Combination Anticytokine Therapies

The widespread use of conventional DMARDs in combination with an apparent increase in efficacy without raising significant regards concerning toxicity or toler-ability has prompted the investigation of combination anti-cytokine therapy (Genovese et al. 2004). The potential attractions of this approach include superior immunomodulation and hence enhanced efficacy. However, in a 24-week randomized controlled trial conducted in 242 patients with rheumatoid arthritis who had not previously been treated with biologic agents and were taking background methotrexate, the combination of etanercept 25 mg twice weekly together with anakinra 100 mg once daily resulted in an incidence of serious infection of 7% and the occurrence of neutropenia in the combination group. The incidence of both infection and neutropenia was higher in the combination group than in the Enbrel alone group and higher than the rate observed in studies using anakinra alone. Furthermore, there was no therapeutic benefit of the combination treatment over etanercept alone. For this reason, the concomitant use of IL-1 blockade and TNF inhibitors is not recommended (Genovese et al. 2004).

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