Infliximab may top cyclosporine for steroid-refractory ulcerative colitis

Last Updated: 2016-02-29

By Will Boggs MD

NEW YORK (Reuters Health) - Infliximab may be slightly better than cyclosporine for treating patients with steroid-refractory ulcerative colitis (UC), according to results from a systematic review and meta-analysis.

"I think physicians have moved toward using infliximab in this setting since it is easier to use and is commonly perceived to be safer than cyclosporine, but the data suggest that adverse events may be similar in patients receiving these two drugs," Dr. Neeraj Narula, from McMaster University, Hamilton, Ontario, Canada, told Reuters Health by email.

Medical rescue therapies aim to avoid colectomy and improve long-term outcomes in the estimated 30% of patients with acute severe UC who fail steroid therapy. A recent head-to-head study failed to demonstrate superiority of either infliximab or cyclosporine in this setting.

Dr. Narula and colleagues compared infliximab and cyclosporine as rescue agents in steroid-refractory acute severe UC in their systematic review and meta-analysis of 16 studies involving 1,473 participants. Five studies were prospective (including three randomized controlled trials), and the rest were retrospective cohort studies.

Therapeutic responses did not differ significantly between infliximab and cyclosporine in the three randomized trials, but pooled response rates were significantly higher for infliximab (74.8%) than for cyclosporine (55.4%) in the nonrandomized trials.

Three-month colectomy rates did not differ significantly between infliximab and cyclosporine, regardless of study design, but 12-month colectomy rates were significantly lower with infliximab (20.7%) than with cyclosporine (36.8%) in the nonrandomized trials.

Adverse drug-related events, serious adverse events, postoperative complications, and mortality did not differ significantly between the treatments, according to the February 9 online report in the American Journal of Gastroenterology.

"Studies are ongoing to determine how to maximize the therapeutic benefit of infliximab in the setting of acute severe UC (Clinicaltrials.gov: NCT01787786, NCT01971814), and prospective studies comparing dose-optimized infliximab to cyclosporine may provide more definitive insight into this debate," the researchers noted.

"Our best-quality evidence would support using either infliximab or cyclosporine in the short term, but the longer term data (12 month colectomy rate) really does support using infliximab preferentially in this setting," Dr. Narula said. "This is likely in part due to transitioning patients off cyclosporine in the long term onto maintenance therapy with thiopurines, which do not tend to have as robust maintenance data for ulcerative colitis compared to infliximab."

"That said, we are learning about ways to optimize use of infliximab in the acute severe UC setting, including the use of higher doses and concurrent immunomodulators, which may lead to even more benefit from infliximab than what we have observed so far," Dr. Narula added.

Dr. Dong Soo Han from Hanyang University Guri Hospital, Guri, Korea, who recently reviewed the role of cyclosporine in steroid-refractory UC (http://1.usa.gov/1SchUMn), told Reuters Health by email, "The choice of rescue drugs should rely on physicians' decision with experience. But, considering long-term side effects by cyclosporine, infliximab is one of the good options."

"But we need more randomized trials comparing both drugs," he said.

Dr. Peter De Cruz, Head of the Inflammatory Bowel Disease Service, Austin Health, Melbourne, Victoria, Australia, recently reviewed the practical management of acute severe ulcerative colitis (http://bit.ly/1RzStCh). He told Reuters Health by email, "Given the lack of significant difference between the two groups, patients' previous thiopurine exposure and individual center's experience with each of the salvage therapies should still guide the choice of which salvage therapy is best suited to each individual patient."

"Further studies are required to determine the optimal dosing regimen for infliximab and to establish which patients are most likely to respond to the salvage therapies," Dr. De Cruz said. "The optimal maintenance strategy following successful induction therapy also needs to be established."

The authors reported no funding. Two coauthors reported relevant relationships with pharmaceutical companies.

SOURCE: http://bit.ly/1T4453I

Am J Gastroenterol 2016.