AAD Reading Room | Meta-analysis Compares Efficacy of Approved Targeted Therapies for Moderate-to-Severe Psoriasis

In people with moderate-to-severe psoriasis, IL-17 and IL-23 inhibitors outperformed other biologics at the 1-year mark, according to a meta-analysis in the Journal of Dermatological Treatment.

The analysis’ primary evaluation included nine randomized clinical trials (RCTs) investigating comparative efficacy at 1 year. Outcomes were measured by the Psoriasis Area and Severity Index (PASI).

The review was conducted by a study team based in the United Kingdom, Denmark, and Sweden, led by first author Najeeda Yasmeen, BSc, a health outcomes researcher with Symmetron Limited, a London-based health consultancy. The following study excerpts have been edited for length and clarity.

What was the impetus for this analysis?

In recent years, the number of treatments available for moderate-to-severe psoriasis has increased, enabling dermatologists to optimize therapy for better outcomes. However, choosing among therapies can be challenging.

Previous meta-analyses have investigated psoriasis therapies over the first few months of treatment, but only two assessed long-term efficacy (one at 6 months and another at 1 year). Since the publication of these studies, four new psoriasis treatments — certolizumab pegol, guselkumab, tildrakizumab, and risankizumab — have been approved.

As new therapies become licensed and new evidence emerges, evaluation of available therapies helps inform treatment decisions.

How was the review designed? What was included?

The objective of this systematic literature review and network meta-analysis was to update available knowledge by analyzing new evidence and recently licensed interventions.

This study aimed to compare the efficacy of approved targeted therapies (brodalumab, ixekizumab, secukinumab, guselkumab, risankizumab, tildrakizumab, ustekinumab, adalimumab, certolizumab pegol, etanercept, infliximab, apremilast) for moderate-to-severe psoriasis after around 1 year of therapy. .

Which therapies were shown to be most effective?

The synthesis of evidence from RCTs reporting PASI outcomes at weeks 48-52 showed that risankizumab, brodalumab, and guselkumab had the highest likelihood of improvement, followed by ixekizumab and secukinumab.

Risankizumab was statistically superior to ixekizumab but not statistically different from brodalumab or guselkumab. Brodalumab and guselkumab produced greater PASI responses than ixekizumab, but the differences were not statistically significant. All drugs in the analysis demonstrated superiority to ustekinumab and etanercept.

In a secondary analysis, studies from the first analysis were supplemented with the inclusion of long-term extensions of placebo-controlled RCTs reporting maintenance phase outcomes for other licensed therapies, including certolizumab pegol, infliximab, and apremilast. Results were consistent across both analyses, suggesting the superiority of IL-17s and IL-23s over other systemic therapies at the 1-year mark.

What are the next potential steps in investigating these treatments?

The current analysis did not investigate adverse events or health-related quality of life indicators because of heterogeneous reporting among trials. To enable a full evaluation of therapies for moderate-to-severe plaque psoriasis, future long-term studies should investigate these outcomes and report them in a more uniform way, researchers wrote.

Further, long-term comparative effectiveness trials in which patients receive a licensed therapy for full induction and maintenance periods are needed to validate the current conclusions.

Clinical implications

  • IL-17 and IL-23 inhibitors were found most effective in helping patients reach therapeutic goals after 1 year of treatment.
  • Risankizumab, brodalumab, and guselkumab were associated with the highest likelihood of response, followed by ixekizumab and secukinumab.
  • All drugs in the analysis demonstrated superiority to ustekinumab and etanercept.

Najeeda Yasmeen and Laura Sawyer are Symmetron employees, as was Kinga Malottki when the work was undertaken; all were consultants to LEO Pharma for this study. Eydna Didriksen Apol is a LEO Pharma employee. Lars-Åke Levin has received consulting fees from LEO Pharma and Gregor B. Jemec has received honoraria from AbbVie, Coloplast, Galderma, Inflarx, LEO Pharma, MSD, Pierre-Fabre, UCB, and his department received grants from AbbVie, Actelion, Janssen -Cilag, LEO Pharma, Novartis, Regeneron, Serono and UCB for his participation as an investigator.

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