Efficacy and safety of tofacitinib by background methotrexate dose in psoriatic arthritis: post hoc exploratory analysis from two phase III trials
Alan J Kivitz, Oliver FitzGerald, Peter Nash, Shirley Pang, Valderilio F Azevedo, Cunshan Wang, Liza Takiya, Alan J Kivitz, Oliver FitzGerald, Peter Nash, Shirley Pang, Valderilio F Azevedo, Cunshan Wang, Liza Takiya
Abstract
Objective: Analyze tofacitinib efficacy and safety by background methotrexate (MTX) dose in patients with psoriatic arthritis (PsA).
Methods: This post hoc analysis pooled data from two phase III, double-blind trials (OPAL Broaden, NCT01877668; OPAL Beyond, NCT01882439) including patients receiving tofacitinib 5 or 10 mg twice daily (BID), or placebo, with stable MTX. Efficacy outcomes at month 3 stratified by MTX dose (≤ 15 month 3 stratified by MTX dose vs > 15 mg/week) were American College of Rheumatology (ACR)20/50/70, Health Assessment Questionnaire-Disability Index (HAQ-DI); Psoriasis Area and Severity Index (PASI)50/75; change from baseline in HAQ-DI; physician's global assessment of PsA (PGA-PsA-visual analog scale [VAS]); patient's global joint and skin assessment (PGJS-VAS), Leeds Enthesitis Index (LEI); and Dactylitis Severity Score (DSS). Safety assessments included adverse events and laboratory parameters.
Results: Five hundred fifty-six patients received tofacitinib 5 mg BID (n = 186), 10 mg BID (n = 178), or placebo (n = 192), plus MTX (≤ 15 mg/week, n = 371; > 15 mg/week, n = 185). At month 3, tofacitinib efficacy was generally greater than placebo. Patients receiving tofacitinib 5 mg BID demonstrated greater numerical improvements in efficacy outcomes at month 3 with MTX > 15 mg/week vs MTX ≤ 15 mg/week; patients receiving tofacitinib 10 mg BID displayed the opposite. The safety profile was generally consistent between groups; headache was associated with MTX > 15 mg/week; decreased hemoglobin levels were observed in patients receiving tofacitinib 10 mg BID and MTX ≤ 15 mg/week.
Conclusion: Efficacy of tofacitinib was generally numerically greater than placebo, regardless of MTX dose. Tofacitinib 5 mg BID was generally more efficacious with MTX > 15 mg/week vs ≤ 15 mg/week; the opposite was observed for tofacitinib 10 mg BID. Headache was more frequent with MTX > 15 mg/week.
Trial registration: ClinicalTrials.gov . Identifier: NCT01877668 (registration: June 14, 2013) and NCT01882439 (registration: June 20, 2013). Key Points • Methotrexate is widely used in the treatment of psoriatic arthritis; however, there are limited data on the impact of varying background methotrexate doses on the efficacy and safety of Janus kinase inhibitors in patients with psoriatic arthritis. • This post hoc analysis assessed the impact of background methotrexate dose (≤ 15 or > 15 mg/week) on tofacitinib efficacy and safety in patients with psoriatic arthritis. • Results indicated that tofacitinib efficacy was generally numerically greater than placebo, regardless of methotrexate dose. Tofacitinib 5 mg twice daily, in combination with a higher dose of background methotrexate, was more efficacious compared with a lower dose of background methotrexate; the opposite was observed for tofacitinib 10 mg twice daily. • Headache was more frequent with the higher methotrexate dose. Data should be interpreted with caution due to the small sample sizes.
Keywords: Disease activity; Disease-modifying anti-rheumatic drugs; Methotrexate; Psoriatic arthritis; Tofacitinib.
Conflict of interest statement
AJK has been a consultant for AbbVie, Genentech, Genzyme, Janssen, Novartis, Pfizer Inc., Sanofi-Regeneron, and UCB and has been involved in speakers’ bureaus for Celgene, Genentech, Genzyme, Horizon, Novartis, Pfizer Inc., and Sanofi-Regeneron. OF has received research grants from AbbVie, Bristol-Myers Squibb, Novartis, and Pfizer Inc. and has been a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Pfizer Inc., and UCB. PN has received research grants and honoraria for lectures and advice on behalf of AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Novartis, Roche, Sanofi, Pfizer Inc., and UCB and has received consulting fees from AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MSD, Novartis, Pfizer Inc., Sun Pharma, and UCB. SP has been involved in speakers’ bureaus for Celgene and Novartis. VFA has been a consultant for AbbVie, Eli Lilly, Genentech, GSK, Pfizer Inc., and UCB and has been involved in speakers’ bureaus for AbbVie, Janssen, Merck-Serono, Novartis, Pfizer Inc., and Sanofi. CW and LT are employees and shareholders of Pfizer Inc.
© 2021. The Author(s).
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Source: PubMed