Long-term efficacy and safety of TNF-alpha-inhibitor infliximab in severe atopic dermatitis

Abstract

Standard therapy of severe atopic dermatitis (steroids, immunosuppressives, UV-therapy) is associated with variable efficacy and considerable side effects when used chronically. Targeted therapeutic approaches, like inhibition of tumor necrosis factor-a (TNF-alpha), a cytokine that can be detected in high concentrations in skin and serum of patients with atopic dermatitis, may be a novel option. Infliximab, a chimeric monoclonal antibody, has proven efficacious for the treatment of several autoimmune and inflammatory skin diseases such as psoriasis with few side effects. The objective of this open, prospective pilot study was to evaluate the long-term efficacy and safety of infliximab in patients with severe atopic dermatitis over 58 weeks; treatment up to week 42, then follow-up period. Responders at week 10 (reduction of EASI >30%) could enter a retreatment phase up to week 42. Infliximab 5mg/kg i.v. was administered to nine patients at weeks 0, 2 and 6 and then at weeks 14, 22, 30 and 38. Efficacy was evaluated by using the Eczema Area and Severity Index (EASI), Pruritus Severity Assessment (PSA) and Dermatology Life Quality Index (DLQI). Infliximab showed an overall significant but clinically moderate efficacy in patients with severe atopic dermatitis at week 2 for EASI and PSA, at week 10 for PSA and DLQI and at week 42 for PSA (week 2 to screening EASI: p = 0.03, PSA: p = 0.03, DLQI: p = 0.08; week 6 to screening EASI: p = 0.07, PSA: p = 0.08, DLQI: p = 0.06; week 10 to screening EASI: p = 0.09, PSA: p = 0.04, DLQI: p = 0.02; week 42 to screening EASI: p = 0.2, PSA: p = 0.03, DLQI: p = 0.1). Induction therapy resulted in a improvement of all parameters, but this was not sustained in maintainance therapy, except for PSA. Three patients terminated the study before week 10, two because of acute exacerbation of the disease and one experienced an infusion reaction. Two additional patients were non responders at week 10 and did not enter retreatment. Two of nine patients achieved a good clinical response over 58 weeks. Besides the single infusion reaction no other side effects were reported up to week 58. Further studies are needed to identify the subpopulation of patients who would maximally benefit from this therapeutic option.