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Selective Costimulation Modulators: Addressing Unmet Needs in Rheumatoid Arthritis Management: Other Considerations of TNF-alpha Inhibitors


Other Considerations of TNF-alpha Inhibitors

TNF-alpha inhibitors are generally safe and well tolerated. The most common safety concerns with TNF-alpha inhibitors include infusion reactions (infliximab)[35,47,48] or injection-site reactions (etanercept and adalimumab).[49,50] There are reports of increased risk of infection with these agents, including upper respiratory tract infections, opportunistic infections, and reactivation of tuberculosis.[51,52] Other adverse effects of treatment include lupus-like syndrome,[34,45,49,53] demyelinating syndrome,[54] and the development of blocking antibodies.[39,47,55] An increased incidence of malignancies (lymphoma) has also been described with TNF-alpha inhibitors,[56] although it remains a matter of debate whether there is a causal relationship between malignancy and the use of TNF-alpha inhibitors.[42]

A study addressed the effects of ceasing and restarting the TNF-alpha inhibitor, infliximab.[9] Seventeen patients who received infliximab during the ATTRACT trial[33] continued to receive MTX alone in a 2-year extension phase. All 17 patients flared after stoppage of infliximab therapy with a mean time to flare ranging from 13.5 to 15 weeks for the 4 treatment groups. No adverse reactions were experienced by the 15 patients who were re-established on infliximab therapy, and the resulting ACR response was comparable to that established in the original trial in 12 of 14 patients (worse in 2). Thus, ongoing, long-term anti- TNF-alpha treatment is required to maintain responses in patients with established RA.