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Background Tofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA). Objectives To report the safety, tolerability and efficacy of tofacitinib in patients (pts) with active PsA from an ongoing, open-label, long-term extension (LTE) study (OPAL Balance, NCT01976364; November 2017 data-cut; database not locked). Methods Eligible pts from 2 Phase (P)3 tofacitinib PsA studies (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) entered a 3 year LTE ≤3 months after completing the P3 study or discontinuing for reasons unrelated to study drug. Pts received tofacitinib 5 mg BID to Month (M)1, after which dose adjustments between 5 and 10 mg BID were permitted to improve efficacy, or for safety reasons. Pts receiving a csDMARD at P3 study entry continued the same csDMARD in the LTE. Primary endpoints were incidence and severity of adverse events (AEs) and changes from baseline (Δ) in laboratory values. Safety data are reported up to M36. Efficacy was evaluated up to M30 (when n>50) as a secondary endpoint. Results 686 pts were treated in OPAL Balance; 468 (68.2%) remained in the study at data cut-off. Mean (range) LTE tofacitinib exposure was 614 (1–1032) days. On Day 1, 675 pts (98.4%) received a csDMARD, which was discontinued in 86 pts (12.7%). To M36, 2189 AEs were reported in 546 pts (79.6%), 95 pts (13.8%) had serious AEs and 59 pts (8.6%) discontinued due to AEs. Serious infections occurred in 12 pts (1.7%), herpes zoster (HZ) in 20 pts (2.9%; 1 serious event), major adverse cardiovascular events in 5 pts (0.7%), malignancies in 24 pts (3.5%; including 12 pts with NMSC) and uveitis in 2 pts (0.3%). No AEs of gastrointestinal perforation or inflammatory bowel disease were reported. There were 5 deaths (not attributed to treatment, as assessed by the investigator) due to metastatic pancreatic carcinoma, acute cardiac failure/hypertensive heart disease, chronic obstructive pulmonary disease, pulmonary embolism and cardiovascular insufficiency. Four AEs of latent tuberculosis were reported in pts whose previously negative QuantiFERON response became positive. ALT was elevated ≥3 x ULN in 27 pts (4.0%), and AST≥3 x ULN in 15 pts (2.2%). Changes in laboratory values observed in P3 studies were generally stable in the LTE, except for a modest decrease in absolute lymphocyte count over time. Eight pts (1.2%) discontinued (protocol-mandated) due to laboratory value changes. ACR responses, ΔHAQ-DI, PASI75 response, ΔLeeds Enthesitis Index, ΔDactylitis Severity Score and ΔPain were maintained up to M30. Conclusions Over 36 months in the LTE, the safety profile of tofacitinib in active PsA pts was generally similar to that of the P3 studies. No new safety risks were identified. Efficacy across various PsA disease domains was maintained over time. Acknowledgements Study sponsored by Pfizer Inc. Medical writing support was provided by A MacLachlan of CMC and funded by Pfizer Inc. Disclosure of Interest P. Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Consultant for: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer Inc, Roche, Sanofi, UCB, L. Coates Grant/research support from: AbbVie, Janssen, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, MSD, Novartis, Pfizer Inc, Sun Pharma, UCB, A. Kivitz Consultant for: AbbVie, Celgene, Genentech, Genzyme, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, UCB, Speakers bureau: AbbVie, Celgene, Genentech, Genzyme, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, UCB, P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Sun, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Sun, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Genentech, Janssen, Novartis, Pfizer Inc, UCB, D. Gladman Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, J. Covarrubias-Cobos Grant/research support from: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, D. Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Kudlacz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, L. Fallon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc more...

Background Tofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). Interim data (database not locked) from ≤24 months9 participation (3 years9 total treatment duration) for patients (pts) with active PsA in an ongoing, open-label, long-term extension study (LTE; NCT01976364 OPAL Balance) is reported. Objectives To evaluate the safety, tolerability and efficacy of tofacitinib in pts with active PsA. Methods Eligible pts from 2 pivotal Phase 3 tofacitinib PsA studies (NCT01877668 OPAL Broaden, NCT01882439 OPAL Beyond) could enter a 3-year LTE ≤3 months after completing the qualifying study or discontinuing for non study-drug-related reasons. Pts were to receive tofacitinib 5 mg twice daily (BID) for 1 month, after which an increase to 10 mg BID or reduction back to 5 mg BID was permitted at any time for efficacy or safety reasons. Concomitant treatment with a single conventional synthetic disease-modifying antirheumatic drug (csDMARD) was allowed but not required. Primary endpoints were incidence and severity of adverse events (AEs) and change from baseline in laboratory values. Efficacy was a secondary endpoint. Results 680/685 enrolled pts were treated. 