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

Abstract

Background: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we report steroid-free efficacy and safety with tofacitinib among patients with UC who received corticosteroids at baseline of the maintenance study (OCTAVE Sustain).

Methods: This analysis included patients with clinical response following OCTAVE Induction 1 and 2 who were re-randomized to receive placebo, or tofacitinib 5 or 10 mg twice daily (b.d.), in OCTAVE Sustain for 52 weeks and were receiving corticosteroids at OCTAVE Sustain baseline. Corticosteroid tapering was mandatory during OCTAVE Sustain. Rates of steroid-free remission, endoscopic improvement, and clinical response were assessed, stratified by baseline characteristics. Adverse events (AEs) were stratified by treatment and steroid-free remission status.

Results: Overall, 289/593 patients had corticosteroid use at OCTAVE Sustain baseline. At week 52, steroid-free remission, endoscopic improvement, and clinical response rates were 10.9%, 11.9%, and 17.8% among patients receiving placebo, 27.7%, 29.7%, and 40.6% among patients receiving tofacitinib 5 mg b.d., and 27.6%, 29.9%, and 43.7% among patients receiving tofacitinib 10 mg b.d., respectively (non-responder imputation; all p < 0.05 tofacitinib 5 or 10 mg b.d. versus placebo). Discontinuations due to AEs were lower among patients with steroid-free remission versus without. AEs of special interest were infrequent.

Conclusion: For patients with baseline corticosteroid use in OCTAVE Sustain, the odds of achieving steroid-free efficacy endpoints were significantly higher for tofacitinib versus placebo, irrespective of tofacitinib dose. There were no apparent differences in AEs of special interest by steroid-free remission status.ClinicalTrials.gov: NCT01458574.

Keywords: steroid-free; tofacitinib; ulcerative colitis.

Conflict of interest statement

Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: S.R.V. has received consulting fees and unrestricted research grants from Abbott, Falk Pharma GmbH, Ferring Pharmaceuticals, Janssen, MSD, Pfizer Inc, Sanofi-Aventis, Takeda, Tillotts, UCB, and Vifor. T.G. has a consultancy contract with Sanofi-Aventis; has received a travel grant from Falk Pharma GmbH and Vifor; and has an unrestricted research grant from Novartis. B.L.C. has served as an advisory board member for and received consulting fees from AbbVie, Celgene-Bristol-Myers Squibb, Pfizer Inc, Sublimity Therapeutics, and TARGET RWE; fees from the CME companies, Cornerstones, and Vindico; and has received speaker fees from AbbVie. W.R. has received research grants from Abbott, AbbVie, AESCA, Centocor, Dr. Falk Pharma, Immundiagnostik, and MSD; lecture fees from Abbott, AbbVie, AESCA, Aptalis, Celltrion, Centocor, Danone, Dr. Falk Pharma, Elan, Ferring Pharmaceuticals, Immundiagnostik, Mitsubishi Tanabe Pharma, MSD, Otsuka, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda, Therakos, Vifor, and Yakult; and consulting fees from Abbott, AbbVie, AESCA, Amgen, AM Pharma, Astellas, AstraZeneca, Avaxia Biologics, Bioclinica, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Cellerix, Celltrion, Centocor, ChemoCentryx, Covance, Danone, Dr. Falk Pharma, Elan, Ferring Pharmaceuticals, Galapagos, Genentech, Gilead Sciences, Grünenthal, ICON, Index Pharma, Inova, Janssen, Johnson and Johnson, Kyowa Hakko Kirin Pharma, Lipid Therapeutics, MedImmune, Millennium, Mitsubishi Tanabe Pharma, MSD, Nestlé, Novartis, Ocera, Otsuka, PDL, Pfizer Inc, Pharmacosmos, Procter & Gamble, Prometheus Laboratories, Robarts Clinical Trials, Schering-Plough, Second Genome, SetPoint Medical, Takeda, Therakos, TiGenix, UCB, Vifor, Zyngenia, and 4SC. F.S. has served as an advisory board member for Pfizer Inc and has received consulting and speaker fees from AbbVie, Eurofarma, Ferring Pharmaceuticals, Janssen, Sandoz, Takeda, and UCB. M.F., X.G., and N.L. are employees and shareholders of Pfizer Inc. J.P. is an employee of Syneos Health, which was a paid contractor to Pfizer in connection with the development of this manuscript and related statistical analysis. L.P.-B. has received honoraria from AbbVie, Allergan, Alma, Amgen Biogen, Arena, Boehringer Ingelheim, Celgene, Celltrion, Enterome, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Hikma, Index Pharmaceuticals, Janssen, MSD, Nestlé, Pfizer Inc, Pharmacosmos, Roche, Samsung Bioepis, Sandoz, Sterna, Takeda, and Tillotts; grants from AbbVie, MSD, and Takeda; and is a stockholder of CTMA.

