An integrated analysis of data from three premarketing randomized, placebo-controlled clinical trials was performed to study infusion reactions associated with infliximab. Reactions were more common in patients treated with infliximab compared with placebo, more frequent with infliximab 3 mg/kg vs. 5 mg/kg, and only very rarely serious.
Dr. Leonardi was the lead author of a poster that presented an integrated analysis pooling data from three randomized, placebo-controlled trials that investigated infliximab in patients with moderate-to-severe plaque psoriasis. The analyzed cohort included 1,373 patients treated with infliximab and 1,170 placebo-treated controls. The patients were participants in one 30-week phase 2 study (Study of Psoriasis with Infliximab [Remicade] Induction Therapy, SPIRIT) or one of two 50-week phase 3 trials (European InfliXimab for Psoriasis [Remicade] Efficacy and Safety Study, EXPRESS; Evaluation of InfliXimab for Psoriasis [Remicade] Efficacy and Safety Study II, EXPRESS II). All three studies began with a 14-week placebo-controlled induction period when infusions of placebo or infliximab 3 mg/kg or 5 mg/kg were administered at weeks zero, two and six.
Through week 14, infusion reactions occurred during 22 (2.3 percent) of 954 placebo infusions, 63 (5.2 percent) of 1,220 infliximab 3 mg/kg infusions and 71 (3.4 percent) of 2,106 infliximab 5 mg/kg infusions.
Analysis of data collected through the end of the studies showed 4.5 percent of placebo patients experienced at least one infusion reaction compared with 25.5 percent of patients treated with infliximab 3 mg/kg and 19.9 percent of patients receiving infliximab 5 mg/kg.
The proportions of placebo, infliximab 3 mg/kg and infliximab 5 mg/kg infusions associated with a reaction were 1.2 percent, 7.1 percent and 4.2 percent, respectively. Serious infusion reactions occurred in only 0.1 percent of all infliximab infusions and in approximately 0.7 percent of infliximab-treated patients.
"We have a very active infusion center in my office where over 100 patients have received more than 1,000 infusions during the past two years, and these clinical trial data are very consistent with my practice experience. They highlight that most infliximab infusion reactions are minor, but reinforce the need to monitor patients because serious reactions can occur," Dr. Leonardi tells Dermatology Times.
FLIP SIDE OF THE COIN
He observes that the inverse relationship between dose and infusion reaction frequency appears counterintuitive.
However, it can be predicted by the drug's pharmacokinetics and the host's immunological response.
"With infusion of a lower dose, the infliximab blood level is more likely to fall to zero between infusions. At the next infusion, the drug is more likely to be discovered immunologically and antibodies may develop. Patients who receive a higher dose are more likely to maintain some low level of drug between infusions and a state of immune tolerance," Dr. Leonardi says.
That mechanism would also suggest that infusion reactions may be more common when the interval between infusions is prolonged. Evidence of that phenomenon was seen in analysis of data from the SPIRIT study, but not in the EXPRESS II trial.
In SPIRIT, patients received the last induction infusion at week six and were retreated only at week 26 if their Physicians' Global Assessment score was 3 (moderate) or worse. The rate of infusion reactions among patients who received a dose at week 26 was higher than in the overall study population during the induction period.
In EXPRESS II, some patients received maintenance doses of infliximab on an as-needed (PRN) schedule. In that study, there was no difference in infusion reaction rates between patients who had a 16-week or greater interval between infusions, compared with the overall PRN group.