Researchers Examine Short-term, Long-term Efficacy of Biologics, Oral Agents for Plaque Psoriasis

In a meta-analysis comparison of biologics and oral treatments for moderate to severe plaque psoriasis, results suggest that brodalumab, guselkumab, ixekizumab, and risankizumab-rzaa were associated with the highest response rates in both short-term and long-term therapy, according to study findings published in JAMA Dermatology.¹

Treatment options for patients with moderate to severe psoriasis have greatly expanded in the past decade, with FDA approved biologics in the US including tumor necrosis factor inhibitors adalimumab, etanercept, infliximab, and certolizumab pegol; the interleukin (IL)-12/23 inhibitor ustekinumab; the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab; and the IL-23 inhibitors tildrakizumab-asmn, guselkumab, and risankizumab-rzaa. While the wide variety in biologic agents and oral treatments promotes innovation within psoriasis treatment, study authors note that it can be difficult for clinicians to compare the efficacy of each medication.

In a separate study published in the Journal of the American Academy of Dermatology, researchers uncovered that biologics ixekizumab and brodalumab exhibited greater cumulative clinical benefit for patients with psoriasis through analyses measured by the Psoriasis Area and Severity Index (PASI).² In those study findings, ixekizumab was shown to have a greater 12-week and 16-week efficacy among all biologics examined, with 22% of patients achieving PASI 100, indicating a complete resolution of all disease.

In the current study, researchers sought to perform a meta-analysis of available biologics and oral treatments for plaque psoriasis by synthesizing data from multiple studies, due to the absence of head-to-head randomized trials. The study authors derived data based on the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines, in which a bayesian network meta-analysis was conducted to estimate short-term PASI response rate and a traditional meta-analysis measured long-term PASI rates.

The systematic literature review included results from the Embase, MEDLINE, and Cochrane Central Register databases, and it was conducted on December 4, 2017, and updated on September 17, 2018. Eligible studies included phase 2, 3, or 4 clinical trials of treatments licensed by the FDA and the European Medicines Agency for adults with moderate to severe psoriasis.

Data was measured using the PASI 75, 90, and 100 assessments at 10 to 16 weeks (short-term) or 44 to 60 weeks (long-term) from baseline. Overall, the meta-analysis included 60 trials that met all inclusion criteria. Treatments included for short-term analyses were risankizumab-rzaa, ixekizumab, brodalumab, guselkumab, secukinumab, infliximab, certolizumab pegol (400 mg and 200 mg), ustekinumab, adalimumab, tildrakizumab-asmn (100 mg and 200 mg), etanercept, apremilast, dimethyl fumarate, and placebo. Long-term analyses excluded certolizumab pegol, tildrakizumab-asmn, and dimethyl fumarate.

Based on short-term analyses the highest PASI 90 rates were seen with biologics risankizumab-rzaa (71.6%; 95% credible interval [CrI], 67.5%-75.4%), brodalumab (70.8%; 95% CrI, 66.8%-74.6%), ixekizumab (70.6%; 95% CrI, 66.8%-74.6%), and guselkumab (67.3%; 62.5%-71.9%).

Similarly, treatments that exhibited short-term efficacy were additionally among those that showed the highest PASI 90 rates for long-term efficacy, but with different effectiveness (risankizumab-rzaa, 79.4% [95% CI, 75.5%-82.9%]; guselkumab, 76.5% [95% CI, 72.1%-80.5%]; brodalumab, 74.0% [95% CI, 69.3%-78.1%]; ixekizumab, 73.9% [95% CI, 69.9%-77.5%]). Findings were consistent for short-term and long-term PASI 75 and 100 responses.

“In the absence of head-to-head randomized clinical trials of treatments for moderate to severe plaque psoriasis, this study provides what we believe to be a comprehensive assessment of the comparative short-term and long-term efficacy among several novel treatments,” the study authors wrote. They noted that because findings of the study are based on clinical trial data, future research may study the comparative efficacy among treatments in real-world settings.

References

1. Armstrong AW, Puig L, Joshi A, et al. Comparison of biologics and oral treatments for plaque psoriasis: a meta-analysis [published online February 5, 2020]. JAMA Dermatol. doi:10.1001/jamadermatol.2019.4029.

2. Warren RB, Gooderham M, Burge R, et al. Comparison of cumulative clinical benefits of biologics for the treatment of psoriasis over 16 weeks: results from a network meta-analysis [published online December 26, 2019]. J Am Acad Dermatol. doi: 10.1016/j.jaad.2019.12.038.