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ObjectiveAssess pooled safety results through the end of the phase II/III studies of guselkumab (GUS; ≤ 2 years) in tumor necrosis factor inhibitor (TNFi)-naïve and -experienced patients with psoriatic arthritis (PsA).MethodsData were pooled from the Phase 2 and DISCOVER-1 (both TNFi-naïve and -experienced), DISCOVER-2 (TNFi-naïve), and COSMOS (TNFi-experienced) studies. Patients with active PsA were randomized to GUS 100 mg every 4 or 8 weeks (Q4W + Q8W = Combined GUS) or placebo (PBO) with crossover to GUS Q4W or Q8W at week 24. Time-adjusted adverse event (AE) rates (events/100 patient-years [PY]) and clinical laboratory findings were assessed during the PBO-controlled period and through end of study (≤ 2 years).ResultsOf 1554 randomized patients (n = 373 [GUS Q4W], 664 [GUS Q8W], and 517 [PBO]), 1138 (73.23%) were TNFi-naïve and 416 (26.77%) were TNFi-experienced. Respective AE rates through week 24 were 220.8/100 PY (TNFi-naïve) and 251.6/100 PY (TNFi-experienced) in the Combined GUS group and 196.1/100 PY (TNFi-naïve) and 303.0/100 PY (TNFi-experienced) in the PBO group. Among all GUS-treated patients (including those who crossed over from PBO), low AE rates were maintained during long-term evaluation in both TNFi-naïve (139.7/100 PY) and TNFi-experienced (174.0/100 PY) patients. Rates/100 PY of AEs leading to treatment discontinuation, serious AEs, and other AEs of interest, as well as occurrence of elevated hepatic transaminase levels and decreased neutrophil counts were consistent between PBO and GUS-treated patients through week 24 regardless of prior TNFi use and remained low through the end of the studies.ConclusionThe safety profile of GUS in TNFi-experienced patients was consistent with that in TNFi-naïve patients, which remained favorable for up to 2 years. [ClinicalTrials.gov: Phase 2 (NCT02319759), DISCOVER-1 (NCT03162796), DISCOVER-2 (NCT03158285), and COSMOS (NCT03796858)]

ObjectivesPsoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients’ overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine learning to analyse data from the phase III DISCOVER-1/DISCOVER-2 clinical trials.MethodsPooled data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 8/4 weeks were retrospectively analysed. Non-negative matrix factorisation was applied as an unsupervised machine learning technique to identify PsA phenotype clusters; baseline patient characteristics and clinical observations were input features. Minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA) low disease activity (LDA) and DAPSA remission at weeks 24 and 52 were evaluated.ResultsEight clusters (n=661) were identified: cluster 1 (feet dominant), cluster 2 (male, overweight, psoriasis dominant), cluster 3 (hand dominant), cluster 4 (dactylitis dominant), cluster 5 (enthesitis, large joints), cluster 6 (enthesitis, small joints), cluster 7 (axial dominant) and cluster 8 (female, obese, large joints). At week 24, MDA response was highest in cluster 2 and lowest in clusters 3, 5 and 6; at week 52, it was highest in cluster 2 and lowest in cluster 5. At weeks 24 and 52, DAPSA LDA and remission were highest in cluster 2 and lowest in clusters 4 and 6, respectively. All clusters improved with guselkumab treatment over 52 weeks.ConclusionsUnsupervised machine learning identified eight PsA phenotype clusters with significant differences in demographics, clinical features and treatment responses. In the future, such data could help support individualised treatment decisions.

ObjectiveEvaluate relationship between radiographic progression and clinical outcomes in post hoc analyses of patients with psoriatic arthritis (PsA) receiving up to 2 years of guselkumab therapy in the phase 3, placebo-controlled, randomised trial, DISCOVER-2.MethodsBiologic-naïve adults with active PsA (≥5 swollen joints /≥5 tender joints ; C reactive protein ≥0.6 mg/dL) were randomised to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at week 0, week 4, then every 8 weeks (Q8W); or placebo→guselkumab 100 mg Q4W (week 24). Radiographs (hands/feet) at week 0, week 24, week 52 and week 100 were scored via PsA-modified van der Heijde-Sharp (vdH-S) methodology. In these post hoc analyses, mean changes in vdH-S scores were summarised according to achievement of American College of Rheumatology 20/50/70 response; low disease activity (LDA) defined by Disease Activity in Psoriatic Arthritis (DAPSA) ≤14 or Psoriatic ArthritiS Disease Activity Score (PASDAS) ≤3.2, or minimal/very low disease activity (MDA/VLDA); and normalised physical function (Health Assessment Questionnaire-Disability Index (HAQ-DI) ≤0.5). Response rates for achieving MDA/VLDA and each component were determined among patients with and without radiographic progression (change in total vdH-S score >0.5). No formal hypothesis testing was performed.Results664 of 739 treated patients in DISCOVER-2 continued study treatment at week 52 and were included in these analyses. Mean changes in vdH-S scores from weeks 0 to 100 among all patients in the Q4W and Q8W groups were 1.7 and 1.5, respectively. Among all guselkumab-randomised patients, those who achieved ACR20/50/70, DAPSA LDA, PASDAS LDA, MDA, VLDA and HAQ-DI ≤0.5 (normalised physical function) had smaller mean changes in vdH-S scores than did non-responders at week 52 (0.2–1.2 vs 1.7–4.1) and week 100 (0.3–1.2 vs 2.0–4.6). Relative to patients with radiographic progression, those without progression were more likely to achieve the MDA criteria related to swollen and tender joint counts, patient-reported pain and global assessment, and normalised physical function through week 100.ConclusionIn these post hoc analyses, the achievement of low levels of disease activity, including MDA, was associated with diminished rates of radiographic progression observed in patients receiving up to 2 years of guselkumab. Radiographic non-progressors were more likely to achieve patient-reported MDA criteria of minimal pain and normalised physical function compared with radiographic non-responders.Trial registration numberNCT03158285.

ObjectivesTo evaluate the efficacy through 52 weeks of guselkumab, an interleukin 23-p19 subunit inhibitor, in subgroups of pooled psoriatic arthritis (PsA) patients from the DISCOVER-1 and DISCOVER-2 trials defined by baseline patient characteristics.MethodsAdults with active PsA despite standard therapies were enrolled in DISCOVER-1 (≥3 swollen and ≥3 tender joints, C reactive protein (CRP) level ≥0.3 mg/dL) and DISCOVER-2 (≥5 swollen and ≥5 tender joints, CRP ≥0.6 mg/dL, biological-naïve). Randomised patients received 100 mg guselkumab at weeks 0, 4, and then every 4 or 8 weeks (Q4W/Q8W) or placebo. Guselkumab effects on joint (ACR20/50/70), skin (IGA 0/1, IGA 0), patient-reported outcome (Health Assessment Questionnaire Disability Index/Functional Assessment of Chronic Illness Therapy-Fatigue) and disease severity (minimal disease activity/PsA Disease Activity Score low disease activity) endpoints were evaluated by patient sex, body mass index, PsA duration, swollen/tender joint counts, CRP level, percent body surface area with psoriasis, Psoriasis Area and Severity Index score, and conventional synthetic disease-modifying antirheumatic drug use at baseline.ResultsBaseline patients characteristics in DISCOVER-1 (N=381) and DISCOVER-2 (N=739) were well balanced across randomised groups. At week 24, 62% (232/373) and 60% (225/375), respectively, of guselkumab Q4W-treated and Q8W-treated patients pooled across DISCOVER-1 and DISCOVER-2 achieved the primary endpoint of ACR20 response versus 29% (109/372) of placebo-treated patients. Guselkumab treatment effect at week 24 was observed across patient subgroups. Within each patient subgroup, response rates across all disease domains were sustained or increased at week 52 with both guselkumab regimens.ConclusionsGuselkumab Q4W and Q8W resulted in robust and sustained improvements in PsA signs and symptoms consistently in subgroups of patients defined by diverse baseline characteristics.Trial registration numbersNCT03162796, NCT03158285.

Background Guselkumab was efficacious in reducing signs and symptoms of psoriatic arthritis in the phase 3 DISCOVER-1 and DISCOVER-2 studies. We aimed to evaluate the efficacy of guselkumab in post-hoc analyses of patients with psoriatic arthritis with imaging-confirmed sacroiliitis consistent with axial involvement. Methods In DISCOVER-1, 381 patients with active psoriatic arthritis (defined as 03 swollen joints, 03 tender joints, and C-reactive protein [CRP] 00middot3 mg/dL) and in DISCOVER-2, 739 patients with active psoriatic arthritis (defined as 05 swollen joints, 05 tender joints, and CRP 00middot6 mg/dL) were randomly allocated to receive guselkumab 100 mg every 4 weeks, guselkumab 100 mg every 8 weeks (week 0, week 4, then every 8 weeks), or placebo. These pooled, post-hoc analyses included patients with axial disease documented by previous imaging or pelvic radiography at screening consistent with sacroiliitis (confirmed by investigator). Efficacy assessments included least squares mean changes, with 95% CIs, in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, modified BASDAI (mBASDAI; excluding peripheral joint pain), spinal pain, and Ankylosing Spondylitis Disease Activity Score (ASDAS), and proportions of patients achieving at least a 50% improvement in BASDAI score (BASDAI50) and achieving ASDAS responses of inactive disease (score

ObjectiveEvaluation of the efficacy and safety of guselkumab, a human monoclonal antibody targeting the interleukin-23p19 subunit, in patients with psoriatic arthritis (PsA) through 1 year.MethodsAdults who met ClASsification criteria for Psoriatic ARthritis, with active disease (≥3 swollen and ≥3 tender joints; C reactive protein ≥0.3 mg/dL) despite standard treatment (31% previously received ≤2 tumour necrosis factor inhibitors (TNFi)), were randomised (1:1:1) to guselkumab 100 mg every 4 weeks (Q4W); guselkumab 100 mg at Week0, Week4, then Q8W; or placebo with cross-over to guselkumab 100 mg Q4W at Week24 (PBO→Q4W) through Week48. Clinical efficacy through Week52 (employing non-responder imputation) and adverse events (AEs) through Week60 were evaluated.ResultsOf 381 treated patients, 90% completed the study. Numerical increases in the proportions of patients achieving ≥20% improvement in ACR criteria (ACR20) were observed post-Week24, reaching 73% (94/128) and 60% (76/127) for Q4W-randomised and Q8W-randomised patients, respectively, by Week52. Proportions of patients achieving ACR50/ACR70/skin responses and minimal/very low disease activity were maintained, as were improvements in physical function and health-related quality of life, through Week52 in guselkumab-randomised patients. Response to guselkumab was maintained in both TNFi-naïve and TNFi-experienced patients. Serious AEs and serious infections occurred in similar proportions of guselkumab Q4W-randomised (3% and 0%) and Q8W-randomised (6% and 2%) patients through Week60, with no new safety concerns versus observations through Week24. No guselkumab-treated patient and two patients receiving placebo died; no study participant developed opportunistic infection or inflammatory bowel disease.ConclusionGuselkumab provided sustained improvement across multiple clinical manifestations of PsA, maintaining a favourable benefit-risk profile, through 1 year regardless of prior TNFi exposure.

Background:In patients (pts) with psoriatic arthritis (PsA), fatigue is a major driver of perceived impact of disease and has been identified as an important domain to be assessed in clinical trials.1,2 The association between fatigue and other PsA domains (eg, physical function) or clinical response is not well understood.Objectives:Fatigue was measured with the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaire in the pivotal DISCOVER-1 and DISCOVER-2 Phase 3 studies of guselkumab (GUS) vs placebo (PBO). This post hoc analysis explores the correlation between FACIT-Fatigue and physical function and clinical response in the DISCOVER program.Methods:This analysis used pooled data from pts (N=1120) treated with GUS or PBO. In DISCOVER-1 and DISCOVER-2, 381 pts with active PsA (swollen joint count [SJC] ≥3, tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) and 739 pts with active PsA (SJC ≥5, TJC ≥5, CRP ≥0.6 mg/dL) and inadequate response to standard therapies, respectively, were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. PBO pts switched to GUS 100 mg Q4W at W24. The FACIT-Fatigue questionnaire has 13 items that assess self-reported fatigue/tiredness over the last 7 days. Items are scored from 0 (very much fatigued) to 4 (not at all fatigued). FACIT-Fatigue response was defined as an increase of ≥4 points from baseline. Physical function was evaluated with the Health Assessment Questionnaire-Disability Index (HAQ-DI). HAQ-DI response was defined as a decrease of ≥0.35 points from baseline. Clinical response was defined as achievement of ≥20% improvement in the American College of Rheumatology (ACR 20) criteria. Relationships between FACIT-Fatigue and HAQ-DI at W8/16/24 were assessed by Pearson correlation coefficients. Mean changes in HAQ-DI scores at W8/16/24 were summarized in FACIT-Fatigue responders and nonresponders. A logistic regression model was applied to estimate odds ratios (ORs) for achievement of HAQ-DI and ACR 20 response by FACIT-Fatigue response status at each visit. A multiple linear regression model was used to evaluate the association between FACIT-Fatigue and HAQ-DI at W24 after adjusting for SJC, TJC, CRP, and pt assessment of pain.Results:FACIT-Fatigue and HAQ-DI scores and changes from baseline were negatively correlated at W8, W16, and W24 (Table 1). Mean changes in HAQ-DI were −0.31, −0.43, and −0.48 at W8, W16, and W24, respectively, in FACIT-Fatigue responders and −0.06, −0.07, and −0.09, respectively, in FACIT-Fatigue nonresponders. FACIT-Fatigue responders were significantly more likely than nonresponders to achieve HAQ-DI and ACR 20 response (OR [95% CI] at W8, 2.8 [2.2-3.7] and 2.4 [1.9-3.1]; at W16, 3.6 [2.8-4.7] and 2.9 [2.3-3.7]; and at W24, 4.4 [3.4-5.7] and 3.2 [2.5-4.2], respectively; Figure 1). Correlations between FACIT-Fatigue and HAQ-DI remained significant after adjusting for SJC, TJC, CRP, and pt assessment of pain.Conclusion:In pts with PsA, fatigue response is a clinically meaningful predictor of improvements in physical function and achievement of ACR 20 response, reinforcing the importance of assessing fatigue in PsA disease management.References:[1]Leung YY et al. J Rheumatol. 2020;96:46-9.[2]Gudu T et al. Joint Bone Spine. 2016;83:439-43.Table 1.Correlation* of FACIT-Fatigue and HAQ-DIVisitHAQ-DI and FACIT Fatigue ScoresChanges From Baseline in HAQ-DI and FACIT-Fatigue ScoresW8−0.61 (p−0.42 (pW16−0.60 (p−0.47 (pW24−0.62 (p−0.50 (p*Determined by Pearson correlation coefficient; p-values derived from hypothesis tests of correlation ρ=0 (ie, no correlation).Figure 1Disclosure of Interests:Arthur Kavanaugh Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Genentech, Janssen, Eli Lilly, Merck, Novartis, Pfizer and UCB, Yan Liu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GSK, Janssen, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB; and personal fees from Boehringer Ingelheim and GlaxoSmithKline, Philip Helliwell Consultant of: Galapagos, Janssen, Novartis, Grant/research support from: Abbvie, Janssen, Pfizer, Laure Gossec Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Biogen, Celgene, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Galapagos, Janssen, Eli Lilly, Pfizer, Sandoz, Sanofi, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Chenglong Han Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.

