The Busy Arena of Psoriasis Treatments: Improving the Clinician’s Ability to Make the Right Therapeutic Choice

Abstract

We read with great interest the recent article by Torres et al. entitled “Drug Survival of IL‐12/23, IL‐17 and IL‐23 Inhibitors for Psoriasis Treatment: A Retrospective Multi‐Country, Multicentric Cohort Study” [1], published in the March 2021 issue of the American Journal of Clinical Dermatology. In this large retrospective multicentric study, the authors stratified interleukin-17/interleukin-23 inhibitors approved for psoriasis by drug survival duration. They found that the biologic agent presenting the greatest cumulative probability of survival at 18 months was risankizumab, followed by guselkumab, brodalumab, ustekinumab, ixekizumab, and secukinumab. In light of these clinically relevant observations, we would like to further portray the current landscape of comparative effectiveness studies of psoriasis therapeutics. In the last decade, treatment options for psoriasis have rapidly expanded and dermatologists face the dilemma of which drug is best for a particular patient [2, 3]. Tailoring the best agent should take into account multiple aspects, including the distribution of lesions, coexistence of arthritis, administration method, patient characteristics (e.g., age, body mass index), and comorbidities. For example, Torres et al. [1] found that not only the use of a specific biologic agent contributed to drug survival, but that female sex, higher body mass index, and previous exposure to biologic agents were all linked with decreased drug survival; Yiu et al. [4] found co-existing psoriatic arthritis had a mixed effect on drug survival, depending on the biologic agent used. Given the complexity of choosing the optimal psoriasis treatment and the limited time frame for treatment selection and patient education during a real-world clinical setting, comparative effectiveness information should guide therapeutic decisions. Moreover, as psoriasis is well characterized by mechanistic studies molecularly identifying disease drivers, there is a need for research methodologies bridging the gap between bench-side findings and reliable clinical data routinely collected at the point of care. Studies utilizing observational comparative effectiveness research collect data in real-world settings often extracted from electronic health records, health insurance, and pharmacy benefits claims, and are useful in comparing alternative methods of prevention, diagnosis, and treatment in daily practice. However, broad assessment of their validity in comparison to gold-standard randomized controlled trials (RCTs) is lacking. Methodologies such as matching-adjusted indirect comparisons between RCTs has been suggested [5, 6], but these may also be subject to significant caveats, primarily because of the loss of complete randomization. Both RCTs and observational comparative effectiveness research may answer which treatment is superior, but each have their own limitations (Table 1) [7]. Major limitations of observational studies include: selection bias, confounding, missing information, and treatment inconsistencies. Randomized controlled trials are designed with better control of the key exposures of interest, but are also generally limited by size and duration, volunteer selection, and the participating patients and settings may be more limited, reducing external validity or generalizability. Network meta-analysis studies are commonly used to aggregate data across multiple studies to compare psoriasis treatments, but may contain potential This comment refers to the article available at: https:// doi. org/ 10. 1007/ s4025702100598-4