Clinical trial: benefits and risks of immunomodulators and maintenance infliximab for IBD‐subgroup analyses across four randomized trials

Abstract

Summary Background Benefits and risks of concomitant immunomodulators and maintenance infliximab in inflammatory bowel disease (IBD) patients have not been adequately evaluated. Aim To assess the effect of concomitant immunomodulator and infliximab maintenance therapy using data from four prospective, randomized Phase 3 trials in IBD patients. Methods Overall, 1383 patients from ACCENT I and ACCENT II [luminal and fistulizing Crohn’s disease trials] and ACT 1 and ACT 2 [ulcerative colitis trials] were analysed. Patients were treated with placebo or infliximab 5 or 10 mg/kg at weeks 0, 2 and 6 followed by every‐8‐week maintenance therapy. Clinical response, clinical remission, fistula response, complete fistula response, infection and infusion reaction rates; serum infliximab concentrations and immunogenicity were summarized by baseline concomitant immunomodulator subgroup (use or non‐use). Results Overall, almost 40% of evaluated IBD patients received concomitant immunomodulators. Efficacy, infection, and serious infection rates were generally similar in patients who received maintenance therapy with or without concomitant immunomodulators. There were no consistent differences in serum infliximab concentrations with or without immunomodulators in patients who received scheduled maintenance therapy. Concomitant immunomodulators reduced infusion reactions and immunogenicity. Conclusion Concomitant immunomodulators did not improve efficacy or pharmacokinetics in IBD patients who received maintenance infliximab.

Efficacy and Safety of Adalimumab Versus Infliximab in Patients Suffered From Moderate to Severe Active Ulcerative Colitis

“…Future studies are needed to determine the exact ways concomitant immunosuppressive therapy might affect anti-TNF antibodies, serum levels, and sustained responses. Nevertheless, ACT and ACCENT trials have shown immunomodulator use to be related to less immunogenicity, fewer infusion reactions, but not to improved efficacy, as compared with anti-TNF therapy alone [38].…”

Frequency, predictors, and consequences of maintenance infliximab therapy intensification in ulcerative colitis

“…Ten of the 36 patients with shortened intervals were de-intensified after 12 months (IQR, [4][5][6][7][8][9][10][11][12][13][14][15][16], and 3 of these were again re-intensified. Two of the seven patients with increased doses were de-intensified after 2 and 4 months, respectively.…”

“…On the other hand, combined therapy has a number of benefits over monotherapy. IMMs, when associated with IFX, reduce infusion-related reactions and immunogenicity (15), increase sustained clinical response rates (14), and reduce steroid needs versus IFX monotherapy (16). Anti-infliximab antibodies develop within the initial 12 months of treatment with IFX (17), and the association of IMMs during this period may preclude their emergence.…”

Infliximab: A Review of Its Use in the Treatment of Inflammatory Bowel Disease

“…The SONIC trial also found that the early use of an infliximab-based strategy improved mucosal healing at week 26 (44% combination therapy and 30% Infliximab monotherapy versus 16% azathioprine monotherapy; P , 0.001 and P = 0.02, respectively). 25 Nevertheless, conflicting data about efficacy of Infliximab mono-versus combination-therapy 26,27 and the cumulative body of evidence that suggests that combined immunosuppressive therapy may increase toxicity require additional long term safety and efficacy studies.…”