BARCELONA, Spain—The increasing use of tumor necrosis factor alpha (TNFα) inhibitors to treat a host of rheumatic, digestive, and cutaneous diseases has led to a corresponding rise in the number of drug-induced lupus cases, reports Manuel Ramos-Casals, MD, at the EULAR 2007 meeting.1 Moreover, there may be significant differences in lupus features based on which anti-TNF agent is used.

"Anti-TNF agents should be included in a list of drugs associated with lupus-like features."—Manuel Ramos-Casals, MD.
Dr. Ramos-Casals, with the Hospital Clinic, in Barcelona, Spain, reported on 92 cases of lupus that developed after anti-TNF therapy. "The cases had a clinical presentation that was highly suggestive of drug-induced lupus," he said. "Anti-TNF agents should be included in a list of drugs associated with lupus-like features."

Of the 92 cases of lupus that developed TNF-blockade after a mean of 41 weeks on anti-TNF therapy, 84% occurred in females and 16% occurred in males. Forty patients were treated with infliximab, 37 with etanercept, and 15 with adalimumab. The main indication for anti-TNF therapy was rheumatoid arthritis (RA).

Clinical, immunologic features documented in 72 of 92 patients

The researchers had clinical and immunological data on the disease features for 72 patients, 68 of whom had positive autoantibodies including antinuclear antibody and antidouble-stranded DNA. Sixty four patients exhibited cutaneous manifestation of lupus, 28 had musculoskeletal symptoms, and 21 had general symptoms including fever, malaise, and asthenia.

Only 51% of patients fulfilled four or more criteria for systemic lupus erythematosus (SLE) classification, 24% fulfilled three criteria, and the remaining 25% fulfilled fewer than two criteria. After controlling for clinical or analytical features that predated the initiation of anti-TNF therapy, 35% of patients still met the criteria for SLE.

"Patients who received etanercept were more likely to develop subacute/chronic SLE-specific cutaneous features, when compared to patients taking the other TNF-inhibitors," Dr. Ramos-Casals said.

Anti-TNF therapy was stopped in 94% of patients. Corticosteroids were used in 40% of patients and immunosuppressive agents in 12%. All but one patient improved, and there were no deaths.
"It happens, but it's very rare," commented David A. Isenberg, MD, with the centre for rheumatology at the University College London, UK, on the risk of developing drug-induced lupus after using anti-TNF agents. His comments were based on data from a British registry of biologic users.
Dr. Ramos-Casals and colleagues collected information of reported cases on the use of biological agents in adult patients from the BIOGEAS multicenter study, which was created by the Study Group on Autoimmune Diseases. Search terms included "anti-TNF," "induced," "lupus," and "autoimmune disease."

Reference

1. Ramos-Casals M, Brito-Zeron P, Soria N, et al, and the BIOGEAS Study Group. Lupus induced by TNF-targeted therapies: clinical and immunologocal characterization of 92 cases. Presented at: EULAR 2007 Meeting; June 13-16, 2007; Barcelona, Spain. Abstract OP0024.