Background:In the Phase 3 DISCOVER-11 & DISCOVER-22 trials, guselkumab (GUS), a human monoclonal antibody targeting the IL-23p19-subunit, was effective in psoriatic arthritis (PsA) across joint & skin endpoints. At Week 24 (W24), GUS benefit was consistent regardless of baseline (BL) demographic & disease characteristics.3Objectives:We assessed whether GUS efficacy was sustained through W52 in pooled DISCOVER-1 & -2 patients (pts) across select BL subgroups.Methods:Adults with active PsA despite standard therapies were enrolled in DISCOVER-1 (swollen [SJC] ≥3 & tender joint count [TJC] ≥3, C-reactive protein [CRP] ≥0.3 mg/dL) & DISCOVER-2 (SJC ≥5 & TJC ≥5, CRP ≥0.6 mg/dL). 31% of DISCOVER-1 pts had received 1-2 prior tumor necrosis factor inhibitors; DISCOVER-2 pts were biologic naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). Pts randomized to PBO received GUS 100 mg Q4W starting at W24 & were excluded from these analyses assessing maintenance of effect from W24 to W52. GUS effects on joint (American College of Rheumatology [ACR]20/50/70) & skin (Investigator’s Global Assessment [IGA=0/1 + ≥2-grade reduction from W0] in pts with ≥3% body surface area [BSA] with psoriasis & IGA ≥2 at W0) endpoints were evaluated by pt BL SJC, TJC, conventional synthetic disease-modifying antirheumatic drug (csDMARD) use, body mass index (BMI), PsA duration, & % BSA with psoriasis. Missing data were imputed as nonresponse through W52.Results:BL pt characteristics in DISCOVER-1 (N=381) & DISCOVER-2 (N=739) were well balanced across randomized groups.1,2 Among 1120 pooled pts, mean SJC was 11, mean TJC was 21, & 68% used csDMARDs (primarily methotrexate [MTX]). At W24, 62% (232/373) & 60% (225/375), respectively, of GUS Q4W- & Q8W-treated pts achieved ACR20 vs 29% (109/372) of PBO, with GUS effect consistently observed across pt BL subgroups (Figure 1). ACR20 response rates were sustained or increased at W52 in the GUS Q4W (72%) & Q8W (70%) groups & across SJC (61-79%), TJC (68-76%), & csDMARD use (68-80%) subgroups (Table 1) & pt subgroups defined by BL BMI, PsA duration, & % BSA with psoriasis (data not shown). ACR50 & 70 response patterns were similar to ACR20 (Table 1). In pts with ≥3% BSA psoriasis & IGA ≥2 at BL, 71% (193/273) & 66% (171/258) of GUS Q4W- & Q8W-treated pts, respectively, vs 18% (47/261) of PBO, achieved IGA 0/1 at W24, with GUS effect consistently observed across pt BL subgroups (Figure 1). IGA 0/1 response rates were also sustained or increased at W52 in the GUS Q4W (80%) & Q8W (71%) groups & across % BSA with psoriasis (67-87%) & csDMARD use (68-87%) subgroups (Table 1) & pt subgroups defined by BL BMI and PsA duration (data not shown).Conclusion:Treatment with GUS 100 mg Q4W & Q8W resulted in sustained improvement in signs & symptoms of active PsA through W52 regardless of pt BL characteristics.References:[1]Deodhar A, et al. Lancet 2020;395:1115-25;[2]Mease P, et al. Lancet 2020;395:1126-36;[3]Deodhar A, et al. American College of Rheumatology 2020; Poster P0908.Figure 1Figure 1Table 1.ACR & IGA Responses at Weeks 24 & 52 & by Select BL CharacteristicsGuselkumab Q4WGuselkumab Q8WN=373N=375Week 24Week 52Week 24Week 52ACR20, %62726070 SJC (15)68/59/5379/61/6757/66/6068/68/76 TJC (15)74/67/5673/76/6962/60/6075/68/68 csDMARD use (none/any/MTX)66/60/6380/68/6862/59/5773/68/68ACR50, %34493145 SJC (15)41/32/2058/39/3834/28/2646/40/49 TJC (15)51/41/2458/53/4340/33/2652/46/43 csDMARD use (none/any/MTX)36/33/3553/46/4836/29/2751/42/40ACR70, %16271627 SJC (15)22/10/732/20/2418/10/1930/23/26 TJC (15)29/19/934/32/2227/15/1435/28/24 csDMARD use (none/any/MTX)21/13/1430/26/2721/14/1434/24/23N=273N=258IGA 0/1, %71806671 BSA % with psoriasis(≥3-61/71/8076/87/7962/64/7267/72/74 csDMARD use (none/any/MTX)84/64/6787/77/7872/63/6477/68/68Disclosure of Interests:Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB Pharma, Wolf-Henning Boehncke Speakers bureau: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Consultant of: AbbVie, Almirall, Celgene, Janssen, Leo, Eli Lilly, Novartis, UCB Pharma, Grant/research support from: Pfizer, John Tesser Speakers bureau: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Crescendo Biosciences/Myriad, GlaxoSmithKline, Genentech, Janssen, Eli Lilly, and Pfizer, Consultant of: AbbVie, AstraZeneca, Bristol Myers Squibb, Gilead, Janssen, Eli Lilly, Novartis, and Pfizer, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Horizon, Janssen, Eli Lilly, Merck KG, Novartis, Pfizer, Sandoz, Sun Pharma, Setpoint, and UCB Pharma, Elena Schiopu Consultant of: Janssen, Grant/research support from: Janssen, Soumya D Chakravarty Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Global Services, LLC, Yusang Jiang Employee of: Cytel, Inc., providing statistical support (funded by Janssen), Shihong Sheng Shareholder of: Johnson & Johnson, of which Janssen Research & Development is a wholly owned subsidiary, Employee of: Janssen Research & Development, LLC, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, Bristol Myers Squibb, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB Pharma, Grant/research support from: Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB Pharma, Atul Deodhar Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, UCB Pharma, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, UCB Pharma.

Background:Guselkumab (GUS), a selective monoclonal antibody targeting the interleukin-23p19 subunit, has demonstrated efficacy in 2 pivotal Ph3 psoriatic arthritis (PsA) studies (DISCOVER-1,1 DISCOVER-22).Objectives:Evaluate GUS efficacy and safety in PsA patients (pts) with inadequate response (IR) to tumor-necrosis-factor inhibition (TNFi) through Week24 (W24) of the Ph3b COSMOS study.Methods:In this randomized, double-blind, placebo (PBO)-controlled trial, 285 pts with active PsA (≥3 swollen & ≥3 tender joints) who demonstrated lack of benefit or intolerance to 1-2 TNFi were randomized 2:1 to subcutaneous GUS 100mg (n=189) or PBO (n=96) at W0, W4, then every 8 weeks (Q8W) through W44 (with PBO crossover to GUS at W24). At W16, pts who met early escape (EE) criteria (Results:Baseline characteristics were similar across GUS and PBO pts, though a higher proportion of females and more severe joint symptoms were seen in the GUS group. At W24, 44.4% of GUS vs 19.8% of PBO pts achieved ACR20 (pTable 1.Baseline characteristics of, and adverse events reported by, randomized and treated COSMOS ptsGUS 100 mg Q8W (N=189)PBO (N=96) Age, y4949 Sex, Female54%46% Duration of PsA, y8.38.7 Body mass index, kg/m22931a Swollen (0-66) / tender (0-68) joint count10 / 219 / 18 Pt pain / Pt global arthritis / Physician global disease, 0-10 cm VAS6.5 / 6.5 / 6.96.0 / 6.2 / 6.4 Health Assessment Questionnaire-Disability Index, 0-31.3b1.2 C-reactive protein, mg/dL1.2b1.2 Methotrexate use at baseline56%53% Psoriatic body surface area, %17.913.4 Number of prior TNFi: 1 / 288% / 12%89% / 11% Reason for prior TNFi discontinuation: Efficacy / Safety84% / 16%* 81% / 19%*Pts with ≥1 AE / SAE37% / 3%48% / 3%Pts with ≥1 infection / serious infection18% / 0%20% / 0%Pts with ≥1 AE leading to study agent discontinuation2%2%Pts with ≥1 malignancy0.4%0Pts with ≥1 injection-site reaction2%1%Data shown are mean or %. aN=95; bN=188. *Missing for 1 pt. SAE – serious adverse events; VAS – visual analog scaleConclusion:In this Ph3b, placebo-controlled study of PsA pts with IR to 1-2 TNFi, GUS 100 mg Q8W elicited a significantly higher ACR20 response rate vs. PBO at W24; results of prespecified sensitivity and subgroup analyses were consistent. GUS safety in TNF-IR PsA pts through W24 is consistent with the favorable GUS safety profile in psoriasis and biologic-naïve PsA pts.3References:[1]Deodhar A. Lancet 2018;391: 2213–24.[2]Mease PJ. Lancet 2020;395: 1126–36.[3]Guselkumab Prescribing Information. Janssen Biotech, Inc.Disclosure of Interests:Laura C Coates Consultant of: AbbVie, Amgen, Biogen, BMS, Boehringer Ingelehim, Celgene, Domain, Eli Lilly, Gilead, Janssen, Medac, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Celgene, Eli Lilly, Gilead, Novartis, Pfizer, Laure Gossec Consultant of: AbbVie, Amgen, BMS, Biogen, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Samsung Bioepis, Sanofi-Aventis, UCB, Grant/research support from: Amgen, Eli Lilly, Galapagos, Janssen, Pfizer, Sandoz, Sanofi, Elke Theander Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Paul Bergmans Shareholder of: Johnson & Johnson, Employee of: Janssen, Marlies Neuhold Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Wim Noel Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, Georg Schett: None declared, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, and UCB

Background:Guselkumab (GUS), an anti-interleukin-23p19-subunit monoclonal antibody, demonstrated efficacy vs placebo (PBO) in achieving American College of Rheumatology 20% improvement (ACR20) response in patients (pts) with active psoriatic arthritis (PsA) in two phase 3 trials, DISCOVER-1 & 2.1,2Objectives:To assess the differential treatment effects of GUS across individual components of ACR response in PsA pts participating in the DISCOVER-1 & 2 trials.Methods:In DISCOVER-1 & 2, 1120 pts were randomized & treated with GUS 100 mg every 4 weeks (Q4W; N=373); GUS 100 mg at Week (W)0 and W4, then Q8W (N=375); or matching PBO (N=372). Pts were evaluated by independent joint assessors at study visits. ACR20 response is defined as ≥20% improvement from baseline in both tender joint count (0-68 [TJC68]) and swollen joint count (0-66 [SJC66]) and ≥20% improvement from baseline in ≥3 of 5 assessments: Patient Assessment of Pain [Pt Pain], Patient Assessment of Global Disease Activity (arthritis) [PtGA], Physician Assessment of Global Disease Activity [PGA], Patient assessment of physical function as measured by Disability Index of the Health Assessment Questionnaire (HAQ-DI), and C-reactive protein (CRP). For each ACR component, achievement of ≥20% improvement from baseline was assessed over time through W24 for the combined (Q4W+Q8W) GUS groups, and median time to onset of treatment effect was determined with Kaplan-Meier curves by randomized group.Results:Median time to response for all components except SJC66 occurred earlier with GUS than PBO. Time to onset of ACR20 treatment effect is shown in Figure 1. CRP data show 56% of GUS-treated pts had diminution of systemic inflammation by W4 (Table 1). Reduction in systemic inflammation was accompanied or rapidly followed by GUS-related improvement in both PtGA and PGA (median W4-8). Although SJC66/TJC68 data showed similar patterns, there was also a high PBO response (data not shown). Consistent with early reductions in systemic inflammation, 48-61% of GUS-treated pts had ≥20% improvement in TJC68/SJC66/PGA at W4 (Table 1), and 45-48% had ≥20% improvement in HAQ-DI, PtGA, and Pt Pain by W8. By W24, >80% of GUS-treated pts had ≥20% improvement in SJC66/TJC68/PGA, followed by 63-64% with this degree of improvement in PtGA, CRP, and Pt Pain, and 57% for HAQ-DI.Conclusion:GUS demonstrated ACR20 improvements with separation from PBO in ACR components as early as W4, which is consistent with reduced inflammation by GUS and prior serological studies.3 At early study time points, both pts and physicians were able to discern improvements in signs and symptoms of arthritis that rapidly followed reductions in systemic inflammation (CRP). The predominant drivers of ACR20 response rates at W24 in GUS pts were SJC66/TJC68/PGA.References:[1]Deodhar A et al. Lancet. 2020;395:1115-25[2]Mease P et al. Lancet. 2020;395:1126-36[3]Siebert S et al. EULAR 2020. Presentation OP0229Table 1.W4W8W12W16W20W24ACR20203950566061HAQ-DI score364552545657SJC66617484868788TJC68486575798081PGA506774788181PtGA354858596264Pt Pain324855586163CRP566062636464Figure 1Disclosure of Interests:Peter Nash Consultant of: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Grant/research support from: AbbVie, Bristol Myers Squibb, Boehringer, Celgene, Gilead, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Sandoz, Sun, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Janssen, Eli Lilly, Gilead, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, and UCB, Wen-Chan Tsai Consultant of: AbbVie, Eli Lilly, Janssen, Pfizer, and Novartis, Ying Ying Leung Consultant of: Abbvie, Eli Lilly, Janssen, and Novartis, Lai-Shan Tam Consultant of: AbbVie, Boehringer Ingelheim, Janssen, Lilly, Pfizer, and Sanofi, Grant/research support from: Amgen, Boehringer Ingelheim, Janssen, GSK, Novartis, and Pfizer, Daniel Furtner Employee of: Janssen, a division of Johnson & Johnson Pte. Ltd., May Shawi Employee of: Janssen Research and Development, LLC, Stephen Xu Employee of: Janssen Research and Development LLC, Shihong Sheng Employee of: Janssen Research and Development, LLC, Alexa Kollmeier Employee of: Janssen Research and Development, LLC, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GlaxoSmithKline, Novartis, Pfizer, and UCB.

