Drug Survival of Psoriasis Biologics Associated With Efficacy, Safety Profile

Drug survival rates of biologics in patients with psoriasis were shown to be associated with their effectiveness and safety profiles, in which incidence of psoriatic arthritis (PsA), nail involvement, and other factors were indicated as effect modifiers. Results were published today in JAMA Dermatology.

As known contributors of inferior health outcomes, frequent discontinuation rates and poor adherence have been associated with biologics approved for the treatment of psoriasis. Drug survival, a proxy measure for the effectiveness, safety, adherence, and tolerability of a medicine, has also been shown to be influenced by effect modifiers in certain groups of patients with different characteristics.

“Identifying effect modifiers for the biologics used for psoriasis management and their drug survival in routine clinical practice may help patients and clinicians identify the best treatment option, potentially avoiding or delaying treatment failure,” said the study authors.

“Network meta-analyses of randomized clinical trials in psoriasis have suggested that newer biologics that target interleukin (IL)-23 p19 and IL-17 generally have a higher treatment efficacy compared with the older biologics that target tumor necrosis factor(TNF)–α and ustekinumab. However, drug response and safety of treatment with biologics for psoriasis in clinical trials do not fully reflect the routine clinical setting."

Researchers conducted a prospective cohort study to investigate drug survival associated with the effectiveness and safety of commonly used biologics for psoriasis and to identify effect modifiers for these biologics and their survival.

Data on patients with psoriasis were supplied by the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2021. These patients were treated with the biologics adalimumab (n = 6607; 41.0%), ustekinumab (n = 5405; 33.5%), secukinumab (n = 2677; 16.6%), guselkumab (n = 730; 4.5%), and ixekizumab (n = 703; 4.4%).

“​​We conducted a survival analysis and fitted separate flexible parametric models for drug survival as a proxy for effectiveness and safety… We included the biologics as a categorical variable and used ustekinumab as the main comparator to report the analyses, as ustekinumab was the drug with highest survival in our previous analyses.”

Noteworthy differences between the biologic cohorts included proportion of patients with PsA (adalimumab, 29.2%; secukinumab, 34.4%; ustekinumab, 23.5%; ixekizumab, 41.0%; guselkumab. 26.0%) and the proportion of biologic-naive patients (adalimumab, 74.8%; secukinumab, 35.8%; ustekinumab, 46.5%; ixekizumab, 18.2%; guselkumab, 23.6%).

Of the 16,122 treatment courses assessed, crude survival functions at year 1 for measures of effectiveness and safety for treatment were provided:

• Crude survival functions at year 1 for measures of effectiveness with adalimumab were 0.81 (95% CI, 0.80-0.82), 0.89 for ustekinumab (95% CI, 0.88-0.89), 0.86 for secukinumab (95% CI, 0.85-0.87), 0.94 for guselkumab (95% CI, 0.92-0.96), and 0.86 for ixekizumab (95% CI, 0.83-0.89)
• Crude survival functions at year 1 for measures of safety with adalimumab were 0.91 (95% CI, 0.90-0.91), 0.94 for ustekinumab (95% CI, 0.94-0.95), 0.94 for secukinumab (95% CI, 0.92-0.94), 0.96 for guselkumab (95% CI, 0.94-0.98), and 0.92 for ixekizumab (95% CI, 0.89-0.94)

Findings derived from adjusted survival curves of the multivariable model for effectiveness indicated that treatment with guselkumab exhibited higher survival (adjusted HR [aHR], 0.13; 95% CI, 0.03-0.56) and adalimumab had lower survival (aHR, 2.37; 95% CI, 2.03-2.76) compared with ustekinumab. Secukinumab and ixekizumab had similar survival curves over time.

Moreover, guselkumab, ustekinumab, and secukinumab showed similar adjusted survival curves for safety, whereas adalimumab (aHR, 1.66; 95% CI, 1.46-1.89) and ixekizumab (aHR, 1.52; 95% CI, 1.13-2.03) had lower survival compared with ustekinumab. PsA, previous biologic exposure, nail involvement, and ethnicity were cited as effect modifiers for survival in association with treatment effectiveness.

“This information on longer-term treatment persistence, safety, and tolerability may help patients and their clinicians make an informed decision to initiate treatment with a biologic therapy,” concluded the study authors.

Reference

Yiu ZZN, Becher G, Kirby B, et al. Drug survival associated with effectiveness and safety of treatment with guselkumab, ixekizumab, secukinumab, ustekinumab, and adalimumab in patients with psoriasis. JAMA Dermatol. Published online July 6, 2022. doi:10.1001/jamadermatol.2022.2909