Safety and efficacy of tofacitinib, an oral janus kinase inhibitor, for the treatment of rheumatoid arthritis in open-label, longterm extension studies

J Rheumatol. 2014 May;41(5):837-52. doi: 10.3899/jrheum.130683. Epub 2014 Apr 1.

Abstract

Objective: To describe the longterm safety and efficacy profile of tofacitinib in patients with moderate to severe active rheumatoid arthritis (RA).

Methods: Data were pooled from 2 open-label studies (NCT00413699, NCT00661661) involving patients who had participated in qualifying phase I, II, or III index studies of tofacitinib. Safety data included over 60 months of observation; efficacy data are reported up to Month 48. Treatment was initiated with tofacitinib 5 or 10 mg twice daily. Primary endpoints were adverse events (AE) and laboratory safety data. Secondary endpoints included American College of Rheumatology (ACR) response rates, and Disease Activity Score (28 joints) (DAS28)-4[erythrocyte sedimentation rate (ESR)] and Health Assessment Questionnaire-Disability Index (HAQ-DI) assessments.

Results: Overall, 4102 patients were treated for 5963 patient-years; mean (maximum) treatment duration was 531 (1844) days; 20.8% of patients discontinued treatment over 60 months. The most common AE were nasopharyngitis (12.7%) and upper respiratory tract infection (10.5%). Serious AE were reported in 15.4% of patients with an exposure-estimated incidence rate of 11.1 events/100 patient-years. Serious infections were reported in 4.5% of patients with an exposure-estimated incidence rate of 3.1 events/100 patient-years (95% CI: 2.66-3.55). Mean values for laboratory variables were stable over time and consistent with phase II and III studies. Persistent efficacy was demonstrated through Month 48, as measured by ACR response rate (ACR20/50/70) DAS28-4-ESR, and HAQ-DI. Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background nonbiologic disease-modifying antirheumatic drugs.

Conclusion: Tofacitinib demonstrated consistent safety and persistent efficacy over 48 months in patients with RA.

Keywords: ANTIRHEUMATIC AGENTS; CLINICAL TRIAL; RHEUMATOID ARTHRITIS; TOFACITINIB.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / administration & dosage
  • Antirheumatic Agents / adverse effects
  • Arthritis, Rheumatoid / drug therapy*
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Female
  • Humans
  • Janus Kinase 3 / antagonists & inhibitors
  • Male
  • Middle Aged
  • Piperidines / administration & dosage*
  • Piperidines / adverse effects*
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / adverse effects*
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects*
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects*

Substances

  • Antirheumatic Agents
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Pyrroles
  • tofacitinib
  • Janus Kinase 3