THU0323 Tofacitinib improves composite endpoint measures of disease in patients with psoriatic arthritis

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