CLEVELAND — Tumor necrosis factor-α blockade should not be instituted in patients with known multiple sclerosis and should be used with caution in patients with family histories or other risk factors for MS, according to Jeffrey A. Cohen, M.D., a neurologist at the Cleveland Clinic, Ohio.
Physicians should also be alert to uncommon CNS manifestations in patients receiving tumor necrosis factor (TNF) blockade for their inflammatory diseases, he said at a meeting on the treatment of autoimmune and inflammatory disorders.
TNF inhibitors currently approved by the Food and Drug Administration include the monoclonal antibodies infliximab (Remicade) and adalimumab (Humira) and the fusion protein etanercept (Enbrel).
TNF blockade both prevents and abrogates demyelinating disease in vitro and in animal studies. In humans, TNF blockade actually increased MS activity, said Dr. Cohen, citing data from two studies of infliximab and the discontinued lenercept. “In addition, treatment of other diseases for which TNF inhibitors are highly effective, including rheumatoid arthritis, Crohn's disease, and psoriasis, on rare occasions leads to CNS inflammatory demyelinating syndromes,” Dr. Cohen said at a summit sponsored by the Cleveland Clinic.
Failure of anti-TNF therapy in MS may be due to pleiotropic aspects of TNF actions, he noted. “In the CNS, TNF mediates cellular apoptosis and tissue damage, has important immunoregulatory functions, and is involved in tissue repair and regeneration. This experience reminds us that in the development of novel therapeutics, one must be cautious in extrapolating from animal models to human disease and from the results in one human disease to another,” he said. CNS demyelination can occur anytime after an anti-TNF agent is started. Demyelination appears to be a class effect of all TNF antagonists.
Dr. Cohen recommends avoiding TNF blockade for patients with or at risk for MS. Withhold TNF inhibitor infusions from patients who have had a previous clinically isolated CNS syndrome and have cranial MRIs that look suggestive of MS but do not yet have clinical manifestations, advised Dr. Cohen.
Dr. Cohen, a neurologist, advised against looking for MS in every patient prior to starting a TNF inhibitor for treatment of inflammatory bowel disease, rheumatoid arthritis, or psoriasis. “In particular, I would not obtain an MRI unless there was some clinical suggestion of potential (for MS).” However, uveitis is a different story: “Uveitis is a manifestation that can occur in MS, so I would look very carefully for any indication of MS involvement” before beginning TNF blockade.