeks (OPAL Broaden only) or PBO (advancing to tofacitinib 5 or 10 mg BID at Month 3, OPAL Broaden and OPAL Beyond), in addition to continuing on a single, stable csDMARD. Composite endpoints assessed: Psoriatic Arthritis Disease Activity Score (PASDAS), Disease Activity Score using 28 joints with C-reactive protein, Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis (DAREA/DAPSA) and Composite Psoriatic Disease Activity Index (CPDAI). Results Demographics and baseline disease characteristics were generally similar between treatment groups within the 2 studies, except for duration of PsA disease (longer in OPAL Beyond) and geographic distribution (OPAL Broaden having more Eastern EU pts). Baseline values for composite endpoints were generally similar across treatment groups and studies (table 1). Both doses of tofacitinib showed improvements in composite endpoints vs PBO at Month 3 in both studies (table 1). In OPAL Broaden, the effects of adalimumab were similar to both doses of tofacitinib across composite endpoints. Effect size for the composite endpoints (using a subpopulation of pts who had all available data for all endpoints) was highest for PASDAS and typically lowest for DAREA/DAPSA; this rank order of effect size was similar across treatment arms and studies. At Month 3, effect sizes in pts receiving active treatment ranged from 0.90 (DAREA/DAPSA for tofacitinib 5 mg BID) to 2.40 (PASDAS for tofacitinib 10 mg BID) in OPAL Broaden, and 0.81 (DAREA/DAPSA for tofacitinib 5 mg BID) to 1.84 (PASDAS for tofacitinib 10 mg BID) in OPAL Beyond (table 1). Standardised response means generally followed the same pattern as effect size across studies with both doses of tofacitinib (table 1). Conclusions In 2 Phase 3 studies, tofacitinib 5 mg and 10 mg BID improved composite endpoint scores vs PBO over 3 months in pts with PsA. The largest effect size and standardised response means were observed for PASDAS. Effect sizes and standardised response means varied across endpoints but were consistent across studies. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by C Viegelmann of CMC and funded by Pfizer Inc. Disclosure of Interest P. Helliwell Grant/research support from: AbbVie, Janssen, Pfizer Inc, Consultant for: AbbVie, Janssen, UCB, Speakers bureau: AbbVie, Amgen, Janssen, Pfizer Inc, L. Coates Grant/research support from: AbbVie, Janssen, Consultant for: AbbVie, Amgen, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc, Sun Pharma, UCB, O. FitzGerald Grant/research support from: AbbVie, BMS, Novartis, Pfizer Inc, Consultant for: Amgen, Celgene, Eli Lilly, Janssen, P. Nash Grant/research support from: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, E. Soriano Grant/research support from: AbbVie, Janssen, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, Janssen, Novartis, Pfizer Inc, UCB, Speakers bureau: AbbVie, BMS, Janssen, Novartis, Pfizer Inc, Roche, UCB, M. E. Husni Consultant for: AbbVie, Amgen, BMS, Eli Lilly, Janssen, Novartis, Pfizer Inc, Regeneron, UCB, M.-A. Hsu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Wu Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Kudlacz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for the treatment of psoriatic arthritis (PsA). Two Phase 3 studies have been completed (NCT01877668; NCT01882439) and a long-term extension (LTE) study is ongoing (database not locked; NCT01976364). Objectives To compare incidence rates (IR) for adverse events (AEs) of special interest in a tofacitinib cohort from the Phase 3 PsA trials with real-world experience in a comparison cohort from the US Truven MarketScan database. Methods The tofacitinib cohort included adult patients (pts) from 2 Phase 3 studies with ≥6 months PsA diagnosis who met ClASsification of Psoriatic ARthritis (CASPAR) criteria, had active plaque psoriasis, and active arthritis (≥3 swollen and ≥3 tender/painful joints) and who were treated with tofacitinib. Pts were grouped by those who received tofacitinib 5 (N=238) or 10 mg (N=236) twice daily (BID) in the 2 Phase 3 studies, and all pts who received ≥1 dose of tofacitinib in the 2 Phase 3 studies or the LTE (tofacitinib all doses, N=783). The comparison cohort (N=5799) comprised pts with moderate to severe PsA, defined by ≥1 inpatient or ≥2 outpatient 696.0 diagnosis codes on 2 unique calendar days (≥1 by a rheumatologist) between Oct 2010 and Sep 2015, initiating therapy with a systemic agent for PsA. Key Phase 3 study exclusion criteria were applied to the