THERAPEUTICS BJD British Journal of Dermatology Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up K.A. Papp, 1 C.E.M. Griffiths, 2 K. Gordon, 3 M. Lebwohl, 4 P.O. Szapary, 5 Y. Wasfi, 5 D. Chan, 5 M.-C. Hsu, 5 V. Ho, 6 P.D. Ghislain, 7 B. Strober 1,8 and K. Reich 9 ; on behalf of the PHOENIX 1, PHOENIX 2 and ACCEPT Investigators 1 Probity Medical Research, 135 Union Street East, Waterloo, ON N2J1C4, Canada 2 Dermatology Centre, University of Manchester, Manchester Academic Health Science Centre, Manchester, U.K. 3 Feinberg School of Medicine, Northwestern University, Chicago, IL, U.S.A. 4 Mount Sinai School of Medicine, New York, NY, U.S.A. 5 Janssen Research & Development, LLC, Spring House, PA, U.S.A. 6 University of British Columbia, Vancouver, BC, Canada 7 Cliniques Universitaires Saint-Luc, Universite ´ Catholique de Louvain, Brussels, Belgium 8 Department of Dermatology, University of Connecticut School of Medicine, Farmington, CT, U.S.A. 9 Dermatologikum Hamburg, Hamburg, Germany Correspondence Kim A. Papp. E-mail: kapapp@probitymedical.com Accepted for publication 2 January 2013 Funding sources Funded by Janssen Research & Development, LLC, Spring House, PA, U.S.A. Conflicts of interest See Appendix. DOI 10.1111/bjd.12214 Summary Background Long-term safety evaluations of biologics are needed to inform patient management decisions. Objectives To evaluate the safety of ustekinumab in patients with moderate-to- severe psoriasis treated for up to 5 years. Methods Safety data were pooled from four studies of ustekinumab for psoriasis. Rates of adverse events (AEs), serious AEs (SAEs) and AEs of interest [infections, nonmelanoma skin cancers (NMSCs), other malignancies and major adverse car- diovascular events (MACE)] per 100 patient-years (PY) of follow-up were ana- lysed by ustekinumab dose (45 or 90 mg) and by year of follow-up (years 1–5) to evaluate the dose response and impact of cumulative exposure. Observed rates of overall mortality and other malignancies were compared with those expected in the general U.S. population. Results Analyses included 3117 patients (8998 PY) who received one or more doses of ustekinumab, with 1482 patients treated for ‡ 4 years (including 838 patients ‡ 5 years). At year 5, event rates (45 mg, 90 mg, respectively) for over- all AEs (242Æ6, 225Æ3), SAEs (7Æ0, 7Æ2), serious infections (0Æ98, 1Æ19), NMSCs (0Æ64, 0Æ44), other malignancies (0Æ59, 0Æ61) and MACE (0Æ56, 0Æ36) were com- parable between dose groups. Year-to-year variability was observed, but no increasing trend was evident. Rates of overall mortality and other malignancies were comparable with those expected in the general U.S. population. Conclusions No dose-related or cumulative toxicity was observed with increasing duration of ustekinumab exposure for up to 5 years. Rates of AEs reported in ustekinumab psoriasis trials are generally comparable with those reported for other biologics approved for the treatment of moderate-to-severe psoriasis. Long-term treatment is required for the management of moderate-to-severe psoriasis. The safety of conventional systemic therapies and phototherapy has been established after several decades of clinical application; 1,2 however, long- term use may be limited due to potential end-organ toxici- ties (methotrexate, ciclosporin) 3 and increased risk of skin cancer [psoralen plus ultraviolet A (PUVA)]. 2 Biologics have been approved for the treatment of psoriasis for 10 years. While the positive benefit–risk assessments demonstrated in the initial short-term studies 4–8 are reassuring, long-term safety evaluations are needed to identify adverse events (AEs) that occur rarely or develop over time with cumulative 844 British Journal of Dermatology (2013) 168, pp844–854 Ó 2013 The Authors BJD Ó 2013 British Association of Dermatologists