Infliximab vs Combination Therapy in Ulcerative Colitis
Infliximab vs Combination Therapy in Ulcerative Colitis
Background The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC).
Aims To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use.
Methods We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4–6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed.
Results Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4–6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34–0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47–0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17–2.06], P = 0.41 (P-heterogeneity = 0.01).
Conclusion Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4–6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) affecting the colon and rectum, with increasing incidence and prevalence. The main goal of UC therapy is the induction and maintenance of long-term corticosteroid-free clinical remission. Mucosal healing is also considered one of the main aims of UC treatment since it has been associated with improved patient outcomes.
Aminosalicylates and corticosteroids have shown to be effective for the induction of clinical remission. However, up to 20% of UC patients become steroid dependent at 1 year. Azathioprine (AZA) and mercaptopurine (MP) are immunosuppressants (IS) commonly used for maintenance of long-term steroid-free clinical remission, as recommended by the European Crohn's and Colitis Organisation guidelines.
The introduction of anti-TNFα agents has led to a revolution in the treatment of IBD. Antibodies directed against TNFα include infliximab (IFX) (Remicade®), a monoclonal chimeric antibody, adalimumab (ADA) (Humira®) and golimumab (GLM) (Simponi®), both humanised monoclonal antibodies. These treatments have proven to be effective for achieving and maintaining clinical remission in UC.
In ulcerative colitis, the benefit of the combination of anti-TNFα agents with an IS (combination therapy) remains debated. In Crohn's disease, the SONIC trial, demonstrated the superiority of combined IFX and AZA therapy over IFX therapy alone for IS naïve patients. Likewise, the SUCCESS trial reported a significantly higher 16 weeks' steroid-free clinical remission rate for the combination therapy compared to IFX alone, for moderate-to-severe active ulcerative colitis. The post hoc analysis of the ACT 1 and 2 trials reported that 6 and 12 month remission rates are not affected by combination therapy. However, a recent prospective cohort from Armuzzi et al. showed that combined IFX-AZA therapy was a predictor of steroid-free clinical remission at 6 and 12 months. Whether all patients with UC, regardless of their prior IS status, should benefit from combination therapy remains unknown. We therefore conducted this meta-analysis to determine whether the combination of infliximab and IS is superior to infliximab alone for achieving and maintaining clinical remission in moderate-to-severe active UC.
Abstract and Introduction
Abstract
Background The benefit of the combination of infliximab (IFX) and immunosuppressant (IS) therapy is debated in ulcerative colitis (UC).
Aims To determine whether the combination of IFX and IS therapy is more effective than infliximab alone for active UC regardless of prior IS use.
Methods We identified all controlled trials including patients with moderate-to-severe active UC, treated by either IFX or combined IFX-IS therapy. The main outcome was clinical remission at 4–6 months. Two statistical methods were used, Mantel-Haenszel and Der-Simonian and Laird. Inter-trial heterogeneity was taken into account and publication bias was assessed.
Results Four controlled trials were analysed and included in the meta-analysis. These four trials included 765 patients, 389 treated with IFX alone and 376 treated with IFX and IS. At 4–6 months' therapy, the clinical remission rate was significantly lower for the IFX monotherapy group OR 0.50, 95% CI [0.34–0.73], P < 0.01 (P-heterogeneity = 0.49). The Harbord test did not show evidence of publication bias (P = 0.29). Calculation of an adjusted OR using the Duval and Tweedie method did not significantly modify results [OR 0.63, 95% CI (0.47–0.85)]. According to Orwin's formula, four additional medium-sized nonsignificant studies would be necessary to reduce the effect size to a nonsignificant value. At 12 months of therapy, there was no significant difference between the two groups: OR 0.60, 95% CI [0.17–2.06], P = 0.41 (P-heterogeneity = 0.01).
Conclusion Combination therapy with IFX-IS is more effective than IFX alone for achieving and maintaining clinical remission at 4–6 months for patients with moderate-to-severe ulcerative colitis, regardless of prior IS use.
Introduction
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) affecting the colon and rectum, with increasing incidence and prevalence. The main goal of UC therapy is the induction and maintenance of long-term corticosteroid-free clinical remission. Mucosal healing is also considered one of the main aims of UC treatment since it has been associated with improved patient outcomes.
Aminosalicylates and corticosteroids have shown to be effective for the induction of clinical remission. However, up to 20% of UC patients become steroid dependent at 1 year. Azathioprine (AZA) and mercaptopurine (MP) are immunosuppressants (IS) commonly used for maintenance of long-term steroid-free clinical remission, as recommended by the European Crohn's and Colitis Organisation guidelines.
The introduction of anti-TNFα agents has led to a revolution in the treatment of IBD. Antibodies directed against TNFα include infliximab (IFX) (Remicade®), a monoclonal chimeric antibody, adalimumab (ADA) (Humira®) and golimumab (GLM) (Simponi®), both humanised monoclonal antibodies. These treatments have proven to be effective for achieving and maintaining clinical remission in UC.
In ulcerative colitis, the benefit of the combination of anti-TNFα agents with an IS (combination therapy) remains debated. In Crohn's disease, the SONIC trial, demonstrated the superiority of combined IFX and AZA therapy over IFX therapy alone for IS naïve patients. Likewise, the SUCCESS trial reported a significantly higher 16 weeks' steroid-free clinical remission rate for the combination therapy compared to IFX alone, for moderate-to-severe active ulcerative colitis. The post hoc analysis of the ACT 1 and 2 trials reported that 6 and 12 month remission rates are not affected by combination therapy. However, a recent prospective cohort from Armuzzi et al. showed that combined IFX-AZA therapy was a predictor of steroid-free clinical remission at 6 and 12 months. Whether all patients with UC, regardless of their prior IS status, should benefit from combination therapy remains unknown. We therefore conducted this meta-analysis to determine whether the combination of infliximab and IS is superior to infliximab alone for achieving and maintaining clinical remission in moderate-to-severe active UC.
