Introduction
Tofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis.
Aims & Methods
This post hoc analysis aimed to 1) identify baseline factors associated with symptomatic remission at Week 8 in patients who received tofacitinib 10 mg twice daily (BID) in OCTAVE Induction 1&2 (NCT01465763; NCT01458951),1 and 2) compare the efficacy of tofacitinib 5 and 10 mg BID after 52 weeks of maintenance treatment in OCTAVE Sustain (NCT01458574)1 in patients who achieved symptomatic remission at maintenance baseline (ie after 8 weeks of induction therapy) vs those who did not. Logistic regression analysis was performed for symptomatic remission as the dependent variable, with each induction baseline predictor as an independent covariate. The proportions of patients in remission, corticosteroid-free remission (CSFR) and sustained CSFR at Week 52 were summarised in those who were symptomatic remitters vs non‑remitters at maintenance baseline.
Results
Prior tumour necrosis factor inhibitor exposure or failure was associated with lower odds of achieving symptomatic remission at Week 8 of induction studies (odds ratio [OR] 0.44, 95% confidence interval [CI] 0.25, 0.77; OR 0.42, 95% CI 0.23, 0.75; respectively). Baseline total Mayo score (<9 vs ≥9) and lower stool frequency (2 vs 3) and endoscopic subscore (2 vs 3) were associated with higher odds of achieving symptomatic remission at Week 8 of induction studies (OR 2.82, 95% CI 1.63, 4.88; OR 3.04, 95% CI 1.63, 5.65; OR 2.86, 95% CI 1.65, 4.97; respectively). A numerically higher proportion of maintenance baseline symptomatic remitters vs non‑remitters achieved remission at Week 52 (47.1% vs 34.2%; all tofacitinib doses). No differences were seen between maintenance baseline symptomatic remitters and non-remitters at Week 52 (all tofacitinib doses) in terms of achievement of CSFR (26.9 vs 26.3%, respectively) and sustained CSFR (41.2% vs 41.0%, respectively; Table).
Table. Proportion of responders in remission endpoints at Week 52 of OCTAVE Sustain, by maintenance treatment group and symptomatic remission status at Week 8 of OCTAVE Induction 1&2a,b
|
|---|
Outcome at Week 52 of OCTAVE Sustain
| Maintenance treatment |
Tofacitinib 5 mg BID
| Tofacitinib 10 mg BID
| All tofacitinib doses |
Remission, n/N (%)
Symptomatic remission status at Week 8 of OCTAVE Induction 1&2:
Yesb
No
|
14/36 (38.9)
41/134 (30.6)
|
18/32 (56.3)
51/135 (37.8)
|
32/68 (47.1)
92/269 (34.2)
|
CSFR, n/N (%)c
Symptomatic remission status at Week 8 of OCTAVE Induction 1&2:
Yesb
No
|
4/16 (25.0)
19/72 (26.4)
|
3/10 (30.0)
16/61 (26.2)
|
7/26 (26.9)
35/133 (26.3)
|
Sustained CSFR, n/N (%)d
Symptomatic remission status at Week 8 of OCTAVE Induction 1&2:
Yesb
No
|
11/36 (30.6)
9/21 (42.9)
|
17/32 (53.1)
7/18 (38.9)
|
28/68 (41.2)
16/39 (41.0)
|
aOnly patients receiving tofacitinib 10 mg BID who achieved a clinical response (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) in OCTAVE Induction 1&2, and were re-randomised to receive tofacitinib 5 or 10 mg BID in OCTAVE Sustain, were included in this analysis
bSymptomatic remission was defined as a total Mayo score of ≤2 with no individual subscore >1, and both rectal bleeding and stool frequency subscores of 0 at the end of OCTAVE Induction 1&2
cIncludes patients who were receiving corticosteroids at OCTAVE Sustain baseline. CSFR at Week 52 was defined as a total Mayo score of ≤2 with no individual subscore >1, and a rectal bleeding subscore of 0 (based on centrally read endoscopic subscores), in addition to not requiring any treatment with corticosteroids for at least 4 weeks prior to the Week 52 visit
dIncludes patients who were in remission at OCTAVE Sustain study baseline. Sustained CSFR was defined as CSFR (based on centrally read endoscopic subscores) at both Week 24 and Week 52 of OCTAVE Sustain
BID, twice daily; CSFR, corticosteroid-free remission; N, number of patients in each treatment subgroup; n, number of patients with specified endpoint
|
Conclusion
A numerically higher proportion of patients who were symptomatic remitters vs non‑remitters after 8 weeks of induction therapy with tofacitinib achieved remission at Week 52 of OCTAVE Sustain, but those who did not achieve symptomatic remission after 8 weeks of induction treatment could still achieve efficacy endpoints with both tofacitinib maintenance doses at Week 52.
References
1. Sandborn WJ et al. N Engl J Med 2017;376:1723–36.
Disclosure
Pierre Desreumaux has received consulting fees from, or been an advisory board member for, Abbott, AbbVie, Amgen, Biocodex, Biofortis, Biogen, BioKuris, Ferring, Fresenius, Intralytix, Janssen, KitoZyme, Lesaffre, MSD, Nestlé, Nogra, Norgine, Pfizer Inc, Roquette, Sandoz, Shire, Takeda, Tillotts and UCB. Filiz Akyüz has received speaker fees from Celltrion, Ferring and Pfizer Inc. Christina Ha has received grants from the Helmsley Charitable Trust and Pfizer Inc, has acted as a consultant for AbbVie and Pfizer Inc, and has been an advisory board member for AbbVie, Bristol Myers Squibb, Genentech, InDex Pharmaceuticals, Pfizer Inc, Roivant and Takeda. Amira Bouzidi is an employee of, and has received personal fees from, Pfizer Inc. Amel Tamzali is an employee of, and has received personal fees from, Pfizer Inc. Sean Gardiner is an employee and shareholder of Pfizer Inc. Joseph Wu is an employee and shareholder of Pfizer Inc. Jerome Paulissen is an employee of Syneos Health which was a paid contractor to Pfizer Inc in connection with the development of this abstract. Lucine Vuitton has received fees from AbbVie, Amgen, Biogen, Celltrion, Eli Lilly, Ferring, Galapagos, Janssen, MSD, Pfizer Inc, Takeda and Viatris. Miguel Regueiro has received grants from AbbVie, Bristol Myers Squibb, Celgene, Genentech, Gilead Sciences, Janssen, Pfizer Inc, Takeda and UCB, has acted as a consultant and/or been an advisory board member for, AbbVie, Alfasigma S.p.A., Allergan, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Genentech, Gilead Sciences, Janssen, Miraca Labs, Pfizer Inc, Prometheus, Salix, Seres, Takeda, Target Pharma Solutions and UCB, has received CME fees from CME Outfitters, Cornerstones, GI Health Foundation, Imedex, MJH Life Sciences and Remedy, and has received royalties from Wolters Kluwer Health as an author/editor of UpToDate.