FRI0509 Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, up to 24 months in patients with active psoriatic arthritis: interim data from opal balance, an open-label, long-term extension study

Abstract

BackgroundTofacitinib is an oral Janus kinase inhibitor under investigation for psoriatic arthritis (PsA). Interim data (database not locked) from ≤24 months' participation (3 years' total treatment duration) for patients (pts) with active PsA in an ongoing, open-label, long-term extension study (LTE; NCT01976364 OPAL Balance) is reported.ObjectivesTo evaluate the safety, tolerability and efficacy of tofacitinib in pts with active PsA.MethodsEligible 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.Results680/685 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).ConclusionsOver 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.AcknowledgementsTo 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 InterestP. Nash Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Eli Lilly, Novartis, Pfizer Inc, Roche, UCB, Consultant ...

An Integrated Analysis of the Safety of Tofacitinib in Psoriatic Arthritis across Phase III and Long-Term Extension Studies with Comparison to Real-World Observational Data

“…Safety data for patients in two global phase III studies (OPAL Broaden [NCT01877668] [10] and OPAL Beyond [NCT01882439] [11]) and one LTE study (OPAL Balance [NCT01976364] [12]) were pooled for analysis.…”

“…OPAL Broaden and OPAL Beyond, studies of 12-or 6-months duration, respectively, have been described previously [11,12]. Briefly, both were double-blind, placebocontrolled, parallel-group studies in patients with active PsA.…”

“…OPAL Balance [12] is an ongoing, open-label LTE study (database not locked) that enrolled patients who had participated in OPAL Broaden or OPAL Beyond. Data up to 10 May 2016 were included in the current analysis, including up to 3 years of tofacitinib exposure per patient.…”

“…Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. We describe the safety profile of tofacitinib in PsA, using pooled data from two phase III [10,11] and one ongoing long-term extension (LTE) study [12], and compare the incidence rates (IRs) for AEs of special interest from the tofacitinib PsA clinical program with those from observational data for other PsA treatments using data from the US Truven MarketScan database.…”

Changes in Lipid Levels and Incidence of Cardiovascular Events Following Tofacitinib Treatment in Patients With Psoriatic Arthritis: A Pooled Analysis Across Phase III and Long‐Term Extension Studies

“…Tofacitinib is an oral Janus kinase inhibitor for the treatment of PsA. The efficacy and safety of tofacitinib have been demonstrated in 2 phase III studies (Efficacy and Safety of Tofacitinib in Psoriatic Arthritis [OPAL Broaden] and Tofacitinib in Patients with Psoriatic Arthritis With Inadequate Response to TNF Inhibitors [OPAL Beyond] ) and 1 ongoing long‐term extension (LTE) study (Open‐Label Extension Study of Tofacitinib in Psoriatic Arthritis [OPAL Balance] ).…”