Efalizumab for severe atopic dermatitis: A pilot study in adults Rodd Takiguchi, MD, Susan Tofte, FNP, Brenda Simpson, BA, Erin Harper, PhD, Andrew Blauvelt, MD, Jon Hanifin, MD, and Eric Simpson, MD Portland, Oregon Background: Severe atopic dermatitis (AD) often cannot be adequately controlled with topical agents. The continuous use of current systemic therapies for AD is limited by end-organ toxicities. A safe and effective systemic therapy for patients with recalcitrant AD is greatly needed. Objective: To evaluate the potential safety and efficacy of efalizumab, an inhibitor of T cell activation and migration, in adults with severe AD. Methods: An investigator-initiated, prospective, open-label, pilot study was conducted involving ten subjects with severe AD. Subjects received an initial conditioning subcutaneous dose of efalizumab of 0.7 mg/kg followed by 1.0 mg/kg weekly for another 11 weeks for a total of 12 doses. The primary efficacy outcome was the change in the mean Eczema Area and Severity Index (EASI) score from baseline as measured at week 12. Monitoring of adverse events continued for 8 weeks after discontinuation of therapy. Results: EASI scores improved from a mean baseline score of 37.1 6 13.5 to 17.6 6 14.5 at week 12 (52.3% improvement; P \.0001). Six out of ten subjects reached at least a 50% improvement in EASI score by week 12. Pruritus levels decreased from 6.9 cm 6 1.8 cm to 4.9 cm 6 2.5 cm utilizing a visual analogue score (P \ .015). Overall, efalizumab was well tolerated. There were three significant adverse events during the course of this study, including thrombocytopenia, viral gastroenteritis, and a subject with worsening of disease beyond baseline levels after drug discontinuation. Limitations: It is difficult to apply these findings to larger populations of patients with AD because this study lacked a control group and involved a small number of subjects with very severe disease. Long-term efficacy and safety of efalizumab in this population is not known. Conclusions: Efalizumab therapy resulted in significant clinical improvements in six of ten subjects with severe AD. Efalizumab may serve as a good alternative to current systemic immunosuppressants used for AD; however, double-blind placebo-controlled studies are needed to test its efficacy and safety. ( J Am Acad Dermatol 2007;56:222-7.) M ost cases of childhood atopic dermatitis (AD) improve or resolve after childhood. A subset of patients, however, retain features of AD as adults, and some continue to have severe disease. Severe AD cannot be adequately controlled with topical agents. Consequently, many patients are treated with phototherapy, systemic corticosteroids, cyclosporine, azathioprine, methotrexate, and other immunosuppressant medications that carry the risk of severe adverse effects. The chronic use of current immunosuppressive agents is limited by cumulative end-organ toxicities. A targeted systemic agent that has long-term efficacy and safety has not been discovered for this chronic disease. T cells play a key role in the pathogenesis of AD as evidenced by immunohistochemical studies reveal- ing an inflammatory infiltrate of primarily CD45RO 1 memory T cells. 1,2 In addition, T cellespecific inhib- itors, such as cyclosporine and tacrolimus, improve disease outcomes. 3,4 Efalizumab, approved for the From the Department of Dermatology at Oregon Health & Science University. Supported by the Dermatology Foundation and Genentech. Conflicts of interest: Dr Simpson has had speaking engagements supported by Genentech, and Susan Tofte and Dr Hanifin have been paid consultants for Genentech. Genentech provided medi- cation for this study and some support for the investigators’ time. Accepted for publication August 14, 2006. Reprint requests: Eric Simpson, MD, Department of Dermatol- ogy, Oregon Health & Science University, 3181 SW Sam Jackson Park Rd, Portland OR 97239-3098. E-mail: simpsone@ohsu.edu. Published online October 18, 2006. 0190-9622/$32.00 ª 2007 by the American Academy of Dermatology, Inc. doi:10.1016/j.jaad.2006.08.031 222