Efficacy of biological therapies and small molecules in induction and maintenance of remission in luminal Crohn’s disease: systematic review and network meta-analysis

Abstract

ObjectiveThere are numerous biological therapies and small molecules licensed for luminal Crohn’s disease (CD), but these are often studied in placebo-controlled trials, meaning relative efficacy is uncertain. We examined this in a network meta-analysis.DesignWe searched the literature to 1 July 2022, judging efficacy according to induction of clinical remission, clinical response and maintenance of clinical remission, and according to previous exposure or non-exposure to biologics. We used a random effects model and reported data as pooled relative risks (RRs) with 95% CIs, ranking drugs according to p-score.ResultsWe identified 25 induction of remission trials (8720 patients). Based on failure to achieve clinical remission, infliximab 5 mg/kg ranked first versus placebo (RR=0.67, 95% CI 0.56 to 0.79, p-score 0.95), with risankizumab 600 mg second and upadacitinib 45 mg once daily third. However, risankizumab 600 mg ranked first for clinical remission in biologic-naïve (RR=0.66, 95% CI 0.52 to 0.85, p-score 0.78) and in biologic-exposed patients (RR=0.74, 95% CI 0.67 to 0.82, p-score 0.92). In 15 maintenance of remission trials (4016 patients), based on relapse of disease activity, upadacitinib 30 mg once daily ranked first (RR=0.61, 95% CI 0.52 to 0.72, p-score 0.93) with adalimumab 40 mg weekly second, and infliximab 10 mg/kg 8-weekly third. Adalimumab 40 mg weekly ranked first in biologic-naïve patients (RR=0.59, 95% CI 0.48 to 0.73, p-score 0.86), and vedolizumab 108 mg 2-weekly first in biologic-exposed (RR=0.70, 95% CI 0.57 to 0.86, p-score 0.82).ConclusionIn a network meta-analysis, infliximab 5 mg/kg ranked first for induction of clinical remission in all patients with luminal CD, but risankizumab 600 mg was first in biologic-naïve and biologic-exposed patients. Upadacitinib 30 mg once daily ranked first for maintenance of remission.

Improving IBD outcomes in the era of many treatment options

“…One such network meta-analysis published in 2022 indicated the superiority of upadacitinib over all other biologic therapies for ulcerative colitis, both in patients who had and in patients who had not previously received biologic therapy 9 . In another similar analysis, infliximab and risankizumab were ranked most highly for the treatment of Crohn’s disease 10 .…”

Is there an optimal sequence of biologic therapies for inflammatory bowel disease?

“… 23 One analysis in CD ranked infliximab or adalimumab first and adalimumab or risankizumab second, 24 while another ranked infliximab first overall, but ranked risankizumab first when dividing patients into biologic-naïve and biologic-exposed cohorts. 25 Putting these data together suggests that patients with UC who are naïve to anti-TNF therapy could start with infliximab, vedolizumab, or upadacitinib, and then switch to ustekinumab or tofacitinib after treatment failure, while TNF-naïve patients with CD could start with infliximab or adalimumab, and then switch to risankizumab as second-line therapy.…”

Whole blood DNA methylation changes are associated with anti-TNF drug concentration in patients with Crohn’s disease

“…Anti-TNF therapies remain the most effective treatment to induce and maintain remission in patients with Crohn’s disease 1, 2 . Successful treatment leads to mucosal healing, reduced surgeries, and improvements in quality of life 3 .…”