Funding sources This study was funded by Janssen Research & Development, LLC, Spring House, PA, U.S.A.
The safety of ustekinumab treatment in patients with moderate-to-severe psoriasis and latent tuberculosis infection
Article first published online: 29 OCT 2012
© 2012 The Authors. BJD © 2012 British Association of Dermatologists
British Journal of Dermatology
Volume 167, Issue 5, pages 1145–1152, November 2012
How to Cite
Tsai, T.-F., Ho, V., Song, M., Szapary, P., Kato, T., Wasfi, Y., Li, S., Shen, Y.K., Leonardi, C., on behalf of the PHOENIX 1, PHOENIX 2, ACCEPT, PEARL and Japanese Ustekinumab Study Groups (2012), The safety of ustekinumab treatment in patients with moderate-to-severe psoriasis and latent tuberculosis infection. British Journal of Dermatology, 167: 1145–1152. doi: 10.1111/j.1365-2133.2012.11142.x
Conflicts of interest Listed in the Appendix.
- Issue published online: 29 OCT 2012
- Article first published online: 29 OCT 2012
- Accepted manuscript online: 14 JUL 2012 10:14AM EST
- Accepted for publication 30 June 2012
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.