A recent Japanese study investigated the use of escalated dosages in treating moderate to severe psoriasis (PsO) with interleukin (IL)-inhibiting biologics.
The study encompassed 982 patients treated with various IL-inhibiting biologics, including brodalumab (BRO; Siliq; Bausch Health Companies Inc.), guselkumab (GUS; Tremfya; Janssen Biotech, Inc.), ixekizumab (IXE; Taltz; Lilly USA, LLC), risankizumab (RIS; Skyrizi; AbbVie Inc.), secukinumab (SEC; Cosentyx; Novartis Pharmaceuticals Corp.), and ustekinumab (UST; Stelara; Janssen Biotech, Inc.).
Findings
Within 12 months, researchers observed dose escalation for all IL-inhibiting biologics except GUS and RIS: 44% for UST, 37.2% for IXE, 3.4% for SEC, and 1.4% for BRO. The odds of dose escalation were significantly lower for all products compared to UST. Notably, no dose escalation was seen for RIS.
Background
IL inhibitors are generally effective in treating PsO; however, some patients may not respond adequately or may lose their response over time, necessitating a treatment change. Dose escalation, which involves increasing the dosage or reducing the dosing interval, has been explored as a strategy to improve patient response.
In Japan, dose escalation is mentioned in the prescription information for UST and IXE. In contrast, above-label dosing is common in other countries due to the lack of efficacy within the first six months of treatment.
Study Details
This non-interventional study utilized data from the Japan Medical Data Center Payer-Based Database (JMDC) from July 1, 2005, to May 31, 2022. Participants were selected based on a claim with the International Classification of Diseases 10th Revision and at least one claim in the same month or later for BRO, GUS, IXE, RIS, SEC, or UST.
Eligibility criteria included having at least six months of data prior to the earliest IL inhibitor claim post-PsO diagnosis and completion of the induction period as per product guidelines. The study evaluated outcomes from the first maintenance claim until the end of data availability.
Researchers calculated the expected daily dose (EDD) as the label-recommended maintenance dose divided by the recommended treatment interval. The average daily dose (ADD) was the actual maintenance dose divided by the actual treatment interval. Dose escalation was defined as a ≥20% increase in ADD over EDD on at least two claims during the follow-up period.
Results
At six months, 32.1% of UST and 29.6% of IXE patients experienced dose escalation, compared to 0.5% for SEC and none for BRO, GUS, and RIS. At twelve months, 44.4% of UST patients experienced dose escalation, compared to 37.2% for IXE, 3.4% for SEC, 1.4% for BRO, and none for GUS and RIS.
The researchers found that the odds of dose escalation for UST were significantly higher than for other treatments, with adjusted odds ratios ranging from 0.003 to 0.546. This indicates that UST’s odds of escalation were roughly twice as high as IXE’s and significantly higher compared to other IL inhibitors.
When considering just one claim above the threshold, the six and twelve-month dose escalation rates were 43.4% and 47.9% for IXE, 40.8% and 49.4% for UST, 10.2% and 17.8% for SEC, 7.7% and 12.3% for BRO, 0.5% and 2.1% for GUS, and none for RIS.
Conclusion
The study observed dose escalation for all IL-inhibiting biologics used to treat PsO in Japan, except for GUS and RIS, aligning with similar findings from US studies. The researchers concluded that dose escalation might indicate an unmet need in PsO treatment. They suggested further research to explore health resource utilization, cost implications of dose escalation, and its underlying causes.