comparison cohort. IRs for serious infection events (SIEs), herpes zoster (HZ), malignancies (excluding non-melanoma skin cancer [NMSC]), NMSC and major adverse cardiovascular events (MACE) were compared. Results Mean age, gender and diabetes history were generally similar between the tofacitinib and comparison cohorts (48.7–49.5 years, 42.4–49.2% male, 12.2–15.7% with diabetes history). Overall more pts treated with tofacitinib had prior experience with corticosteroids (15.7–28.2%), conventional synthetic disease-modifying antirheumatic drugs (100%) and tumour necrosis factor inhibitors (48.1–55.9%) vs the comparison cohort (11.9%, 46.6% and 36.6%, respectively). IRs for SIEs were lower for the tofacitinib vs the comparison cohort (Table 1). The tofacitinib cohort had a higher rate of HZ vs the comparison cohort (Table 1). IRs for malignancies and MACE were similar between cohorts (Table 1). Conclusions IRs of AEs of special interest reported in tofacitinib PsA Phase 3 studies were generally comparable to those in a general PsA population comprising pts receiving a range of biologic agents, except HZ, which was higher for pts treated with tofacitinb but similar to the incidence observed with tofacitinib treatment in other indications. Acknowledgements This study was sponsored by Pfizer Inc. Editorial support was provided by A Pedder of CMC and was funded by Pfizer Inc. Disclosure of Interest J. Curtis Grant/research support from: Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, H. Yun Grant/research support from: Pfizer Inc, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Speakers bureau: Celgene, Janssen, Novartis, K. Winthrop Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Pfizer Inc, UCB, V. Azevedo Grant/research support from: Bristol-Myers Squibb, GSK, Pfizer Inc, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Serono, Novartis, Pfizer Inc, G. Burmester Grant/research support from: UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Hexal, Janssen, MSD, Medimmune, Novartis, Pfizer Inc, Sanofi, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Hexal, MSD, Novartis, Pfizer Inc, Roche, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Rojo Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Palmetto Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). Objectives To describe the safety profile of tofacitinib from integrated Phase (P)3 and long-term extension (LTE) studies. Methods Data were analysed for patients (pts) who received ≥1 dose of tofacitinib 5 or 10 mg BID or placebo (PBO), integrated across 2 P3 studies (OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]) and 1 LTE study (OPAL Balance [ongoing, database not locked; NCT01976364]). Common adverse events (AEs; occurring in ≥2% of tofacitinib pts in any group) were analysed in the PBO-controlled portion (Months 0–3) of the P3 studies (Cohort 1 [C1]). Serious AEs (SAEs) and discontinuations due to AEs were analysed over 12 months in pts randomised to tofacitinib 5 or 10 mg BID in P3 studies (Cohort 2a [C2a]); pts randomised to PBO were excluded from this analysis. Deaths and AEs of special interest (serious infections [SI], herpes zoster [HZ], opportunistic infections [OI] including HZ, major adverse cardiac events [MACE], malignancies, non-melanoma skin cancer [NMSC]) were evaluated in all tofacitinib-treated pts in the P3 and LTE studies (Cohort 3 [C3]). Incidence rates (IR; pts with events/100 pt-years [PY] and 95% confidence intervals) are reported. Laboratory results will be reported in future publications. Results C1 included 474 tofacitinib- and 236 PBO-treated pts; C2a included 474 tofacitinib-treated pts; and C3 included 783 tofacitinib-treated pts (exposure: 776 PY). Nasopharyngitis (5.9%) and headache (8.5%) were the most commonly reported AEs at Month 3 in pts receiving tofacitinib 5 and 10 mg BID, respectively (Table). In pts randomised to tofacitinib 5 or 10 mg BID, over 12 months (C2a), the IRs for SAEs were 7.92 (4.09, 13.84) and 8.11 (4.19, 14.17), respectively. Discontinuation due to AEs occurred in 11 (4.6%) and 11 (4.7%) pts randomised to tofacitinib 5 and 10 mg BID, respectively, with IRs of 7.16 (3.58, 12.82) and 7.31 (3.65, 13.08), respectively, over 12 months (C2a). Across all tofacitinib-treated pts in the P3 and LTE studies (C3), SIs occurred in 11 pts (1.4%; IR 1.40 [0.70, 2.50]). HZ was reported in 16 pts (2.0%; IR 2.05 [1.17, 3.33]) receiving tofacitinib. All 3 cases of multidermatomal HZ were adjudicated as OIs; these