Background:Psoriatic arthritis (PsA), a chronic inflammatory disease characterized by peripheral arthritis, axial inflammation, dactylitis, enthesitis & skin/nail psoriasis, causes impaired physical function, disability & loss of work productivity.Objectives:Evaluate associations between PsA clinical characteristics & outcomes including fatigue & work productivity using Work Productivity & Activity Impairment Questionnaire: PsA (WPAI-PsA).Methods:The Phase 3 DISCOVER-2 trial assessed guselkumab (GUS), an anti-IL-23p19 subunit monoclonal antibody, in bio-naïve adults with active PsA (swollen joint count [SJC] ≥5 & tender joint count [TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL) despite standard therapies.1 Patients (Pts) were randomized 1:1:1 to GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or placebo (PBO). WPAI-PsA assesses PsA-related work time missed (absenteeism), impairment while working (presenteeism), productivity loss (absenteeism+presenteeism), & daily activity during the previous week. Spearman correlation testing evaluated relationships between pt demographics & disease characteristics of PsA & WPAI domain scores based on observed values at baseline. Univariate linear regression assessed associations between WPAI & these variables based on observed data at W0 & at W24. Variables with pResults:As reported elsewhere,2 least-squares mean % changes from baseline at W24 were -3.8/-19.5/-20.0/-20.5 for GUS Q4W, -3.1/-19.4/-19.7/-21.5 for GUS Q8W, & -3.5/-10.2/-10.9/-10.3 for PBO for absenteeism, presenteeism, absenteeism+presenteeism, & daily activity impairment, respectively. Among 738 pts, WPAI domain scores were moderately to strongly correlated (ie, ≥0.4) with pt-reported pain (0-10 visual analog scale), physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]), fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue [FACIT-F] scale) & 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) score, but weakly correlated with other variables (Figure 1). Based on univariate analyses & evaluation of collinearity between variables, attributes included in multivariate models were age, body mass index (BMI), gender, CRP, FACIT-F, pain, Psoriasis Area Severity Index (PASI), TJC, SJC, enthesitis & dactylitis. In final model, CRP, FACIT-F, & pain were statistically significantly associated with all WPAI domains (Table 1). Presence of enthesitis & higher PASI score were significantly associated with higher loss of work productivity & activity outside work.Conclusion:In PsA pts, extra-articular symptoms, fatigue, pain & elevated CRP were significantly associated with WPAI-assessed work & activity impairment. Treating all major clinical manifestations of PsA is needed to help pts improve work & activity impairment. GUS effectively treats all major clinical manifestations1 & improves work & activity impairment in PsA.2References:[1]Mease P. Lancet 2020;395:1126-36.[2]Curtis J. ACR 2020; Poster 0332.Table 1.Multivariate analysis of clinical characteristics/outcomes & WPAI domains at W0 & W24ParameterAbsenteeismaPresenteeismaProductivity LossaActivity ImpairmentbEstimatep-valueEstimatep-valueEstimatep-valueEstimatep-valueAge-0.050.42-0.27-0.28-0.060.17Female0.910.46-1.540.22-1.740.202.380.02CRP0.730.040.970.011.010.010.89FACIT-F-0.31-0.67-0.73-0.75Pain1.034.154.254.02PASI0.060.360.160.020.140.050.150.003SJC0.080.48-0.050.61-0.050.660.030.75TJC-0.100.130.110.090.090.190.100.04Dactylitis (Y/N)-1.100.392.470.052.580.050.540.57Enthesitis (Y/N)1.520.202.380.042.990.012.400.01aPts working at baselinebAll pts in studyDisclosure of Interests:Jeffrey Curtis Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Eli Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corrona, Janssen, Eli Lilly, Myriad, Pfizer, Regeneron, Roche, and UCB, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer and UCB, Feifei Yang Shareholder of: Janssen, Employee of: Janssen, Steve Peterson Shareholder of: Janssen, Employee of: Janssen, Prasheen Agarwal Shareholder of: Janssen, Employee of: Janssen, Alexa Kollmeier Shareholder of: Janssen, Employee of: Janssen, Elizabeth C Hsia Shareholder of: Janssen, Employee of: Janssen, Chenglong Han Shareholder of: Janssen, Employee of: Janssen, May Shawi Shareholder of: Janssen, Employee of: Janssen, William Tillett Speakers bureau: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, MSD, Pfizer, and UCB, Grant/research support from: AbbVie, Celgene, Eli Lilly, Janssen, and Novartis, Philip J Mease Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, SUN, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, SUN, and UCB, Proton Rahman Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis

Background:DISCOVER 1&2 (PsA) and VOYAGE 1&2 (PsO) are Phase 3 trials of guselkumab (GUS).Objectives:Compare safety results through up to 1yr of GUS in PsA and PsO pts.Methods:In DISCOVER, 1120 pts with active PsA despite standard therapy were treated. Most pts were biologic-naïve; ~30% in DISCOVER 1 had previous exposure to 1-2 TNFi. Concomitant MTX (57%), oral corticosteroids (17%), and NSAIDs (64%) were permitted. Pts were randomized to SC GUS 100mg at W0, W4, then Q8W; GUS 100mg Q4W; or PBO. At W24, PBO patients were switched to GUS 100mg Q4W. In VOYAGE, in which concomitant MTX use was prohibited, 1245 pts with moderate to severe PsO were treated and randomized to SC GUS 100 mg at W0, W4, W12, then Q8W; or PBO at W0, W4, W12, with crossover to GUS at W16, W20, then Q8W. AEs and laboratory parameters, analyzed by National Cancer Institute-Common Terminology Criteria for AEs [NCI-CTCAE] toxicity grades, were summarized through the PBO-controlled periods and 1yr.Results:Safety profiles were generally consistent across the GUS PsO and PsA clinical programs (Table 1). Time-adjusted incidence rates for numbers of AEs, serious AEs, serious infections, malignancy, MACE and AEs leading to d/c were generally similar between PsO and PsA. No cases of anaphylaxis or opportunistic infections were reported. Proportions of pts with decreased neutrophil counts and elevations in hepatic transaminases were slightly higher in PsA vs PsO. These abnormalities were mostly of NCI-CTCAE Grade 1 or 2 (3 for neutrophils; Conclusion:The GUS safety profile was generally consistent in PsA and PsO GUS-treated pts through 1yr of the DISCOVER and VOYAGE trials.Table 1.Treatment-Emergent AEs During PBO-controlled Period and Through 1Yr: VOYAGE & DISCOVER TrialsPooled VOYAGE 1&2Pooled DISCOVER 1&2Time PeriodW0-16Through 1YrW0-24bThrough 1Yr(N=)PBO(422)GUS Q8W(823)Combined GUSa(1221)PBOc(372)GUS Q8W(375)GUS Q4W (373)GUS Q8W(375)GUS Q4W (373)Combined GUS† (1100)Total pt-yrs of follow-up128255974173173172384385973Incidence/100 pt-yrs (95% CI)dAEs317 (287,349)330 (308,353)259 (249, 270)219 (198,243)256 (232,281)221 (200, 245)218 (203,233)177 (164,191)191 (182, 199)SAEs5 (2, 10)6 (4, 10)6 (5, 8)9 (5, 15)4 (2, 8)5 (2, 10)6 (4, 9)4 (2, 7)6 (4, 7)AEs leading to study agent d/c3 (0.9, 8)4 (2, 8)2 (2, 4)4 (2, 8)3 (1, 7)7 (4, 12)2 (1, 4)4 (2, 6)3 (2, 5)Infections86 (71, 104)98 (86, 111)98 (92, 104)58 (48, 71)58 (47, 71)63 (51, 76)58 (50, 66)53 (46, 61)55 (50, 60)Serious Infections0. 8 (0, 4)0.4 (0, 2)1 (0.5, 2)4 (2, 8)0.6 (0, 3)2 (0.4, 5)2 (0.6, 3)1 (0, 2)2 (0.9, 3)All Malignancy0 (0, 2)0.4 (0, 2)1 (0.4, 2)0.6 (0, 3)1 (0, 4)0 (0, 2)0.5 (0, 2)0 (0, 0. 8)0 (0, 1)MACE0 (0, 2)0.4 (0, 2)0.4 (0, 1)0.6 (0, 3)0 (0, 2)0.6 (0, 3)0 (0, 0.8)0.3 (0, 1.4)0.1 (0, 0.6)% pts with ≥1 injection site rxn3.14.55.00.31.31.11.62.41.7aPlacebo crossover pts were included in the combined GUS column after crossover to GUSbFor all pts who d/c study treatment early with the last dose of PBO/GUS prior to W24 and who did not receive any PBO/GUS at or after Wk24, all data including the final safety follow-up visit collected through 1yr were includedcFor pts in PBO group who switched to GUS due to cross-over or inadvertently, only data prior to first administration of GUS were included.dCI based on an exact method assuming observed number of events follows a Poisson distributionDisclosure of Interests:Alice B Gottlieb Consultant of: Anaptyps Bio, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers-Squibb, Eli Lilly, Janssen, LEO Pharma, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Grant/research support from: Boehringer Ingelheim, Janssen, Novartis, Sun Pharmaceuticals, UCB, and Xbiotech, Joseph F. Merola Consultant of: AbbVie, Arena, Biogen, BMS, Dermavant, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, UCB, April Armstrong Consultant of: AbbVie, Janssen, Lilly, Leo, Novartis, UCB, Ortho Dermatologics, Dermira, KHK, Sanofi, Regeneron, Sun Pharma, BMS, Dermavant, and Modernizing Medicine, Richard Langley Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Janssen, LEO Pharma, Merck, Novartis, Pizer, Sun Pharmaceutical, and UCB Pharma, Mark Lebwohl Consultant of: Aditum Bio, Allergan, Almirall, Arcutis, Inc., Avotres Therapeutics, BirchBioMed Inc., BMD skincare, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Evelo, Evommune, Facilitate International Dermatologic Education, Foundation for Research and Education in Dermatology, Inozyme Pharma, Kyowa Kirin, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Serono, Theravance, and Verrica., Grant/research support from: Abbvie, Amgen, Arcutis, Boehringer Ingelheim, Dermavant, Eli Lilly, Evommune, Incyte, Janssen, Leo Pharmaceutucals, Ortho Dermatologics, Pfizer, and UCB, Christopher E.M. Griffiths Speakers bureau: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Consultant of: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., Grant/research support from: AbbVie, Amgen, Almirall, BMS, Boehringer Ingelheim Celgene, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma., May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Ya-Wen Yang Shareholder of: Johnson & Johnson, Employee of: Janssen Global Services, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Miwa Izutsu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Yin You Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Megan Miller Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Christopher T. Ritchlin Consultant of: AbbVie, Amgen, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB Pharma, Grant/research support from: AbbVie, Amgen, and UCB Pharma, Iain McInnes Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, and Janssen, Novartis, Pfizer, and UCB, Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Proton Rahman Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Grant/research support from: Janssen and Novartis.

