A recent study from Sweden investigated dose escalation practices among psoriasis patients treated with biologic therapies, specifically adalimumab (ADA), etanercept (ETN), and ustekinumab (UST). The retrospective analysis, utilizing registry data from 2009 to 2021, aimed to determine the frequency and outcomes associated with dose escalation in these treatments. The results shed light on the comparative effectiveness and potential cost implications of dose adjustments in managing moderate-to-severe psoriasis.
The study included 554 patients undergoing 946 treatment episodes with ADA, ETN, or UST. Standard dosing was defined as 40 mg of ADA every two weeks, 50 mg of ETN weekly, and 45 or 90 mg of UST every 12 weeks, adjusted for patient weight. Data collected encompassed patient demographics, disease severity (measured by Psoriasis Area and Severity Index - PASI, and Dermatology Life Quality Index - DLQI), and treatment details. Dose escalation was defined as exceeding these standard dosing regimens.
Dose Escalation Frequency and Drug Survival
The analysis revealed that 17% of treatment episodes involved dose escalation. Notably, UST exhibited the highest cumulative incidence of dose escalation compared to ETN and ADA. Researchers reported significantly higher hazard ratios for dose escalation with UST. Specifically, the cumulative incidence of dose escalation at two years was approximately 10% for ADA and ETN, but 25% for UST.
Despite the higher frequency of dose escalation with UST, treatment discontinuation within one year post-escalation was lower (less than 10%) compared to ADA and ETN (approximately 50%). Hazard ratios indicated a higher likelihood of discontinuation after dose escalation for ADA and ETN relative to UST, suggesting UST may offer more sustained treatment efficacy following dose adjustments. PASI scores improved after dose escalation for ETN, but not significantly for ADA or UST.
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.
Implications and Limitations
The study's findings highlight potential cost-effectiveness concerns for ADA and ETN, particularly with the increasing availability of biosimilars. The authors suggest that further research should compare dose escalation with alternative strategies and assess the broader impacts on clinical effectiveness and patient quality of life.
The researchers acknowledged limitations, including potential biases due to changes in treatment practices over time and the non-randomized study design. Discrepancies in reported frequencies of dose escalation compared to existing literature may stem from differences in definitions and study methodologies.