were the only OIs (0.4%; IR 0.38 [0.08, 1.11]). In C3, 2 deaths occurred (0.3%; IR 0.25 [0.03, 0.91]); all were considered unrelated to the study drug. MACE were reported in 3 pts (0.4%; IR 0.38 [0.08, 1.11]), malignancies (excluding NMSC) in 5 pts (0.6%; IR 0.63 [0.21, 1.48]) and NMSC in 4 pts (0.5%; IR 0.51 [0.14, 1.30]). Conclusions Tofacitinib was well tolerated in pts with PsA, with a safety profile consistent to that seen in RA; no new risks were identified. Longer-term follow-up and larger pt populations will provide further information on the safety profile of tofacitinib in pts with PsA. Acknowledgements These studies were sponsored by Pfizer Inc. Editorial support was provided by C Viegelmann of CMC and was funded by Pfizer Inc. Disclosure of Interest G. Burmester Grant/research support from: UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Hexal, Janssen, MSD, MedImmune, Novartis, Pfizer Inc, Sanofi, Roche, Speakers bureau: AbbVie, Bristol-Myers Squibb, Hexal, MSD, Novartis, Pfizer Inc, Roche, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Speakers bureau: Celgene, Janssen, Novartis, K. Winthrop Grant/research support from: Bristol-Myers Squibb, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Pfizer Inc, UCB, G. Williams Consultant for: Pfizer Inc, V. Azevedo Grant/research support from: Bristol-Myers Squibb, GSK, Pfizer Inc, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Janssen, Merck Novartis, Pfizer Inc, Serono, W. F. Rigby Grant/research support from: Amgen, Pfizer Inc, Roche, Consultant for: Bristol-Myers Squibb, Eli Lilly, Pfizer Inc, Roche, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, P. Biswas Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Jones Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, N. Palmetto Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, R. Rojo Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Background An updated psoriatic arthritis (PsA) core domain set (COS) for randomized controlled trials (RCTs) was endorsed at the Outcome Measures in Rheumatology (OMERACT) meeting in 2016 and reflects the patient and physician perspectives.[1] Objectives To synthesise the evidence on measurement properties of Patient Reported Outcome Measures (PROMs) in PsA in order to contribute to the development of a PsA core outcome measurement set (COMS) for RCTs adhering to the OMERACT filter 2.0 Framework.[2] Methods A systematic literature search was performed in EMBASE, MEDLINE and PsycINFO to identify studies published in English on PROM measurement properties in PsA. Two independent reviewers rated the quality of studies according to COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines,[3] extracted data on measurement properties and performed a qualitative evidence synthesis. Results Of 4703 identified references, 162 were read in full-text and 44 included in the systematic review (SR). Thirty-nine instruments, consisting of one or more scales, were analysed. PROMs measuring core set domains with at least fair quality evidence for good validity and reliability (and without evidence for inadequate measurement properties) were: Stockerau Activity Score for PsA (German) for the Musculoskeletal Disease Activity domain; the Psoriatic Symptom Inventory for Skin Disease Activity; the 36-Item Short Form Health Survey Physical Function scale and to a lesser extent the Health Assessment Questionnaire Disability Index and Bath Ankylosing Spondylitis Functional Index for Physical Function; the Psoriatic Arthritis Quality of Life Questionnaire, the Psoriatic Arthritis Impact of Disease questionnaire and VITACORA-19 (Spanish) for Health related Quality of Life/Life Impact; the Functional Assessment of Chronic Illness Therapy-Fatigue Scale for Fatigue, and the Social Role Participation Questionnaire for Participation. Evidence for content validity was lacking for most of these PROMs. Conclusions At least one PROM with some evidence for good validity and reliability was available for five out of eight inner circle domains of the PsA COS. Lack of content validity evidence constitutes a critical barrier for application to the PsA COS per the OMERACT Filter 2.0 Instrument Selection Algorithm [2]. This SR serves as a guide for additional research to increase knowledge of PROM measurement properties in PsA followed by stakeholder consensus for developing a PsA COMS. PROSPERO:CRD42016032546 References Orbai AM, de WM, Mease P et al. International patient and physician consensus on a psoriatic arthritis core outcome set for clinical trials. Ann Rheum Dis 2016. doi: 10.1136. Martin Boers, John Richard Kirwan, Peter Tugwell et al. The OMERACT handbook. Updated May 2016, http://www.omeract.org. Terwee CB, Mokkink LB, Knol DL et al. Rating the methodological quality in systematic reviews of studies on measurement properties: a scoring system for the COSMIN checklist. Qual Life Res 2012;21:651–7. Disclosure of Interest P. Hojgaard Speakers bureau: Received speaking fees once from Celgene and UCB not related to the current work, L. Klokker: None declared, A.