Background:DISCOVER 1 & 2 are phase 3 psoriatic arthritis (PsA) trials investigating guselkumab (GUS), an IL-23 inhibitor that specifically binds the IL-23p19 subunit. In both studies, GUS showed significant improvement vs placebo (PBO) through week (W) 24 in the PBO-controlled period.1,2Objectives:To present integrated safety results of DISC 1 & 2 through the PBO-controlled periods.Methods:Adult patients (pts) with active PsA despite standard therapy were enrolled. All pts were biologic-naïve, except ~30% in DISC 1 with previous exposure to 1-2 TNF inhibitors. Pts were randomized to SC GUS 100 mg Q4W; GUS 100 mg at W0, W4, then Q8W; or PBO. Adverse events (AEs) and lab results were analyzed from pooled data.Results:The rates of pts experiencing ≥1 AE, serious AE, infection, serious infection, and discontinuation due to an AE were similar between GUS and PBO (Table 1). There were 2 deaths, 3 malignancies, 2 Major Adverse Cardiac Events (MACE), and no opportunistic infections (treatment group not shown to prevent unblinding). Among the AEs reported by ≥5% pts in any group (Table 1), nasopharyngitis and elevated serum hepatic aminotransferases were more common with GUS vs PBO. Laboratory ALT and AST elevations were mostly mild, transient, and not associated with significant bilirubin elevation. There was a trend to decreased neutrophil count (mostly Grade 1, transient, and not associated with infection) with GUS vs PBO (Table 2). Low rates of injection-site reactions were seen with GUS vs PBO. Anti-drug antibody development was also low (Table 1).Table 1.Patient Reported AEs, n (%)GUS100 mgQ8WGUS100 mgQ4WPBON375373372≥1 AE182 (48.5)182 (48.8)176 (47.3)≥1 Serious AE7 (1.9)8 (2.1)12 (3.2)Discontinuation due to AE5 (1.3)8 (2.1)7 (1.9)≥1 Infection73 (19.5)80 (21.4)77 (20.7)≥1 Serious infection1 (0.3)3 (0.8)3 (0.8)≥1 Opportunistic Infection (including Candida)000Active Tuberculosis000≥1 Injection-site reaction5 (1.3)4 (1.1)1 (0.3)Anti-GUS antibody +, n/N (%)6/373 (1.6)9/371 (2.4)--AEs* reported by ≥5% of patients in any treatment groupNasopharyngitis26 (6.9)19 (5.1)17 (4.6)Upper respiratory tract infection13 (3.5)23 (6.2)17 (4.6)Increased ALT23 (6.1)28 (7.5)14 (3.8)Increased AST23 (6.1)14 (3.8)9 (2.4)*Medical Dictionary for Regulatory Activities (MedDRA) preferred termTable 2.Lab Results*GUS100 mgQ8WGUS100 mgQ4WPBON373371370ALT Increased (%)Grade 128.235.030.121.12.71.43-40.81.10.8Neutrophil Count Decreased (%)Grade 15.65.93.221.61.60.83-400.30.3*NCI toxicity gradeALT=Alanine aminotransferaseConclusion:GUS was safe and well tolerated through the PBO-controlled period in 2 randomized, phase 3 trials of patients with active PsA. There were no meaningful safety differences between the Q8W and Q4W groups, no significant safety issues identified when comparing GUS to PBO, and no safety signals with regards to infections, malignancy, and MACE. The safety profile of GUS Q4W and Q8W in PsA pts was generally consistent with that in the Phase 3 trials of GUS Q8W for psoriasis.3,4References:[1]Deodhar et al. ACR 2019 (#807). Arth Rheum 2019;71 S10:1386[2]Mease et al. ACR 2019 (#L13). Arth Rheum 2019;71 S10:5247[3]Blauvelt et al. J Am Acad Derm 2017;76:405[4]Reich et al. J Am Acad Derm 2017;76:418Acknowledgments:NoneDisclosure of Interests:Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Philip Helliwell: None declared, Wolf-Henning Boehncke Grant/research support from: Janssen Research & Development, LLC, Consultant of: Janssen, 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, Alice B Gottlieb Grant/research support from:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Consultant of:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Speakers bureau:: Research grants, consultation fees, or speaker honoraria for lectures from: Pfizer, AbbVie, BMS, Lilly, MSD, Novartis, Roche, Sanofi, Sandoz, Nordic, Celltrion and UCB., Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Paraneedharan Ramachandran Employee of: Janssen Research & Development, LLC, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB

Background:Guselkumab (GUS), an interleukin-23 inhibitor, was efficacious in reducing signs and symptoms of active psoriatic arthritis (PsA) in patients (pts) in two phase 3 trials (DISCOVER-1 and DISCOVER-2).Objectives:To evaluate the efficacy of GUS in PsA pts with imaging-confirmed axial involvement consistent with sacroiliitis in DISCOVER-1&2.Methods:In DISCOVER-1, 381 pts with active PsA (≥ 3 swollen joints, ≥ 3 tender joints; C-reactive protein ≥ 0.3mg/dL despite standard therapies) and in DISCOVER-2, 739 pts with active PsA (≥ 5 swollen joints, ≥ 5 tender joints, CRP ≥ 0.6mg/dL despite standard therapies) were randomized 1:1:1 to GUS 100mg Q4W, GUS 100mg Q8W (Wk0, Wk4, then Q8W), or PBO. This analysis included pts with sacroiliitis at baseline who had either documented imaging confirmation of sacroiliitis in the past or pelvic X-ray confirmation of sacroiliitis at screening (pooled data from DISCOVER-1&2) based on investigators’ judgment of presence/absence of sacroiliitis. Efficacy was assessed by BASDAI score, BASDAI50, modified BASDAI (mBASDAI; excludes Q#3), spinal pain (BASDAI Q#2), ASDAS-CRP score, and ASDAS responses of inactive disease (Results:312 pts presented with axial involvement (PBO, n= 118; GUS q8w, n = 91; GUS q4w, n = 103). The LS mean changes from baseline to wk24 in BASDAI, spinal pain, mBASDAI, and ASDAS-CRP were greater in the two GUS groups vs PBO (Table). Greater proportions of GUS-treated pts achieved BASDAI50 (Table) and ASDAS responses of inactive disease, major improvement, and clinically important improvement (Figure) at wk24 vs PBO.Conclusion:GUS improved axial symptoms over 24 weeks in active PsA patients with imaging-confirmed sacroiliitis.Table.Efficacy of GUS in PsA patients with axial involvement at week 24.aPBO(n=118)GUS 100 mg every 8 weeks(n=91)GUS100 mg every 4 weeks(n=103)LS Mean change in BASDAI-1.35-2.67*-2.68*LS Mean change in spinal painb-1.30-2.73*-2.48*BASDAI50c, %21/110 (19.1%)34/84 (40.5%)**36/95 (37.9%)**LS Mean change in modified BASDAId-1.13-2.16*-2.18*LS Mean change in ASDAS-CRP-0.71-1.43*-1.46*aPts with axial involvement consistent with sacroiliitis at baseline and either a history of imaging confirmation or pelvic X-ray at screening (pooled data from DISCOVER-1 & 2)bQuestion 2 of the BASDAI.cPts with BASDAI > 0 at baseline.dExcludes question 3 of the BASDAI.Unadjusted p-values as noted: *p < 0.001, ** p < 0.01Acknowledgments:NoneDisclosure of Interests:Philip Helliwell: None declared, 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, Denis Poddubnyy Grant/research support from: AbbVie, MSD, Novartis, and Pfizer, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, UCB, Philip J Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Janssen, Eli Lilly, Novartis, Pfizer, Sun Pharma, UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Galapagos, Gilead, Novartis, Pfizer, Sun Pharma, UCB Pharma, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer, UCB Pharma, Xenofon Baraliakos Grant/research support from: Grant/research support from: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Consultant of: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Speakers bureau: AbbVie, BMS, Celgene, Chugai, Merck, Novartis, Pfizer, UCB and Werfen, Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Soumya D Chakravarty Shareholder of: Johnson & Johnson, Employee of: Janssen Scientific Affairs, LLC, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, 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

Background:Guselkumab (GUS), a novel monoclonal antibody that specifically binds to the p19-subunit of IL-23, demonstrated efficacy in the Ph 3 DISCOVER-1 (D1) & DISCOVER-2 (D2) trials of pts with active psoriatic arthritis (PsA).1,2Dactylitis & enthesitis, key PsA clinical manifestations, can be difficult to treat and may portend more significant disease burden.3,4Objectives:In pts with dactylitis or enthesitis at baseline, assess: 1) changes in symptoms over time and 2) relationships between improvements in dactylitis or enthesitis and other PsA domains.Methods:Adults with active PsA despite standard therapies were eligible for D1 & D2. Approx. 30% of D1 pts previously received 1-2 TNF inhibitors; D2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100mg Q4W; GUS 100mg at W0, W4, Q8W; or PBO. Independent assessors evaluated dactylitis (total score: 0-60) & enthesitis (Leeds Enthesitis Index [LEI]; total score 0-6). Dactylitis and enthesitis findings through W24 were prespecified to be pooled across D1 & D2. P-values are unadjusted. We assessed changes in dactylitis and LEI scores over time (ANCOVA); associations between dactylitis or enthesitis resolution and ACR/PASI responses at W24 (Chi-square); and correlations between dactylitis or LEI and HAQ-DI/SF-36 change scores at W24 (Spearman’s correlation). AEs through W24 were reported.1,2Results:At W0, 42% of pooled D1+D2 pts had dactylitis; 65% had enthesitis. GUS improved dactylitis and LEI scores vs PBO at W8, W16, W24. GUS vs PBO differences were significant for dactylitis changes at W16 & W24 and LEI changes at W8 (Q4W only), W16 & W24; no dose response was observed (Fig). Rates of dactylitis or enthesitis resolution by W24 were consistently significantly (pTable). In GUS-treated pts at W24, significant correlations were observed between dactylitis change scores and PASI (pConclusion:In PsA pts with dactylitis or enthesitis at W0, GUS improved dactylitis or LEI scores vs PBO by W8; treatment differences were significant at W16 & W24. Resolution of dactylitis or enthesitis was significantly associated with clinically meaningful improvements in PsA joint & skin symptoms. Improved dactylitis scores correlated with improved skin symptoms and mental health; improved LEI scores correlated with improved physical function.References:[1]Deodhar A (A#807),[2]Mease P (A#L13), Arthritis Rheumatol 2019;71(suppl 10);[3]DOI: 10.1186/s13075-017-1399-5;4DOI: 10.1016/j.semarthrit.2018.02.002Table.Pooled DISCOVER-1&2: associations between dactylitis/enthesitis resolution and joint/skin responseACR20ACR50ACR70PASI75aPASI90aDactylitis resolutionbN%pts%pts%ptsN%pts%pts Q4W37355*34*16*12178*55* Q8W37553*31*16*11680*65* PBO37226*12*5*11519*10*Enthesitis resolutionc Q4W24334*31*11*18782*63* Q8W23040*7*12*16277*62* PBO25514*13*5*18219*9** p < 0.001 (Chi-square)aIn pts with ≥3% BSA psoriasis & IGA ≥2 at W0bIn pts with D at W0cIn pts with E at W0Acknowledgments:NoneDisclosure of Interests:Dennis McGonagle Grant/research support from: Janssen Research & Development, LLC, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, 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, May Shawi Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shelly Kafka Employee of: Janssen Scientific Affairs, LLC, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Alexa Kollmeier Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Elizabeth C Hsia Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Xie L Xu Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Shihong Sheng Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Prasheen Agarwal Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Bei Zhou Shareholder of: Johnson & Johnson, Employee of: Janssen Research & Development, LLC, Christopher T. Ritchlin Grant/research support from: UCB Pharma, AbbVie, Amgen, Consultant of: UCB Pharma, Amgen, AbbVie, Lilly, Pfizer, Novartis, Gilead, Janssen, Proton Rahman Grant/research support from: Janssen and Novartis, Consultant of: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, and Pfizer., Speakers bureau: Abbott, AbbVie, Amgen, BMS, Celgene, Lilly, Janssen, Novartis, Pfizer

Telomeres serve to camouflage chromosome ends from the DNA damage response machinery. Telomerase activity is required to maintain telomeres. One consequence of telomere dysfunction is cellular senescence, a permanent growth arrest state. We review the key regulators of cellular senescence and recent in vivo evidence which supports p53-dependent senescence induced by short telomeres as a potent tumor suppressor pathway. The in vivo link between cellular senescence and tumor regression is also discussed. The relationship between short telomere length and ageing or disease states in various cells of the body is increasingly reported. Paradoxically, the introduction of telomerase is proposed as a method to combat ageing via cell therapy and a possible method to regenerate tissue, while telomerase inhibition and telomere shortening is suggested as a possible therapy to defeat cancers with intact p53. Researchers thus face the challenge of understanding the complex processes which regulate the potential benefits of both telomerase inhibition and activation.

Proteosome-based vaccines have TLR2-based adjuvant activity and show promise for mucosal immunization. We examined the effects of proteosomes on mucosal uptake in Peyer's patches in vivo . Proteosomes accelerated transepithelial transport of microparticles by M cells and induced migration of dendritic cells (DCs) into the follicle-associated epithelium (FAE); both effects were dependent on TLR2. Proteosomes induced the release of the DC-attracting chemokine MIP3α from Caco-2 epithelial cells in vitro . In HEK cells, proteosome-mediated MIP3α release was dependent on TLR2 expression and matrix metalloproteinase activation. Thus, TLR2 activation by proteosomes may promote mucosal uptake of particulate vaccines, and this may contribute to their adjuvanticity.

We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR), can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1) if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2) the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo) on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku) to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells.

Background Motivational communication (MC) is an evidenced-based communication style designed to enhance patients9 intrinsic motivation to engage in a healthy lifestyle and adhere to treatment. Due to its efficacy and popularity, the demand for physician training has risen markedly over the past decade. Despite the widespread dissemination of these programs, there is little empirical data on the extent to which they impact physician knowledge and attitudes. Objectives This study assessed the impact of a 1.5 hour introduction to MC workshop (phase I of Language of Change) on MC attitudes among rheumatologists. Methods This was a single group pre-post intervention trial. The MC training program, called The Language of Change, was developed by rheumatology and behavior change experts. The program being assessed consisted of 1 live workshop (a 1.5 hour introductory session) delivered by an MC expert alongside a dermatologist/nurse, to 53 rheumatologists from across Canada. Participants completed a battery of validated questionnaires measuring MC motivation, self-efficacy, outcome expectancies, and short term (30 day) intention to change, at baseline and after the session. T-tests were conducted to assess the effects of the introductory workshop on each questionnaire. Results Analyses revealed significant post introductory workshop effects on motivation to use MC (+.87, p Conclusions This study indicates that a 1.5 hour introductory workshop on MC significantly increased motivation to use MC and MC self-efficacy, and had a uniformly positive impact on outcome expectancies and intention to use MC in practice. Results suggest that even low doses of MC training may impact healthcare professional attitudes and intention to change. Disclosure of Interest K. Lavoie: None declared, M. Bell: None declared, T. Taylor: None declared, R. Arendse: None declared, M. Saum Employee of: Janssen Canada Inc., D. Faucher: None declared, M. Shawi: None declared, M. Camerlain: None declared

Bacterial flagellin activates innate immune responses by signaling through Toll-like receptor 5 and is a potential vaccine adjuvant. Mucosal lymphoid follicles, inductive sites for adaptive mucosal immune responses, are covered by a follicle-associated epithelium (FAE) specialized for the uptake of antigens. This study demonstrates that mucosal application of Salmonella dublin flagellin enhanced transepithelial transport of microparticles by the FAE of mouse Peyer's patches in vivo. Flagellin also induced rapid, matrix metalloproteinase-dependent migration of subepithelial dendritic cells (DCs) into the FAE, better positioning DCs for antigen capture. These innate responses to flagellin enhance FAE functions and may promote adaptive immune responses in the mucosa.

