Differences in Psoriasis Treatment: Ustekinumab Dose Escalation vs Adalimumab, Etanercept Discontinuation

Dose escalations were more frequent with ustekinumab in patients with psoriasis compared with adalimumab and etanercept, highlighting varied outcomes for dose optimization in psoriasis management. | Image Credit: Daniel Beckemeier - stock.adobe.com

Patients with psoriasis treated with either adalimumab, etanercept, or ustekinumab underwent dose escalations more frequently with ustekinumab compared with the other 2 treatments and discontinued treatment after dose escalation occurred more often with adalimumab and etanercept than with ustekinumab, according to a study published in the Journal of Dermatological Treatment.¹

Treatment options for psoriasis, a chronic inflammatory skin disease, have increased significantly with the most recent approvals, with IL [interleukin]-17 and IL-23 inhibitors as the most effective. For the past decade, IL-17 and IL-23 inhibitors have improved in efficacy and safety, providing an unprecedented change in treatment management.² As psoriasis treatment continues to evolve, researchers identify new potential therapeutic targets to create a future treatment.

New and currently available treatments have helped improve the understanding of immunology and reduce costs, leading to precision medicine becoming more viable.¹ Tailored dosing includes one aspect of precision medicine where clinicians achieve dose escalation either by increasing the amount of drug administered or reducing the interval between administrations. In a previous study, researchers determined above-label dosing of biologics for psoriasis treatment was linked with substantial additional pharmacy costs but few significant safety concerns.³

Researchers conducted a retrospective study on prospectively collected registry data with the objective of exploring the frequency and outcomes of dose escalation among patients treated with adalimumab, etanercept, and ustekinumab.¹ A total of 554 patients received 946 treatment episodes of adalimumab, etanercept, or ustekinumab from 2009 to 2021. Patients treated with ustekinumab had numerically higher peak Psoriasis Area and Severity Index (PASI), peak Dermatology Life Quality Index, prevalence of psoriatic arthritis, and prevalence of nail lesions compared with patients treated with adalimumab and etanercept.

Out of the 946 treatment episodes, 17% had at least 1 instance of the above-labeled dosing. Researchers estimated the cumulative incidence of dose escalation at 4.1 per 100 treatment years. During the follow-up period, ustekinumab had HRs for dose escalation of 2.27 (95% CI, 1.55-3.35) and 2.46 (95% CI, 1.69-3.60), compared with etanercept and adalimumab, respectively, in unadjusted models. In the adjusted models, ustekinumab had HRs for dose escalation of 1.93 (95% CI, 1.25-2.98) and 2.20 (95% CI, 1.42-3.41), compared with etanercept and adalimumab, respectively.

About 50% of patients treated with adalimumab and etanercept discontinued treatment within 1 year of dose escalation, while patients treated with ustekinumab remained on treatment for more than 5 years after dose escalation. Researchers estimated the HRs for treatment discontinuation after dose escalation with adalimumab and etanercept compared with ustekinumab at about 2.41 (95% CI, 1.32-4.38) and 5.08 (95% CI, 3.06-8.46), respectively, in the unadjusted models. After dose escalation, the HRs for treatment discontinuation with adalimumab and etanercept compared with ustekinumab were 3.10 (95% CI, 1.56-6.18) and 7.15 (95% CI, 3.96-12.94), respectively.

The median PASI score was higher after compared with before dose escalation for etanercept (P = .036), and researchers found no statistically significant difference between after and before dose escalation PASI scores for adalimumab (P = .832) or ustekinumab (P = .300). The proportion of patients on treatment with above-standard dosing at given time points was comparatively low for adalimumab and etanercept. The proportion of patients on the above-labeled dosing for ustekinumab increased from each time interval evaluated to the next.

The study faces limitations due to the data collection methods that took place over a long period of time and treatment practices that may have changed throughout the timeframe of the study. It is important to consider that between 2009 and 2015, ustekinumab was the most recently approved biologic for psoriasis treatment and therefore potentially the last-line agent for many patients. Researchers may have residual confounding because the study was not randomized, and readers should interpret estimated differences in frequency of dose escalation with caution. The overall generalizability and transportability of the findings may be limited, particularly as the flat pricing of the 2 ustekinumab dosing options and the lack of formulary restrictions in Sweden may reduce the transportability of the results to settings where pricing and formulary rules are different.

“Furthermore, data on the safety of treatments that are used for more prolonged periods at above standard dosing would be important to consider,” study authors concluded.

References

1. Svedbom A, Wennerström C, Hjelm F, Tjärnlund A, Ståhle M. Frequency and outcomes of treatment dose escalation with biologics in moderate-to-severe psoriasis: a Swedish register study. J Dermatolog Treat. 2024;35(1):2398170. doi:10.1080/09546634.2024.2398170

2. Batta S, Khan R, Zaayman M, Limmer A, Kivelevitch D, Menter A. IL-17 and -23 inhibitors for the treatment of psoriasis.  EMJ Allergy & Immunology. Published online April 12, 2023. doi:10.33590/emjallergyimmunol/10301362

3. Bagel J, Glick B, Wu JJ, et al. Dose escalation and associated costs in biologic treatment of psoriasis based on real-world data. J Med Econ. 2021;24(1):782-791. doi:10.1080/13696998.2021.1937187