-M. Orbai: None declared, K. Holmsted: None declared, E. Bartels: None declared, Y. Y. Leung: None declared, N. Goel Employee of: QuintilesIMS, M. de Wit: None declared, D. Gladman: None declared, P. Mease: None declared, L. Dreyer: None declared, L. Kristensen: None declared, O. FitzGerald: None declared, W. Tillett: None declared, L. Gossec: None declared, P. Helliwell: None declared, V. Strand: None declared, A. Ogdie: None declared, C. Terwee: None declared, R. Christensen: None declared

Background Patients (pts) with PsA experience significant impairment of work productivity (WP) and health-related QoL (HRQoL). Secukinumab (SEC) has previously been shown to rapidly improve symptoms, physical function and HRQoL in pts with active PsA. 1,2 Objectives To assess the impact of SEC on WP and HRQoL through 2 years (yrs) in TNF inhibitor (TNF)-naive PsA pts and those with an inadequate response or intolerance to TNF inhibitors (TNF-IR). Methods 606 and 397 pts were randomized to SEC or placebo (PBO) in FUTURE 1 (10 mg/kg IV followed by 150 or 75 mg SC) and FUTURE 2 (300, 150 or 75 mg SC), respectively. PBO pts were re-randomized to SEC at Wk 16/24. WP was assessed using the WP and Activity Impairment–General Health (WPAI-GH) questionnaire. WPAI-GH includes 6 questions to measure absenteeism, presenteeism, work productivity and impairments in unpaid activity because of health problems during the preceding 7 days. HRQoL was assessed using the PsAQoL questionnaire, encompassing 20 statements that pts rate as true or false on the day of completion. Across both trials, approximately 68% of pts were TNF-naive and 32% were TNF-IR. Observed data are presented from the full analysis set and in subgroups stratified by prior TNF exposure. Only data with approved doses of SEC (300 and 150 mg) are shown. Results In FUTURE 1, 88 of 202 in the SEC 150 mg group were employed and working at baseline (BL); 61 of 100 and 59 of 100 were employed and working at BL in the SEC 300 mg and 150 mg groups of FUTURE 2, respectively. Improvements in all elements of WPAI were reported with SEC 300 and 150 mg in the overall population at Wk 16; responses were sustained through Wk 104 (Table). The greatest improvements were seen in presenteeism (–10.0), work productivity (–10.3) and activity impairment (–14.1), which corresponded to improvements from BL of approximately 29%, 26% and 30%, respectively in the overall population of FUTURE 1 at Wk 104; similar improvements were seen in FUTURE 2 at Wk 104 (300 mg: –14.4 [42%], –11.2 [33%] and –17.7 [38%]; 150 mg: –16.8 [50%], –16.8 [45%] and –18.5 [38%]). Sustained improvements in all elements of WPAI were also evident with SEC in TNF-naive and TNF-IR pts in both FUTURE 1 and FUTURE 2. Improvements in PsAQoL were reported as early as Wk 4 and sustained through Wk 104. At Wk 104 of FUTURE 2, PsAQoL scores had improved by approximately 46% from BL with SEC 300 mg and 49% with SEC 150 mg in the overall population. Similar improvements were seen in TNF-naive (47% and 51%, respectively) and TNF-IR pts (45% and 45%, respectively). Consistent results were reported in FUTURE 1. The efficacy of SEC was consistent regardless of concomitant MTX use. Conclusions SEC provided sustained improvements in WP and PsAQoL in pts with PsA for up to 104 wks, regardless of prior TNF exposure. References McInnes. Lancet 2015;386:1137–46. Mease. NEJM 2015;373:1329–39. Disclosure of Interest V. Strand Consultant for: AbbVie, Amgen, BMS, Celgene, Celltrion, CORRONA, Genentech/Roche, GSK, Janssen, Lilly, Merck, Novartis, Pfizer, Regeneron, Samsung, Sanofi, and UCB, O. FitzGerald Grant/research support from: Abbvie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Sun Pharma, UCB, L. Coates Grant/research support from: Abbvie, BMS, Celgene, Janssen, Lilly, MSD, Novartis, Pfizer, Sun Pharma, UCB, J. Walsh Consultant for: Novartis, J. Canete Consultant for: AbbVie, Boehringer Ingelheim, Celgene, Janssen, Lilly, Novartis, V. Bhosekar Employee of: Novartis, L. Pricop Employee of: Novartis, K. Gandhi Shareholder of: Novartis, Employee of: Novartis, S. Jugl Shareholder of: Novartis, Employee of: Novartis

