Study Identifies Unreported Adverse Drug Reaction Linked to Tildrakizumab for Psoriasis

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There is a potential signal for new adverse drug reactions (ADRs) among those with psoriatic disease treated with tildrakizumab, according to recent findings, and this might allow for valuable support for clinical monitoring as well as prediction of risk.¹

This new research was led by Jinger Lin, from the department of dermatology at Fujian Medical University’s Union Hospital in Fujian, China. Lin et al. sought to describe ADRs which had been linked to tildrakizumab monotherapy by gathering US Food and Drug Administration Adverse Event Reporting System (FAERS) data.

The FAERS is the largest repository of pharmacovigilance data in the world, with its design involving recording of ADRs and medication errors by such individuals as manufacturers, healthcare professionals, clinicians, and others.

“It greatly facilitates the FDA’s comprehensive assessment of drug safety after a drug is marketed,” Lin and colleagues wrote. “Our findings have potential to provide physicians and health policymakers with meaningful insights in monitoring (tildrakizumab)-associated ADRs, thereby fostering rational use of clinical medications.”²

Trial Design

The investigators carried out a retrospective pharmacovigilance analysis in which they implemented FAERS database information. The FAERS database includes a comprehensive set of information spread among 7 categories: ADR data, drug information, treatment dates, demographic and administrative details, reporting source data, patient outcomes, and drug administration indications.

The research team focused their assessments on individuals who implemented the interleukin (IL)-23 inhibitor tildrakizumab from the first quarter of 2018 through to the fourth quarter of 2023. The team decided on this specific timeframe given the tildrakizumab approval by FDA officials in March 2018.

A disproportionality analysis was implemented by the investigators to look into potential signals. Signals are statistical indicators with a potentially causal relationship between ADRs and the administration of a particular drug.

As they compared all reported ADRs in their analysis, the research team quantified such signals through the use of several different methods. These included the proportional reporting ratio (PRR), reporting odds ratio (ROR), multi-item gamma Poisson shrinker (MGPS) algorithms, and Bayesian confidence propagation neural network (BCPNN).
Study Findings

The investigators found 1,177 reports between Q1 2018 - Q4 2023 in which tildrakizumab monotherapy was shown to be the primary suspect drug within the FAERS database, following their exclusion of duplicates. These reports were part of a 10,530,937-ADR report dataset in FAERS.

ADRs which were shown to be linked with tildrakizumab treatment were reported by the research team across 27 system organ classes. The team found 32 significant disproportionality signals based on Preferred Terms which had matched the algorithms.

The investigators noted that subjects’ median time to onset for their ADRs was shown to be 194 days, adding that there was an interquartile range of 84 - 329 days. They found that most ADRs took place within the initial 1 - 3 months follwoing tildrakizumab treatment’s initiation.

There were several unexpected significant ADRs, including herpes simplex, coronavirus infection, atrial fibrillation, diverticulitis, and aortic valve incompetence.

“It is crucial to understand that signal detection should not be interpreted as a direct causal relationship, but rather the association between drugs and ADRs should be analysed to provide real-world evidence,” they wrote. “Therefore, it is important to use this database to assess the relationship between TIL and its ADRs to provide a more comprehensive perspective on TIL vigilance analyses.”

References

1. ^{Lin J, Chen X, Luo M, Zhuo Q, Zhang H, Chen N, Zhuo Y, Han Y. Safety of tildrakizumab: a disproportionality analysis based on the FDA adverse event reporting system (FAERS) database from 2018-2023. Front Pharmacol. 2024 Jul 10;15:1420478. doi: 10.3389/fphar.2024.1420478. PMID: 39050749; PMCID: PMC11267582.}
2. ^{Hosoya R, Ishii-Nozawa R, Kurosaki K, Uesawa Y (2021). Analysis of factors associated with hiccups using the FAERS database. Pharm. (Basel) 15 (1), 27. 10.3390/ph15010027.}