SAN ANTONIO — Postmarketing trial data indicate that at the standard dosage, infliximab is not associated with an excess risk of infection during the first year of therapy, but higher doses may be, David Yocum, M.D., reported at the annual meeting of the American College of Rheumatology.
Dr. Yocum's investigation included patients with a history of active or latent TB and found no evidence that the biologic therapy reactivated infection.
“I think this reaffirms the positive risk-benefit ratio of the approved dose of infliximab,” said Dr. Yocum, who presented the results of the safety trial, which was initiated by the manufacturer, Centocor, to satisfy Food and Drug Administration requirements.
From the outset, the trial was designed to include patients with comorbidities in an effort to discern the risks from therapy in a “real-life” clinical setting, as opposed to the typical study population, he added.
In the trial, 1,082 patients were divided nearly equally into three treatment arms. The first group of study participants received placebo and then crossed over to receive standard-dose infliximab, 3 mg/kg, at weeks 22, 26, 30, 38, and 46.
The second group received standard-dose infliximab until week 22, at which point the dosage increased by 1.5-mg/kg increments every 8 weeks, as deemed necessary. The third group received infliximab 10 mg/kg through week 46.
All patients continued to receive concomitant methotrexate at a dose of 25 mg/wk or greater.
During the first 22-week phase of the trial, the group treated with standard-dose infliximab had the same rate of serious infections as the methotrexate-only group (1.7%).
By comparison, the infection rate among patients treated at the 10-mg/kg dose was nearly three times higher (5.3%), said Dr. Yocum who conducted the study at the University of Arizona, Tucson.
During the entire 54-week trial, infection rates were equal among the group on placebo that started infliximab therapy at 22 weeks and the group taking standard-dose therapy with the option to increase the dosage (3.6% each).
By comparison, 8.9% of those patients on the 10-mg/kg dosage developed serious infections.
The data suggest that if and when infections do occur in patients on infliximab, they tend to occur early. In addition, dose escalation is not a factor as long as the dose remains below 10 mg/kg, Dr. Yocum said.
Of the 54 patients who took escalating doses, 93% needed only two increases (1.5 mg/kg each time), and only 7 patients required 9 mg/kg.
The most common serious infection, pneumonia, occurred in 1.5% of the group that started infliximab later and in 1.4% of the group with the option of increasing the dosage.
Pneumonia developed in 1.9% of the high-dose group.
The multicenter trial included patients who had a history of active or latent tuberculosis.
There was one case of tuberculosis in the group who started late, two cases in the group who escalated, and four cases in the high-dose group.