THE EFFECT OF TOFACITINIB ON EXTRAINTESTINAL MANIFESTATIONS AT BASELINE IN PATIENTS WITH MODERATE TO SEVERE ULCERATIVE COLITIS IN THE OCTAVE PROGRAM

Background: Extraintestinal manifestations (EIMs) occur in approximately one-third of patients (pts) with ulcerative colitis (UC).1 Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC. The effect of tofacitinib on EIMs is currently unknown. We explore whether tofacitinib treatment impacts EIMs in pts with moderate to severe UC enrolled in the Phase 3 OCTAVE clinical program. Methods: We report data from 3 double-blind, placebo-controlled, Phase 3 studies in pts with moderate to severe UC.: two 8-week (wk) induction studies (tofacitinib 10 mg twice daily [BID] or placebo; OCTAVE Induction 1&2, NCT01465763 and NCT01458951) and a 52-wk maintenance study (tofacitinib 5 or 10 mg BID or placebo; OCTAVE Sustain, NCT01458574). The frequency and proportion of predefined quiescent prior and active EIMs at baseline, and the change from baseline in EIMs at the end of the treatment period (Wk8 or Wk52), or at early termination, were evaluated. The predefined EIMs included arthritis but did not separate arthralgia. Results: Overall, 1,139 and 592 pts were randomized into OCTAVE Induction 1&2 and OCTAVE Sustain, of which 27.0% and 9.0% had a history of quiescent prior or active EIMs, respectively. At Wk8 of OCTAVE Induction 1&2, 4.6% of tofacitinib-treated pts and 5.3% of placebo-treated pts experienced a change (improvement, worsening, or new occurrence) from baseline in EIMs. At Wk52 of OCTAVE Sustain, 4.6%, 3.1%, and 7.3% of pts in the tofacitinib 5 mg BID, tofacitinib 10 mg BID, and placebo groups experienced a change from baseline in EIMs, respectively. In OCTAVE Induction 1&2, the most frequent active EIMs at baseline were peripheral arthritis, sacroiliitis, and oral ulcer/stomatitis (Table). Similar proportions of pts in each treatment group with active baseline peripheral arthritis experienced no change or an improvement from baseline at Wk8 (Table). Three tofacitinib-treated pts experienced worsening symptoms compared with no placebo-treated pts. At OCTAVE Sustain baseline, 21 pts had active peripheral arthritis; the majority of these pts experienced no change in their peripheral arthritis at Wk52. Improved symptoms occurred in 2 tofacitinib-treated and no placebo-treated pts; worsened symptoms occurred in 2 placebo-treated and no tofacitinib-treated pts. Conclusion: In OCTAVE Induction 1&2 and OCTAVE Sustain, 27.0% and 9.0% of pts experienced EIMs at baseline, respectively. The most common active EIM was peripheral arthritis, for which the majority of pts in OCTAVE Induction 1&2 and OCTAVE Sustain reported either no change or improvement from baseline. These post hoc analyses should be interpreted with caution; they are limited by low pt numbers and a predefined EIM list. Additional studies are required. Reference: 1. Ungaro R et al. Lancet 2017;389:1756-70