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Infliximab Licensing Expands to Include Halting Arthritis Progression

Cheryl A. Thompson

Licensing for infliximab (Remicade, Centocor), a monoclonal antibody used as an alternative agent in reducing the signs and symptoms of moderately to severely active rheumatoid arthritis (RA) and Crohn's disease, has been expanded to include inhibiting the progression of structural damage from RA. The biologic agent should be administered with methotrexate when used in patients with RA.

Infliximab targets tumor necrosis factor (TNF), a promoter of inflammation. Evidence of infliximab's ability to alter the natural destructive course of RA came from a randomized, double-blind, placebo-controlled study conducted in North America and Europe. The Anti-TNF Trial in Rheumatoid Arthritis with Concomitant Therapy involved 428 patients who received methotrexate once weekly and either infliximab or placebo.1 Infliximab, at a dose of 3 or 10 mg/kg by intravenous infusion, was administered at weeks 0, 2, and 6 and then every four or eight weeks. After 54 weeks of therapy, 52% of infliximab-treated patients had decreased signs and symptoms of RA, compared with 17% of the control patients.

The company has told FDA that further studies of infliximab's safety will be conducted and that separate registries of patients with RA or Crohn's disease will be maintained. Of particular concern is the unusually high frequency of infections in patients who receive the biologic agent along with other drugs.

According to researchers at Boston University and FDA, about 20% of postlicensure adverse events associated with infliximab or etanercept therapy described infections. Neither TNF antagonist had been associated with a high frequency of infections during the prelicensure studies. As of October 2000, 17 infliximab-treated and 3 etanercept-treated patients had been reported to have tuberculosis. Two of these infliximab-treated patients died. Other opportunistic infections have also been reported. The researchers noted the important role TNF plays in the immune system and raised the possibility that TNF blockade increases the risk of infection.

Infliximab’s package insert already contains warnings about the risk of serious or fatal infections and use in patients with chronic infections. The recently revised package insert for etanercept (PDF) emphasizes and elaborates on these warnings. It also notes the "very rare" occurrence of cutaneous vasculitis in children with juvenile RA

  1. Lipsky PE, van der Heijde DMFM, St. Clair EW et al., for the Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. N Engl J Med. 2000; 343:1594-602.