798 Predictors of Delayed Response to Tofacitinib: Results of the OCTAVE Open Study for Delayed Responders

Abstract

INTRODUCTION: Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Tofacitinib efficacy and safety were shown in 3 Phase 3 trials in patients (pts) with UC. 1 Pts who received tofacitinib 10 mg twice daily (BID) for 8 weeks in OCTAVE Induction 1/2 (NCT01465763/NCT01458951) and did not achieve clinical response could receive tofacitinib 10 mg BID in a Phase 3, open-label, long-term extension (OLE) study (NCT01470612). 2 OLE data (up to 3 years) for pts achieving clinical response with an additional 8 weeks of tofacitinib (delayed responders) have been reported. 3 METHODS: We evaluated potential predictors of delayed response (clinical response [≥3-point and ≥30% decrease from induction study baseline (BL) total Mayo score, and ≥1-point decrease in rectal bleeding subscore (RBS) or absolute RBS ≤1] after 16 weeks of 10 mg BID [8 weeks induction, 8 weeks in OLE]). Characteristics at OCTAVE Induction 1/2 BL and BL and Month 1 of the OLE study were evaluated in induction responders (clinical response to 8 weeks of 10 mg BID), delayed responders, or complete non-responders (non-response to 16 weeks of 10 mg BID). RESULTS: Characteristics at OCTAVE Induction 1/2 BL were generally similar between subgroups (Table 1). The proportion of pts with prior tumor necrosis factor inhibitor (TNFi) failure was numerically higher in complete non-responders vs delayed responders (Table 1). Induction study BL mean C-reactive protein was numerically higher in complete non-responders vs induction responders and delayed responders with a similar trend at OLE BL (Table 1). At OLE Month 1, stool frequency subscore (SFS) and RBS were numerically lower in delayed responders vs complete non-responders, and partial Mayo score (PMS) reduction from OLE BL was greater for delayed responders vs complete non-responders (Table 1). CONCLUSION: Numerically higher proportions of complete non-responders and delayed responders had prior TNFi failure vs induction responders. In pts with UC, early improvement at Month 1 during extended induction in SFS, RBS, and PMS may indicate likelihood of response to extended induction. The post-hoc data suggest tofacitinib 10 mg BID treatment beyond 8-week induction may be associated with clinical response in initial non-responders. Further evaluation with a larger sample size is needed.