Dataset Information

Tofacitinib in Patients with Ulcerative Colitis: Inflammatory Bowel Disease Questionnaire Items in Phase 3 Randomized Controlled Induction Studies.

ABSTRACT:

Background

Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). We examined the effect of tofacitinib induction treatment on Inflammatory Bowel Disease Questionnaire (IBDQ) items in adults with moderate to severe UC.

Methods

Data were pooled from the randomized, 8‑week, double-blind, phase 3 OCTAVE Induction 1 and 2 studies. The IBDQ was self-administered by patients at baseline, week 4, and week 8, with higher scores indicating better health-related quality of life (HRQoL). Change from baseline in IBDQ items was analyzed for 10 mg of tofacitinib twice daily (BID) vs placebo using a linear mixed-effects model, with no multiplicity adjustment performed. Effect sizes were calculated. Subgroup analyses by tumor necrosis factor inhibitor (TNFi) experience were performed.

Results

Significant improvements (nominal P < 0.05) were observed in all IBDQ items with 10 mg of tofacitinib BID vs placebo at weeks 4 and 8. For the overall population, the largest treatment differences across all items were reported for "bowel movements been loose" at weeks 4 and 8, and "problem with rectal bleeding" at week 8 (mean treatment differences all 1.1; both in bowel symptoms domain). These items also showed the largest effect sizes. Treatment benefits were generally slightly numerically higher in TNFi-experienced vs TNFi-naïve patients.

Conclusions

Tofacitinib induction therapy improved all IBDQ items vs placebo in patients with UC, reflecting improvements in HRQoL, with greatest benefits reported in bowel symptoms domain items (Funded by Pfizer Inc; OCTAVE Induction 1 and OCTAVE Induction 2; ClinicalTrials.gov, NCT01465763 and NCT01458951, respectively).

SUBMITTER: Dubinsky MC

PROVIDER: S-EPMC8205629 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTofacitinib is an oral small molecule Janus kinase inhibitor for the treatment of ulcerative colitis.AimTo report efficacy and infection rates in patients receiving tofacitinib induction treatment, by baseline corticosteroid status.MethodsWe evaluated efficacy and safety data from OCTAVE Induction 1&2 in patients with moderately-to-severely active ulcerative colitis who received tofacitinib 10 mg twice daily or placebo for 8 weeks, based on induction baseline oral corticosteroid use (Corticosteroid-Yes/No) and dose (< 20/ ≥ 20 mg/day). Infections of interest included serious infections, herpes zoster (HZ), and adjudicated opportunistic infections (OIs).ResultsAt OCTAVE Induction 1&2 baseline, 478/1092 (43.8%) patients were receiving corticosteroids. Tofacitinib demonstrated significant induction efficacy versus placebo for both Corticosteroid-Yes and Corticosteroid-No. With adjustment for prior tumor necrosis factor inhibitor and immunosuppressant failure, there were no statistically significant differences in remission and clinical response rates for Corticosteroid-Yes versus Corticosteroid-No. Among tofacitinib-treated patients, HZ and OIs occurred more frequently in Corticosteroid-Yes versus Corticosteroid-No, regardless of dose (< 20 mg vs. ≥ 20 mg). Infection incidence rates (regardless of severity/seriousness) during tofacitinib induction were generally similar regardless of baseline corticosteroid use. The proportion of tofacitinib-treated patients with HZ was 0.2% for Corticosteroid-No versus 1.1% for Corticosteroid-Yes < 20 mg and 1.0% for Corticosteroid-Yes ≥ 20 mg. Two out of three patients had HZ OIs.ConclusionsTofacitinib induction efficacy (clinical response and remission) was similar in baseline corticosteroid subgroups. Infections of interest were rare; HZ and OIs occurred more frequently among those receiving tofacitinib and corticosteroids versus those receiving tofacitinib without corticosteroids.Trial registrationhttp://www.Clinicaltrialsgov (NCT01465763[21/10/2011]; NCT01458951[21/10/2011]).