Study Compares Dose Escalation with Biologics in Psoriasis

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Psoriasis has seen a significant expansion in treatment options, particularly with the advent of IL-17 and IL-23 inhibitors, which are among the most effective treatments available.¹ Precision medicine, facilitated by advances in immunology and reduced sequencing costs, is making tailored dosing more feasible.² Dose escalation, either by increasing the drug dose or shortening administration intervals, is a strategy for patients with moderatetosevere psoriasis who do not respond adequately to standard treatments.³ While guidelines for dose escalation are limited to a few biologics, this approach is commonly used in other conditions like inflammatory bowel disease.

Researchers hypothesize the economic benefits of dose escalation may be enhanced by the availability of biosimilars. A recent review highlighted that dose escalation is prevalent in psoriasis treatment but lacked data on its outcomes.3 To address this, a retrospective study out of Sweden was planned to analyze the frequency and effects of dose escalation using registry data for adalimumab (ADA), etanercept (ETN), and ustekinumab (UST).⁴

“Whilst direct comparisons are difficult, reflecting differences in definitions, data sources, patient populations, and follow-up, it may be noted that the cumulative incidence of dose escalation at 2 years was approximately 10% for ADA and ETN, and 25% for UST,” researchers wrote.

Materials and Methods

This retrospective study analyzed dose escalation patterns for ADA, ETN, and UST.Standard doses were 40 mg of ADA every 2 weeks, 50 mg of ETN weekly, and 45 or 90 mg of UST every 12 weeks, with specific considerations based on patient weight. Data collected for the study included patient demographics, disease severity, and treatment details, with psoriasis area and severity index (PASI) and dermatology life quality index (DLQI) assessed throughout follow-up. Outcomes included the frequency of dose escalation and drug survival, with drug survival analyzed using Kaplan-Meier estimators and Cox Proportional Hazards models to compare treatments, with UST as the reference.

Results

From 2009 to 2021, 554 patients included in the study underwent 946 treatment episodes with ADA, ETN, or UST. Researchers found patients receiving UST generally had more severe disease, with higher peak PASI and DLQI scores and a greater prevalence of psoriatic arthritis and nail lesions compared to those on ADA and ETN. Among these treatment episodes, the study reported 17% involved dose escalation beyond labeled dosing. UST had the highest cumulative incidence of dose escalation, with researchers reporting hazard ratios for dose escalation being “significantly higher” for UST compared to ETN and ADA.

In terms of effectiveness, the study found that about 50% of ADA and ETN patients discontinued treatment within a year of dose escalation, while UST patients typically continued treatment for over 5 years post-escalation. The study stated hazard ratios indicated a higher likelihood of discontinuation after dose escalation for ADA and ETN compared to UST. PASI scores improved after dose escalation for ETN but not significantly for ADA or UST.

The study found the prevalence of above-standard dosing was low for ADA and ETN but increased for UST, rising from 13% at 6 months to 54% at 60 months. For UST, dose escalation was evenly split between increased frequency and dose. Scenario analysis considering body weight showed that 40% of UST patients were on above-standard dosing at 6 months, increasing to 62% at 60 months.

Conclusion

The study found that roughly 17% of treatment episodes involved dose escalation, with UST showing the highest frequency of such dosing compared to ADA and ETN. Despite the higher frequency of dose escalation with UST, treatment discontinuation within a year was lower for UST (less than 10%) compared to about 50% for ADA and ETN. Researchers stated this suggests UST may be more effective in maintaining treatment over time.

The study's findings highlight potential cost-effectiveness concerns for ADA and ETN, especially as biosimilars become more common. Although the study aligns with existing literature regarding dose escalation, discrepancies in reported frequencies might stem from differences in definitions and study methodologies. Researchers stated the study’s limitations include potential biases due to changes in treatment practices over time and non-randomized study design. They suggested that further research should compare dose escalation with alternative strategies and assess the broader impacts on clinical effectiveness and patient quality of life.

References

1. Sbidian E, Chaimani A, Garcia-Doval I, et al. Systemic pharmacological treatments for chronic plaque psoriasis: a network meta‐analysis. Cochrane Database of Syst Rev. 2022;2022(8):1–744. doi: 10.1002/14651858.CD011535.pub5
2. Gunter NV, Yap BJM, Chua CLL, et al. Combining understanding of immunological mechanisms and genetic variants toward development of personalized medicine for psoriasis patients. Front Genet. 2019;10:395. doi:10.3389/fgene.2019.00395
3. Gambardella A, Licata G, Sohrt A. Dose adjustment of biologic treatments for moderate-to-severe plaque psoriasis in the real world: A systematic review. Dermatol Ther (Heidelb). 2021;11(4):1141-1156. doi:10.1007/s13555-021-00559-z
4. Svedbom A, Wennerström C, Hjelm F, et al. 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