Risankizumab (Skyrizi) Dose Optimization Effective, Safe for Patients with Psoriasis

Jensen Yeung, MD

Credit: Dermatology Update

Patients with moderate-to-severe plaque psoriasis using dose optimization for risankizumab will find it efficacious and safe, according to new findings, aligning with the positive results of dose optimization seen with other biologics.¹

These findings represent the conclusion of a recent letter to the editor highlighting research into optimizing dosing for risankizumab, an interleukin (IL)-23 inhibitor for the chronic inflammatory skin disease psoriasis. This research was authored in part by Jensen Yeung, from the division of dermatology at Women's College Hospital in Toronto, Canada.

“While optimized dosing strategies have been elucidated for other biologics, risankizumab's potential has not been fully explored,” Yeung and colleagues wrote. “This study aims to explore the effectiveness and safety of risankizumab dose optimization in adult patients with moderate-to-severe plaque psoriasis.”^1,2

Study Design

A multicenter, international, retrospective study was conducted by the investigators, during which the team reviewed patient records from tertiary academic dermatology clinics found within both Canada and Portugal. They determined their primary outcome would be a 90%-or-greater improvement in participants’ Psoriasis Area and Severity Index (PASI90) scores and the achievement of a Physician Global Assessment (PGA) score of clear or almost clear (PGA 0/1).

The research team made up their study population of adults aged 18 years and older who had moderate-to-severe psoriasis. These subjects were treated with the standard on-label risankizumab regimen of 150 mg administered subcutaneously at the 0 and 4-week mark, followed every 12 weeks.

Adjustments to treatments, including shifts in the dosing intervals, were decided upon based on individual needs of the participants. The team monitored participant safety in their documentation of adverse events (AEs) and rates of treatment cessation.

Among the 511 subjects in the study treated with subcutaneous risankizumab, 16% were shown to require dose optimization. These subjects’ average age was found to be 51.4 years, with 63.4% of the group being male.

Before beginning risankizumab, these individuals had failed approximately 1.1 non-biologic systemic treatments and 0.91 biologics. Among the prior biologics were guselkumab, adalimumab, and ustekinumab, while the most commonly used non-biologic options were acitretin, methotrexate, and cyclosporine.

Notable Findings on Optimization

The research team reported that the average PASI score among subjects was 3.7 at the time of the subjects dose optimization. The team added that participants had been on the standard dose of risankizumab for an average of 212.2 days.

The investigators found that 72% of subjects switched to an 8-week dosing schedule, noting that this was chiefly due to their initial regimen response being inadequate. Only 4.8% were reported to have chosen to extend their predetermined dosing intervals for personal reasons, and these individuals had a PASI score of 0 prior to the optimization decision.

Following the trial participants’ dose optimization, the researchers noted that the average follow-up period had been 190.2 days, concluding that 90.2% of participants were successful in achieving either PASI90 or a PGA 0/1 score. The team also highlighted that 37.8% reached PASI100 and that 80.5% attained a PASI score of 2 or lower.

They added that 54.9% had a PASI score which was under 1. The subjects who opted for a longer dosing interval maintained their PASI response, while 89.7% of the subjects who optimized to a shorter interval were successful in achieving PASI90 or PGA 0/1.

The investigators highlighted the fact that only 3 participants reported at least a single AE, suggesting that AEs were rare. A single case of alopecia resulted in cessation of treatment, and there was 1 unrelated thrombosis event reported.

All AEs transpired in individuals who had a shortened dosing schedule. After the dose was optimized, it was found that 18.3% of subjects discontinued risankizumab. 73% of these discontinuations resulted from insufficient efficacy.

“Dose optimization of biologics is relatively well-studied in moderate-to-severe plaque psoriasis, with our previous reports affirming enhancement of patient outcomes without compromising safety,” they wrote. “Our current study aligns with these findings, marking, to our knowledge, the first to showcase the effectiveness and safety of dose optimized risankizumab for plaque psoriasis.”

The investigators did acknowledge, however, that their outcomes’ generalizability may be held back by their study’s heterogeneous population and its limited sample size, suggesting a need for rigorous and controlled studies.

References

1. ^{Bagit, A., Maliyar, K., Mansour, M., Georgakopoulos, J.R., Rankin, B., Lytvyn, Y., Zaaroura, H., Park, Y.J., Wang, E., Mufti, A., Torres, T., Le, A.M., Vender, R., Prajapati, V.H. and Yeung, J. (2024), Effectiveness and safety of risankizumab dose optimization in adult patients with plaque psoriasis: An international multicentre retrospective cohort study. J Eur Acad Dermatol Venereol. https://doi.org/10.1111/jdv.20373.}
2. ^{Benzaquen M, Munshi M, Bossart S, Feldmeyer L, Emelianov V, Yawalkar N, et al. Long-term dose optimization of adalimumab via dose spacing in patients with psoriasis. Bioengineering (Basel). 2022; 9(8): 387.}