SAT0293 Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, up to 36 months in patients with active psoriatic arthritis: data from the third interim analysis of opal balance, an open-label, long-term extension study

Abstract

BackgroundTofacitinib is an oral Janus kinase inhibitor for the treatment of psoriatic arthritis (PsA).ObjectivesTo 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).MethodsEligible 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.Results686 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.ConclusionsOver 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.AcknowledgementsStudy sponsored by Pfizer Inc. Medical writing support was provided by A MacLachlan of CMC and funded by Pfizer Inc.Disclosure of InterestP. Nash Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer I...

<p>Tofacitinib in the management of active psoriatic arthritis: patient selection and perspectives</p>

“…OPAL Balance is an ongoing, open-label, long-term extension (LTE) study evaluating the safety and efficacy of tofacitinib in patients with PsA. 5,21,22 Patients from OPAL Broaden and OPAL Beyond were invited to participate in a three year LTE study within three months of completing or discontinuing the parent study. This study treated 686 patients, who were treated with tofacitinib 5 mg BID or 10 mg BID, depending on treatment response.…”

“…No new safety risks were reported and efficacy was maintained. 5,22 A 52 week, randomized, double-blind, phase III clinical trial evaluated the safety and efficacy of tofacitinib in Japanese patients with moderate to severe plaque psoriasis (n=87), PsA (n=12), or both (n=5). Patients were randomized 1:1 to tofacitinib 5 mg or 10 mg twice daily for 16 weeks, open-label 10 mg twice daily for 4 weeks, then the dose was adjust to tofacitinib 5 mg or 10 mg at the investigator's discretion to 52 weeks.…”

“…Integrated safety analyses of phase III studies 38 and the LTE study 22 found tofacitinib to be well tolerated in patients with psoriatic arthritis with a safety profile that is comparable to other biologics. 11,39 The adverse events reported in psoriatic arthritis trials were similar to those reported for rheumatoid arthritis and psoriasis.…”

Phase 1 Dose‐Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Tofacitinib in Japanese Healthy Volunteers

“…The most frequently reported adverse event in [1][2][3][4][5][6][11][12][13][14][15][16]33,34 All adverse events resolved before the completion of the study. No serious adverse events or deaths were reported, and no volunteers had clinically significant laboratory abnormalities.…”

Efficacy of Tofacitinib for the Treatment of Psoriatic Arthritis: Pooled Analysis of Two Phase 3 Studies

“…Finally, this analysis focuses on the efficacy of tofacitinib in treating PsA; safety data are reported in the primary manuscripts [ 20 , 21 ] as well as in a pooled safety analysis [ 30 ]. No new safety risks were identified in an interim analysis of data from patients with active PsA receiving tofacitinib for up to 36 months in the ongoing LTE study, OPAL Balance (NCT01976364; data-cut: November 2017; database not locked; data may change) [ 31 ].…”