SAN DIEGO, CA—Tofacitinib 5mg or 10mg twice daily showed a consistent safety profile and sustained efficacy over 5 years in long-term extension studies for patients with rheumatoid arthritis (RA), presented Jürgen Wollenhaupt, MD, from Schoen-Klinik Hamburg-Eilbek Teaching Hospital of the University of Hamburg, Hamburg, Germany, at the 2013 ACR/ARHP Annual Meeting.
Tofacitinib is a novel, oral JAK inhibitor approved for the treatment of RA.
Dr. Wollenhaupt and his team pooled data from two open-label studies (A3921024 and A3921041) of patients who previously participated in randomized Phase 2 or 3 tofacitinib studies, to assess the safety, tolerability, and durability of response up to 60 months in long-term extension (LTE) studies. Treatment was initiated with tofacitinib 5mg or 10mg twice daily as monotherapy or with background disease-modifying antirheumatic drugs (DMARDs); data from both doses with or without background DMARDs were pooled.
The study’s primary endpoints were adverse events and confirmed (2 sequential) laboratory safety data. Secondary endpoints included ACR responses, DAS28‑4 (ESR) (DAS28), and HAQ‑DI.
A total of 4,827 patients were treated with a mean (maximum) treatment duration of 687 (2,187) days. The most commonly reported AE classes were infections and infestations (55.8%), GI disorders (25.4%), and musculoskeletal/connective tissue disorders (27.8%).
Decreased hemoglobin (≥2g/dL change from baseline, or <8g/dL) was observed in 4.7% of patients. Raised aminotransferases (>3×ULN) were observed in 4.1% (ALT) and 2.1% (AST) of patients. Moderate-to-severe neutropenia (absolute neutrophil count [ANC] 0.5–1.5 × 103/mm3) was reported in 1.0% of patients, and there were no cases of ANC <0.5 × 103/mm3. Absolute lymphocyte counts <0.5 × 103/mm3 were reported in <1.0% of patients.
In addition, researchers noted increases of >50% from baseline in creatinine for 3.6% of patients. “Mean values for laboratory safety measures were consistent with findings in Phase 2 and Phase 3 studies and stable over time,” noted Dr. Wollenhaupt.
Sustained efficacy was seen for tofacitinib + background DMARDs between Month 1 and Month 60: ACR20 (60.2% and 77.9%), ACR50 (39.8% and 56.7%), and ACR70 (22.7% and 40.4%). Mean DAS28(ESR) was 6.2 at baseline, 3.7 at Month 1, and 3.6 at Month 60. Mean HAQ-DI score was 1.4 at baseline, 0.8 at Month 1, and 0.7 at Month 60.
Dr. Wollenhaupt and his team also added, “Safety and efficacy were similar for patients receiving tofacitinib as monotherapy or with background DMARDs.”