608 (89.4%) remained at data cut-off. Mean (range) duration of tofacitinib exposure in this LTE was 206 (3–741) days. 661 (97.2%) pts took a csDMARD on Day 1, and 73 (11.0%) later discontinued csDMARD. To Month 24, 860 AEs were reported in 367 (54.0%) pts, 41 (6.0%) pts had serious AEs and 24 (3.5%) pts discontinued due to AEs. Special interest AEs included 6 serious infections (0.9%), 10 herpes zoster events (1.5%) including 1 serious event, 2 major adverse cardiovascular events (0.3%) and 2 malignancies (0.3%). There were 3 deaths (not attributed to treatment, as assessed by the investigator) due to metastatic pancreatic carcinoma, acute cardiac failure and pulmonary embolism. No GI perforation, inflammatory bowel disease or uveitis cases were reported. One AE of latent TB was reported. One pt met discontinuation criteria for laboratory values due to increased serum creatinine >50% and >0.5 mg/dL over the average of screening and baseline creatinine. Small mean decreases in absolute lymphocyte and neutrophil counts, and small mean increases in serum lipid markers, were observed; 18 (2.6%) pts started new lipid-lowering medication during the LTE (80 [11.8%] pts were on lipid-lowering drug at baseline). Efficacy was maintained in the LTE (Table 1). Conclusions Over 24 months in the LTE, the safety profile of tofacitinib in pts with active PsA was generally similar to that of the pivotal Phase 3 studies. No new safety signals were identified. Efficacy was maintained over time. Acknowledgements To be presented at AAD 2017 and reproduced with permission. This study was sponsored by Pfizer Inc. Editorial support was provided by S Morgan of CMC and was funded by Pfizer Inc. Disclosure of Interest P. Nash Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Roche, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Merck, Novartis, Pfizer Inc, Sanofi, Roche, UCB, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Pfizer Inc, Roche, UCB, L. Coates Speakers bureau: Pfizer Inc, A. Kivitz Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Pfizer Inc, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Pfizer Inc, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Genentech, Pfizer Inc, P. Mease Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Sun, UCB, Consultant for: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Corrona, Dermira, Janssen, Eli Lilly, Merck, Novartis, Pfizer Inc, Sun, UCB, Zynerba, Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Crescendo, Genetech, Janssen, Novartis, Pfizer Inc, UCB, D. Gladman Grant/research support from: Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer Inc, Novartis, UCB, Consultant for: Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer Inc, Novartis, UCB, Speakers bureau: Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Pfizer Inc, Novartis, UCB, J. Covarrubias-Cobos Grant/research support from: Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer Inc, D. Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, C. Wang Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, E. Kudlacz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Menon Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc more...

Background Tofacitinib is an oral Janus kinase inhibitor. The minimally important changes (MICs) for the SPondyloArthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint (SIJ) and spine scores based on agreement with global change scores by readers are ≥2.5 and ≥5, respectively.1 Objectives To assess whether MIC in SIJ and spine can discriminate between tofacitinib and placebo (PBO) in patients (pts) with ankylosing spondylitis (AS) and if this is concordant with clinical responses. Methods In this 16-week (wk), Phase 2, double-blind, dose-ranging study (NCT01786668),2 207 adult pts meeting modified New York AS criteria were randomised 1:1:1:1 to PBO or tofacitinib 2, 5 or 10 mg twice daily (BID) for 12 wks. Clinical endpoints included in this post-hoc analysis were: Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) and ASAS 40% improvement (ASAS40) response rates, AS disease activity score major improvement (ASDAS MI; change ≥2.0 from baseline), ASDAS inactive disease (ASDAS ID; Results MRI data for 164 pts were evaluated. Baseline demographics were generally balanced between treatment groups and typical of AS populations.2 Tofacitinib 2, 5 and 10 mg BID improved mean (range) SPARCC scores vs PBO (SIJ: -2.2 [-22.0, 10.5], -3.5 [-34.5, 11.0], -3.6 [-29.0, 0.5] vs -0.7 [-9.5, 6.5]; spine: -3.2 [-34.5, 20.5], -5.5 [-36.5, 8.0], -6.7 [-32.5, 7.5] vs -0.8 [-8.0, 14.0]). Approximately 3 times more pts achieved MIC in SIJ or spine in the pooled tofacitinib group vs PBO (SIJ: 34.1% vs 11.8%, p Conclusions Pts who received tofacitinib who had AS experienced clinically meaningful reductions in axial MRI inflammation. Pts achieving MIC for MRI inflammation had increased clinical response rates. References Maksymowych WP et al. J Rheumatol 2012; 39: 1666–1674. van der Heijde D et al. Ann Rheum Dis 2016; In press. Acknowledgements Previously presented at ACR 2016 and reproduced with permission. This study was sponsored by Pfizer Inc. Editorial support was provided by A Pedder of CMC and funded by Pfizer Inc. Disclosure of Interest W. Maksymowych Grant/research support from: AbbVie, Pfizer Inc, Sanofi, UCB, Consultant for: AbbVie, Amgen, Eli Lilly, Janssen, Merck, Novartis, Pfizer Inc, Sanofi, UCB, D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, Bristol-Meyers Squibb, Boehringer Ingelheim, Celgene, Daiichi, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer Inc, Roche, Sanofi-Aventis, UCB, Employee of: Imaging Rheumatology BV, X. Baraliakos Grant/research support from: AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Novartis, Pfizer Inc, Roche, MSD, UCB, A. Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer Inc, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer Inc, UCB, M. Brown Grant/research support from: AbbVie, Janssen, Leo Pharma, UCB, Consultant for: AbbVie, Janssen, Novartis, Pfizer Inc, UCB, Speakers bureau: AbbVie, Janssen, Novartis, Pfizer Inc, UCB, S. Sherlock Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Li Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Hendrikx Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, K. Kanik Shareholder of: Pfizer Inc, Employee of: Pfizer Inc more...