Dose Escalation of Biologic PsO Treatment in Japan

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A recent study out of Japan examined the use of escalated dosage in patients treating moderate to severe psoriasis (PsO) with interleukin (IL)-inhibiting biologics.¹

The study included a total of 982 patients treated with a variety of 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.).

Within 12 months, researchers from the investigation said dose escalation was used for all IL-inhibiting biologics other than GUS and RIS: 44% for UST, 37.2% for IXE, 3.4% for SEC, and 1.4% for BRO. Tada et al reported odds of dose escalation were significantly lower from all products relative to UST, and that escalation was seen for all products except for RIS.

Background

Although IL inhibitors can be effective in treating PsO, investigators recognized that some patients may fail to respond or lose response over time, requiring a change in treatment. Dose escalation has been explored for improved response and can be implemented by reducing dosing interval or increasing dose amounts.

According to the study, dose escalation is mentioned in prescription information for UST and IXE in Japan. In most other countries however, above-label dosing is common for most biologics, primarily due to the lack of efficacy in the first 6 months.

Based on prior studies, such as a US analysis of dose escalation of RIS compared to other biologic treatments, Tada et al hypothesized that dose escalation could be effective for patients not achieving disease control on standard dosing.²

Study

In this non-interventional study, data was collected from the Japan Medical Data Center Payer-Based Database (JMDC) from July 1, 2005, through May 31, 2022. Participants were selected based on a claim with International Classification of Disease 10th Revision and at least one claim in the same month or after the earliest PsO diagnosis for BRO (n = 104), GUS (n = 207), IXE (n = 159), RIS (n = 135), SEC (n = 215), or UST (n = 196).

To be eligible for the study, patients had to have ≥ 6 months of data availability prior to the earliest IL inhibitor claim following PsO diagnosis (index date), completed the induction period according to each products’ guidelines, and to have ≥ 6 month of data availability following the first maintenance claim. Outcomes were evaluated during follow-up period from the first maintenance claim until the end of data availability.

Expected daily dose (EDD) was calculated by researchers as the label recommended maintenance dose divided by the recommended treatment interval. Average daily dose (ADD) was calculated as the actual maintenance dose divided by the actual treatment interval. Dose escalation was defined by the researchers as ≥ 20% increase in ADD over EDD on ≥2 claims during the follow-up period.

The study evaluated the proportion of patients experiencing dose escalation at 6 and 12 months, and statistically significant differences were tested using multivariable regressions.

Results

At 6 months, Tada et al reported that 32.1% of UST and 29.6% of IXE patients experienced dose escalation, compared to 0.5% for SEC and 0.0% for BRO, GUS and RIS. At 12 months, they reported that 44.4% of UST patients experienced dose escalation, compared to 37.2% for IXE, 3.4% for SEC, 1.4% for BRO, and 0.0% for GUS and RIS.

The researchers noted that relative to UST, differences in escalation rates at 6 and 12 months were significantly lower for all other treatments, with adjusted odds ratios ranging from 0.003 to 0.546. Tada et al wrote this means odds of escalation for UST were roughly twice as high as IXE, 30 times higher than SEC and hundreds of times higher than other IL inhibitors. 

When requiring just 1 claim above the threshold, Tada et al reported 6/12-month dose escalation rates were 43.4/47.9% for IXE, 40.8/49.4% for UST, 10.2/17.8% for SEC, 7.7/12.3% for BRO, 0.5/2.1% for GUS and 0.0/0.0% for RIS. No escalation was seen for patients treated with RIS in any scenario.

Conclusion

Tada et al observed dose escalation for all IL-inhibiting biologics used to treat PsO in Japan except for GUS and RIS. This is consistent with the findings from similar US studies, which found that RIS had the lowest rate of dose escalation when compared to other biologic PsO treatments.²

Investigators concluded that dose escalation could indicate unmet need in PsO treatment, and additional research should look at health resource use and cost association with escalation, as well as the cause of escalation itself.

References

1. Tada Y, Soliman AM, Ishii K, et al. Dose escalation of biologic treatment in patients with moderate-to-severe psoriasis in Japan. Exp Dermatol. 2024; 33:e15067. doi:10.1111/exd.15067
2. Wu JJ, Patel M, Zeng F, et al. Real-world dose escalation of biologics for moderate-to-severe psoriasis in the United States. J Dermatolog Treat. 2023;34(1):2200869. doi:10.1080/09546634.2023.2200869