Abstract
Background: Short-term interleukin-23p19 inhibition by tildrakizumab improves plaque psoriasis and appears to be well tolerated. Objectives: Safety and tolerability were assessed for up to 64 weeks of tildrakizumab therapy using pooled data from three randomized controlled trials for moderate-to-severe psoriasis. Methods: Data pools for the placebo-controlled (up to 16 weeks) and full trial periods (up to 64 weeks) were analysed (n = 2081). Results: In the placebo-controlled period, frequencies of treatment-emergent adverse events (TEAEs; range 47·9–54·0%), serious TEAEs (range 1·4–2·3%), discontinuations due to AEs (range 0·6–1·9%), major adverse cardiovascular events (MACEs; range 0·0–0·1%) and severe infections (range 0·0–0·3%) were comparable between tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept. In the full trial period, exposure-adjusted rates (patients per 100 patient-years) for TEAEs, serious TEAEs and discontinuations due to AEs with tildrakizumab 100 mg and 200 mg were lower than or comparable with the placebo rates, and lower than with etanercept. Exposure-adjusted rates of MACEs (range 0·0–0·5) and severe infections (range 0·9–2·0) were comparable among groups. No TEAEs of inflammatory bowel disease or suicide were reported. Candida skin infections were infrequent at frequencies of 0·1%, 0·3%, 0·0% and 0·0% for the tildrakizumab 100 mg, tildrakizumab 200 mg, placebo and etanercept groups, respectively, in the placebo-controlled period, and exposure-adjusted rates of 0·2, 0·7, 0·0 and 0·0, respectively, in the full trial period. Oral candidiasis was also infrequent. Conclusions: Up to 64 weeks of tildrakizumab was well tolerated, with low rates of serious TEAEs, discontinuations due to AEs, and AEs of clinical interest.
| Original language | English |
|---|---|
| Journal | British Journal of Dermatology |
| Volume | 179 |
| Issue number | 3 |
| Pages (from-to) | 615-622 |
| Number of pages | 8 |
| ISSN | 0007-0963 |
| DOIs | |
| Publication status | Published - 09.2018 |
Funding
This research was supported by Merck & Co., Inc., Kenilworth, NJ, U.S.A. Medical writing and editorial assistance were provided by Erin P. Scott, PhD, of Scott Medical Communications, LLC. This assistance was funded by Merck & Co., Inc. A.B. has served as a scientific adviser and clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Amgen, Boehringer Ingelheim, Celgene, Dermavant, Dermira, Eli Lilly and Company, Genentech/Roche, GlaxoSmithKline, Janssen, LEO Pharma, Meiji, Merck & Co. Inc., Novartis, Pfizer, Purdue Pharma, Regeneron, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB, Valeant and Vidac; and as a paid speaker for Eli Lilly and Company, Janssen, Regeneron and Sanofi Genzyme. K.R. has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Amgen, Biogen Idec, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Lilly, Medac, Merck & Co. Inc., Novartis, Pfizer, Vertex and Takeda. K.A.P. has been a scientific and medical consultant for AbbVie, Amgen, Anacor, Active Biotech, Allergan, Arcutis, Astellas, AstraZeneca, Basilea, Baxalta, Bayer, Biogen Idec, BMS, Boehringer Ingelheim, CanFite, Celgene, Coherus, Dermira, Eli Lilly, Forward Pharma, Galderma, Genentech, GSK, Janssen, Kyowa Hakko Kirin, Kythera, LEO Pharma, Merck Sharpe and Dohme, Merck Serono, Novartis, Pfizer, Regeneron, Rigel, Roche, Sanofi Genzyme, Sun Pharma, Takeda, UCB, Valeant and Xenon; an investigator for AbbVie, Amgen, Anacor, Allergan, Arcutis, Astellas, Basilea, Biogen Idec, BMS, Boehringer Ingelheim, Celgene, Coherus, Dermira, Eli Lilly, Galderma, Genentech, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck Sharpe and Dohme, Merck-Serono, Novartis, Pfizer, Regeneron, Roche, Takeda, UCB and Valeant; and a speaker for AbbVie, Amgen, Allergan, Astellas, Biogen Idec, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Genen-tech, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck Sharpe and Dohme, Merck-Serono, Novartis, Pfizer, Sanofi Genzyme, Sun Pharma, Takeda, UCB and Valeant. A.B.K. has served as a consultant and investigator for Merck & Co. Inc., AbbVie, Janssen, Novartis, Dermira and UCB; served as a consultant to Lilly; and received fellowship funding from Janssen and AbbVie. M.G. has been an investigator, advisor and/or speaker for Amgen, AbbVie, BMS, Boehringer Ingelheim, Celgene, Dermira, Galderma, GSK, Janssen, Kyowa Hakko Kirin, LEO Pharma, Lilly, Merck, Merck Serono, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Valeant and UCB. S.K.T. has participated in trials supported by grants from Merck & Co. Inc. R.S. has provided professional services to LEO Pharma, Amgen, Novartis, Merck & Co. Inc., Celgene, Coherus Biosciences, Janssen, Regeneron, MedImmune, GlaxoSmithKline, Cutanea, Samson Clinical, Boehringer Ingel-heim, Pfizer, MSD, Oncobiologics, Roche, Eli Lilly and Company and Bayer. D.T. has served as a consultant, advisory board member and/or investigator for AbbVie, Almirall, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Dignity, Galderma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Lilly, Maruho, Medac, Medimmune, MSD, Novartis, Regeneron, Sandoz, Sanofi Aventis, Sun Pharma, Takeda and Pfizer. Q.L.,
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
