University of Liverpool Academic Rheumatology Unit, Clinical Sciences Centre, University Hospital Aintree, Longmoor Lane, Liverpool L9 7AL, UK
SIR, Anti-tumour necrosis factor (TNF-
) therapy is being used with considerable success to suppress disease activity in patients with Behçet's syndrome (BS) [13]. We report a patient with refractory BS who failed to respond to etanercept but who responded dramatically to infliximab.
A 38-yr-old Caucasian woman was diagnosed with BS on the basis of recurrent orogenital ulceration, arthralgia, severe iritis, positive pathergy test and many episodes of erythema nodosum. At presentation her orogenital ulceration was being treated with topical triamcinolone with minimal effect. She also had marked fatigue, severe ulceration of the nasopharynx and multiple ulcerations of the labia and vulva with areas of scarring. The patient was commenced on colchicine without effect. This was soon followed by sequential courses of cyclosporin, pulsed high-dose intravenous methylprednisolone, chlorambucil and thalidomide, all of which were ineffective at therapeutic doses.
After some months with highly active disease (but inactive eye disease) that did not respond to conventional therapies, she was commenced on etanercept, a TNF- receptor p75Fc fusion protein, 25 mg subcutaneously twice a week, after full discussion and consent. There was no improvement in her orogenital ulceration after 3 months of such therapy. She was then switched to infliximab, a chimeric anti-TNF-
monoclonal antibody, in an attempt to control the disease. Infusions of 3 mg/kg were given at 0 and 2 weeks and then at intervals of 8 weeks, as for treatment of rheumatoid arthritis, together with methotrexate 7.5 mg orally once a week. There was a remarkable response soon after the first infusion, with marked improvement in arthralgia, resolution of orogenital ulceration and erythema nodosum and reduction of fatigue. She remains well 1 yr later and continues to enjoy remission on continued therapy with infliximab.
Proinflammatory cytokines, including TNF-, are known to be elevated in BS [4], suggesting that anti-TNF-
therapy might be effective. We are not aware of any other reports of the differential response of BS to the two currently licensed anti-TNF-
drugs. Our observation highlights a difference in the efficacy of these two drugs in BS, also observed in Crohn's disease, which has clinical similarities with BS. The reasons for this differential effect are not known. Whilst both drugs inhibit TNF-
, they have significant differences in various ways. For example, infliximab has a much longer half-life than etanercept and can bind surface-bound TNF-
, lysing cells expressing this molecule by complement fixation, whereas etanercept does not. The differential effect of TNF-
therapies in BS, as in Crohn's disease, needs further evaluation and has the potential to provide important insights into both the pathogenesis of these conditions and new pharmacological strategies for their treatment.
Notes
Correspondence to: R. J. Moots.
References