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Anti-TNF plus immunomodulators no more effective than anti-TNF monotherapy in Crohn's patients
Results from a meta-analysis showed combination therapy with anti-tumor necrosis factor agents and immunomodulators was not superior to anti-TNF monotherapy in patients with Crohn’s disease.
“We performed this study because there is still a lot of controversy over using anti-TNF monotherapy versus combination therapy with anti-TNF together with an immunomodulator for the treatment of Crohn's disease,” Corey A. Siegel, MD, from Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told Healio Gastroenterology. “The SONIC study was clear that combination therapy is better in patients naive to both of these drugs, but this did not address the common clinical scenario of a patient who is not doing well on immunomodulators, and the plan is to add an anti-TNF. The clinical question is if it is necessary to continue the immunomodulator at that point, or just switch them to anti-TNF monotherapy.”
Corey A. Siegel
Siegel and colleagues performed a systematic review and meta-analysis of Crohn’s patient subgroups from randomized controlled trials to compare the safety and efficacy of anti-TNF and immunomodulatory (IM) combination therapy vs. anti-TNF monotherapy. They reviewed literature published from 1980 through 2008, and after excluding studies involving only patients who were naive to anti-TNF and IM therapy, they identified 11 trials of anti-TNF agents in a total of 1,601 patients with luminal or fistulizing Crohn’s disease, 40% of whom were on IM therapy at baseline.
Clinical response at weeks 4 to 14 and 24 to 30, and maintenance of remission between 24 and 30 weeks served as the primary endpoints, while infusion/injection site reactions and certain adverse events served as secondary endpoints. Subgroup analyses assessed fistula closure, safety and efficacy of combination therapy with different anti-TNF agents.
They found that combination therapy was no more effective overall than monotherapy for induction of clinical remission (OR = 1.02; 95% CI, 0.8-1.31), induction of clinical response (OR = 1.08; 95% CI, 0.79-1.48), maintenance of clinical response (OR = 1.53; 95% CI, 0.67-3.49), induction of partial fistula closure (OR = 1.25; 95% CI, 0.84-1.88) or induction of complete fistula closure (OR = 1.1; 95% CI, 0.68-1.78).
However, combination therapy with Remicade (infliximab, Janssen) was found to be associated with increased clinical response from weeks 4 to 14 (OR = 2.02; 95% CI, 1.09-3.72), which “is consistent with a recent review suggesting that there are more data supportive of the importance of combination therapy for infliximab,” the researchers wrote.
Subgroup analyses showed combination therapy was no more effective than monotherapy for induction of 6-month clinical remission with infliximab (OR = 1.73; 95% CI, 0.97-3.07), Humira (adalimumab, AbbVie; OR = 0.88; 95% CI, 0.58-1.35) or Cimzia (certolizumab, UCB; OR = 0.93; 95% CI, 0.65-1.34). Adverse events were comparable between combination and monotherapy, although combination therapy with infliximab was associated with fewer injection site reactions (OR = 0.46; 95% CI, 0.26-0.79).
“Our meta-analysis found that overall it didn't seem to matter if the immunomodulator was continued,” Siegel said. “In subgroup analyses, combination therapy may be more important for infliximab as opposed to adalimumab or certolizumab. However, because of the weight and consistency of indirect evidence that has demonstrated the unequivocal beneficial effect of immunomodulators on drug clearance for all anti-TNFs, we urge caution in using monotherapy and believe that a prospective RCT is necessary to better answer this important clinical question.” – by Adam Leitenberger
Disclosures: Siegel reports he has received research funding from AbbVie, Janssen, Takeda, and UCB, delivered CME lectures for AbbVie, Janssen, Merck, and Takeda, and served as an advisor/consultant for AbbVie, Amgen, Janssen, Lilly, Pfizer, Prometheus Laboratories, Takeda, and Theradiag. Please see the full study for a list of all other researchers’ relevant financial disclosures.