Objectives This analysis aimed to describe the pattern of specific joint involvement (tender and/or swollen) pre- and post-TNFi treatment and the impact of specific joint pattern involvement on composite score outcomes and pain. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab (IFX) or golimumab (GLM). In this analysis, RA patients included those treated with IFX between 2002-2014 or with GLM between 2010-2014. Based on joint involvement 7 groups were created: shoulder(s), elbow(s), metacarpophalangeal (MCP(s)), wrist(s), proximal interphalangeal (PIP(s)), knee(s), and thumb(s). The impact of specific joints on disease activity indices and pain was assessed with the independent-samples t-test; linear regression produced adjusted estimates. Results A total of 1030 RA patients were included with 5177 assessments. At baseline, MCP(s) (84.8%) and wrist(s) (66.1%) were the most commonly swollen joints. Tenderness was most frequent at baseline in these two joint types (81.1% and 70.9% of patients, respectively). Swelling/tenderness rates in all joint groups were significantly lower (p Swelling and tenderness in all joint groups were associated with significantly (P DAS28 =0.25, P=0.006; B CDAI =2.09, P=0.001; B SDAI =2.66, P=0.001). Conclusions Although joint swelling/tenderness documented at anti-TNF initiation has decreased over time, the profile of affected joints has remained stable. Swelling/tenderness in specific joint groups was differentially associated with pain, with larger joints having the greatest impact. Furthermore, differences were observed in levels of disease activity based on the type of affected joint which could be attributed to their impact on patient global assessment. These results suggest that location of joint involvement, in addition to the number of affected joints, has an independent impact on pain. Disclosure of Interest R. Arendse Consultant for: Janssen, J. Kelsall Consultant for: Janssen, A. Avina-Zubieta Consultant for: Janssen, P. Baer Consultant for: Janssen, J. Rodrigues Consultant for: Janssen, A. Jovaisas Consultant for: Janssen, I. Fortin Consultant for: Janssen, M. Sheriff Consultant for: Janssen, M. Khraishi Consultant for: Janssen, E. Rampakakis: None declared, J. Sampalis: None declared, F. Nantel Employee of: Janssen, M. Shawi Employee of: Janssen, C. Tkaczyk Employee of: Janssen, S. Otawa Employee of: Janssen, A. Lehman Employee of: Janssen

Background Despite the importance of the Health Assessment Questionnaire (HAQ) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in assessing patient-reported functional status and disease activity, they have been critiqued for being time-consuming, not convenient on a daily-basis and thus not contributing to decisions in routine care. Objectives The aim of this analysis was to describe the correlation of individual HAQ and BASDAI questions with patient and physician reported measures used in AS and to examine whether the instruments could be reduced to better reflect routine clinical practice. Methods BioTRAC is an ongoing prospective registry of patients initiating infliximab or golimumab. Data from AS patients treated in 2005-2014 were used. The correlation of individual HAQ and BASDAI questions with patient (pain, BASDAI, HAQ and BASFI) and physician (MDGA) reported measures was described with the Pearson9s correlation coefficient. The impact of each question on the need for help in each HAQ domain was assessed with logistic regression. Factor analysis was used to assess the variability due to each individual question in HAQ and BASDAI. Results A total of 413 AS patients with 1660 BASDAI and 1654 HAQ assessments were included. HAQ and BASDAI questions correlated at different extents with each AS measure. Questions related to “eating” and “gripping” showed the lowest correlation with patient and physician reported measures. All HAQ questions had higher correlations with patient reported measures than with MDGA. The BASDAI question on “fatigue and tiredness” showed the highest correlation with BASFI, while the question on “other joints pain/swelling” showed the lowest correlation with MDGA. None of the HAQ and BASDAI questions were associated with needing help for eating. All other HAQ individual questions were significantly associated with the need for help within their corresponding category, with the exception of Q5C and Q7A. BASDAI question on level of discomfort was significantly associated with the need for help in all HAQ categories, with the exception of “eating” and “walking”. Q2A and Q7C accounted for 59.6% of the HAQ variance. The level of morning stiffness accounted for 73.8% of the BASDAI variance. When combining the HAQ and BASDAI, Q2A and Q3A from HAQ and Q1 from BASDAI accounted for 63.5% of the variance. Conclusions Variability exists in the correlation of HAQ and BASDAI questions with patient and physician reported AS measures. The results suggest that “standing up straight from an armless chair” and “turning faucets on/off” are the main drivers of HAQ, while the level of morning stiffness drives the BASDAI. Three questions were found to drive the combined HAQ and BASDAI which may have implications in the design of self-report instruments. Disclosure of Interest P. Rahman Consultant for: Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer, Roche, M. Zummer: None declared, W. Olszynski: None declared, M. Khraishi: None declared, D. Sholter: None declared, R. Faraawi Consultant for: Janssen, W. Bensen Consultant for: Janssen, M. Baker: None declared, A. Chow: None declared, J. Vaillancourt Employee of: JSS Medical Research, J. Sampalis Shareholder of: JSS Medical Research, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen, A. Lehman Employee of: Janssen, C. Tkaczyk Employee of: Janssen, M. Shawi Employee of: Janssen

Background Several standardized response criteria and disease activity indices are used to assess treatment efficacy in rheumatoid arthritis (RA). These measures comprise different types and number of variables resulting in different weighting of individual variables within each of them. Objectives The aim of this analysis was to compare the performance of ACR, SDAI major and minor, and HAQ response criteria and to determine their level of agreement with the DAS28, SDAI, and CDAI definitions of low disease activity (LDA) and remission in RA patients treated with infliximab (IFX) or golimumab (GLM) in a real-world, Canadian, clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with IFX or GLM. The analysis was based on RA patients treated with IFX between 2002-2014 or GLM between 2010-2014. Response was assessed with ACR20, ACR50, ACR70, HAQ improvement of 0.22 and 0.5, SDAI major (≥22) and minor improvement (≥10). Disease state was assessed with DAS28, SDAI, and CDAI definitions of LDA ( Results A total of 830 RA patients with 4,100 available observations were included. The criteria for each definition of response/disease state were met for the following proportion of cases: ACR20 (66.4%), ACR50 (44.5%), ACR70 (26.4%), ΔHAQ≥0.22 (65.5%), ΔHAQ≥0.5 (53.4%), SDAI major improvement (55.8%), SDAI minor improvement (80.8%), DAS28 remission (29.4%), CDAI remission (20.4%), SDAI remission (21.8%), CDAI LDA (57.5%), SDAI LDA (58.1%), and DAS28-ESR LDA (46.0%). Statistically significant (Kappa P Conclusions This analysis showed that significant variation exists in the agreement between the various efficacy outcome measures. Thus, the choice of outcome measure used to make treatment decisions could have a significant impact on patient management. Disclosure of Interest E. Keystone Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, P. Baer Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, A. Avina-Zubieta: None declared, A. Jaroszynska: None declared, J. Rodrigues: None declared, R. Arendse Consultant for: Janssen, D. Sholter: None declared, M. Starr Consultant for: Janssen, A. Masetto: None declared, J. Sampalis Shareholder of: JSS Medical Research, Employee of: JSS Medical Research, E. Rampakakis Employee of: JSS Medical Research, C. Tkaczyk Employee of: Janssen, M. Shawi Employee of: Janssen, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen

Background The Health Assessment Questionnaire (HAQ) is commonly used for assessing patient-reported functional status and disease activity in psoriatic arthritis (PsA). However, it has been critiqued for being time-consuming, not easily scored and thus, not contributing to decisions in routine care (1) Objectives The aim of this analysis was to describe the correlation of individual HAQ questions with patient and physician reported measures used in PsA and to examine whether the instrument could be reduced to better reflect routine clinical practice. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab or golimumab. Data from PsA patients treated with infliximab or golimumab in 2006-2013 were used. The correlation of each HAQ question with patient and physician (pain, patient global assessment (PtGA), SJC28, TJC28 and physician global assessment (MDGA)) reported measures were described with the Pearson9s correlation coefficient. The impact of each HAQ question on the need for help in each HAQ domain was assessed with logistic regression. Factor analysis was used to assess the variability due to each question in HAQ. Results A total of 183 PsA patients with 596 HAQ assessments were included. Individual HAQ questions correlated at different extents with each PsA measures. All questions showed higher correlations with PtGA and pain compared to MDGA. Regarding patient reported outcomes, Question 5A (“Wash/dry your entire body”) showed the highest correlation, specifically with pain. The majority of HAQ questions were significantly associated with the need for help within their corresponding ability category, with the exception of questions Q3B, Q3C, Q4B, Q5C and Q8B. The results of factor analysis showed that 2 (Q1A and Q3B) out of the 20 HAQ questions accounted for 61.5% of its matrix variance, suggesting that the question on the ability to “dress, tie shoelaces and do buttons”, as well as the question on the ability to “lift a full cup or glass” may be the main drivers of HAQ in PsA. Conclusions Variability exists in the correlation of individual HAQ questions with patient and physician reported PsA measures. Pain and PtGA are significantly associated with the various domains of HAQ, while clinical outcomes (SJC28 and TJC28) and MDGA are less important. Among PsA patients, the HAQ is driven by components related to dressing and grooming and to eating abilities, suggesting that PsA patients may be facing different challenges than RA patients. This may have implications from an occupational health perspective and in the design of a shorter self-report instrument more suitable for PsA patients. References Khanna D, et al. Arthritis Care Res. 2011;63:S486-S490. Disclosure of Interest D. Choquette Consultant for: AbbVie, Amgen, Celgene, BMS Canada, Janssen, Pfizer, C. Thorne: None declared, M. Khraishi: None declared, I. Fortin: None declared, R. Arendse: None declared, A. Chow: None declared, J. Kelsall Consultant for: Janssen, M. Baker: None declared, J. Vaillancourt Employee of: JSS Medical Research, J. Sampalis Shareholder of: JSS Medical Research, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen, A. Lehman Employee of: Janssen, C. Tkaczyk Employee of: Janssen, M. Shawi Employee of: Janssen

Background PtGA is included in the formula of all disease activity indices despite the fact that it may not accurately reflect RA disease activity, but rather reflect symptoms related to fibromyalgia, low back pain, depression or other conditions. We previously assessed the impact of the PtGA on the ability to achieve Boolean ACR/EULAR remission state. Objectives The aim of this analysis was to assess the proportion of patients failing to achieve DAS, CDAI and SDAI remission based on a real-world, routine clinical care setting in Canada. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with IFX or GLM. In this analysis, RA patients treated with infliximab between 2002-2014 or with golimumab between 2010-2014 were included. Modified versions of DAS28 (mDAS28), CDAI (mCDAI), and SDAI (mSDAI) were calculated by omitting PtGA from the formulas. Correlation of the standard and modified versions of each index was assessed with the Pearson9s correlation coefficient. In the absence of validated thresholds for remission and LDA for the modified versions, the standard definitions were considered as the gold standard and ROC curve analysis was used to identify new thresholds for the modified versions. Cross-tabulations with the Chi-square test were used to assess the agreement between the standard and modified definitions of remission and LDA. Results One thousand nineteen RA patients with a mean (SD) age of 56.1 (13.5) years and disease duration of 8.5 (9.1) were included in the analysis. A strong correlation was observed between the standard and modified versions of DAS28 (r=0.98; P Conclusions The results of this analysis have shown that PtGA could account for up to 10% of non-remission cases and up to 20% of non-LDA cases as measured by DAS, CDAI and SDAI. Further analyses are required to identify the determinants of patient global assessment. Disclosure of Interest P. Baer Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, E. Keystone Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, W. Bensen: None declared, C. Thorne Consultant for: Janssen, B. Haraoui Grant/research support from: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, UCB, Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, UCB, D. Choquette Consultant for: AbbVie, Amgen, Celgene, BMS Canada, Janssen, Pfizer, R. Arendse Consultant for: Janssen, J. Kelsall Consultant for: Janssen, M. Sheriff Consultant for: Janssen, J. Sampalis Shareholder of: JSS Medical Research, Employee of: JSS Medical Research, E. Rampakakis Employee of: JSS Medical Research, C. Tkaczyk Employee of: Janssen, M. Shawi: None declared, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, S. Otawa: None declared

