Use of Herpes Zoster Prophylaxis in Myeloma Patients Treated with Proteasome Inhibitors

Background

Multiple myeloma patients on proteasome inhibitors (PIs) have an increased risk for herpes zoster infections. As a result, the U.S. National Comprehensive Cancer Network guidelines recommend antiviral prophylaxis. We examined the use of, and adherence to, antiviral agents in myeloma patients who are on PIs.

Methods

We performed a retrospective cohort analysis in the Truven MarketScan Database, from January 2009 to December 2013. Patients with myeloma continuously receiving PIs (bortezomib or carfilzomib) for ≥3 months were selected. Use of herpes zoster prophylaxis was determined by having one or more pharmacy claims for acyclovir and valacyclovir. Adherence was defined as having a medication possession ratio (MPR; ratio of the sum of all days supplied by the pharmacy divided by the number of days between the first and last prescription) ≥80% over 3 months in patients who filled ≥2 prescriptions for an antiviral agent. Rates of herpes infections were determined in users, users who were adherent, users who were non-adherent, and non-users. Covariates examined included age, calendar year, geographic location, living in a metropolitan area, employment status, health plan, type of pharmacy, prior herpes infection, antiviral use prior to initiation of PI, and Charlson comorbidity score. Patients were followed until end of continuous PI use, end of enrollment from MarketScan, or December 31, 2013, whichever occurred earliest. Multivariable logistic regression analyses were used to examine factors associated with both use and adherence. Cox proportional hazards model was used to examine time to claim for herpes infection.

Results

Amongst a total of 70,786 patients with a diagnosis of myeloma between 2009-2013, we identified 6,934 patients who received PI. Of these, 3,632 (52%) filled a prescription for an antiviral agent at least once during the follow-up period. Acyclovir was more commonly used than valacyclovir (74% vs 26%). Factors associated with antiviral use included more recent calendar year (odds ratio [OR] 2.27 for 2013 versus 2009; 95%CI 1.91-2.71) and being on more chemotherapy agents concurrently (OR 1.82 for 3 agents compared to 1; 95%CI 1.56-2.12). Amongst users who received an antiviral agent more than once (N=2,803), adherence to zoster prophylaxis was 84% over 3 months. Factors associated with adherence included retiree status (OR 1.70; 95%CI 1.20-2.42), and use of mail order pharmacies (OR 2.22; 95%CI 1.19-4.61). Patients on antiviral agents were less likely to develop zoster (hazard ratio 0.40; 95%CI 0.30-0.52).

Conclusions

Although use of antiviral therapy was associated with a decreased risk of herpes infections, we found that half of myeloma patients in the U.S. did not receive this guideline-recommended care. More efforts are needed to prevent this important complication in myeloma patients on PIs.