TY - JOUR
T1 - Efficacy and Safety of Tofacitinib Re-Treatment for Ulcerative Colitis after Treatment Interruption
T2 - Results from the OCTAVE Clinical Trials
AU - Panés, Julian
AU - Vermeire, Séverine
AU - Dubinsky, Marla C.
AU - Loftus, Edward V.
AU - Lawendy, Nervin
AU - Wang, Wenjin
AU - Salese, Leonardo
AU - Su, Chinyu
AU - Modesto, Irene
AU - Guo, Xiang
AU - Colombel, Jean Frederic
N1 - Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation.
PY - 2021/11/1
Y1 - 2021/11/1
N2 - Background and Aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Here, we evaluate the efficacy and safety of tofacitinib re-Treatment following treatment interruption in patients with ulcerative colitis. Methods: Here, patients with clinical response to tofacitinib 10 mg b.d. induction therapy were randomised to receive placebo in OCTAVE Sustain. Those experiencing treatment failure after Week 8 of OCTAVE Sustain entered OCTAVE Open and re-initiated tofacitinib 10 mg b.d. [re-Treatment subpopulation]; efficacy and safety data are presented up to Month 36 of OCTAVE Open. Results: Median time to treatment failure following interruption was 169 (95% confidence interval [CI], 94.0-179.0) and 123 [95% CI, 91.0-168.0] days for induction remitters, and induction responders but non-remitters, respectively. Following re-Treatment with tofacitinib, rates (non-responder imputation after a patient discontinued; latest observation carried forward imputation after a patient advanced to a subsequent study [NRI-LOCF]) of clinical response, remission, and endoscopic improvement were 74.0%, 39.0%, and 55.0% at Month 2, and 48.5%, 37.4%, and 42.4% at Month 36, respectively. Among induction remitters and induction responders but non-remitters, clinical response rates at Month 36 were 60.6% and 42.4% [NRI-LOCF], respectively. Efficacy was recaptured regardless of prior tumour necrosis factor inhibitor failure status. The safety profile of tofacitinib 10 mg b.d. re-Treatment was consistent with the overall cohort and demonstrated no new safety risks associated with exposure of ≤36 months. Conclusions: Median time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-Treatment in a substantial proportion of patients [ClinicalTrials.gov:NCT01458574;NCT01470612].
AB - Background and Aims: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis. Here, we evaluate the efficacy and safety of tofacitinib re-Treatment following treatment interruption in patients with ulcerative colitis. Methods: Here, patients with clinical response to tofacitinib 10 mg b.d. induction therapy were randomised to receive placebo in OCTAVE Sustain. Those experiencing treatment failure after Week 8 of OCTAVE Sustain entered OCTAVE Open and re-initiated tofacitinib 10 mg b.d. [re-Treatment subpopulation]; efficacy and safety data are presented up to Month 36 of OCTAVE Open. Results: Median time to treatment failure following interruption was 169 (95% confidence interval [CI], 94.0-179.0) and 123 [95% CI, 91.0-168.0] days for induction remitters, and induction responders but non-remitters, respectively. Following re-Treatment with tofacitinib, rates (non-responder imputation after a patient discontinued; latest observation carried forward imputation after a patient advanced to a subsequent study [NRI-LOCF]) of clinical response, remission, and endoscopic improvement were 74.0%, 39.0%, and 55.0% at Month 2, and 48.5%, 37.4%, and 42.4% at Month 36, respectively. Among induction remitters and induction responders but non-remitters, clinical response rates at Month 36 were 60.6% and 42.4% [NRI-LOCF], respectively. Efficacy was recaptured regardless of prior tumour necrosis factor inhibitor failure status. The safety profile of tofacitinib 10 mg b.d. re-Treatment was consistent with the overall cohort and demonstrated no new safety risks associated with exposure of ≤36 months. Conclusions: Median time to treatment failure was numerically higher in induction remitters versus induction responders but non-remitters. Following treatment interruption, efficacy was safely and successfully recaptured with tofacitinib 10 mg b.d. re-Treatment in a substantial proportion of patients [ClinicalTrials.gov:NCT01458574;NCT01470612].
KW - Re-Treatment
KW - tofacitinib
KW - ulcerative colitis
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U2 - 10.1093/ecco-jcc/jjab065
DO - 10.1093/ecco-jcc/jjab065
M3 - Article
C2 - 33884415
AN - SCOPUS:85108819797
SN - 1873-9946
VL - 15
SP - 1852
EP - 1863
JO - Journal of Crohn's and Colitis
JF - Journal of Crohn's and Colitis
IS - 11
ER -