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Thomas F. Schaible
Centocor Inc.
Malvern, PA

Clinical Benefits of Anti-TNF cA2 Monoclonal Antibody in Crohn’s Disease and Rheumatoid Arthritis

Crohn’s disease is a chronic inflammatory disease of the bowel characterized by segmental transmural inflammation and granulomatous changes. Because of its unknown cause, no specific therapy for Crohn’s disease is available. Tumor necrosis factor a (TNFa) is thought to play an important role in Crohn’s disease and other granulomatous diseases. Infliximab (cA2 monoclonal antibody) is an anti-TNFa antibody developed as a therapeutic agent for diseases in which TNFa is thought to mediate chronic inflammation. Two placebo-controlled, randomized, double-blind studies have demonstrated the efficacy and safety of infliximab in the treatment of Crohn’s disease. In patients with treatment-resistant, moderate to severe Crohn’s disease, 65% of patients treated with infliximab demonstrate a definitive clinical response (a 70-point decrease in the Crohn’s Disease Activity Index [CDAI]) compared to 17% of placebo-treated patients (p<0.001). Approximately one-half of the responding patients achieved clinical remission (CDAI <150). The clinical benefit of infliximab treatment was commensurate with healing of mucosal inflammation and ulcers. The onset of benefit was rapid, occuring within 2 weeks of treatment, and lasted 8 weeks or longer following a single infusion in the majority of responding patients. The initial treatment benefit of infliximab was effectively and safely sustained with retreatment infusions given 8 weeks apart. In another controlled trial in patients with fistulizing Crohn’s disease, treatment with infliximab was effective in healing enterocutaneous fistulae in 62% of patients treated with infliximab compared to 26% of placebo-treated patients (p=0.002). This study was the first controlled clinical trial to demonstrate a statistically significant benefit of a therapeutic agent in patients with fistulizing Crohn’s disease. The treatment benefit of infliximab was consistently observed in patient subgroups based on demographic factors, disease characteristics and concomitant medications. Therefore, anti-TNF therapy with infliximab in Crohn’s disease represents a new and effective treatment in patients with Crohn’s disease not responding adequately to currently available therapies.