Skin reactions to tumor necrosis factor-α-blocking drugs for rheumatoid arthritis might be more common and more varied than previous studies have indicated, results of a new prospective study show.
The study authors, led by Marcel Flendrie, M.D., of Radboud University Nijmegen (the Netherlands) Medical Centre, said theirs is the first large prospective study of dermatologic conditions in rheumatoid arthritis (RA) patients taking TNF-α-blocking medications.
Overall, 25% of the 289 patients taking the biologics had a dermatologic event, compared with 13% of the same number of control patients.
The odds ratio for a patient taking the biologics to require a dermatologic referral was 2.26 (Arthritis Res. Ther. 2005;7:R666-76). The study was published online at BioMed Central's Web site on April 4 (www.arthritis-research.com/content/7/3/r666
There seemed to be no characteristic at baseline that predicted which patients might be susceptible to a dermatologic event, the authors said.
In the trial, 289 consecutive patients with RA who were started on TNF-α-blocking therapy—infliximab, etanercept, adalimumab, or the experimental agent lenercept—were compared with 289 patients from a cohort of 500 who have been followed at the medical center since 1985 but who had never taken a TNF-α-blocking agent.
Any patient who visited a dermatologist during the follow-up period was identified, and any new manifestation or exacerbation of a skin disease or any drug-related eruptions were recorded. The researchers also recorded diagnoses, topical and systemic therapeutic actions, outcome of the event, and any information on rechallenge.
Median follow-up time was 2.3 years. Among the patients taking anti-TNF therapy, 70 (24%) had received more than one agent, 8 (3%) had a history of taking more than two.
Overall, 167 patients were given infliximab, 108 received adalimumab, 78 received etanercept, and 31 were treated with lenercept. In total, there were 128 dermatologic events in the TNF group; 56 events occurred with adalimumab, 49 with infliximab, 16 with etanercept, and 13 with lenercept.
Skin infections accounted for the largest proportion of these therapy-related events, with 33 fungal, bacterial, and viral infections recorded. TNF-α-blocking therapies are known to increase susceptibility to infections, and the study findings suggest that the immunosuppressive agents might also make patients more vulnerable to skin infections, said the authors.
Eczema was diagnosed 20 times in 19 patients, and 3 patients stopped therapy as a result. One patient was hospitalized. The others were treated with topical corticosteroids.
There were frequent cases of drug-related eruptions in the first 5 months, in particular, said the authors.
Most common was a combination of exanthema, urticarial eruptions, lichenoid skin lesions, and purpura. Of 15 patients diagnosed with an eruption, 7 stopped therapy, and 8 continued. One patient was hospitalized.
In smaller numbers, patients also experienced ulcers, benign and malignant skin tumors, vasculitis, actinic keratosis, edema, chronic venous insufficiency/varices, xerosis cutis, and stasis dermatitis.
The occurrence of psoriasiform eruptions in three patients was “particularly interesting,” given that etanercept is approved for psoriasis, and infliximab may soon get that approval, the researchers said.
The time between the start of therapy and onset of skin conditions varied, but some events looked more likely to be drug related, including the eruptions, cutaneous vasculitis, a case of systemic lupus erythematosus, dermatomyositis, and a lymphomatoid papulosis-like eruption, the authors continued.
Overall, 19 of the 72 patients who experienced skin problems stopped taking the TNF-α-blocking therapy.