© The Author(s), 2022.

Figures

Figure 1.

Proportion of patients with baseline corticosteroid use who achieved steroid-free (a) remission, (b) endoscopic improvement, and (c) clinical response at week 24, week 52, and at both time points (sustained) in OCTAVE Sustain (FAS,a NRI). Steroid-free was defined as not requiring any treatment with corticosteroids for ⩾4 weeks prior to the visit. Remission was defined as a total Mayo score of ⩽2 with no individual subscore >1, and a rectal bleeding subscore of 0. Endoscopic improvement [defined as mucosal healing in the OCTAVE Sustain protocol (NCT01458574)] was defined as a Mayo endoscopic subscore of 0 or 1. Clinical response was defined as a decrease from induction study baseline total Mayo score of ⩾3 points and ⩾30%, plus a decrease in rectal bleeding subscore of ⩾1 point or an absolute rectal bleeding subscore of 0 or 1. p values were based on logistic regression. b.d., twice daily; FAS, full analysis set; N, number of patients in each subgroup of the treatment and used as denominator in percentage calculation; n, number of patients meeting the endpoint criteria; NRI, non-responder imputation; % = n/N1. aOnly patients who received corticosteroids at baseline of OCTAVE Sustain are included in this analysis.

Figure 2.

Proportion of patients with baseline corticosteroid use who achieved steroid-free remission at week 24, week 52, and at both time points (sustained) in OCTAVE Sustain, stratified by (a) prior TNFi failure status, (b) prior immunosuppressant failure status, and (c) CRP at baseline of OCTAVE Sustain (FAS,a NRI). Steroid-free remission was defined as a total Mayo score of ⩽2 with no individual subscore >1, and a rectal bleeding subscore of 0, in addition to not requiring any treatment with corticosteroid for ⩾4 weeks prior to the visit. b.d., twice daily; CRP, C-reactive protein; FAS, full analysis set; N, number of patients in each subgroup of the treatment and used as denominator in percentage calculation; n, number of patients meeting the endpoint criteria; NRI, non-responder imputation; TNFi, tumor necrosis factor inhibitor; % = n/N1. aOnly patients who received corticosteroids at baseline of OCTAVE Sustain are included in this analysis.

Figure 3.

Univariate logistic regression results for assessment of association of baseline factors with (a) steroid-free remission and (b) steroid-free endoscopic improvement at week 52 of OCTAVE Sustain (FAS,a NRI). Steroid-free was defined as not requiring any treatment with corticosteroids for ⩾4 weeks prior to the visit. Remission was defined as a total Mayo score of ⩽2 with no individual subscore >1, and a rectal bleeding subscore of 0. Endoscopic improvement [defined as mucosal healing in the OCTAVE Sustain protocol (NCT01458574)] was defined as a Mayo endoscopic subscore of 0 or 1. Odds ratios and p values were based on logistic regression, with treatment in the model, for each explanatory variable. CI, confidence interval; CRP, C-reactive protein; NRI, non-responder imputation; OR, odds ratio; TNFi, tumor necrosis factor inhibitor. aOnly patients who received corticosteroids at baseline of OCTAVE Sustain are included in this analysis. In addition, patients receiving placebo were excluded. *Overall p value for factor effect.