Aromatase Inhibitors and Musculoskeletal Symptoms: Prevalence, Predictors, and Impact on Adherence and Persistence to Therapy Among Older Women with Early-stage HR+/HER2- Breast Cancer



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Background: Randomized clinical trials and cross-sectional studies have shown that musculoskeletal adverse events associated with aromatase inhibitor (AI) therapy are prevalent, and these have a negative impact on adherence and persistence, but the current literature lacks information from real-world settings. Methods: This was a retrospective cohort study conducted using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2010-2017 in older women with early-stage HR+/HER2- breast cancer (BC). The prevalence and predictors of musculoskeletal symptoms (MSS) in the 180 days after initiation of AI therapy were evaluated and the impact of MSS on subsequent adherence and persistence was determined. Chi-square tests and logistic regression were used to determine the predictors of MSS. Adherence to therapy was calculated using proportion of days covered (PDC). Monthly PDCs were modeled using group-based trajectory modeling (GBTM) and a multinomial logistic regression was conducted comparing the lower adherence groups to the adherent group. Time to discontinuation (defined as a gap in medication fills of ≥90 days) differences between the group with MSS diagnosis and the group without MSS diagnosis were examined using Kaplan–Meier (KM) analysis and log-rank test. An extended multivariable Cox proportional hazard model was employed to evaluate the association of diagnosis of MSS with time to discontinuation of therapy. Results: Among the 28,896 patients who initiated AI therapy, 46.0% reported MSS within 180 days of therapy initiation. The GBTM identified a 4-group model that best described the adherence patterns in this cohort. The 4 groups were: (1) patients who were consistently adherent (61.4%); (2) patients who were moderately adherent (22.1%); (3) patients whose adherence gradually declined (5.3%); (4) patients who were non-adherent (11.2%). MSS were a strong predictor for membership in lower adherence groups. The rate of discontinuation was higher among patients with MSS diagnosis when compared to those without any MSS diagnosis (20.8% vs 16.6%, respectively). The diagnosis of MSS was significantly associated with treatment discontinuation (aHR: 1.28 (1.20 - 1.36), p <0.0001). Conclusions: There is a high prevalence of MSS within 180 days of treatment initiation with AIs and this was a strong predictor of lower medication adherence and early treatment discontinuation. Factors associated with patients at risk for poor adherence and persistence to therapy will help inform customized interventions to improve adherence and persistence.



Aromatase inhibitors, Breast cancer, Musculoskeletal symptoms, Predictors, Prevalence, Surveillance, Epidemiology, And End Results (SEER)-Medicare, Adherence, Persistence