Background Two versions of DAS28 are available, DAS28-4 comprising 4 variables [tender and swollen joint counts, acute phase reactant (APR), and patient global assessment] and DAS28-3 where patient global has been omitted. Despite the difference between DAS28-4 and DAS28-3 thresholds for remission and low disease activity (LDA) are the same. The APR used to calculate DAS may be either ESR or CRP. Objectives This analysis describes the agreement between these four possible indices, DAS28-4-ESR, DAS28-4-CRP, DAS28-3-ESR and DAS28-3-CRP and compares them in terms of classifying remission and LDA in a real-world, routine clinical care setting. Methods BioTRAC is a prospective registry of patients initiating treatment with infliximab or golimumab. In this analysis, data from RA patients who were treated with infliximab between 2002-2014 or with golimumab between 2010-2014 and had available information in all indices were used. The definitions for remission were: DAS28-3/4 Results 869 RA patients who had 3,517 complete assessments were included in the analysis. Non-remission was classified by all indices in 61.4% of cases, while remission was achieved in one (5.9%), two (10.3%), three (5.3%), or all four (17.2%) indices. Similarly, non-LDA was classified by all indices in 46.1% of cases, while LDA was achieved in one (6.2%), two (10.9%), three (5.4%), or all four (31.3%) indices. Overall, a strong linear positive correlation (r>0.8) was observed between all indices. When looking at the internal consistency in terms of classifying disease state, the CA was 0.905 for remission and 0.923 for LDA suggesting an overall high internal consistency. However, when looking at individual inter-item correlations, agreement between indices was variable with DAS28-3CRP and DAS28-4CRP showing highest correlation and DAS28-3-ESR and DAS28-4-CRP showing lowest correlation. When comparing DAS28-4-ESR with DAS28-3-ESR, the latter categorized 16.5% of DAS28-4-ESR remission cases as non-remission and 3.0% of DAS28-4-ESR non-remission cases as remission. With respect to LDA, DAS28-3-ESR categorized 9.1% of DAS28-4-ESR LDA cases as non-LDA and 4.7% of DAS28-4-ESR non-LDA cases as LDA. Similar results were observed with DAS28CRP. Conclusions The results of this analysis show that, despite being highly correlated, variability exists in the classification of remission and LDA by the various DAS indices. Decision making based on disease state achieved may vary significantly based on type of APR used in the DAS index. Disclosure of Interest W. Bensen Consultant for: Janssen, E. Keystone Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, P. Baer Consultant for: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, Speakers bureau: AbbVie, Amgen, BMS, Janssen, Pfizer, Roche, J. Rodrigues: None declared, A. Avina-Zubieta: None declared, W. Olszynski: None declared, D. Choquette Consultant for: AbbVie, Amgen, Celgene, BMS Canada, Janssen, Pfizer, S. Kapur: None declared, J. Sampalis Shareholder of: JSS Medical Research, Employee of: JSS Medical Research, E. Rampakakis Employee of: JSS Medical Research, C. Tkaczyk Employee of: Janssen, M. Shawi Employee of: Janssen, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen

Background The present standard for measuring disease activity in Ankylosing Spondylitis (AS) is the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) which focuses on five major symptoms including fatigue, axial pain, peripheral pain, enthesitis and morning stiffness (severity and duration). Objectives Given that the BASDAI instrument contains two pain questions, the objective was to assess whether pain symptoms are the main drivers of BASDAI scores among AS patients treated with anti-TNFs in routine clinical practice. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab (IFX) or golimumab (GLM). Patients with AS treated with IFX or GLM and enrolled between 2005 and 2014 were included in this analysis. A modified weighted BASDAI score (m-BASDAI) was calculated excluding the axial (Q2) and peripheral (Q3) pain questions of the BASDAI. The correlation of BASDAI, each of its components, and the modified BASDAI (m-BASDAI) was assessed with the Pearson correlation coefficient. BASDAI low disease activity (LDA) and m-BASDAI LDA were defined as a score ≤3. The association between the number of administered analgesics (0, 1, >1) and BASDAI/m-BASDAI was assessed with one-way ANOVA. Results A total of 413 AS patients with 1,709 assessments were included in this analysis. Correlation analysis showed a strong correlation between the full BASDAI and m-BASDAI scores (r=0.98, P Increased use of analgesics (0 vs. 1 vs. >1) over 2 years of follow-up was associated with significantly (P Conclusions Higher levels of AS pain are significantly associated with a higher BASDAI score and increased use of analgesic medications among patients treated with anti-TNFs. In addition to pain, fatigue, tenderness, and morning stiffness are likewise important contributing components in the BASDAI score and the disease burden of AS. Disclosure of Interest P. Rahman Consultant for: Abbott, AbbVie, Amgen, BMS, Celgene, Janssen, Novartis, Pfizer, Roche, A. Jovaisas: None declared, W. Bensen Consultant for: Janssen, W. Olszynski: None declared, A. Jaroszynska: None declared, P. Baer Consultant for: AbbVie, Amgen,BMS, Janssen, Pfizer, Roche, M. Sheriff: None declared, D. Sholter: None declared, E. Psaradellis Employee of: JSS Medical Research, J. Sampalis Shareholder of: JSS Medical Research, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen, A. Lehman Employee of: Janssen, C. Tkaczyk Employee of: Janssen, M. Shawi Employee of: Janssen

Objective To describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care. Methods Biological naive patients with RA followed in the Biologic Treatment Registry Across Canada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression. Results 838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28 (95% CI) 1.40 (0.95 to 2.06); HRCDAI 1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28 (95% CI) 1.78 (1.00 to 3.19); HRCDAI 2.38 (1.14 to 4.99)). Conclusions Oral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti-TNF for the shortest period possible to achieve remission, and then tapered. Trial registration number NCT00741793.

Background The aim of rheumatoid arthritis (RA) treatment is to optimize symptom control and, when possible, achieve sustained remission. Therefore, identification of clinical signs predicting future remission is valuable to clinical decision making. One question faced by clinicians is whether the achievement of a lower disease activity value or a higher rate of change of disease activity is indicative of better future disease outcomes. Objectives To determine whether change in disease activity measures or the actual values achieved at 6 months were more predictive of remission at 12 months in RA patients treated with infliximab (IFX) in a real-world, clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA with IFX or golimumab as first biologics or after having been treated with a biologic for Results 436 patients were included with mean age of 56.1 yrs and disease duration of 10.4 yrs. With respect to 12-month DAS28 remission, a stronger association was observed with the actual DAS28 score compared to the percent improvement in DAS28 at 6 months. The Wald statistic for the percent change and actual value of DAS28 at 6 months was 5.38 and 46.88, respectively, while the change in log-likelihood was 4.98 (P=0.026) and 61.64 (P For SDAI remission at 12 months, the respective Wald values for percent change and actual value at 6 months were 0.075 and 18.28 and log-likelihood changes were 0.07 (P=0.788) and 24.08 (P Conclusions These results demonstrate that the actual disease outcome value achieved at 6 months is a stronger predictor of remission at 12 months than the percent change in disease activity. These findings suggest that the treatment target in a real-world setting should be set as specific endpoints and not as change over time. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.4443

Background Unlike rheumatoid arthritis (RA), the pattern of joint involvement in psoriatic arthritis (PsA) is usually asymmetric. Furthermore, PsA may demonstrate oligoarthritis or polyarthritis, while RA usually manifests in multiple joints. Objectives To describe the most commonly affected joints in patients with RA and PsA at baseline and after 6 months (mos) of treatment with infliximab (IFX) in a clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, ankylosing spondylitis, or PsA with IFX as first biologics or after having been treated with a biologic for

Objectives To assess in a clinical practice the 4-year outcomes in patients with AS treated with infliximab and the performance of ASDAS, a new disease activity measure in AS. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab or golimumab as first biologics or after having been treated with a biologic for less than 6 mos. AS patients treated with infliximab between 2005 and 2012 were included. Descriptive statistics were produced for clinical outcome measures and patient reported outcomes at baseline and follow-up assessments over four years. Within-group changes were assessed for statistical significance with the paired-samples Student9s t-test. The correlation of ASDAS with BASDAI and BASFI was assessed with the Pearson correlation coefficient. The correlation of these measures with MDGA was assessed with the Spearman9s rho. Results A total of 230 AS patients who had at least one follow-up assessment were included in this analysis, with a mean (SD) age of 45.7 (11.5) years and mean (SD) disease duration since diagnosis of 10.0 (10.1) years. At the time of enrollment, mean (SD) patient parameters were: C-reactive protein (CRP) =16.9 (20.2) mg/dL, erythrocyte sedimentation rate (ESR) =25.8 (20.2) mm/hr, morning stiffness =74.6 (40.2), health assessment questionnaire (HAQ-DI) =1.20 (0.61), physician global assessment of disease activity (MDGA) =6.6 (1.9), BASDAI =6.4 (2.1), BASFI =6.1 (2.5), and ASDAS =3.8 (1.0). By 6 mos of treatment significant improvements (P Similar significant changes were observed in ASDAS, BASDAI, and BASFI over time providing evidence of construct validity and sensitivity to change. A strong positive linear correlation between ASDAS and BASDAI (r=0.85; P 3.5) decreased from 62.4% at baseline to 6.9% at 48 months. Conclusions Treatment with infliximab over four years is effective in reducing symptom severity and improving outcomes in patients with AS. Furthermore, the data from this registry confirm the validity and sensitivity to change of the ASDAS score in a real-world AS cohort. Disclosure of Interest P. Rahman: None declared, D. Choquette: None declared, M. Khraishi: None declared, W. Bensen: None declared, S. Shaikh: None declared, D. Sholter: None declared, M. Sheriff: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, F. Nantel Employee of: Janssen, S. Otawa Employee of: Janssen, A. Lehman Employee of: Janssen, M. Shawi Employee of: Janssen DOI 10.1136/annrheumdis-2014-eular.2381

Background Early achievement of remission is associated with improved clinical, functional and radiographic outcomes1. Recent recommendations of the Canadian Rheumatology Association dictate that treatment target should be remission or, when not possible, low disease activity. Objectives To define the predictive factors of time to disease remission in established rheumatoid arthritis (RA) patients treated with infliximab. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with infliximab or golimumab as first biologics or after having been treated with a biologic for Results A total of 671 patients were included of whom 494 (73.6%) were female. At baseline, mean (SD) age was 56.0 (13.5) years and mean (SD) disease duration was 10.3 (10.1) years. Median time to CDAI and Boolean remission was 47.3 and 54.1 months, respectively. In univariate analysis, the following factors showed a statistical trend in their association with longer time to CDAI remission: earlier enrolment period (P=0.117), increased age (P=0.070), longer disease duration (P=0.008), female gender (P=0.143), and increased baseline disease activity as indicated by TJC28 (P Conclusions Upon adjusting for potential confounders, increased disease duration before anti-TNF initiation is an independent predictor of longer time to remission. The results of these real-world Canadian data support findings that earlier initiation of anti-TNF agents may be associated with increased remission rates when stringent definitions of remission are considered. References Smolen JS et al. Ann Rheum Dis. 2009;68:823-7. Disclosure of Interest : B. Haraoui: None declared, M. Sheriff: None declared, M. Khraishi: None declared, M. Starr: None declared, J. Kelsall: None declared, M. Baker: None declared, R. Arendse: None declared, S. Dixit: None declared, W. Bensen: None declared, P. Baer: None declared, R. Faraawi: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, S. Otawa Employee of: Janssen, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, M. Shawi Employee of: Janssen DOI 10.1136/annrheumdis-2014-eular.2365

Background A definition of minimal disease activity (MDA) in PsA was derived from the opinion of 60 PsA experts including fulfillment of ≥5 of the 7 following criteria: tender joint count (TJC) ≤1, swollen joint count (SJC) ≤1, PASI ≤1 or body surface area ≤3%, pain (VAS) ≤15, patient global disease activity (PtGA) (VAS) ≤20, HAQ ≤0.5, and tender entheseal points ≤1 (1). Objectives To describe the rate of MDA achievement over time and to assess the association between MDA achievement and DAS28 remission in PsA patients treated with anti-TNF in a routine clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), ankylosing spondylitis (AS), or PsA with infliximab or golimumab as first biologics or after having been treated with a biologic for Results A total of 123 PsA patients with mean (SD) age of 50.5 (10.5) yrs and mean (SD) duration since diagnosis of 6.1 (7.3) yrs were included in this analysis, providing information from 340 assessments. At the time of enrollment in the registry, mean (SD) patient parameters were: DAS28 =4.2 (1.5), PASI =2.7 (4.8), SJC28 =4.1 (3.5), TJC28 =6.1 (5.6), morning stiffness =45.4 (43.0) min, health assessment questionnaire (HAQ-DI) =1.09 (0.65), physician global assessment of disease activity (MDGA) =5.3 (2.1), patient global assessment of disease activity (PtGA) =49.3 (27.3) mm, and pain =46.5 (25.2) mm. By 6 mos of treatment, statistically significant (P The proportion of patients with MDA significantly increased from 12.3% at baseline to 45.0% after 6 months of treatment (P Conclusions MDA has high discriminatory power for remission as defined by the DAS28 criteria, while being more rigorous than DAS28. Furthermore, treatment with anti-TNF is effective in inducing MDA in 45% of patients as early as 6 mos from treatment initiation. References Coates LC, Cook R, Lee KA, Chandran V, Gladman DD. Arthritis Care Res (Hoboken). 2010 Jul;62(7):970-6. Disclosure of Interest P. Rahman: None declared, S. Shaikh: None declared, M. Starr: None declared, W. Bensen: None declared, D. Choquette: None declared, W. Olszynski: None declared, M. Sheriff: None declared, M. Zummer: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, A. Lehman Employee of: Janssen, S. Otawa Employee of: Janssen, F. Nantel Employee of: Janssen, V. Letourneau Employee of: Janssen, M. Shawi Employee of: Janssen DOI 10.1136/annrheumdis-2014-eular.2382

Background Spondyloarthritis, including psoriatic arthritis (PsA), is characterized by inflammatory arthritis affecting axial and peripheral joints. It is commonly associated with extra-articular and peri-articular manifestations (PAMs) including dactylitis and enthesitis. Objectives To evaluate the point prevalence of enthesitis and dactylitis at the time of anti-TNF initiation, their impact on disease severity, and their evolution over time in patients with active PsA treated in a routine clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), ankylosing spondylitis (AS), or PsA with infliximab or golimumab as first biologics or after having been treated with a biologic for

Objectives Patient (PtGA) and physician (MDGA) global assessment of disease activity measure the same construct from two different perspectives. The objective of this study was to assess the agreement between these two measures over time as ascertained in Canadian routine clinical practice in patients with RA treated with infliximab or golimumab. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with infliximab or golimumab as first biologics or after having been treated with a biologic for less than six months. In this analysis, people with RA treated with infliximab who were enrolled between 2002 and 2012 and had at least one follow-up assessment and up to 60 months of follow up were included. PtGA and MDGA were measured on a 10-point Numerical rating scale (NRS) and 10 cm visual analog scale (VAS), respectively. The association between treatment duration and difference between MDGA and PtGA was assessed with linear regression. Internal consistency was assessed with the intra-class correlation coefficient (ICC) and Cronbach9s alpha (CA). Results A total of 675 patients assessed over 4193 visits during a mean follow up time of 20 months were included in the analyses. The overall mean (SD) PtGA and MDGA was 3.73 (2.89) and 3.38 (2.67), respectively (P Conclusions The results of this Canadian longitudinal observational registry have shown that there is poor agreement between physician-based and patient-based assessments of disease activity. In addition, the rate of reduction in disease activity over time is considerably higher when rated by physicians when compared to patients. In this chronic condition, physicians should be aware of this increasing discordance between the patient and physician global when making treatment decisions and managing patient expectations over time. Acknowledgements We thank Dr. Mary Bell, Sunnybrook Health Sciences Centre, for her contribution to the development of this analysis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3902

