Dermatological conditions during TNF-a-blocking therapy in patients with rheumatoid arthritis: a prospective study

Various dermatological conditions have been reported during tumor necrosis factor (TNF)-a-blocking therapy, but until now no prospective studies have been focused on this aspect. The present study was set up to investigate the number and nature of clinically important dermatological conditions during TNF-ablocking therapy in patients with rheumatoid arthritis (RA). RA patients starting on TNF-a-blocking therapy were prospectively followed up. The numbers and natures of dermatological events giving rise to a dermatological consultation were recorded. The patients w ith a dermatological event were compared with a group of prospectively followed up RA control patients, naive to TNF-a-blocking therapy and matched for follow-up period. 289 RA patients started TNF-a-blocking therapy. 128 dermatological events were recorded in 72 patients (25%) during 911 patient-years of follow-up. TNF-a-blocking therapy was stopped in 19 (26%) of these 72 patients because of the dermatological event. More of the RA patients given TNF-ablocking therapy (25%) than of the anti-TNF-a-naive patients (13%) visited a dermatologist during follow-up (P < 0.0005). Events were recorded more often during active treatment (0.16 events per patient-year) than during the period of w ithdrawal of TNF-a-blocking therapy (0.09 events per patient-year, P < 0.0005). The events recorded most frequently were skin infections (n = 33), eczema (n = 20), and drug-related eruptions (n = 15). Other events with a possible relation to TNF-ablocking therapy included vasculitis, psoriasis, drug-induced systemic lupus erythematosus, dermatomyositis, and a lymphomatoid-papulosis-like eruption. This study is the first large prospective study focusing on dermatological conditions during TNF-a-blocking therapy. It shows that dermatological conditions are a significant and clinically important problem in RA patients receiving TNF-a-blocking therapy. Introduction The introduction of biological agents such as TNF-a-blocking agents has dramatically changed the therapeutic approach to rheumatic diseases in recent years. TNF-a-blocking therapy has had a remarkable effect on disease activity in an increas­ ing number of rheumatic diseases, including rheumatoid arthri­ tis (RA) [1-3], juvenile id iopathic arthritis [4], ankylosing spondylitis [5,6], and psoriatic arthritis [7]. A t present, two monoclonal anti-TNF-a antibodies (infliximab and adalimumab) and one soluble p75 TNF-a receptor (etanercept) are being used in rheumatological practice. Various skin conditions have been reported in clinical trials, including urticaria, rash, and stom atitis (during infliximab ther­ apy) [8]; rash and injection-site reactions (during adalimumab therapy) [3,9]; and injection-site reactions (during etanercept therapy) [2]. However, clinical trials are not designed to provide information about the occurrence of rare adverse events associated with TNF-a-blocking therapy. More severe cutaneous reactions, such as erythema multiforme, discoid and subacute cutaneous lupus erythematosus, atop ic dermatitis, necrotizing vasculitis, and bullous skin lesions, have been reported, mostly as s ingle­ case observations [10-15]. Larger observational studies such CI = confidence interval; DAS28 = disease activity score including 28-joint counts; DMARD = disease-modifying antirheumatic drug; ELISA = enzyme-linked immunosorbent assay; pt-yr = patient-year; RA = rheumatoid arthritis; Th1/Th2 = T helper cell type 1/2; TNF = tumor necrosis factor. R666 A rthritis Research & Therapy Vol 7 No 3 Flendrie et al. as biological registries are needed to provide information on the nature and number of such derm atological adverse events during TNF-a-blocking therapy. The aim of this study was to investigate whether derm atologi­ cal conditions after TNF-a-blocking therapy are a significant and clinically important problem in RA patients receiving TNFa-b locking therapy. Materials and methods Study design In a prospective cohort study, all consecutive patients w ith a diagnosis of RA according to the criteria of the American Rheumatism Association [16] who were starting on TNF-ablocking therapy at the Department O f Rheumatology of the Radboud University Nijmegen Medical Centre were followed as part of a Bio logical Registry [1 7]. Approval was obtained by the hospital's eth ics committee. Patients were required to meet the criteria set out in the Dutch guidelines fo r biological therapies: a moderate to high disease activity score (DAS) based on 28 jo ints (D A S28 > 3.2), and failure or intolerability of at least tw o disease-modifying antirheumatic drugs (DMARDs), including methotrexate, in adequate dosage regimens. Besides therapy w ith registrated TNF-a-blocking agents infliximab, etanercept, and adalimu­ mab some patients were treated in clinical trials w ith lenercept, a soluble p55 TNF-a-receptor [18]. The number and nature of derm atological conditions that led patients in this cohort to consult a derm atologist during followup were investigated. The RA patients treated w ith TNA-ablocking agents who experienced derm atological events was compared w ith a contro l group of patients who had RA but had never had TNF-a-blocking therapy. The contro l patients were selected from the Nijmegen inception cohort, in which 500 RA patients have been fo llowed since 1985 [19]. Each contro l was paired w ith a TNF-a-treated patient for duration and season of the fo llow -up period, within a 2-month w indow.