The safety of ustekinumab treatment in patients with moderate-to-severe psoriasis and latent tuberculosis infection

• Published in: British journal of dermatology (1951) Vol. 167; no. 5; pp. 1145 - 1152
• Main Authors: Tsai, T.-F., Ho, V., Song, M., Szapary, P., Kato, T., Wasfi, Y., Li, S., Shen, Y.K., Leonardi, C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-11-2012; Wiley-Blackwell
• Subjects: Adult; Alanine transaminase; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antitubercular Agents - therapeutic use; Bacterial diseases; Biological and medical sciences; Case-Control Studies; Clinical trials; Data processing; Dermatology; Double-Blind Method; Female; Human bacterial diseases; Humans; Immunity; Infection; Infectious diseases; Interleukin 12; Interleukin-12 - immunology; Interleukin-23 - immunology; Isoniazid; Isoniazid - therapeutic use; Latent Tuberculosis - prevention & control; Male; Medical sciences; Middle Aged; Monoclonal antibodies; Mycobacterium tuberculosis; Prophylaxis; Psoriasis; Psoriasis - complications; Psoriasis - drug therapy; Psoriasis - immunology; Psoriasis. Parapsoriasis. Lichen; Randomized Controlled Trials as Topic; Severity of Illness Index; Skin tests; Toxicity; Tuberculin; Tuberculin Test; Tuberculosis; Tuberculosis and atypical mycobacterial infections; Ustekinumab; Human; Latent tuberculosis; Skin disease; Treatment; Psoriasis; Dermatology
• ISSN: 0007-0963; 1365-2133
• 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®‐TB test (Cellestis, Carnegie, Vic., Australia) without evidence of active tuberculosis.
Results  At baseline, 101/2898 (3·5%) non‐Asian and 66/279 (23·7%) 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 incidences between control and ustekinumab‐treated patients. The rate of study agent discontinuation due to INH toxicity was low (5/167, 3·0%) 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.
See also the Commentary by Shear