IL-17, IL-23 Inhibitors Show Fastest Times to Meaningful Clinical Response for Psoriasis

Risankizumab, ixekizumab, bimekizumab, secukinumab, and guselkumab have the fastest time to achieve a 90% or greater reduction in Psoriasis Area and Severity Index (PASI 90) score from baseline, new findings suggest, and no major differences between the drugs are noted.¹

These findings suggest that interleukin (IL)-17 and IL-23 inhibitors may be considered by dermatologists as necessitating the shortest time for meaningful clinical response for those with psoriasis. These data were the conclusion of new research led by Pushkar Aggarwal, from the department of dermatology at the University of Cincinnati College of Medicine.

“A network meta-analysis can factor in indirect comparisons and determine if the differences are significant as long as there are a certain number of direct comparisons to connect the network between each of the therapeutic options,” Aggarwal et al. wrote. “The objective of this analysis was to compare the time to onset of action among the various systemic therapies available for plaque psoriasis using a weighted mean average analysis and a network meta-analysis.”^1,2

Trial Design

The investigators focused their analysis on published data from clinical research on drugs with recent approvals from the US Food and Drug Administration (FDA) for treatment of plaque psoriasis. A MEDLINE database search was conducted to look into randomized clinical trials (RCTs) that evaluated the use of biologics, immunomodulators, or oral small molecule inhibitors.

The analysis used search terms such as "randomized clinical trial," "plaque psoriasis," and "PASI,” excluding findings involving other forms of psoriasis, such as nail or pustular psoriasis. The research team also only looked at data assessing FDA-approved doses for the anti-psoriasis drugs evaluated in their analysis.

The team’s criteria for selection further narrowed the research to those presenting graphical data indicating the percentage of subjects who achieved PASI 75 or PASI 90 over time, assessed using weeks. The team required the RCTs to have 10 participants minimum in each treatment cohort and they excluded research which only used a placebo comparator. This is due to the fact that placebo groups typically do not reach the PASI 75 or PASI 90 thresholds among 50% of subjects.

The studies the investigators included in their evaluation were required to have at least 2 active treatment cohorts, allowing the investigators to make direct comparisons between different agents. They also excluded studies if neither the medication of interest nor the active comparator were able to achieve a 50% response rate by the study’s conclusion.

Independent reviews of these studies were carried out by the authors, with the aim being determining that the RCTs meet inclusion criteria. As the analysis was based on publicly available data, no IRB approval or informed consent was shown to be necessary.

Drug Comparison Findings

Overall, the research team concluded that IL-17 inhibitors were shown to be the quickest therapeutic options to achieve both PASI 75 and PASI 90 responses among trial subjects. They found that risankizumab followed closely in the weighted mean analysis.

During the study’s meta-analysis, the investigators noted that the shortest time to PASI 75 was observed with brodalumab, bimekizumab, and ixekizumab therapy, though they added that there was not a statistically significant distinction observed between these medications.

Bimekizumab was shown by the research team to have been significantly faster than other drugs in successfully achieving PASI 75. In terms of PASI 90, the team noted that the fastest responses were observed with bimekizumab, ixekizumab, risankizumab, secukinumab, and guselkumab, They added that there were no significant distinctions between these drug options, although they explained that bimekizumab outperformed the others in speed to PASI 90.

“Clinical trials involving some therapeutics, such as deucravacitinib and infliximab, did not meet the eligibility criteria in this analysis,” they wrote. “As such, we were unable to compare these therapeutics. In addition to the time to onset, the safety profile of each drug and its contraindications need to be heavily weighed when deciding on a therapeutic to initiate for a patient.”¹

References

1. ^{Aggarwal P, Fleischer AB Jr. IL-17 and IL-23 Inhibitors Have the Fastest Time to Meaningful Clinical Response for Plaque Psoriasis: A Network Meta-Analysis. J Clin Med. 2024 Aug 29;13(17):5139. doi: 10.3390/jcm13175139. PMID: 39274352; PMCID: PMC11396496.}
2. ^{Rouse B., Chaimani A., Li T. Network meta-analysis: An introduction for clinicians. Intern. Emerg. Med. 2017;12:103–111. doi: 10.1007/s11739-016-1583-7.}