Tofacitinib, an Oral Janus Kinase Inhibitor, in the Treatment of Ulcerative Colitis: An Interim Analysis of an Open-Label, Long-Term Extension Study With up to 4.9 Years of Treatment

Abstract

Introduction: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib was demonstrated as induction and maintenance therapy in patients (pts) with moderate to severe UC in 3 Phase 3, randomized, placebo-controlled studies [1]. Safety and efficacy of tofacitinib for UC are being evaluated in an ongoing, open-label, long-term extension (OLE) study [2]. Methods: We present an update (as of Nov 10 2017) of previous safety and efficacy data [2] of the OLE study (NCT01470612) in completers or treatment failures in OCTAVE Sustain (NCT01458574) and nonresponders in OCTAVE Induction 1/2. Eligibility was determined per Week (Wk) 8 data from OCTAVE Induction 1/2, or Wk 52 data (for completers) or early termination data from OCTAVE Sustain. Pts in remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore of 0) at Wk 52 of OCTAVE Sustain (per central read) were assigned to tofacitinib 5 mg twice daily (BID) in the OLE study; all others were assigned to 10 mg BID. At Month 2, all pts underwent endoscopy; induction nonresponders were mandated to withdraw if they did not show a clinical response. Binary efficacy endpoints were derived from Mayo score per local read. Results: Of 944 pts who received ≥1 dose of study drug (for up to 4.9 years), 326 (34.5%) discontinued due to insufficient clinical response, and 65 (6.9%) due to adverse events (AEs) excl. worsening UC. Serious and severe AEs occurred in 14.8% and 9.9% of pts, respectively. Serious infections were reported in 5 (2.9%) and 23 (3.0%) pts, herpes zoster in 10 (5.7%) and 47 (6.1%) pts, and major adverse cardiovascular events in 1 (0.6%) and 1 (0.1%) pts, in the 5 and 10 mg BID groups, respectively. Malignancies excl. nonmelanoma skin cancer (NMSC) were reported in 1 (0.6%) and 12 (1.6%) pts, and NMSC in 4 (2.3%) and 9 (1.2%) pts, in the 5 and 10 mg BID groups, respectively (no clustering of malignancy type). No new safety risks were identified. Available efficacy data up to Month 24 are shown (Table). Conclusion: In pts with moderate to severe UC in the OLE study, no new safety risks emerged compared with those observed with tofacitinib in rheumatoid arthritis. Efficacy data from the OLE study continue to support long-term efficacy with tofacitinib 5 or 10 mg BID up to 24 months beyond Wk 52 of OCTAVE Sustain.571 Figure 1 No Caption available.