THERAPEUTICS BJD British Journal of Dermatology The safety of ustekinumab treatment in patients with moderate-to-severe psoriasis and latent tuberculosis infection T.-F. Tsai, 1 V. Ho, 2 M. Song, 3 P. Szapary, 3 T. Kato, 4 Y. Wasfi, 3 S. Li, 5 Y.K. Shen, 5 and C. Leonardi 6 on behalf of the PHOENIX 1, PHOENIX 2, ACCEPT, PEARL and Japanese Ustekinumab Study Groups 1 Department of Dermatology, National Taiwan University Hospital, 7 Chung-Shan S. Road, Taipei, Taiwan 2 Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada Departments of 3 Immunology and 5 Biostatistics Janssen Research & Development, LLC, Spring House, PA, U.S.A. 4 Division of Clinical Science, Janssen Pharmaceutical K.K., Tokyo, Japan 6 Department of Dermatology, St Louis University, St Louis, MO, U.S.A. Correspondence Tsen-Fang Tsai. E-mail: tftsai@yahoo.com Accepted for publication 30 June 2012 Funding sources This study was funded by Janssen Research & Development, LLC, Spring House, PA, U.S.A. Conflicts of interest Listed in the Appendix. DOI 10.1111/j.1365-2133.2012.11142.x Summary Background Ustekinumab is a monoclonal antibody that targets interleukin (IL)- 12 ⁄ 23 p40 to treat psoriasis. The IL-12 pathway is also important in regulating immunity to Mycobacterium tuberculosis. Objectives To evaluate the safety of isoniazid (INH) prophylaxis for newly identified latent tuberculosis infection (LTBI) in ustekinumab-treated patients with psoriasis. Methods Safety data from 3177 psoriasis patients evaluated across five phase III trials of ustekinumab (45 or 90 mg) conducted in North America, Europe and Asia were analysed. LTBI was diagnosed based on positive tuberculin skin test or QuantiFERON Ò -TB test (Cellestis, Carnegie, Vic., Australia) without evidence of active tuberculosis. Results At baseline, 101 ⁄ 2898 (3Æ5%) non-Asian and 66 ⁄ 279 (23Æ7%) Asian patients were newly identified with LTBI, and all were treated with INH. Through week 12, among patients who received INH, rates of adverse events (AEs) representative of INH toxicity were generally comparable between control and ustekinumab-treated patients, as well as between ustekinumab dose groups. Markedly abnormal alanine transaminase values occurred with comparable inci- dences between control and ustekinumab-treated patients. The rate of study agent discontinuation due to INH toxicity was low (5 ⁄ 167, 3Æ0%) and comparable between control and ustekinumab groups through week 12. The rate of INH- related AEs did not increase disproportionately through week 28. No cases of active tuberculosis were reported in patients who received concomitant INH starting at baseline. Conclusions Across five trials of ustekinumab-treated patients with psoriasis, no cases of LTBI reactivation were observed in patients receiving concomitant INH prophylaxis for LTBI. INH prophylaxis was generally well tolerated by these patients with psoriasis. The incidence of tuberculosis varies worldwide, with the highest global burden in South-East Asia (35%), Africa (30%) and Western Pacific regions (21%). 1 Of those infected with Mycobacterium tuberculosis, only about 5–10% develop active tuberculosis during their lifetime. 2 Most other patients carry latent tuberculosis infection (LTBI), remaining asymptomatic and noninfectious while their host immune response contains the infection. The immune system may then eradicate the LTBI, or the infection may remain and become activated at a later point in time, sometimes several years later. 3 However, patients with LTBI and an impaired immune system, such as those co-infected with human immunodeficiency virus or those receiving immunosuppressive treatment, have a much higher likelihood of developing active tuberculosis. 4,5 Ó 2012 The Authors BJD Ó 2012 British Association of Dermatologists 2012 167, pp1145–1152 1145