LIVERPOOL, ENGLAND — Drug-induced lupus that occurs in patients taking tumor necrosis factor-blocking drugs typically manifests cutaneously rather than systemically.
The induction of autoantibodies in patients being treated with tumor necrosis factor (TNF) blockers is a well recognized phenomenon, but the fuller lupus-like syndrome is much less common and its incidence is uncertain. In one clinical trial of infliximab that included 156 patients, 60% developed antinuclear antibodies (ANA) and 10% developed anti-double stranded DNA antibodies, but only one patient developed lupus, according to Dr. Jennifer Thornhill.
Complicating efforts to understand the scope of the problem of drug-induced lupus is the fact that there are no specific diagnostic criteria for the condition, according to Dr. Thornhill of the Arthritis Research Campaign Epidemiology Unit, University of Manchester (England).
Nonetheless, an investigation was undertaken of patients in the British Biologics Register, using the diagnostic criteria for systemic lupus erythematosus, to ascertain the incidence and manifestations of drug-induced lupus associated with anti-TNF therapy.
A total of 11,394 patients on biologics were included, along with 2,559 controls who were receiving conventional disease-modifying antirheumatic drugs (DMARDs). Mean age was 54 years for the anti-TNF patients and 60 years for the DMARD group, and 70% in both groups were women.
The anti-TNF and DMARD patients had been followed for about 25,000 and 4,000 patient-years, respectively.
Review of data from the register, as well as from patient and physician questionnaires and the office of national statistics, identified 44 lupus events in 41 patients.
Of these, 17 events were in patients on etanercept, 19 in patients on infliximab, 7 in patients taking adalimumab, and 1 in a patient on a conventional DMARD.
The most common events were rashes. There were ten malar rashes, nine discoid rashes, and nine “unspecified” rashes. Arthritis was reported by 17 patients, but this may reflect underlying rheumatoid arthritis rather than an effect of treatment, Dr. Thornhill said.
Oral ulcers also were common, but there were no cases of lupus nephritis or central nervous system lupus.
Overall, the event rate was 1.49 per 1,000 patient-years for the anti-TNF group and 0.25 per 1,000 patient-years for the DMARD group, she said.
Following adjustment for age, gender, disease duration, and Disease Activity Score (DAS) 28, the incidence rate ratio of lupus events in the anti-TNF group compared with the DMARD group was 3.17.
Increasing DAS28 score was associated with an increased rate of lupus events, with an adjusted incidence rate ratio of 1.39, as was female gender, with an adjusted incidence rate ratio of 2.47.
A total of 23 patients were ANA positive and 13 were anti-double stranded DNA positive, but at least 7 of the patients were antibody positive at baseline so the significance of this remains uncertain, Dr. Thornhill said at the annual meeting of the British Society for Rheumatology.
“In conclusion, we found that lupus events were rare and primarily cutaneous. This study also highlights the necessity for the establishment of diagnostic criteria for drug-induced lupus,” said Dr. Thornhill, who declared no conflicts of interest.
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