Background While, a Treat-to-Target strategy (T2T), treating patients with rheumatoid arthritis (RA) towards a certain target (eg. clinical remission; T2T-REM), is highly recommended, several patients in clinical remission often have residual synovitis on ultrasound-imaging (US). This may result in silent radiographic progression and clinical flare. It is arguable whether targeting US-synovitis may result in “deeper” remission in clinical practice. Objectives To assess whether using US in a T2T strategy leads to more patients meeting clinical remission than using only clinical information. Methods Patients with RA who started or changed csDMARD and/or anti-TNF treatment followed in centers with expertise in US and participating in BIODAM (2-year multicenter prospective observational cohort) were included. Clinical and US data [by the US7-score that includes 7 joints of the clinically dominant hand and foot for synovitis and tenosynovitis on gray-scale US (GSUS) and power-doppler US (PDUS) and erosions on GSUS] were collected every 3 months. Per visit was decided whether the patient was treated according to the clinical definition of T2T with remission as benchmark (T2T-CLIN-REM). Though not mandatory, US-data could also be used for this purpose. T2T-CLIN-REM was considered correctly applied if: either i) a patient already had a disease activity score below the remission target (i.e. ACR/EULAR boolean remission) or ii) if not, treatment was intensified. A T2T strategy taking also US data into account (T2T-CLIN-US-REM) was considered correctly applied if: either i) both clinical and US remission (all joints included in the US7-score with GSUS synovitis Results In total 963 visits of 130 patients were included. T2T-CLIN-US-REM was correctly followed in 33% of the visits, T2T-CLIN-REM in 14%, and any of these in 52%. Remission according to the ACR/EULAR-boolean definition was achieved in 19.6% of the visits. Compared to the conventional T2T-CLIN-REM strategy, using a combined clinical and US benchmark for T2T led to a lower – instead of higher - likelihood of ACR/EULAR-boolean remission 3 months later [OR (95% CI): 0.39 (0.24; 0.63] (table). Conclusions Our results, from a non-randomized study, did not suggest an advantage of using US of 7 joints in addition to clinical examination as a T2T benchmark as compared to clinical examination alone in getting RA patients into clinical remission. Disclosure of Interest None declared

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for treatment of psoriatic arthritis (PsA). Objectives To assess the efficacy and safety of tofacitinib vs placebo (PBO) in patients (pts) with active PsA. Methods Eligible pts in this randomised, PBO- and active-controlled, 12-month Phase 3 trial had ≥6-months9 PsA diagnosis, fulfilled CASPAR criteria, had active arthritis (≥3 tender/painful and ≥3 swollen joints) and active plaque psoriasis at screening, inadequate response to ≥1 csDMARD, and were tumour necrosis factor-inhibitor (TNFi)-naive. 422 pts were randomised 2:2:2:1:1 to tofacitinib 5 or 10 mg twice daily (BID), adalimumab 40 mg subcutaneous injection every 2 weeks, or PBO (advancing to tofacitinib 5 or 10 mg BID at Month [M]3). Stable treatment with 1 csDMARD was required. Primary endpoints comparing tofacitinib vs PBO were ACR20 response rate and change from baseline in Health Assessment Questionnaire Disability Index (ΔHAQ-DI) at M3. Secondary endpoints included: ACR20 response rates and ΔHAQ-DI through M12; pts achieving ACR50, ACR70, ≥75% improvement of PASI and PsARC at all time points; and changes from baseline in LEI, Dactylitis Severity Score and SPARCC Enthesitis Index. Radiographic progression was assessed by van der Heijde-modified Total Sharp Score (mTSS). Results 96.9% of pts were white and 53.3% were female; mean age was 47.9 years. 