LONDON -- The TNF-alpha inhibitor Remicade (infliximab) decreased the number of asthma exacerbations in a small clinical trial, but the drug had no significant effect on peak expiratory flow, the study's primary efficacy endpoint.
LONDON, Oct. 4 -- Remicade (infliximab) decreased the number of asthma exacerbations in a small clinical trial, but the drug had no significant effect on peak expiratory flow, the study's primary efficacy endpoint, researchers here reported.
In patients with moderate asthma who were symptomatic despite inhaled corticosteroids, Remicade did not improve morning peak expiratory flow levels over placebo, but it significantly lowered diurnal variations of peak flow, Trevor T. Hansel, M.D., Ph.D., of the Royal Brompton Hospital here, and colleagues, reported in the American Journal of Respiratory & Critical Care Medicine.
Remicade, a TNF-alpha inhibitor, is FDA-approved for the treatment of rheumatoid and psoriatic arthritis, Crohn's disease, ulcerative colitis, psoriasis, and ankylosing spondylitis-but not for asthma.
Because the monoclonal antibody has been shown to be effective against inflammatory conditions, researchers have hypothesized that it could be effective as a treatment option for asthma patients who were not responsive to inhaled corticosteroids.
In a randomized, double-blind, parallel group study, Dr. Hansel and colleagues compared Remicade with placebo in 32 moderate asthma patients who were taking inhaled corticosteroids but were symptomatic during a two- to four-week run in phase. The analysis included data on 14 patients on Remicade and 18 on placebo.
The patients all had a diagnosis of moderate-to-severe persistent asthma as defined by the Global Initiative on Asthma (GINA) for at least one year, with an forced expiratory volume at one minute (FEV1) of 40% - 90% of predicted at screening. The patients also had to have at screening a reversible airway obstruction with at least a 12% increase in FEV1 compared with baseline within 30 minutes of taking 200 ?g of albuterol.
During the study patients continued using their inhaled corticosteroids at a stable dose, and were allowed to use albuterol as rescue medication for symptomatic relief. No other asthma drugs were allowed during the study.
The primary efficacy endpoint was the change from baseline (measured during the last week of a two to four week run-in period) to study days 50 to 56 (eight weeks), in mean morning peak expiratory flow obtained from patients' diary data.
In patients who received Remicade, there was a mean increase in morning peak flow from baseline to week eight of 15.0 + 50.8 L/min (95% confidence interval, -13.1 to 43.2m), compared with a decrease of 15.6 + 46.6 L/min in the placebo group (95% CI, -38.8 to 7.6, P=0.17).
The mean between-group difference of 29.49 was also not significant (95% CI, -4.6 to 63.5, P=0.09).
The investigators did see significant differences, however, in Remicade's effect on mean diurnal peak flow variation vs. placebo, in favor or Remicade for both the change from baseline within the active-drug group, and between the groups.
There was also a decrease in the number of patients with exacerbations of asthma on Remicade versus placebo. In all, 13 of the 18 patients on placebo (72%) experienced exacerbations during the study, compared with four out of 14 patients (29%) on Remicade (P=0.01 on the chi-square test).
Patients on Remicade also had an increased probability of being free of exacerbations over time, the authors wrote.
There were no significant differences between the drug and placebo groups in lung function at clinic visits, asthma symptom scores, or use of rescue beta-2 agonists.
The only serious adverse event in the study was not treatment-related: one patient died in a parachute accident one week after receiving the last Remicade infusion.
The authors noted that the definitions of exacerbation are controversial and subject to interpretation.
"Hence, our data on exacerbations are preliminary and require confirmation in a study of appropriate power and length," they wrote "In addition, some aspects of the definitions of exacerbations and loss of asthma control overlap, and it is possible to infer from our study that infliximab may provide superior asthma control in terms of decreased diurnal variability."
The study was underwritten by Remicade's maker Centocor, a subsidiary of Johnson & Johnson, and one of the co-authors is a Centocor employee.