Long-term safety experience of ustekinumab in patients with moderate to severe psoriasis (Part II of II): Results from analyses of infections and malignancy from pooled phase II and III clinical trials

• Published in: Journal of the American Academy of Dermatology 2012-05, Vol.66 (5), p.742-751
• Main Authors: Gordon, Kenneth B., MD, Papp, Kim A., MD, Langley, Richard G., MD, Ho, Vincent, MD, Kimball, Alexa B., MD, Guzzo, Cynthia, MD, Yeilding, Newman, MD, Szapary, Philippe O., MD, MSCE, Fakharzadeh, Steven, MD, PhD, Li, Shu, MS, Hsu, Ming-Chun, PhD, Reich, Kristian, MD
• Format: Article
• Language: English
• Subjects: Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Dermatology; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Humans; Infection - epidemiology; Infection - etiology; Long-Term Care; Male; malignancy; Medical sciences; Middle Aged; Neoplasms - epidemiology; Neoplasms - etiology; nonmelanoma skin cancer; psoriasis; Psoriasis - diagnosis; Psoriasis - drug therapy; Psoriasis. Parapsoriasis. Lichen; Risk Assessment; safety; Safety Management; serious infection; Severity of Illness Index; Time Factors; Treatment Outcome; Ustekinumab
• ISSN: 0190-9622; 1097-6787
• DOI: 10.1016/j.jaad.2011.06.041

Background Ustekinumab targets interleukin (IL)-12 and IL-23 in the treatment of moderate to severe psoriasis. Objective We sought to evaluate the impact of ustekinumab on infections and malignancies, both theoretical risks of blocking IL-12 and IL-23, in patients exposed up to 3 years. Methods Rates of infections and malignancies were evaluated in cumulative safety data from 3117 ustekinumab-treated patients across 4 studies. Results During the placebo-controlled periods, rates of overall infections per 100 patient-years were similar among placebo (121.0), ustekinumab 45-mg (145.7), and ustekinumab 90-mg (132.2) groups, with overlapping confidence intervals, and remained stable through 3 years in ustekinumab groups. Rates of serious infections during the placebo-controlled periods were similar between placebo (1.70) and 90-mg (1.97) groups, yet lower in the 45-mg group (0.49). Rates remained stable (90 mg) or decreased (45 mg) over time, and were comparable with those for the US psoriasis population based on a managed care database. Rates of malignancies during the placebo-controlled periods were comparable among groups (placebo: 1.70; 45 mg: 0.99; 90 mg: 0.98) and remained stable over time in ustekinumab groups. Rates of malignancies, excluding nonmelanoma skin cancer, were comparable with rates expected in the general US population based on the Surveillance, Epidemiology, and End Results database. Limitations Controlled periods do not extend beyond 12 to 20 weeks. Only 1247 patients were treated for at least 2 years, to date. Comparator database populations may not fully represent the clinical trial population. Conclusions The emerging safety profile of ustekinumab remains favorable and does not suggest increased rates of infection or malignancy through 3 years.