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DOP85 Corticosteroid-free efficacy and safety outcomes in patients receiving tofacitinib in the OCTAVE Sustain maintenance study

Vavricka, S.R.(1);Greuter, T.(2);Cohen, B.L.(3);Reinisch, W.(4);Steinwurz, F.(5);Fellmann, M.(6);Guo, X.(7);Lawendy, N.(7);Paulissen, J.(8);Peyrin-Biroulet, L.(9)

(1)Department of Gastroenterology and Hepatology- University Hospital Zurich, and Center for Gastroenterology and Hepatology, Zürich, Switzerland;(2)Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland;(3)Department of Gastroenterology- Hepatology- and Nutrition, Digestive Disease and Surgery Institute- Cleveland Clinic, Cleveland- Ohio, United States;(4)-, Medical University of Vienna, Vienna, Austria;(5)Unit of Inflammatory Bowel Disease, Hospital Israelita Albert Einstein, São Paulo, Brazil;(6)Pfizer Switzerland AG, Zürich, Switzerland;(7)Pfizer Inc, Collegeville, Pennsylvania, United States;(8)Pfizer Inc, New York, New York, United States;(9)Department of Gastroenterology, Inserm U1256 NGERE- Nancy University Hospital- Université de Lorraine, Vandœuvre-lès-Nancy, France

Background

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. Here, we report corticosteroid-free efficacy and safety among patients (pts) who received oral corticosteroids at baseline of the maintenance study (OCTAVE Sustain).

Methods

Pts with clinical response following OCTAVE Induction 1&2 who were re-randomised to receive placebo or tofacitinib 5 or 10 mg twice daily (BID) in OCTAVE Sustain, and who were receiving oral corticosteroids at baseline of OCTAVE Sustain, were included. Corticosteroid tapering was mandatory at the beginning of OCTAVE Sustain. Steroid-free (not requiring any treatment with corticosteroids for ≥4 weeks prior to the visit) rates of remission, endoscopic improvement and clinical response were assessed at Week 24 and/or Week 52. The association between baseline characteristics and steroid-free efficacy outcomes was evaluated using logistic regression. Safety outcomes were stratified by tofacitinib dose and steroid-free remission status.

Results

Of 593 pts entering OCTAVE Sustain, 289 had oral corticosteroid use at baseline. Of these, 101 (34.9%) received placebo and 188 received tofacitinib (101 [34.9%] 5 mg BID; 87 [30.1%] 10 mg BID) in OCTAVE Sustain. Among pts receiving oral corticosteroids on Day 1 of OCTAVE Sustain, the mean dose (mg/day [standard deviation], prednisone equivalent) received was 15.8 (6.2), 14.9 (6.2) and 14.4 (6.0) in the placebo, tofacitinib 5 mg BID and tofacitinib 10 mg BID groups, respectively. At Week 24 or Week 52 of OCTAVE Sustain, there was a significant treatment effect for tofacitinib 5 or 10 mg BID vs placebo for steroid-free efficacy endpoints (Table 1). Prior immunosuppressant failure was associated with lower odds of achieving steroid-free remission at Week 52 of OCTAVE Sustain (odds ratio [OR] 0.47 [95% confidence interval (CI) 0.23, 0.95]), while prior tumour necrosis factor inhibitor (TNFi) failure status only had a limited effect, which was not statistically significant (OR 0.53 [95% CI 0.27, 1.02]). Oral corticosteroid dose received at baseline of OCTAVE Sustain did not affect the likelihood of achieving steroid-free remission at Week 52. Adverse events of special interest were infrequent (Table 2). Discontinuations were numerically higher among pts without steroid-free remission (Table 2).

Conclusion

For pts with baseline oral corticosteroid use in OCTAVE Sustain, the odds of achieving steroid-free efficacy endpoints were significantly higher for tofacitinib 5 or 10 mg BID compared with placebo. Prior TNFi failure was not associated with lower odds of achieving steroid-free remission at Week 52. There were no apparent differences in safety by steroid-free remission status. Data interpretation is limited by small pt numbers.

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