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 ...
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...
BackgroundTofacitinib is an oral Janus kinase inhibitor under investigation for treatment of psoriatic arthritis (PsA). The safety and efficacy of tofacitinib for the treatment of PsA has been investigated in two Phase 3 randomised controlled trials (RCTs: OPAL Broaden [12 months; NCT01877668]; OPAL Beyond [6 months; NCT01882439]).ObjectivesTo evaluate patient-reported outcomes (PROs) in patients (pts) with active PsA enrolled in OPAL Broaden (N=422) and OPAL Beyond (N=394). OPAL Broaden pts had an inadequate response (IR) to ≥1 conventional synthetic disease-modifying antirheumatic drug and were naïve to tumour necrosis factor inhibitors (TNFi) whilst OPAL Beyond pts had an IR to ≥1 TNFi.MethodsPts were randomised to tofacitinib 5 mg twice daily (BID), tofacitinib 10 mg BID, placebo (PBO)→ tofacitinib 5 mg BID, PBO→ tofacitinib 10 mg BID and, in OPAL Broaden, also to adalimumab 40 mg subcutaneously every two weeks (active comparator). Pts receiving PBO advanced to either tofacitinib 5 mg BID or 10 mg BID at month 3 (M3) in both RCTs. Least squares mean changes from baseline in: Patient's Global Assessment of Arthritis (PtGA; Visual Analogue Scale [VAS]); Arthritis Pain (Pain; VAS); Short Form-36 Health Survey (SF-36); Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F); Dermatology Life Quality Index (DLQI) and Ankylosing Spondylitis Quality of Life (ASQOL) questionnaires are reported. Nominal p values are reported without adjustments for multiple comparisons.ResultsPatients with active PsA in OPAL Broaden and OPAL Beyond RCTs receiving tofacitinib 5 mg and 10 mg BID reported improved PROs compared with PBO (Table 1). Greater improvements in PtGA and Arthritis Pain were observed as early as Week 2 through M3 with both tofacitinib doses compared with PBO in both studies (p≤0.05). Greater improvements were also reported in SF-36 Physical Component Summary, DLQI and ASQOL scores at M1 and M3 with both tofacitinib doses compared with PBO (p≤0.05). There were greater improvements in SF-36 physical functioning, bodily pain and vitality domains with both tofacitinib doses compared with PBO in both studies (p≤0.05) at M3. SF-36 social functioning domain showed greater improvement with tofacitinib 5 mg BID in OPAL Broaden and both tofacitinib doses in OPAL Beyond compared with PBO at M3 (p≤0.05). SF-36 role-physical domain showed greater improvement with tofacitinib 10 mg BID in OPAL Beyond at M3 compared with PBO (p≤0.05). FACIT-F showed a greater improvement in both studies at M3 with both tofacitinib doses compared with PBO (p≤0.05). In OPAL Broaden, improvements in PROs were similar between tofacitinib and adalimumab.ConclusionsPts with active PsA receiving tofacitinib reported greater improvements in PROs compared with PBO at M3 that were maintained throughout both RCTs.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 InterestV. Strand Consulta...
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