Hedgehog inhibitor treatment patterns vary by grace period

Patients with basal cell carcinoma who discontinued hedgehog inhibitors had differing odds for reinitiation that varied by grace period, according to a presentation at Maui Derm for Dermatologists.

“Patients treated with HHIs commonly experience side effects, which may require permanent or temporary treatment discontinuation,” Jessica J. Jalbert, PhD, and colleagues wrote in the poster. They also wrote that hedgehog inhibitors (HHIs) “are generally dispensed in 30-days’ supply, benefit of treatment is continuously assessed, and treatment interruptions are commonly employed during HHI therapy.”

Jalbert and colleagues conducted a retrospective, observational cohort study using data from the IBM MarketScan Commercial and Medicare claims databases. They included 526 patients (mean age, 67 years; men, 65.4%) with basal cell carcinoma who were new users of HHIs. Most patients initiated HHI therapy with vismodegib (99.2%) and were treated only with HHIs (69.6%), although some patients had HHIs as an adjuvant (22.2%) or neoadjuvant (3.8%) therapy.

Researchers assessed discontinuation and reinitiation, with discontinuation defined as “the lack of an HHI dispensation before the exhaustion of the days’ supply and allotted grace period;” they wrote that a grace period was “the gap between the exhaustion of the days’ supply and a subsequent refill that is permitted for treatment to be considered continuous.” Risk for HHI discontinuation at 12 months and median time to discontinuation were the primary outcomes of interest.

Median treatment durations increased while risk for discontinuation at 6 months and probability of reinitiation at 12 months decreased with longer grace periods.

For the 14-day grace period, the median treatment duration was 94 days (95% CI, 90-109). These patients had a 78.8% risk (95% CI, 74.5-82.4) for discontinuation at 6 months and 40.9% probability (95% CI, 35.6-45.7) of reinitiation at 12 months. After reinitiation, the median time to second discontinuation was 64 days (95% CI, 59-81).

In the 60-day grace period, median treatment duration was 144 days (95% CI, 131-162), and risk for discontinuation at 6 months was 60.1% (95% CI, 55.0-64.6). Among patients who discontinued treatment, there was a 19.7% (95% CI, 15.0-24.2) probability for reinitiation at 12 months and subsequently a median 118 days (95% CI, 89-172) to second discontinuation.

The 120-day grace period had the longest median treatment duration at 172 days (95% CI, 155-190), with a 52.5% (95% CI, 47.4-57.2) risk for discontinuation at 6 months. Patients who discontinued had the lowest probability of reinitiation at 12 months at 13.6% (95% CI, 9.3-17.6); however, among those who did reinitiate, median time to second discontinuation was the longest of any grace period at 171 days (95% CI, 114-318).

“Characterizing real-world persistence on HHIs is challenging due to the likely use of drug holidays, as treatment discontinuations, treatment duration and reinitiations were sensitive to the duration of the grace period selected,” researchers wrote. “Real-world studies of medications with tolerability issues should consider use of drug holidays, and in oncology, the intent of treatment (ie, adjuvant/neoadjuvant) use should be considered when characterizing drug exposure.”