Background & Aims
There is debate over whether patients with Crohn’s disease who start anti–tumor necrosis factor (TNF) therapy after failed immunomodulator therapy should continue to receive concomitant immunomodulators. We conducted a meta-analysis of subgroups from randomized controlled trials (RCTs) of anti-TNF agents to compare the efficacy and safety of concomitant immunomodulator therapy vs anti-TNF monotherapy.

Methods
We performed a systematic review of literature published from 1980 through 2008 and identified 11 RCTs of anti-TNF agents in patients with luminal or fistulizing Crohn’s disease. We excluded RCTs of patients who were naive to anti-TNF and immunomodulator therapy. The primary end points were clinical response at weeks 4–14 and 24–30 and remission at weeks 24–30. Secondary end points included infusion site or injection site reactions and selected adverse events. A priori subgroup analyses were performed to evaluate fistula closure and the efficacy and safety of combination therapy with different anti-TNF agents.

Results
Overall, combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.80–1.31), inducing a response (OR, 1.08; 95% CI, 0.79–1.48), maintaining a response (OR, 1.53; 95% CI, 0.67–3.49), or inducing partial (OR, 1.25; 95% CI, 0.84–1.88) or complete fistula closure (OR, 1.10; 95% CI, 0.68–1.78). In subgroup analyses of individual anti-TNF agents, combination therapy was not more effective than monotherapy in inducing 6-month remission in those treated with infliximab (OR, 1.73; 95% CI, 0.97–3.07), adalimumab (OR, 0.88; 95% CI, 0.58–1.35), or certolizumab (OR, 0.93; 95% CI, 0.65–1.34). Overall, combination therapy was not associated with an increase in adverse events, but inclusion of infliximab was associated with fewer injection site reactions (OR, 0.46; 95% CI, 0.26–0.79.)

Conclusions
On the basis of a meta-analysis, continued use of immunomodulator therapy after starting anti-TNF therapy is no more effective than anti-TNF monotherapy in inducing or maintaining response or remission. RCTs are needed to adequately assess the efficacy of continued immunomodulator therapy after anti-TNF therapy is initiated.

Ceci est cohérent avec les données récentes publiées qui suggèrent qu'il y a plus de données  pour l’intérêt de la combothérapie en échec de l’IS uniquement pour l’infliximab (effet bénéfique sans équivoque sur la formation d'anticorps anti-IFX). Les résultats de cette étude soulignent la nécessité d'une étude prospective, randomisée contrôlée contre placebo avec  une plus longue durée de suivi pour répondre définitivement à la question de savoir si un traitement en combothérapie est supérieure à la monothérapie à l’introduction d’anti-TNF chez un patient en échec d’IS.