Systematic Review and Network Meta-Analysis: Comparative Efficacy and Safety of Biosimilars, Biologics and JAK1 Inhibitors for Active Crohn Disease

Abstract

Background: Crohn disease (CD) is a chronic inflammatory disease that affects quality of life. There are several drugs available for the treatment of CD, but their relative efficacy is unknown due to a lack of high-quality head-to-head randomized controlled trials.Aim: To perform a mixed comparison of the efficacy and safety of biosimilars, biologics and JAK1 inhibitors for CD.Methods: We searched PubMed, Web of Science, embase and the Cochrane Library for randomized controlled trials (RCTs) up to Dec. 28, 2020. Only RCTs that compared the efficacy or safety of biosimilars, biologics and JAK1 inhibitors with placebo or another active agent for CD were included in the comparative analysis. Efficacy outcomes were the induction of remission, maintenance of remission and steroid-free remission, and safety outcomes were serious adverse events (AEs) and infections. The Bayesian method was utilized to compare the treatments. The registration number is CRD42020187807.Results: Twenty-eight studies and 29 RCTs were identified in our systematic review. The network meta-analysis demonstrated that infliximab and adalimumab were superior to certolizumab pegol (OR 2.44, 95% CI 1.35–4.97; OR 2.96, 95% CI 1.57–5.40, respectively) and tofacitinib (OR 2.55, 95% CI 1.27–5.97; OR 3.10, 95% CI 1.47–6.52, respectively) and revealed the superiority of CT-P13 compared with placebo (OR 2.90, 95% CI 1.31–7.59) for the induction of remission. Infliximab (OR 7.49, 95% CI 1.85–34.77), adalimumab (OR 10.76, 95% CI 2.61–52.35), certolizumab pegol (OR 4.41, 95% CI 1.10–21.08), vedolizumab (OR 4.99, 95% CI 1.19–25.54) and CT-P13 (OR 10.93, 95% CI 2.10–64.37) were superior to filgotinib for the maintenance of remission. Moreover, infliximab (OR 3.80, 95% CI 1.49–10.23), adalimumab (OR 4.86, 95% CI 1.43–16.95), vedolizumab (OR 2.48, 95% CI 1.21–6.52) and CT-P13 (OR 5.15, 95% CI 1.05–27.58) were superior to placebo for steroid-free remission. Among all treatments, adalimumab ranked highest for the induction of remission, and CT-P13 ranked highest for the maintenance of remission and steroid-free remission.Conclusion: CT-P13 was more efficacious than numerous biological agents and JAK1 inhibitors and should be recommended for the treatment of CD. Further head-to-head RCTs are warranted to compare these drugs.

Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials

“…Overall, our findings were supported by these studies. For example, one study in CD included patients treated with unlicensed dosages of upadacitinib (i.e., 3, 6, 12, or 24 mg two times a day and 24 mg QD), and reported that there were no statistically significant differences in the rates of any AE between upadacitinib and TNF blockers (adalimumab, certolizumab pegol, and infliximab), IL-12/23 receptor antagonist (ustekinumab), and integrin receptor antagonist (vedolizumab) [ 56 ]. Similarly, we reviewed one study in PsA [ 57 ] and one study in AD [ 58 ] which did not specify upadacitinib dosage and concluded that upadacitinib has comparable risk of MACE compared to TNF blockers (adalimumab, certolizumab pegol, etanercept, golimumab), IL-17A receptor antagonist (secukinumab), IL-23 receptor antagonist (guselkumab), and phosphodiesterase 4 inhibitor (apremilast).…”

Comparison of Clinical Outcomes in Pediatric Patients with Ileocolonic Crohn Disease Treated with Infliximab Versus Adalimumab

“…Although no head‐to‐head randomized clinical trial of infliximab versus adalimumab was conducted in patients with IBD, multiple studies have shown comparable outcomes in patients with CD, including systematic reviews and network meta‐analysis (27,28). However, a specific study focusing on patients with fistulizing CD showed superiority of infliximab over adalimumab in inducing response and remission (29).…”

The Optimal Management of Fistulizing Crohn’s Disease: Evidence beyond Randomized Clinical Trials

“…In a meta-analysis of 15 observational studies, the risk of serious infection increased with the combination of anti-TNF and an immunosuppressive agent (in six cohorts; RR, 1.19; 95% CI, 1.03–1.37), especially in the case of anti-TNF and corticosteroids (in four cohorts; RR, 1.64; 95% CI, 1.33–2.03) or the use of all three drugs (in two cohorts; RR, 1.35; 95% CI, 1.04–1.77) compared to anti-TNF monotherapy [ 77 ]. A network meta-analysis of patients with active CD also showed no significant difference regarding the rate of adverse events and infections or serious/severe infections among biological/small molecule therapies (IFX, ADA, VDZ, UST, tofacitinib and CT-P13) [ 78 ].…”