Prior Biologic Use, Body Weight May Impact Guselkumab Efficacy in Psoriasis

Real-world patients with moderate-to-severe psoriasis were shown to exhibit impaired efficacy with guselkumab treatment if they had history of prior biologic use, particularly anti-interleukin (IL)-17 exposure, with heavier patients linked with delayed onset of therapeutic response.

Higher body weight and prior biologic use may impact the effectiveness of guselkumab among patients with moderate-to-severe plaque psoriasis, according to study findings published online in Therapeutic Advances in Chronic Disease.

Despite prior randomized clinical trials (RCTs) indicating the FDA-approved anti-interleukin (IL)-23 inhibitor guselkumab as effective and safe in the treatment of psoriasis, researchers highlight that external validity via real-world data is warranted due to factors that cause certain patients to be excluded from these studies, including those with significant comorbidities, history of combination therapy use, and prior biologic use.

“In previous studies, the Psoriasis Area Severity Index (PASI) improvements after receiving biologics were lower in real-life settings than in RCTs. The efficacy could be determined by various factors including age, weight, baseline PASI, prior biologic failures, and prior exposure to biologics,” they said.

Notably, guselkumab was shown in the German multi-center PERSIST trial to be safe and effective in improving health-related quality-of-life and skin manifestations of patients with moderate-to-severe psoriasis in a real-world setting, but researchers of this study acknowledged that increased data will expand understanding of the drug’s real-world performance profile in psoriasis.

In the current study, authors retrospectively investigated use of guselkumab in an Asian cohort of patients with moderate-to-severe plaque psorasis being treated at 4 dermatology centers in Taiwan between June 2018 until November 2020 (N = 135; mean [SD] age, 46.46 [13.32] years; 78% male).

Effectiveness of guselkumab was assessed using the degree of improvement in the PASI scores at baseline and after 4, 12, 20, 28, and 36 weeks. Additionally, predictors of effectiveness were also evaluated, including body weight and the impact of prior biologic use (tumor necrosis factor [TNF]-α, IL-12/23, and IL-17 inhibitors) on PASI 75 response.

Among the study cohort, 67% of patients achieved PASI 75 at week 36. Compared with biologic-naive patients, multivariate logistic regression analysis findings indicated that significantly fewer participants exposed to 1 prior biologic achieved PASI 75 at weeks 4 (OR, 0.08; 95% CI, 0.01-0.48), 20 (OR, 0.21; 95% CI, 0.05-0.74), 28 (OR, 0.04; 95% CI, 0.00-0.35), and 36 (OR, 0.07; 95% CI, 0.00-0.68).

Patients previously treated with more than one biologic were also less likely to achieve PASI 75 at weeks 12 (OR, 0.05; 95% CI, 0.01-0.22), 20 (OR, 0.03; 95% CI, 0.01-0.16), 28 (OR, 0.00; 95% CI, 0.00-0.03), and 36 (0.00; 95% CI, 0.00-0.044), compared with biologic-naive patients.

Furthermore, those previously treated with anti-IL-17 agents, compared with TNF-α and IL-12/23 inhibitors, were shown to have lower PASI improvements to guselkumab than biologic-naive patients at weeks 12 (OR, 0.19; 95% CI, 0.03-0.90), 20 (OR, 0.10; 95% CI, 0.02-0.55), and 28 (OR, 0.03; 95% CI, 0.00-0.29).

Patients with higher body weight exhibited a reduced PASI 75 response at week 4 with guselkumab treatment (OR, 0.94; 95% CI, 0.88-0.99), but this association was attenuated after week 12 until the end of our study.

“Body weight only influences the effectiveness in the early phase of treatment, suggesting delayed onset of a therapeutic effect in patients with higher body weight,” concluded the study authors. “Patients who had a switch from anti-IL-17 showed a worse response than those who switched from other classes of biologics.”

Reference

Hung YT, Lin YJ, Chiu HY, Huang YH. Impact of previous biologic use and body weight on the effectiveness of guselkumab in moderate-to-severe plaque psoriasis: a real-world practice. Ther Adv Chronic Dis. Published online September 29, 2021. doi:10.1177/20406223211046685