96.2% and 88.4% of pts completed M3 and M12, respectively. At M3, tofacitinib 5 and 10 mg BID significantly improved ACR20 response rates (50.5% [p≤0.05] and 60.6% [p 91% of pts were radiographic non-progressors at M12 (defined as an increase from baseline in mTSS ≤0.5). M12 safety findings were similar between groups (Fig 1E). The most common adverse events were upper respiratory tract infection (7.5–10.6%), nasopharyngitis (7.5–11.5%) and headache (3.8–10.6%). Conclusions In TNFi-naive pts with active PsA, tofacitinib was superior to PBO in ACR20 response rates and ΔHAQ-DI at M3, with superiority vs PBO as early as Week 2 for ACR20, which was maintained to M12. No new safety risks were identified vs previous studies in other indications. Acknowledgements Previously presented at ACR 2016, to be presented at AAD 2017 and reproduced with permissions. This study was sponsored by Pfizer Inc. Editorial support was provided by AG McCluskey of CMC and was funded by Pfizer Inc. Disclosure of Interest P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, Sun, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, CORRONA, Dermira, Janssen, Eli Lilly, Merck, Novartis, Pfizer Inc, Sun, UCB, Zynerba, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Genentech, Janssen, Novartis, Pfizer Inc, UCB, S. Hall Consultant for: AbbVie, Celgene, Eli Lilly, Janssen, Pfizer Inc, Roche, O. FitzGerald Grant/research support from: AbbVie, Bristol-Myers Squibb, Consultant for: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, Speakers bureau: Celgene, Janssen, Novartis, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer Inc, Roche, Sanofi-Aventis, UCB, Employee of: Imaging Rheumatology BV, J. Merola Grant/research support from: Biogen Idec, Consultant for: AbbVie, Amgen, Biogen Idec, Eli Lilly, Janssen, Momenta, Mallinckrodt, Novartis, Pfizer Inc, Speakers bureau: AbbVie, Eli Lilly, F. Avila-Zapata: None declared, D. Cieślak: None declared, D. Graham Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc

Rheumatoid arthritis (RA) is the most common form of inflammatory disease, affecting 1-2% of the population. Posteroanterior (PA) and Brewerton projections are well established in radiographic practice for scoring and monitoring RA, but there is little evidence to demonstrate the diagnostic efficacy of these techniques. This work, by varying the positioning of a cadaveric hand, investigates whether an alternative radiographic projection could yield greater diagnostic information than the traditional techniques. Phase I of the study evaluated moving the hand 15 degrees from the anteroposterior position and then in 5 degrees increments in four directions: medial rotation, lateral rotation, flexion of the wrist and extension of the wrist. Phase II of the study took the optimum projections from Phase I and further manipulated these positions in a direction at right angles to the original position. Images were scored based on joint space visualisation in 29 joints. Results demonstrated that significantly higher diagnostic efficacy was evident with 15 degrees lateral rotation of the hand or 15 degrees flexion at the wrist compared to the Brewerton projection. Either projection is recommended, but on the basis of patient comfort, the latter of these novel positions, now known as the UCD projection, was chosen as the optimum procedure to replace the Brewerton projection. The value of using cadavers for the establishment of optimum radiographic procedures is highlighted.

Cationic amphiphiles have received increasing attention as antimicrobials given their unique ability to disrupt bacteria cell membranes. While extensive research has demonstrated that amphiphiles' hydrophobic-to-charge ratio significantly modulates antibacterial activity, less work has focused on elucidating the specific impact of charge location on amphiphile bioactivity. In this study, two series of cationic amphiphiles, termed bola-like and gemini-like, were synthesized with analogous hydrophobic-to-charge ratios yet differing charge location, and their resulting antibacterial activity was assessed. Bola-like amphiphiles exhibited preferential activity against two Gram-positive bacteria, with activity increasing with increasing hydrophobicity, whereas gemini-like amphiphiles were active against both Gram-positive and Gram-negative bacteria, with activity decreasing with increasing hydrophobicity. After identifying lead compounds from each amphiphile series (bola- and gemini-like), biophysical experiments indicated that both amphiphiles were membrane-active; notably, the lead gemini-like amphiphile exhibited a strong dependence on electrostatic interactions for membrane interaction. In contrast, the lead bola-like amphiphile exhibited a reliance on both hydrophobic and electrostatic contributions. These results demonstrate that charge location significantly impacts cationic amphiphiles' antibacterial and membrane activity.