Background Assessment of functional (dis)ability in rheumatoid arthritis (RA) is subject to patient judgment when appraising their ability to do daily activities. Objectives The aim of this analysis was to describe the impact of specific joint involvement on patient reported outcomes (PROs) - functional activity, pain and patient global assessment of disease activity (PtGA) - and to identify joints most resistant to treatment over time. Methods Biologic Treatment Registry Across Canada (BioTRAC) is an ongoing, prospective, registry of patients initiating treatment for RA, AS, or PsA with infliximab or golimumab as first biologics or after having been treated with a biologic for less than six months. In this analysis, data were included from RA patients treated with infliximab between 2002 and 2012 or with golimumab between 2010 and 2012. Based on joint involvement seven groups were created: shoulder(s), elbow(s), metacarpophalangeal (MCP), wrist(s), proximal interphalangeal (PIP), knee(s), and thumb(s). The impact of specific joints on patient outcomes was assessed with the independent-samples t-test. Linear regression was used in order to produce adjusted estimates. Results A total of 935 RA patients with 4,854 assessments were included. Swelling, tenderness, and swelling and/or tenderness in all joint groups were associated with significantly (P Conclusions Significant variability in PROs exists based on the presence of swelling and/or tenderness in specific joint groups. Swelling/tenderness of shoulders, wrists, knees and elbows were the main drivers of HAQ-DI, PtGA and pain. The results have important implications for the achievement of disease remission and suggest that the joint type in addition to the number of affected joints has unique impact on PROs. Disclosure of Interest R. Arendse: None declared, W. Bensen: None declared, A. Chow: None declared, J. Rodrigues: None declared, S. Dixit: None declared, D. Sholter: None declared, P. Baer: None declared, M. Baker: None declared, D. Choquette: None declared, I. Fortin: None declared, A. Jovaisas: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, F. Nantel Employee of: Janssen Inc Canada, S. Otawa Employee of: Janssen Inc Canada, M. Shawi Employee of: Janssen Inc Canada, A. Lehman Employee of: Janssen Inc Canada DOI 10.1136/annrheumdis-2014-eular.5185

Background According to current treatment guidelines short-term treatment with corticosteroids (CS) can be considered in rheumatoid arthritis (RA) patients treated with a traditional and/or biologic DMARD,and should be tapered as rapidly as clinically feasible 1,2 . Objectives The aim of the current analysis was to examine the use of systemic CS among patients in remission, to evaluate their usefulness in sustaining disease remission, and assess their impact on the incidence of infections in RA patients treated with infliximab in a real-world, routine clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with IFX or golimumab as first biologics or after having been treated with a biologic for Results Six-hundred twenty-eight RA patients were included in the analyses. Mean (SD) age was 55.8 (13.6) years and mean (SD) duration since diagnosis was 10.2 (10.0) years. Remission as defined by the DAS28 and CDAI was achieved by 46.5% and 30.4% of patients, respectively. Despite the achievement of remission, CS use was continued in 16.4% and 16.7% of cases, respectively. In these patients, survival analysis did not show a significant positive effect of CS use on sustainability of remission [HR DAS28 (95%CI) =1.40 (0.95-2.06); HR CDAI (95%CI) =1.19 (0.75-1.88)]. Conversely, time to acquiring an infection was significantly shorter among patients treated with a CS when compared to the absence of CS treatment [HR CDAI (95%CI) =2.38 (1.14-4.99)]. Conclusions The results of this real-world observational study have shown that, despite the achievement of remission, CS use was continued in approximately 16% of cases. Treatment with CS was associated with an increased risk for acquiring an infection without having an impact on sustainability of remission. The results of this analysis support the recommendation that CS should be used concomitantly with anti-TNF treatment for the shortest period possible to achieve remission but not thereafter. References Bykerk VP et al. J Rheumatol 2012;39;1559-1582 Smolen JS et al. Ann Rheum Dis. 2013; Epub ahead of print Disclosure of Interest B. Haraoui: None declared, A. Jovaisas: None declared, W. Bensen: None declared, R. Faraawi: None declared, J. Kelsall: None declared, S. Dixit: None declared, J. Rodrigues: None declared, M. Sheriff: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, A. Lehman Employee of: Janssen, S. Otawa Employee of: Janssen, F. Nantel Employee of: Janssen, M. Shawi Employee of: Janssen DOI 10.1136/annrheumdis-2014-eular.2386

Background The efficacy of anti-TNF in the management of psoriatic arthritis (PsA) and rheumatoid arthritis (RA) has been demonstrated in numerous controlled clinical trials. Objectives The objective of this analysis was to assess in Canadian routine clinical practice the durability of treatment with infliximab (IFX) in PsA and RA and the determinants associated with sustainability of IFX. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab or golimumab as first biologics or after having been treated with a biologic for less than six months. Patients with PsA or RA treated with IFX who were enrolled between 2002 (2005 for PsA patients) and 2012 were included in this analysis. Dose optimization was defined as an increase in the frequency and/or dosing of IFX. Kaplan Meier (KM) estimates and Cox proportional models were used in the analysis. Results A total of 92 PsA and 830 RA patients were included in the analysis. Mean (SD) age of the PsA and RA patient cohorts was 48.7 (9.9) and 55.8 (13.4) years, respectively, and mean (SD) duration since diagnosis was 6.8 (9.1) and 10.2 (10.1) years, respectively. Twenty seven (29.3%) PsA patients and 407 (49.0%) RA patients had discontinued treatment. Overall KM-based mean (SE) duration of treatment was 41.4 (3.6) months and 61.3 (2.2) months for PsA and RA patients, respectively. Longer treatment duration was associated with significantly greater improvements in pain (parameter estimate PsA: -0.21, P=0.020; RA: -0.27, P Conclusions The results of this observational study have shown a high durability of treatment with IFX for patients with PsA or RA in a real-world setting. Concomitant medication use significantly impacts treatment durability. Furthermore, longer disease duration, higher TJC, less severe skin disease at initiation and previous biologic use in PsA, and absence of IFX dose optimization in RA, may be associated with reduced treatment durability. Disclosure of Interest J. Kelsall: None declared, A. Jovaisas: None declared, P. Rahman: None declared, D. Sholter: None declared, M. Starr: None declared, W. Bensen: None declared, M. Sheriff: None declared, W. Olszynski: None declared, M. Zummer: None declared, R. Faraawi: None declared, A. Chow: None declared, S. Kapur: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, F. Nantel Employee of: Janssen Inc Canada, S. Otawa Employee of: Janssen Inc Canada, M. Shawi Employee of: Janssen Inc Canada, A. Lehman Employee of: Janssen Inc Canada DOI 10.1136/annrheumdis-2014-eular.4013

Background Achievement of clinical remission in rheumatoid arthritis (RA) is a process that may take several months. Identification of clinical signs predicting future remission may assist physicians in clinical decision making. Objectives The aim of this analysis was to describe the association between DAS28-ESR scores at 6 months and remission at 12 months in RA patients treated with infliximab (IFX) in a real-world, clinical practice setting. Methods BioTRAC is an ongoing, prospective Canadian registry of patients initiating treatment for RA, ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with IFX or golimumab as first biologics or after having been treated with a biologic for Results A total of 293 patients were included with a mean (SD) age of 56 (13.5) years and disease duration of 10.0 (9.7) years. Mean (SD) DAS28 was 3.8 (1.5) and 3.5 (1.5) at 6 and 12 months, respectively, and the percent with DAS28-ESR remission was 24.6% and 27.0%. Of the patients in remission at 6 months, 65.3% sustained the remission at 12 months, while of those not in remission at 6 months, 14.5% achieved remission at 12 months (P Conclusions The results of this analysis demonstrate that a DAS28-ESR target of ≤3.54 at 6 months maximizes the likelihood of remission at 12 months while a value of ≤2.13 should be targeted for optimal sustainment of remission. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4755

Background Patient (PtGA) and physician (MDGA) assessment of global disease activity have been used as outcome measures individually or as part of composite scores in the measurement of rheumatoid arthritis (RA) disease severity and the evaluation of treatment effectiveness. However, discordance between the two is common 1 . The question arising is which global measure is a more valid predictor of disease remission. Objectives The aim of the analysis was to compare PtGA and MDGA with respect to their association with remission based on DAS-28, SDAI and CDAI, using a sequential cross-sectional analysis. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with infliximab (IFX) or golimumab as first biologics or after having been treated with a biologic for Results A total of 657 patients were included with mean (SD) age of 56.2 (13.5) years and disease duration of 10.1 (10.0) years. Significant (P Conclusions The results of this analysis show that PtGA is a better predictor of DAS28 disease remission compared to MDGA. This could be explained by the fact that DAS28 includes PtGA and not MDGA. However, for CDAI and SDAI, physicians were better in predicting remission although the superiority of the MDGA was not consistent over time. References Bensen WG et al. Identification of Four Parameters that Drive the Discordance Between the Patient and Physician Global Assessment in Rheumatoid Arthritis. Canadian Rheumatology Association Annual Scientific Meeting, 2013, Ottawa, ON, Canada. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4276

Background The prevalence of ankylosing spondylitis (AS) is 2-3 times higher in men compared to women whereas psoriatic arthritis (PsA) is generally considered a disease affecting both genders equally. Recent studies have suggested that clinical differences exist between men and women with the latter experiencing a higher burden of disease (1-4). Objectives This analysis examined gender-specific differences with respect to patient and disease parameters at initiation of the first anti-TNF agent (infliximab; IFX) for the treatment of AS and PsA in a Canadian routine clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with IFX or golimumab as first biologics or after having been treated with a biologic for Results Among the 303 AS patients and 91 PsA patients, 189 (62.4%) and 49 (53.3%) were male, respectively. Mean age and disease duration at initiation of IFX treatment were comparable between genders (Table 1). Overall, disease parameters in AS patients were similar between genders with the exception of CRP which was significantly lower in female patients and HAQ-DI which was significantly higher (Table 1). Among PsA patients, females reported a significantly greater functional disability and showed a higher DAS28 compared to men. Conclusions Overall, some significant differences in disease parameters were observed between genders in AS and PsA at anti-TNF initiation. Female AS patients experience greater functional impairment compared to men. Female PsA patients, in addition to higher HAQ, also show greater disease activity as measured by DAS28. These results suggest that female patients appear to be receiving their first biologics at a higher level of disease activity. Whether this represents a gender bias in prescribing, or a gender based difference in the acceptance of biologic treatment, requires additional research. References Lee W et al. Ann Rheum Dis. 2007 May;66(5):633-8. van der Horst-Bruinsma IE et al. Ann Rheum Dis. 2013 Jul;72(7):1221-4. Queiro R et al. Clin Dev Immunol. 2013;2013:482691. Eder L et al. Ann Rheum Dis. 2013 Apr;72(4):578-82. Disclosure of Interest W. Bensen: None declared, J. Kelsall: None declared, M. Sheriff: None declared, N. Jones: None declared, I. Fortin: None declared, A. Chow: None declared, S. Shaikh: None declared, D. Choquette: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, F. Nantel Employee of: Janssen Inc Canada, M. Shawi Employee of: Janssen Inc Canada, S. Otawa Employee of: Janssen Inc Canada, A. Lehman Employee of: Janssen Inc Canada DOI 10.1136/annrheumdis-2014-eular.1911

Background Patient (PtGA) and physician (MDGA) global assessment of disease activity are standard outcome measures used in clinical practice and research to ascertain patient and physician subjective perception of disease activity in psoriatic arthritis (PsA). Given that the PtGA and MDGA measure the same construct from two different perspectives, assessing their concordance may provide valuable insight on patient and physician differences with respect to the relative importance placed on specific disease parameters. Objectives The aim of this analysis was to assess the agreement between PtGA and MDGA, and to compare the correlation of PtGA or MDGA with the Psoriasis Area and Severity Index (PASI) in PsA patients treated with infliximab (IFX) in a Canadian real-world, routine clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis, ankylosing spondylitis, or PsA with IFX or golimumab as first biologics or after having been treated with a biologic for Results A total of 92 patients (52.2% male) were included with a mean (SD) age of 48.7 (9.9) years and disease duration of 6.8 (9.1) years. At baseline, mean (SD) disease parameters were: PASI =3.3 (5.6); swollen joint count (SJC28) =4.0 (3.8); tender joint count (TJC28) =5.9 (5.3); PtGA =5.0 (2.8); MDGA =5.8 (2.2) cm. Prior to IFX initiation, 78 (84.8%) patients had been treated with a traditional DMARD (71.7% with methotrexate). Overall, a strong agreement was observed between PtGA and MDGA (r=0.632). The correlation of PASI with PtGA was low (r=0.213), whereas it was moderate with MDGA (r=0.343) (Figure 1). Overall, internal consistency was poor between PASI and both PtGA (CA =0.373, ICC =0.229) and MDGA (CA =0.445, ICC =0.286) although it was higher with the latter. Multivariate linear regression resulted in the exclusion of PtGA from the model, also supporting the stronger association of MDGA with PASI. When considering other disease parameters, PtGA showed a very strong correlation with pain (r=0.885) and strong with HAQ-DI (r=0.596), whereas a strong correlation was observed between MDGA and both pain and HAQ-DI (r=0.652 and r=0.520, respectively). Conclusions The results of this analysis shows that the association of PASI is stronger with MDGA when compared to PtGA. However, patient-reported pain and HAQ-DI were better correlated with PtGA and MDGA when compared to PASI, suggesting that both patients and rheumatologists place more emphasis on pain and functional activity than on skin symptoms when evaluating the global status of PsA. Disclosure of Interest : D. Sholter: None declared, P. Rahman: None declared, J. A. Avina-Zubieta: None declared, J. Kelsall: None declared, R. Arendse: None declared, M. Khraishi: None declared, S. Shaikh: None declared, W. Bensen: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, F. Nantel Employee of: Janssen Inc Canada, M. Shawi Employee of: Janssen Inc Canada, S. Otawa Employee of: Janssen Inc Canada, A. Lehman Employee of: Janssen Inc Canada DOI 10.1136/annrheumdis-2014-eular.5316

