Extraintestinal Manifestations at Baseline, and Effect of Tofacitinib in Patients With Moderate to Severe Ulcerative Colitis in the OCTAVE Program

BACKGROUND: Extraintestinal manifestations (EIMs) occur in approximately one-third of patients with ulcerative colitis (UC) (1). Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC. The effect of tofacitinib on EIMs is currently unknown. We explore whether tofacitinib treatment impacts EIMs in patients with moderate to severe UC enrolled in the Phase 3 OCTAVE clinical program.

METHODS: We report data from three double-blind, placebo-controlled, Phase 3 studies in patients with moderate to severe UC: two 8-week induction studies (tofacitinib 10 mg twice daily [BID] or placebo; OCTAVE Induction 1&2, NCT01465763 and NCT01458951) and a 52-week maintenance study (tofacitinib 5 or 10 mg BID or placebo; OCTAVE Sustain, NCT01458574). The frequency and proportion of pre-defined quiescent prior and active EIMs at baseline, and the change from baseline in EIMs at the end of the treatment period (Week 8 or Week 52), or at early termination, were evaluated in patients with non-missing data.

RESULTS: Overall, 1139 and 592 patients were randomized into OCTAVE Induction 1&2 and Sustain, of which 27.0% and 9.0% had a history of quiescent prior or active EIMs, respectively. At Week 8 of OCTAVE Induction 1&2, 4.6% of tofacitinib-treated patients and 5.3% of placebo-treated patients experienced a change (improvement, worsening, or new occurrence) from baseline in EIMs. At Week 52 of OCTAVE Sustain, 4.6%, 3.1%, and 7.3% of patients in the tofacitinib 5 mg BID, tofacitinib 10 mg BID, and placebo groups experienced a change from Sustain baseline in EIMs, respectively. The most frequent active EIMs at Induction baseline were peripheral arthritis (11.2% of patients [127/1135]), sacroiliitis (1.0% of patients [11/1135]), and oral ulcers/stomatitis (0.7% of patients [8/1135]). In OCTAVE Induction 1&2, similar proportions of patients in each treatment group with active baseline peripheral arthritis experienced no change (tofacitinib 10 mg BID, 78/96 [81.3%]; placebo, 24/28 [85.7%]) or an improvement (15/96 [15.6%] and 4/28 [14.3%], respectively) from baseline at Week 8. Three (3.1%) tofacitinib-treated patients experienced worsening of symptoms compared with no placebo-treated patients. At OCTAVE Sustain baseline, 20 patients had active peripheral arthritis. The majority of these patients experienced no change in their peripheral arthritis at Week 52 (tofacitinib 5 mg BID, 5/6 [83.3%]; tofacitinib 10 mg BID, 2/3 [66.7%]; placebo, 9/11 [81.8%]). Two tofacitinib-treated patients experienced an improvement at Week 52 (tofacitinib 5 mg BID, 1/6 [16.7%]; tofacitinib 10 mg BID, 1/3 [33.3%]) and no tofacitinib-treated patients reported a worsening of symptoms. Two placebo-treated patients (2/11 [18.2%]) reported a worsening of symptoms and none reported improvement.

CONCLUSION(S): In OCTAVE Induction 1&2 and OCTAVE Sustain, 27.0% and 9.0% of patients experienced EIMs at baseline, respectively. The most common active EIM was peripheral arthritis, for which the majority of patients in Induction and Sustain reported either no change or improvement from baseline. These post-hoc analyses should be interpreted with caution; they are limited by low patient numbers and collection of data via a predefined EIM list which did not include a specific arthralgia category (ie arthralgia may have been recorded as peripheral arthritis). Additional studies are required.