A Pilot Study Using Anakinra/Kineret for the Treatment of Patients With Severe Atopic Dermatitis

Severe refractory atopic dermatitis is a chronic inflammatory pruritic skin condition that affects both children and adults. The disease is marked by periods of exacerbation and remission. Symptoms of atopic dermatitis may resolve by adolescence; however, it is estimated that the disease may persist in 50 percent of affected children well into adulthood. Current possible treatments of atopic dermatitis include the use of topical corticosteroids, calcineurin inhibitors, phototherapy, as well as systemic medications i.e., methotrexate, cyclosporine, azathioprine, mycophenolate mofetil and interferon gamma. The difficulty with long-term treatment of this disease lies in its chronic nature associated with severe episodes. The combination of chronicity and severity of episodes of this diseases demands more effective and better-tolerated therapeutic options than those that are currently available. While the pathways of allergic inflammation are different than those of other inflammatory conditions, certain elements may overlap, providing targets for immune modulation. One of these targets is the interleukin-1 (IL-1) receptor. The IL-1 receptor plays an important role in the development and maintenance of Th2 responses. Genetic, in vivo and in vitro data demonstrate a significant role for IL-1 signaling allergic and skin inflammatory conditions. This pilot study is therefore designed to assess the safety and efficacy of IL-1ra, a natural inhibitor of the IL-1 receptor, in disrupting atopic pathophysiologic pathways. Specifically, we will treat severe refractory atopic dermatitis associated with evidence of multiple specific allergic sensitivities. Up to 8 patients ages 10-30 with severe refractory dermatitis will be enrolled. Patients will be initially evaluated to establish the diagnosis of severe refractory AD as evidenced by SCORAD score greater than 40, followed by a 2 month (8 week) run-in period, a 3 month (12 week) treatment period of 3mg/kg/day anakinra given subcutaneously, followed by a 3 month (12 week) post-treatment evaluation period. In order to be considered evaluable for response, patients must have received a minimum of 67 out of 84 doses (80 percent) of anakinra. The primary endpoint is lack of an increase in serious infections, the secondary endpoint is a reduction of 30 percent or more in SCORAD score, and tertiary endpoints are cellular phenotypic and cytokine responses to IL-1 receptor blockade in atopic patients.