Objectives Efficacy of TNFi agents in the management of rheumatoid arthritis (RA) has been demonstrated in clinical trials. Variations with respect to patient (pt) profile, extent of physician familiarization with TNFi agents, and pt management may affect real-world outcomes. The aim of this analysis is to compare the pt profile and outcomes of RA pts treated with infliximab under routine clinical practice in biologic treatment registry sites of different sizes. Methods BioTRAC is an ongoing, prospective registry of pts initiating treatment for RA with infliximab as first biologics or treated with a biologic for 35pts. Total pts enrolled in each type of practice site was; Group A:n=324, Group B:n=239, Group C:n=269. Results Mean age was 55.8 yrs with 76% of pts being female and 74.2% RF+. No significant differences in demographic characteristics and RF status were observed between the subgroups. Pts seen at larger sites had significantly shorter disease duration (Group A: 11.9 years, Group B: 10.9 years, Group C: 7.5 years; P Upon adjusting for baseline disease activity, DAS28-CRP remission (P=0.013) and clinically meaningful improvement in HAQ-DI (Δ≥0.25; P=0.025) over 24mons of treatment was significantly greater among pts seen in larger sites. Conclusions Consistent with findings from a Canadian early RA registry 1 , results of this real-world observational study demonstrate that significant variation in disease characteristics, pt management and outcomes exist within the BioTRAC registry based on the size of the site. A trend towards earlier infliximab initiation and improved outcomes was observed with larger enrolment sites. References Harris J, et al. Improving outcomes in early RA by determining best practices: Does site size matter or is best treatment early? An analysis of the Canadian ERA cohort. CRA 2013 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3740

Background The prevalence of rheumatoid arthritis (RA) is 2-4 times higher in women compared to men. Furthermore, RA incidence in women increases from the age of menarche peaking around menopause, while it is rare in men younger than 45 years (1). Several studies have shown that treatment outcomes are worse in women (2). Objectives This analysis examined gender-specific differences with respect to disease parameters at initiation of the first anti-TNF agent for RA treatment in a Canadian routine clinical practice setting. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for RA, AS, or PsA with infliximab or golimumab as first biologics or after having been treated with a biologic for less than six months. In this analysis, data were assessed from RA patients treated with golimumab subcutaneous as a first biologic who were enrolled between 2010 and 2012. Results 121 RA patients were included with mean (SD) disease duration of 9.3 (9.6) years. Eighty-nine patients (73.6%) were female. In the overall population, rheumatoid factor positivity was observed in 67% of patients and 17.5% were smokers, without any significant differences between genders. Patient reported disease parameters differed significantly between genders. Despite the younger age (56.6 vs. 62.0 years; P=0.051), female patients reported significantly higher pain (56.6 vs. 44.5 mm; P=0.045), patient global assessment (PtGA: 6.0 vs. 4.7 cm; P=0.034), tender joint count (10.2 vs. 6.8; P=0.022), and functional disability (HAQ-DI: 1.43 vs. 1.06; P=0.024). In addition, a statistical trend towards higher morning stiffness in female patients was observed (55.7 vs. 38.9; P=0.063). However, physician assessment of global disease activity (MDGA: 5.7 vs. 5.5; P=0.581), SJC (7.9 vs. 8.5; P=0.641), DAS28-ESR (5.3 vs. 4.7; P=0.086), CDAI (29.7 vs. 24.5; P=0.120) and SDAI (32.1 vs. 30.2; P=0.675) were statistically comparable between genders. Conclusions Objective measures (SJC, CRP/ESR), MDGA and composite outcomes were similar for male and female patients at golimumab initiation, with the exception of TJC being higher in women. Patient reported outcomes (PROs: pain, PtGA, HAQ-DI), however, were worse at baseline for female patients at biologic treatment initiation. These findings are similar to our previous research on patients initiating anti-TNF IV therapy (3). Overall, the results may suggest gender bias in the interpretation and use of PROs during the treatment decision making process in Canadian RA patients. References Wilder RL. J Rheumatol Suppl. 1996 Mar;44:10-2. Forslind K. et al. Ann Rheum Dis. 2007 Jan;66(1):46-52. Bensen W. et al. J Rheumatol Suppl. 2013 Jun:40:1020-1. Disclosure of Interest D. Sholter: None declared, W. Bensen: None declared, D. Choquette: None declared, I. Fortin: None declared, R. Arendse: None declared, J. Kelsall: None declared, M. Sheriff: None declared, R. Faraawi: None declared, J. Rodrigues: None declared, M. Zummer: None declared, S. Dixit: None declared, M. Starr: None declared, E. Rampakakis: None declared, J. Sampalis: None declared, F. Nantel Employee of: Janssen Inc Canada, M. Shawi Employee of: Janssen Inc Canada, S. Otawa Employee of: Janssen Inc Canada, A. Lehman Employee of: Janssen Inc Canada DOI 10.1136/annrheumdis-2014-eular.3979

Objectives The objective of this study was to describe and compare over time the demographics and disease parameters at infliximab treatment initiation and to assess the effectiveness of treatment at 6 and 12 months in real life cohort AS patients. Methods BioTRAC is an ongoing, prospective registry of patients initiating treatment for rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) with infliximab or golimumab as first biologics or after having been treated with a biologic for less than six months. People with AS treated with infliximab who were enrolled between 2002 and 2013 were included in this analysis (N=303) and stratified to two groups (2005-2007: n=135; 2008-2013: n=168) based on the year of enrolment in the registry. Results Patient demographics were comparable in the two cohorts with a mean (SD) age of 45.72 (11.74) years and the majority being males (62.4%). A significant change in the geographic distribution of patients enrolled in the BioTRAC registry was observed (P=0.001) and more patients with provincial coverage were enrolled in 2008-2013 compared to 2005-2007 (P=0.012). A trend towards earlier initiation of infliximab was observed in more recent years as indicated by the shorter disease duration (11.12 vs. 8.24 years; P=0.013) and the lower number of prior traditional DMARDs used (0.83 vs. 0.59; P=0.078). Furthermore, overall, patients recruited in 2008-2013 had lower disease activity compared to those enrolled in 2005-2007. ESR (29.96 vs. 19.91 mm/hr; P Treatment for 6 months resulted in a greater proportion of patients in the 2008-2013 cohort achieving inactive disease (ASDAS Conclusions The results of this analysis show that the profile of the AS patient population in the BioTRAC registry has changed over time towards lower disease activity and earlier initiation in the patient management process. These results may reflect differences in patient management over time or may be related to earlier access to care. Irrespective of enrolment period, 6-month treatment with infliximab was effective in reducing disease activity in AS patients. Disclosure of Interest D. Choquette: None declared, M. Starr: None declared, M. Khraishi: None declared, W. Bensen: None declared, S. Shaikh: None declared, J. Rodrigues: None declared, D. Sholter: None declared, M. Sheriff: None declared, J. Vaillancourt: None declared, J. Sampalis: None declared, A. Lehman Employee of: Janssen, S. Otawa Employee of: Janssen, F. Nantel Employee of: Janssen, M. Shawi Employee of: Janssen DOI 10.1136/annrheumdis-2014-eular.2375

Eukaryotic translation initiation factor 4E (eIF4E) is a rate-limiting factor for cap-dependent protein synthesis regulated by the PI3K/AKT/mTOR signaling pathway as well as MNK1/2-mediated phosphorylation.1, 2 In addition to its cytoplasmic functions in translation, nuclear eIF4E aids in the cytoplasmic export of specific mRNAs.1, 3 eIF4E is overexpressed in many cancers and has been reported to have important roles in the development and progression of hematological malignancies in animal models.2 However, the role of eIF4E in drug resistance in primary human cancer cells is less well documented.4, 5, 6 In this study, we sought to assess the contribution of eIF4E to fludarabine (FLU) resistance in primary chronic lymphocytic leukemia (CLL) lymphocytes as this nucleoside analog is used as a first-line treatment for the disease.7 To this end, we used a panel of primary CLL samples from 26 affected patients (Supplementary Table). To interfere with eIF4E function, we used Ribavirin, a well-characterized antiviral drug that has also been shown to target eIF4E in a variety of systems, including patients with acute myeloid leukemia (AML).6, 8, 9 A clinically achievable concentration of Ribavirin (10 μM), which was not cytotoxic to primary CLL lymphocytes in culture, significantly sensitized 76% of the samples tested to FLU with the sensitization index (R) ranging from 1.25 to eightfold (Figures 1a, P

Background Despite the importance of HAQ in assessing patient-reported functional status, it was originally developed primarily for research studies. As a result, HAQ has been critiqued for being time-consuming, not easily scored, and, thus, not contributing to decisions in routine care, and being influenced by comorbidities[ref][1]. Objectives To describe the correlation of individual HAQ questions with outcome measures used in Rheumatoid Arthritis (RA). To examine whether the instrument could be reduced to better reflect routine clinical practice. Methods BioTRAC is an ongoing, prospective registry of RA, AS, or PsA patients initiating infliximab or golimumab as first biologics or after

Background In recent years, disease remission in rheumatoid arthritis (RA) has been assessed using various disease activity indices such as the DAS28, SDAI, CDAI, ACR/EULAR-recommended Boolean definition and the Patient Activity Scale (PAS). Objectives The aim of this analysis is to describe the agreement between these five indices in classifying remission as well as to assess their correlation in a routine clinical care setting. Methods BioTRAC is an ongoing, prospective Canadian registry of rheumatology patients initiating treatment with infliximab or golimumab. In this analysis, data from RA patients who were treated with infliximab between January 2002 and June 2011 and had available information in all indices were used. The definitions for remission were as follows: DAS28-ESR Results Seven hundred twenty five RA patients who had 2,897 complete assessments were included in the analysis. Non-remission was classified by all indices in 68.8% of the cases, while 31.2% achieved remission in one (12.4%), two (3.5%), three (3.4%), four (4.2%) and all five types (7.7%) of indices. Factor analysis showed that PAS accounted for 71.5% of the matrix variance, followed by DAS28-ESR (12.4%), SDAI (9.2%), CDAI (5.2%), and Boolean remission (1.6%), suggesting that PAS may reflect different aspects than the clinical indices. PAS remission revealed the lowest correlation with remission classified by the remaining indices (Table 1) and removal of any index, except PAS, would result in a lower overall Cronbach’s alpha. Conclusions The results of this analysis show that variability exists in the classification of remission by various disease activity indices. This variability was found to be predominantly due to the Patient Activity Scale, a patient-driven composite tool, suggesting that the patient perception of disease activity may differ from that captured by clinical outcome measures. Disclosure of Interest W. Bensen: None Declared, A. Jovaisas: None Declared, C. Thorne: None Declared, P. Baer: None Declared, M. Khraishi: None Declared, S. Dixit: None Declared, D. Choquette: None Declared, M. Starr: None Declared, I. Fortin: None Declared, D. Sholter: None Declared, E. Rampakakis Employee of: JSS Medical Research, J. Sampalis Employee of: JSS Medical Research, A. Lehman Employee of: Janssen, F. Nantel Employee of: Janssen, M. Shawi: None Declared, S. Otawa Employee of: Janssen

Background Clinical trials of anti-TNF therapies have shown that concurrent methotrexate (MTX) therapy enhances the efficacy of infliximab (IFX) 1 . Data on the benefits of combination therapy with MTX and IFX in a real-life clinical setting are scarce. Objectives Describe changes in the use of MTX at IFX initiation in patients enrolled in routine clinical practice and assess the impact of the MTX dose on the real-life effectiveness of IFX. Methods BioTRAC is an ongoing, prospective registry of RA, AS or PSA patients initiating treatment with IFX or golimumab as first biologics or after having been treated with a biologic Results 790 RA patients were included with a mean (SD) age of 55.75 (13.46) yrs, mean (SD) disease duration of 10.15 (10.08) yrs. The concomitant use of MTX at infliximab initiation increased across enrolment periods (66.5% vs. 73.3% vs. 77.6%; P=0.022) which was also associated with decreased disease activity at baseline. Concomitant use of azathioprine (5.2% vs. 0.2%; P 25mg/week of MTX in recent yrs. Survival analysis shows that, upon adjusting for baseline disease activity, use of MTX over time was associated with an increased hazard ratio [HR (95%CI)] of attaining disease DAS28-CRP [1.35 (1.06-1.71)], CDAI [1.33 (1.02-1.72)], and SDAI [1.62 (1.14-2.32)] remission. This effect was observed across all MTX dose categories except for DAS28-CRP and CDAI in the >25mg/week dose category. Conclusions Clinical practice has changed over time with physicians using concomitant MTX at IFX initiation more frequently in recent years despite lower disease activity in patients today. The data support improved outcomes among patients treated with IFX in routine clinical care when receiving concomitant MTX. This is consistent with the current label and recent recommendations of the Canadian Rheumatology Association. References Arthritis Rheum 1998;41:1552–63 Disclosure of Interest D. Choquette: None Declared, C. Thorne: None Declared, J. Kelsall: None Declared, M. Zummer: None Declared, M. Starr: None Declared, M. Sheriff: None Declared, W. Bensen: None Declared, A. Chow: None Declared, P. Baer: None Declared, E. Rampakakis Employee of: JSS Medical Research, J. Sampalis Employee of: JSS Medical Research, F. Nantel Employee of: Janssen, A. Lehman Employee of: Janssen, S. Otawa Employee of: Janssen, M. Shawi Employee of: Janssen