Prevalence of Cutaneous Adverse Events Associated with TNF-α Therapy for Rheumatic Diseases

Tumor necrosis factor α (TNF-α) antagonists are widely used for rheumatic diseases. Cutaneous adverse reactions, ranging from local injection site reactions to the new onset of psoriasiform dermatitis or cutaneous autoimmune disease, are common and sometimes limit continued use.

Researchers reviewed the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases and identified 5437 patients whose use of infliximab, adalimumab, or etanercept totaled 17,330 patient-years of exposure. In raw numbers, 592 patients had one or more cutaneous adverse reactions, which were judged to be serious in 89.

The mean time to onset of a reaction was 1.78 years. The incidence rate (IR) of any cutaneous adverse event was 53 per 1000 patient-years. IRs per 1000 patient-years for other events were 28 for cutaneous infection; 15 for infusion reaction; 5 for autoimmune disease, including new-onset psoriasis; and 3 for cutaneous malignancy. Roughly one third of patients with an adverse reaction had to stop TNF-α therapy. Higher risk for a cutaneous adverse reaction was linked to female sex, infliximab use, or concomitant therapy with either corticosteroids or leflunomide. Psoriasis topped the list of autoimmune reactions, and herpes infection or bacterial skin infection were the most frequent within the infectious category. Nonmelanoma skin cancers were noted in 34 patients, 19 judged to be serious; melanoma occurred in 3 patients.