Biologic Discontinuation: Older Versus Younger Patients with Psoriasis

An increase in biologic therapy discontinuation is observed among elderly individuals with psoriasis versus younger adult patients, according to new findings, especially if elderly patients are treated with interleukin (IL)-23 inhibitors.¹

These findings were the conclusions of new research conducted to assess the drug survival of IL-23 or IL-17 inhibitor treatments approved for moderate-to-severe psoriasis treatment, specifically comparing patients aged ≥65 years to those younger than 65.

This research was led by Andrea Chiricozzi, from the department of dermatology at the Università Cattolica Del Sacro Cuore in Rome, Italy. The investigators sought to expand upon real-world data connected to the management of psoriasis in elderly patients as the population is frequently kept out of clinical research into biologics due to various reasons.²

“We compared cumulative drug survival rates of both IL-17 and IL-23 inhibitors in elderly vs younger patients, identifying predictive factors associated with the increased risk of discontinuation due to different causes in the subcohort of elderly patients,” Chiricozzi and colleagues wrote.

Background and Methods

The research team used a subset derived from data drawn from a previously published multicenter, retrospective, multinational cohort study for their analysis. The team selected patients from the entire cohort who were aged 65 years or older who also had moderate-to-severe chronic plaque psoriasis.

These individuals would also have received treatment with an IL-23 inhibitor such as guselkumab, tildrakizumab, or risankizumab, or with an IL-17 inhibitor such as secukinumab, ixekizumab, or brodalumab. Such therapies would have been provided as either a first-line biological treatment or as a switching option between February 2015 - October 2021.

The investigators compared the complementary age group of individuals under the age of 65 years from the same set of information, for the purposes of comparison. They determined their age threshold of 65 years based upon standard definitions of elderly populations and other real-world data studies in the psoriasis space.

There were 19 hospitals and non-hospital-based dermatology centers used for data collection across Canada, Italy, the Czech Republic, Greece, Spain, Portugal, and Switzerland. Multiple treatment courses would have been permitted due to switching observed among the aforementioned therapeutic options. All information was drawn from subjects’ medical records.

The research team’s primary objective was to assess the cumulative probability of drug survival for each of the biologic therapies evaluated. Survival of the drugs was defined as the duration of each course of therapy, from initiation to the point of patient withdrawal or final clinical observation.

The team categorized the biologics as IL-23 or IL-17 inhibitors. They evaluated the cumulative probability of drug survival by class and drug, looking at interruption due to any possible cause, lack of efficacy, or presence of adverse events (AEs), comparing both the older and younger subcohorts.

Findings

Overall, there were 4178 participants and 4866 treatment courses assessed within the investigators’ research. They had involved 934 older subjects and 3244 younger subjects in their research, finding that the individuals under 65 years were shown to have a higher drug survival rate compared to elderly ones (log-rank P < .006).

This distinction was substantial and seen in treatment courses involving IL-23 inhibitors (P < .001), though it was not seen among those treated with IL-17 inhibitors (P = .2). The research team found that in their univariable and multivariable analyses, there was a link between older age and a risk increase of discontinuation (univariable analysis: HR: 1.229, 95% CI 1.062–1.422; P < .006; multivariable analysis: HR: 1.199, 95% CI 1.010–1.422; P = .0377).

Once they adjusted for confounders, the investigators noted that anti-IL-23 agents had diminished the risk of subjects’ choice to discontinue (HR: 0.520, 95% CI 0.368–0.735; P < .001). Prior IL-17 inhibitor therapy was shown by the team to raise the likelihood of cessation.

“In summary, our study revealed lower drug survival rates of IL-23 inhibitors in elderly patients compared to a younger population, which is not observed with IL-17 inhibitors,” they wrote. “In elderly patients, drug survival of IL-23 inhibitors was better than that of IL-17 inhibitors… treatment with guselkumab or risankizumab was protective as regards drug survival, whereas prior treatment with IL-17 inhibitors increased the hazard of treatment discontinuation.”

References

1. ^{Chiricozzi A, Coscarella G, Puig L, Vender R, Yeung J, Carrascosa J-M, et al. Age affects drug survival rates of interleukin (IL)-17 and IL-23 inhibitors in patients with plaque psoriasis: Results from a retrospective, multicentric, multi-country, cohort study. J Eur Acad Dermatol Venereol. 2024; 00: 1–11. https://doi.org/10.1111/jdv.20143.}
2. ^{Torres T, Puig L, Vender R, Yeung J, Carrascosa JM, Piaserico S, et al. Drug survival of interleukin (IL)-17 and IL-23 inhibitors for the treatment of psoriasis: a retrospective multi-country, multicentric cohort study. Am J Clin Dermatol. 2022; 23(6): 891–904.}