Guidelines for the prevention of glucocorticoid (GC) induced osteoporosis (GIOP) were implemented in a level 5 Irish Hospital with cross sectional audit of inpatient prescribing undertaken before and after. Prior to guideline implementation, elemental calcium (Ca) with Vitamin D (VitD) was prescribed for 11/66 (17%) of patients on GCs with 2/66 (3%) also receiving bisphosphonate (BP) therapy. Subsequent to guideline implementation, Ca with VitD was prescribed for 19/55 (35%) of patients on GCs with 11/55 (20%) also receiving BP therapy, representing a 2 and 6 fold respective increase. Internal promotion of guidelines is an effective strategy for healthcare improvement but needs refinement with or without repetition to achieve better patient outcomes.

At the 2014 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the psoriatic arthritis (PsA) working group of OMERACT (Outcome Measures in Rheumatology) presented a review of the progress made at the OMERACT 12 meeting, held in 2014. Members of the PsA OMERACT working group presented work from the Patient Involvement in Outcome Measures for PsA initiative to improve the incorporation of patient research partners in PsA outcomes research, the results of discussions within the OMERACT breakout groups, and finally the voting results. The OMERACT 12 participants had endorsed the need to update the PsA core set according to the Filter 2.0 framework. The breakout group discussions identified potential opportunities for revising the core set, including consolidating existing redundancy within the core set, improving incorporation of the patient perspective, and including disease effects such as fatigue as a core criterion. GRAPPA members of the OMERACT working group now have a program of research to update the core set with the goal of seeking endorsement at OMERACT 13, to be held in 2016.

To compare the pattern of joint responses in patients with rheumatoid arthritis and psoriatic arthritis treated with TNF inhibitor (TNFi) therapy.A total of 182 PsA/Rheumatoid arthritis (RA) patients attending the rheumatology unit of a tertiary referral centre in Ireland were recruited and prospectively followed up by the attendant rheumatologists. Clinical progress of the patients was noted at baseline and 6 months after starting TNFi therapy.A total of 114 RA and 68 PsA patients were assessed; 20% of the patients had one of either tender joints or swollen joints after 6 months of therapy. Rheumatoid arthritis patients had a significantly higher proportion of non-tender swollen joints compared with PsA patients, whereas PsA patients had a higher proportion of tender non-swollen joints (p0.05).Residual joint swelling was found more commonly in RA patients than in PsA patients following TNFi therapy, whereas residual tender joints occurred more frequently in PsA; this may reflect enthesiopathy or periostitis.

Psoriasis and psoriatic arthritis (PsA) affect skin, and/or joints and quality of life (QoL).To better assess the success in multiple attributes in subjects with both active psoriasis and PsA, the objective was to quantify the proportion of those who achieved substantial improvement in a composite measure of skin symptoms, joint manifestations, and QoL, on one of two treatment regimens.Subjects (n=752) with psoriasis and PsA (mean age: 46.5 years, 62.9% male) received etanercept (ETN) 50mg twice weekly (BIW; n = 379) or 50 mg weekly (QW; n=373) for 12 weeks, followed by open-label ETN 50mg QW for 12 weeks. Skin and joint symptoms and QoL were assessed using psoriasis area and severity index (PASI), American College of Rheumatology criteria (ACR) and Euro-QoL (EQ-5D), respectively. By week 24, 30.6% and 25.8% of subjects receiving ETN 50 mg BIW/QW and ETN 50 mg QW/QW, respectively (P = 0.198) achieved the composite measure of efficacy for skin plus joints plus QoL (PASI 75 + ACR 50 + EQ-5D VAS82).At 24 weeks, 25.8-30.6% met the triad of rigorous efficacy outcomes. Evaluation of treatment efficacy should address the multiple components of this disease complex; therefore it may be important to consider this composite measure in future trials.

