Network Meta-analysis to Evaluate the Comparative Efficacy of Advanced Therapies as First-Line Treatment for Maintenance Treatment of Adult Patients With Moderate to Severe Crohn's Disease
Background:
Subcutaneous (SC) CT-P13 provides patients and physicians with a new opportunity for maintenance treatment of Crohn’s disease (CD). Given the rapidly expanding therapeutic armamentarium for CD and lack of direct comparative evidence, an updated network meta-analysis (NMA) of data from Phase 3 randomized controlled trials (RCTs) was performed to evaluate the comparative efficacy of advanced CD therapies licensed in Europe or the US.
Methods:
Eligible studies, identified by systematic literature review (PROSPERO no: CRD42023413752), evaluated the efficacy of maintenance therapy using intravenous (IV) or SC infliximab, SC adalimumab, IV or SC vedolizumab, SC ustekinumab, SC risankizumab or oral upadacitinib, in patients with moderate to severe CD who responded to induction therapy. Head-to-head studies (including with treat-through designs) comparing licensed advanced therapies were also eligible. Studies were placebo- (PBO) or active-controlled and included 52–64 weeks of follow-up. Only patients who were naïve to biologic or Janus kinase inhibitor treatment were included in the analysis. Clinical remission and endoscopic response rates achieved with maintenance treatment were synthesized and analyzed in a frequentist NMA random-effects model. Rank probabilities for each comparator arm were summarized with <italic>P-</italic>scores while indirect comparison of all tested regimens was summarized in a league table.
Results:
There were 9 eligible RCTs (ACCENT I, LIBERTY-CD, CHARM, SEAVUE, GEMINI 2, VISIBLE 2, IM-UNITI, FORTIFY, U-ENDURE). Among 14 compared treatment arms, SC infliximab 120 mg every 2 weeks (Q2W) showed the highest risk difference (RD) versus PBO for achieving clinical remission during the maintenance phase (0.38 [95% confidence interval (CI): 0.23, 0.53]), followed by SC adalimumab 40 mg QW (0.32 [0.17, 0.48]) and oral upadacitinib 30 mg once daily (0.30 [0.08, 0.53]). Rank probability evaluated with <italic>P-</italic>scores showed that SC infliximab 120 mg Q2W ranked first (<italic>P-</italic>score 0.9095), followed by SC adalimumab 40 mg QW (0.8133) and oral upadacitinib 30 mg QD (0.7454). Based on indirect comparison, SC infliximab 120 mg Q2W and SC adalimumab 40 mg QW both showed significantly higher RD (P< 0.05) than SC vedolizumab 108 mg Q2W; SC infliximab 120 mg Q2W also was better than IV infliximab 5 mg/kg Q8W, SC ustekinumab 90 mg Q12W, and SC risankizumab 360 mg Q8W. Endoscopic response data were available from LIBERTY-CD, FORTIFY and U-ENDURE: among 5 treatment arms, SC infliximab 120 mg Q2W showed the highest RD (95% CI) versus PBO for achieving endoscopic response (0.39 [0.29, 0.49]), followed by SC risankizumab 180 mg Q8W (0.37 [0.17, 0.56]) and SC risankizumab 360 mg Q8W (0.27 [0.06, 0.48]). In rank probability analyses, SC infliximab 120 mg Q2W ranked first (<italic>P-</italic>score 0.8423), followed by SC risankizumab 180 mg Q8W (0.778) and SC risankizumab 360 mg Q8W (0.5008). Based on indirect comparison, all tested regimens were better than PBO but no advanced therapy demonstrated significantly higher RD over others.
Conclusions:
In this updated NMA, SC infliximab 120 mg Q2W demonstrated a favorable profile in achieving clinical remission and endoscopic response when administered as a first-line advanced therapy for maintenance treatment of patients with moderate to severe CD.
