Tofacitinib, an oral Janus Kinase inhibitor, in the treatment of ulcerative colitis: open-label, long-term extension study

Introduction: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). The efficacy and safety of tofacitinib was demonstrated as induction and maintenance therapy in three Phase 3, randomised, placebo‐controlled studies (OCTAVE Induction 1, NCT01465763; OCTAVE Induction 2, NCT01458951; OCTAVE Sustain, NCT01458574) in patients (pts) with moderate to severe UC.1, 2 Aims & Methods: We present interim safety and efficacy data up to 3 years of treatment (as of 08 July 2016) from an ongoing Phase 3, multicentre, open‐label, long‐term extension study (OLE, NCT01470612) in pts who had completed or demonstrated treatment failure in OCTAVE Sustain, or who were non‐responders after completing OCTAVE Induction 1 or 2. Eligibility for this study was determined based on Week (Wk) 8 data from OCTAVE Induction 1 & 2, or Wk 52 data (for completers) or early termination data from OCTAVE Sustain. Pts who were in remission at Wk 52 of OCTAVE Sustain were assigned to tofacitinib 5mg twice daily (BID); all others were assigned 10 mg BID. At Month 2, all pts underwent endoscopy, and non‐responders from induction were mandated to withdraw if they did not show evidence of clinical response. Remission was defined by a Mayo score ≤2 with no individual subscore >1, and rectal bleeding subscore of 0. Binary efficacy endpoints were derived from Mayo score based on local‐read endoscopic subscore. Results: A total of 914 pts (5 mg BID, N=156 [17.1%]; 10mg BID, N=758 [82.9%]) received at least one dose of study drug, of whom 381 (41.7%) discontinued (reasons included adverse events [AEs]: 23 [2.5%] and insufficient clinical response: 283 [31.0%]). The most frequent AE leading to discontinuation was worsening of UC. Serious and severe AEs occurred in 10.4% and 7.8% of pts, respectively (5 and 10 mg BID groups combined). The two most frequent treatment‐ emergent AE (TEAE) system organ classes in both dose groups were 'infections and infestations' and 'gastrointestinal disorders'. The two most frequent TEAEs by preferred term were nasopharyngitis and worsening of UC. Serious infections AEs were reported in four (2.6%) and 14 (1.8%) pts in the 5 and 10mg BID groups, respectively. Malignancies excluding non‐melanoma skin cancer were reported in nine (1.2%) pts in the 10 mg BID group (with no clustering of malignancy type); none were reported in the 5mg BID group. No new safety risks were identified. The available data 'as observed' for remission and mucosal healing at Months 2, 12 and 24 are shown in the Table. Remission was defined as a Mayo score ≤2 with no individual subscore >1, and rectal bleeding subscore of 0; Mucosal healing was defined by a Mayo endoscopic subscore ≤1; AE, adverse event; FAS, full analysis set; GI, gastrointestinal; n, number of patients with the specified response within the given category; N, number of randomised patients in the total population; N1, number of patients in the specified category with non‐missing values; SAEs, serious adverse events; SOC, system organ class; TEAEs, treatment‐emergent adverse events; UC, ulcerative colitis. Conclusion: In pts with moderate to severe UC who remained in the OLE study, no new safety concerns emerged compared with those observed with tofacitinib in rheumatoid arthritis. The efficacy results from this OLE study support sustained efficacy with both tofacitinib 5 and 10 mg BID.