The impact of body mass index on efficacy and safety in the tofacitinib OCTAVE ulcerative colitis clinical programme

Abstract

Background: Obesity may affect efficacy and safety of biologic treatments for ulcerative colitis (UC). Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of UC.

Aims: To assess efficacy and safety of tofacitinib in patients with UC, by baseline body mass index (BMI).

Methods: This post hoc analysis evaluated patients with UC receiving placebo or tofacitinib from the 8-week OCTAVE Induction 1 and 2 (NCT01465763, NCT01458951) and 52-week OCTAVE Sustain (NCT01458574) studies. Patients were stratified by BMI at OCTAVE Induction 1 and 2 baseline (<25, 25 to <30 and ≥30 kg/m2 ). Outcomes included remission, endoscopic improvement, clinical response, sustained steroid-free remission, Inflammatory Bowel Disease Questionnaire total score and Short Form-36 Health Survey scores. Adverse events were evaluated.

Results: At Week 8 of OCTAVE Induction 1 and 2, and Week 52 of OCTAVE Sustain, higher proportions of patients receiving tofacitinib 5 or 10 mg twice daily (b.d.) achieved clinical response vs placebo, regardless of baseline BMI subgroup (all P < 0.05). Proportions of patients achieving efficacy endpoints were generally similar across BMI subgroups; in univariate and multivariate regression analyses, BMI was not a significant predictor (all P ≥ 0.05; univariate BMI [continuous] odds ratio for remission: 0.98 [95% confidence interval 0.95, 1.02]). There was no consistent trend between BMI and adverse events. Among patients receiving tofacitinib 10 mg b.d. in OCTAVE Induction 1 and 2, serious infections were numerically greater in the BMI ≥30 subgroup (3.2%) vs other subgroups (0.4%). Limitations included small patient numbers in the BMI ≥30 subgroup.

Conclusions: Efficacy and safety of tofacitinib were similar in patients with UC regardless of baseline BMI.

© 2021 Pfizer Inc. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

Figures

FIGURE 1

Proportion of patients in remission at (A) Week 8 of OCTAVE Induction 1 and 2 and (B) Week 52 of OCTAVE Sustain, by baseline BMI subgroup (FAS, NRI). *P < 0.05; ***P < 0.0001. All comparisons are with placebo; chi‐squared test. Patients were stratified by BMI at baseline of OCTAVE Induction 1 and 2. All BMI are reported as kg/m2. Remission was defined as a total Mayo score of ≤2 with no individual subscore > 1, and a rectal bleeding subscore of 0. Abbreviations: Δ, treatment difference; b.d., twice daily; BMI, body mass index; FAS, full analysis set; N, total number of patients in each treatment group; n, number of patients with the specified response; NRI, non‐responder imputation

FIGURE 2

Proportion of patients with endoscopic improvement at A) Week 8 of OCTAVE Induction 1 and 2 and B) Week 52 of OCTAVE Sustain, by BMI subgroup (FAS, NRI). *P < 0.05; **P < 0.001; ***P < 0.0001. All comparisons are with placebo; chi‐squared test. Patients were stratified by BMI at baseline of OCTAVE Induction 1 and 2. All BMI are reported as kg/m2. Endoscopic improvement was defined as a Mayo endoscopic subscore of 0 or 1. Abbreviations: Δ, treatment difference; b.d., twice daily; BMI, body mass index; FAS, full analysis set; N, total number of patients in each treatment group; n, number of patients with the specified response; NRI, non‐responder imputation

FIGURE 3

Proportion of patients with clinical response at A) Week 8 of OCTAVE Induction 1 and 2 and B) Week 52 of OCTAVE Sustain, by BMI subgroup (FAS, NRI). *P < 0.05; **P < 0.001; ***P < 0.0001. All comparisons are with placebo; chi‐squared test. Patients were stratified by BMI at baseline of OCTAVE Induction 1 and 2. All BMI are reported as kg/m2. 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. Abbreviations: Δ, treatment difference; b.d., twice daily; BMI, body mass index; FAS, full analysis set; N, total number of patients in each treatment group; n, number of patients with the specified response; NRI, non‐responder imputation

FIGURE 4

Proportion of patients with sustained steroid‐free remission in OCTAVE Sustain, by BMI subgroup (FAS, NRI). *P < 0.05; **P < 0.001. All comparisons are with placebo; chi‐squared test. Patients were stratified by BMI at baseline of OCTAVE Induction 1 and 2. All BMI are reported as kg/m2. Sustained steroid‐free remission was defined as being in remission and steroid‐free at both Week 24 and Week 52; N was reduced for this outcome compared with other outcomes, as shown. Abbreviations: Δ, treatment difference; b.d., twice daily; BMI, body mass index; FAS, full analysis set; N, total number of patients in each treatment group; n, number of patients with the specified response; NRI, non‐responder imputation