Abstract
Background: Tildrakizumab is a specific anti-interleukin-23p19 monoclonal antibody approved for the treatment of plaque psoriasis. Objectives: To evaluate the long-term efficacy and safety of tildrakizumab treatment for patients with moderate-to-severe psoriasis for up to 148 weeks. Methods: Pooled analysis from two double-blind, randomized controlled trials: reSURFACE 1 and reSURFACE 2. Efficacy was assessed for responders (≥ 75% improvement in Psoriasis Area and Severity Index; PASI 75) and partial responders (PASI 50–75) to tildrakizumab 100 mg and 200 mg at week 28 who were maintained on the same dose (administered every 12 weeks), and for partial responders or nonresponders (PASI < 50) to etanercept 50 mg at week 28 who, after a 4-week washout, were switched to tildrakizumab 200 mg (administered at weeks 32 and 36, and every 12 weeks thereafter). Safety was assessed in the all-patients-as-treated population. Three different methods of imputing missing data were used: nonresponder imputation (NRI), multiple imputation and observed cases. The Clinicaltrials.gov numbers are NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). Results: At week 148 (NRI), 72·6%, 53·8% and 28·9% of tildrakizumab 100-mg responders and 80·2%, 59·9% and 32·6% of tildrakizumab 200-mg responders had PASI 75, 90 and 100 responses, respectively. For partial responders to tildrakizumab 100 mg and 200 mg, the proportions of patients achieving PASI 75, 90 and 100 responses were 32·5%, 25·0% and 10·0%; and 47·1%, 27·5% and 12·8%, respectively. For patients who were partial responders or nonresponders to etanercept, the proportions of patients achieving PASI 75, 90 and 100 responses were 66·9%, 43·8% and 14·9% at week 148. Rates of discontinuations due to adverse events [tildrakizumab 100 mg: 1·7 per 100 patient-years (PYs); tildrakizumab 200 mg: 1·2 per 100 PYs] and exposure-adjusted rates of serious adverse events (5·9 per 100 PYs; 5·5 per 100 PYs), severe infections (1·1 per 100 PYs; 1·1 per 100 PYs), malignancies (0·6 per 100 PYs; 0·4 per 100 PYs) and major adverse cardiovascular events (0·4 per 100 PYs; 0·5 per 100 PYs) were low. Conclusions: Tildrakizumab was well tolerated and efficacy was well maintained in week 28 responders who continued tildrakizumab treatment through 3 years, or improved among etanercept partial responders or nonresponders who switched to tildrakizumab. What's already known about this topic?. Tildrakizumab 100 mg and 200 mg are efficacious and well tolerated with short-term use in the treatment of patients with moderate-to-severe plaque psoriasis. What does this study add?. High levels of efficacy are maintained for up to 3 years of psoriasis treatment with tildrakizumab. There is a favourable long-term safety profile with both tildrakizumab 100 mg and 200 mg, with a low incidence of adverse events of special interest through 3 years.
| Original language | English |
|---|---|
| Journal | British Journal of Dermatology |
| Volume | 182 |
| Issue number | 3 |
| Pages (from-to) | 605-617 |
| Number of pages | 13 |
| ISSN | 0007-0963 |
| DOIs | |
| Publication status | Published - 01.03.2020 |
Funding
This publication was funded by Almirall R&D, Barcelona, Spain. Conflicts of interest: K.R. has served as an advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Biogen, Boehringer Ingel-heim, Celgene, Centocor, Covagen, Forward Pharma, Fresenius Medical Care, GlaxoSmithKline, Janssen-Cilag, Kyowa Hakko Kirin, LEO Pharma, Lilly, Medac, Merck Sharp & Dohme, Mil-tenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Sam-sung Bioepis, Sanofi, Takeda, UCB, Valeant and Xenoport. R.B.W. has received grants and/or honoraria from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Celgene, Janssen, Lilly, LEO Pharma, Novartis, Pfizer, Sanofi, UCB Pharma and Xenoport. L.I. has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Almirall, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Janssen-Cilag, Kyowa, LEO Pharma, MSD, Novartis, Pfizer and UCB. L.P. has received grants or research support from or participated in clinical trials (paid to the institution) for AbbVie, Almirall, Amgen, Boehringer Ingelheim, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Roche, Sanofi and UCB; has received honoraria or consultation fees from AbbVie, Almirall, Amgen, Baxalta, Biogen, Boehringer Ingelheim, Celgene, Gebro, Janssen, LEO Pharma, Lilly, Merck-Serono, Merck Sharp & Dohme, Mylan, Novartis, Pfizer, Regeneron, Roche, Samsung Bioepis, Sandoz, Sanofi and UCB; and has participated in company-sponsored speakers’ bureaus for Celgene, Janssen, Lilly, Merck Sharp & Dohme, Novartis and Pfizer. A.I. has received honoraria for serving on advisory boards from Maruho, Janssen, AbbVie, Novartis, Eli Lilly Japan, Celgene and Sun Pharma Japan. M.O. has received honoraria for serving on advisory boards from Maruho, Janssen, AbbVie, Novartis, Eli Lilly Japan, Celgene, Eisai, Kyowa Hakko Kirin, LEO Pharma, Pfizer Japan, Mit-subishi Tanabe Pharma, Boehringer Ingelheim, Bristol-Myers Squibb Company and Sun Pharma Japan. I.P.-C. and M.F. are employees of Almirall. M.H. has served as a statistical consultant for Almirall. S.R. is an employee of Sun Pharmaceuticals. M.G.L. has received research funds (paid to the institution) from AbbVie, Amgen, Boehringer Ingelheim, Celgene, Eli Lilly, Incyte, Janssen/Johnson & Johnson, Kadmon, LEO Pharma, Medimmune/AstraZeneca, Novartis, Ortho-dermato-logics, Pfizer, Sciderm, UCB5 and Vidac; and is a consultant for Allergan, Aqua, Arcutis, Boehringer Ingelheim, Bristol-Myers Squibb, LEO Pharma, Menlo, Mitsubishi Pharma/Neu-roderm LTD, Promius/Dr Reddy, Regeneron, Theravance Bio-pharma and Verrica. W.C. has received honoraria or fees for serving on advisory boards or as a speaker from Sun Pharmaceuticals, Lilly, Novartis and Janssen. A.B. has served as a scientific adviser and/or clinical study investigator for AbbVie, Aclaris, Akros, Allergan, Almirall, Amgen, Arena, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Der-mira, Inc., Eli Lilly and Company, FLX Bio, Galderma, Genen-tech/Roche, GlaxoSmithKline, Janssen, LEO, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant and Vidac; and as a paid speaker for Janssen, Regeneron and Sanofi Genzyme. D.T. has received honoraria or fees for serving on advisory boards, or as a speaker or consultant, from AbbVie, Almirall, Bioskin, Boehringer Ingelheim, Celgene, Dignity, Galapagos, GlaxoSmithKline, Janssen, LEO Pharma, Lilly, Medac, Merck Sharp & Dohme, Morphosys, Novartis, Pfizer, Regeneron, Samsung, Sandoz-Hexal, Sanofi, Sun Pharmaceuticals and UCB; and has received grants from Celgene and Novartis.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
