Five-year safety of tildrakizumab in patients with moderate-to-severe psoriasis from two phase 3 trials (reSURFACE 1 and reSURFACE 2): number needed to harm for occurrence of adverse events of special interest

Abstract

Background

Five-year tildrakizumab safety data have been reported as exposure-adjusted incidence rates (EAIRs) of patients with events per 100 patient-years (PYs) of exposure.

Objectives

To present 5-year safety data from reSURFACE 1/2 phase 3 trials as EAIRs of events per 100 PYs of exposure, and the number needed to harm (NNH) for one adverse event of special interest (AESI) to occur.

Methods

Pooled analysis from two randomized controlled trials in patients with moderate-to-severe plaque psoriasis (n = 1800). PSOLAR registry was used as safety reference data for NNH estimation.

Results

Rates of AESI with tildrakizumab were comparable with rates reported in PSOLAR. The NNH for one-year severe infection occurrence was 412 with tildrakizumab 200 mg, and negative for tildrakizumab 100 mg due to lower rates in reSURFACE trials; the NNH for malignancy was 990 for one year with tildrakizumab 100 mg (negative for tildrakizumab 200 mg); and the NNH for major adverse cardiovascular events was 355 for one year with tildrakizumab 200 mg (negative for tildrakizumab 100 mg).

Conclusion

Tildrakizumab demonstrated a favorable safety profile over 5 years with low rates of AESI, comparable to those of the PSOLAR. Consequently, the NNH for AESI with tildrakizumab were very high or negative due to lower event rates for tildrakizumab.

Keywords:

• Adverse event of special interest
• number needed to harm
• psoriasis
• tildrakizumab

Acknowledgments

Medical writing and editorial support was provided by Eva Mateu PhD of TFS HealthScience and funded by Almirall R&D, Barcelona, Spain.

Ethics statement

The original reSURFACE 1 and reSURFACE 2 trials were conducted following the ethical principles of the Helsinki Declaration and were approved by local institutional review boards or ethics committees at each study site (7). All patients provided written informed consent before their inclusion in the trials.

Author contributions

AE, DJ and KGdJ substantially contributed to the conception and design of the work, analysis and interpretation of data, and drafted the work and revised it critically for important intellectual content. DT substantially contributed to the conception and design of the work, acquisition, analysis and interpretation of data, and drafted the work and revised it critically for important intellectual content. All authors approved the final version of the manuscript.

Disclosure statement

AE has received research funding from Pfizer, Eli Lilly and Company, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation, and honoraria as consultant and/or speaker from AbbVie, Almirall, LEO Pharma, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly and Company, Novartis, Galderma, Union Therapeutics, Dermavant, UCB, Mylan, Bristol-Myers Squibb and Janssen Pharmaceuticals; KGdJ is an employee of Almirall. DJ has received funding from AbbVie, Almirall, Amgen, Biogen, Boehringer ingelheim, Bristol Myers Squibb, Celgene, Fresenius Kabi, Janssen-Cilag, Leo, Lilly, MSD, MEDAC, Novartis, Pfizer, UCB and Sanofi; DT has received honoraria as an advisor, speaker and/or investigator from AbbVie, Almirall, Amgen, Biogen-Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen-Cilag, LEO Pharma, Novartis, Pfizer, Regeneron, Roche-Possay, Samsung, Sanofi and UCB.

Data availability statement

The datasets generated or analyzed during this study are available from the corresponding author on reasonable request.

Additional information

Funding

This publication was funded by Almirall R&D, Barcelona, Spain.