Abnormalities of the thyroid gland are said to be common in patients with dermatitis herpetiformis (DH), treated with dapsone (Thyroid abnormalities in dermatitis herpetiformis. Cunningham andZone, Annals Int.Med. 1985: 102, 194-196). Thepossibility that the goitrogenic effects of dapsone may play a role in this has not been evaluated. We therefore studied thyroid abnormalities in 40 patients with DH, 25 of whom were taking dapsone and 15 of whom were on a gluten free diet alone. All patients were examined clinically for evidence of thyroid dysfunction and blood was drawn for total thyroxine, thyrotrophin levels and thyroid microsomal antibdy titres. Six (24%) of dapsone treated patients had thyroid abnormalities, compared to 1 (7%) of the 15 patients treated with diet alone. Two patients became thyrotoxic when on treatment with dapsone. One patient had myxoedema prior to diagnosis of DH and one developed myxoedema while on dapsone. Two patients with asymptomatic goitres at the time of screening were taking dapsone and one patient on dapsone had thyroid antibodies. Thus it seems likely that the increased incidence of thyroid abnormalities in DH may be related to the effects of the sulphonamide on thyroid function.

Survivin, an inhibitor of apoptosis protein (IAP), has been implicated in endothelial cell stability, through inhibition of apoptosis and in cell proliferation.To evaluate the effect of antitumour necrosis factor (TNF)-alpha therapy on survivin expression in psoriasis skin at 0, 2 and 12 weeks after infliximab therapy.Skin biopsies were obtained from 16 patients; 11 also had arthritis with active skin/joint disease. Clinical scores [Psoriasis Area and Severity Index (PASI), involved body surface area (BSA), Disease Activity Score (DAS28) and Health Assessment Questionnaire] were recorded. Inflammatory infiltration and survivin protein expression were examined and graded by immunohistochemical staining, and mRNA levels were determined by real-time polymerase chain reaction.Survivin mRNA and protein were demonstrated in all baseline lesional biopsies. Survivin mRNA and protein expression was significantly greater in lesional compared with nonlesional baseline skin (P0.05). Differential cellular localization of survivin was demonstrated with cytoplasmic survivin protein expression localized to the perivascular/endothelial regions and strong nuclear staining localized in the basal layer of the epidermis. Infliximab produced a dramatic clinical response in skin and joints (P0.05), paralleled by significant reduction in the inflammatory infiltrate and survivin protein expression (P0.05) which was reflected at the mRNA level where expression was significantly reduced by week 12 (P0.01). Survivin protein levels before and after treatment significantly correlated with PASI (r = 0.478, P0.05) and BSA scores (r = 0.528, P0.024). PASI strongly correlated with BSA (r = 0.949, P0.0001) and DAS28 (r = 0.717, P0.002) scores.Survivin correlates with disease activity in patients with psoriasis and is significantly downregulated following anti-TNF-alpha treatment. Understanding the role of IAPs in cell survival/antiapoptosis and proliferation mechanisms may provide important insights into downstream therapeutic targeting in inflammation.

Psoriatic arthritis (PsA), recognised for over 100 years, is common representing the second most frequent diagnostic category after RA and occurring in up to 10% of patients with skin psoriasis. The pathogenic connection between psoriasis and arthritis is not yet clear although our understanding of the mechanisms of disease has progressed significantly in recent years. Factors including immunogenetics, infection, autoimmunity, angiogenesis, trauma and the nervous system are implicated in the pathogenesis of PsA. Organ involvement is largely restricted to the connective tissue of the skin and joints, including both the synovial tissue and sites of entheseal attachment. This restricted inflammatory response suggests that either a common antigen driving the immune response or that antigenic proteins or cells are present at these sites only having migrated the or arising de novo. The epidemiology of Psoriasis has been extensively examined since the 1960's, however there have been few large epidemiological studies of PsA. In addition, the lack of diagnostic criteria for the diagnosis of PsA until 1973, and the diffuse clinical manifestations of this condition have hindered meaningful conclusion regarding the epidemiology of this form of arthritis.

Rheumatoid arthritis (RA) is a common cause of disability and deformity for which treatment is often of limited value in controlling the disease process and outcome.1 Infliximab (chimeric antibody to tumour necrosis factor α (TNFα)) is clearly efficacious in up to 70% of patients, but treatment may be complicated by the development of infections that are occasionally serious and life threatening. Pooled analysis reported a 21% incidence of infection among 453 patients treated with infliximab compared with an 11% incidence in 109 placebo recipients.2 Infections considered serious occurred in 3.4% and 1.8% of patients, respectively. As of August 2001, 84 of 170 000 patients treated with infliximab world wide had developed active tuberculosis, including 14 deaths. Here we present the case of a 57 year old man with a five year …