CLINICAL RESEARCH STUDY Thalidomide for the treatment of resistant cutaneous lupus: efficacy and safety of different therapeutic regimens Maria J. Cuadrado, MD, PhD, Yousuf Karim, MD, Giovanni Sanna, MD, PhD, Elaine Smith, MD, Munther A. Khamashta, MD, PhD, Graham R. V. Hughes, MD Lupus Research Unit, The Rayne Institute, St. Thomas’ Hospital, London, United Kingdom. PURPOSE: Thalidomide is effective for the treatment of severe cutaneous lupus. Our aim was to study the safety and efficacy of different doses of thalidomide in this condition. METHODS: We studied patients with severe cutaneous lupus that was unresponsive to antimalarials, prednisolone, methotrexate, azathioprine, and cyclosporin A. Starting doses of 100 mg daily (n = 16 patients), 50 mg daily (n = 17), or 50 mg on alternate days (n = 15) were compared. The response to thalidomide was categorized as complete remission, partial remission, or no visible improvement. All patients received a baseline electromyogram (EMG) followed by repeat EMG every 3 to 6 months, or sooner if neuropathic symptoms developed. RESULTS: Forty-eight patients (46 female; mean [ SD] age, 44  12 years; range, 22 to 71 years) with discoid lupus (n = 18), subacute cutaneous lupus (n = 6), or systemic lupus erythematosus with skin involvement (n = 24) were included. The response rate was 81%, including 29 patients (60%) in complete remission and 10 (21%) in partial remission. Nine patients (19%) failed to respond. Thirteen patients (27%) developed peripheral neuropathy, which was EMG-proven in 11, including 4 patients in the 50-mg alternate-day group. Other side effects included drowsiness, constipation or abdominal pain, and amenorrhea. The relapse rate after stopping thalidomide was 67% (26/39). There was no association between a positive response to the drug and either starting doses or cumulative dose. Similarly, no association was found between peripheral neuropathy and the starting or cumulative dose. CONCLUSION: Thalidomide is effective for the treatment of severe cutaneous lupus. There were no clear dose-dependent effects. However, the high incidence of neurotoxicity, even at low doses, suggests that it may be most useful as a remission-inducing drug. © 2005 Elsevier Inc. All rights reserved. KEYWORDS: Cutaneous lupus; Neuropathy; Remission; Therapeutic Thalidomide (-N-phthalimidoglutarimide) was used initially as an over-the-counter sedative 1 and then for the treatment of morning sickness in pregnancy. It was with- drawn from use in 1961 due to its association with up to 12 000 cases of birth defects, particularly phocomelias. 2 Its reintroduction into clinical practice in 1965 followed Sheskin’s discovery of its clinical efficacy in erythema nodo- sum leprosum. 3 Since then, it has been used successfully in several conditions, including rheumatoid arthritis, 4 Behçet syn- drome, 5 multiple myeloma, 6 wasting syndrome associated with human immunodeficiency virus infection, 7 graft-versus- host disease, 8 and cutaneous features of lupus erythematosus. 9 Requests for reprints should be addressed to Maria J. Cuadrado, MD, PhD, Lupus Research Unit, The Rayne Institute, St. Thomas’ Hospital, London SE1 7EH, United Kingdom. E-mail address: mjcuadrado@yahoo.com. 0002-9343/$ -see front matter © 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2004.04.030 The American Journal of Medicine (2005) 118, 246 –250