Infliximab Fails Test in Two Rheumatologic Diseases

CLEVELAND, April 30 -- Infliximab (Remicade) showed no efficacy against two related rheumatic diseases, according to researchers here and in Italy.

In separate randomized controlled studies, investigators tested infliximab, the tumor necrosis factor-alpha inhibitor, for giant cell arteritis and polymyalgia rheumatica.

The goal was to prevent relapse or recurrence in disease that was controlled by corticosteroids, but both groups of researchers concluded that the drug had no benefit and might even be harmful, the investigators reported in the May 1 issue of Annals of Internal Medicine.

The failure of infliximab means that both diseases "remain therapeutic challenges," commented Raashid Luqmani, D.M., of Oxford University in England in an accompanying editorial. For clinicians, "the message is that steroids are still the cornerstone of treatment" for these diseases.

The giant cell arteritis study, a multicenter international trial, was stopped halfway through when a planned interim analysis showed no benefit from infliximab, according to Gary Hoffman, M.D., of Cleveland's Lerner School of Medicine.

The researchers enrolled 44 patients with a new diagnosis of giant cell arteritis that was in steroid-induced remission. They were randomized on a two-to-one ratio to infliximab (at 5 mg/kg) or a placebo in addition to steroids.

But at the 22-week interim analysis, Dr. Hoffman and colleagues reported, the proportion of patients who had not relapsed was 43% for infliximab and 50% for placebo. Similarly, the proportion of infliximab patients who were able to have their steroid dose tapered off was 61%, compared with 75% of placebo patients.

The study was too small to be definitive, Dr. Hoffmann and colleagues acknowledged, but "if infliximab has benefit, it is unlikely to be great."

For polymyalgia rheumatica, Carlo Salvarani, M.D., of Arcispedale S. Maria Nuova in Reggio Emilia, Italy, and colleagues, enrolled 51 patients with newly diagnosed disease and began treating them with oral prednisone, which was tapered from 15 mg/day to 0 over a 16 weeks

At the same time, the patients were randomly assigned to receive infusions of a placebo or infliximab (3 mg/kg of body weight) at week zero, two, four, six, 14, and 22.

The primary goal was to see whether infliximab reduced the rate of relapse or recurrence, the researchers said, but at week 52, there was no evidence that it did: The proportion of infliximab patients who had not relapsed was 30%, compared to 37% of those getting placebo.

The researchers conceded that the sample size was too small to rule out a modest effect of the drugs, but as things stand, "if there is benefit, it is unlikely to be large."

Giant cell arteritis and polymyalgia rheumatica are related in that they have some overlapping symptoms, and strike the same population. Some have suggested they are different phases of the same disease.

Infliximab is approved in other rheumatic disorders, Dr. Salvarani and colleagues noted, and had been used successfully in an open-label pilot study in polymyalgia rheumatica.

The study of giant cell arteritis was supported by Centocor Research and Development Inc. Dr. Hoffman and several of his co-authors report being consultants for and receiving grants and honoraria from Centocor. Three of the authors are employees of the company.

The study of polymyalgia rheumatica was also supported by Centocor, which provided the infliximab and placebo. Dr. Salvarani and colleagues reported no potential financial conflicts.