Switching Patterns Affect Latanoprost Adherence in Patients with Glaucoma

Better adherence and persistence were observed among patients with glaucoma treated with latanoprost who received a preservative-free formulation or who switched between different formulations, according to new real-world evidence.¹

The research showed those who identified as switchers showed greater medication adherence and persistence than those identified as non-switchers, despite the investigative team expecting reduced adherence and persistence in these patients, based on previously observed variation in tolerability among different formulations of latanoprost.

“Due to the observational nature of our study, we can only assume that there are reasons for the increased adherence and persistence among switchers,” wrote the investigative team, led by Miriam Kolko, MD, PhD, from the department of ophthalmology at the University of Copenhagen in Denmark. “One explanation is that with a chronic disease, such as glaucoma, the cost differences between medications become significant over time.”

Intraocular pressure (IOP) lowering eye drops are the most common treatment for chronic use by patients with glaucoma. As a result of the reimbursement system in Denmark, pharmacists can dispense medication at the lowest cost among those available on the pharmaceutical market.² With price variations, it is possible for patients to experience shifts between different medicines with the same active ingredient, such as latanoprost.

However, it is possible to switch between different latanoprost eye drops that differ in composition and physician properties, but it does not apply to all formulations. Current clinical practice in Demark does not allow a switch from a preservative-free to a preservative-containing medicine with the same active ingredient. The current analysis evaluated switching patterns to assess the impact of multiple shifts on adherence and persistence in patients in Denmark who were naive to latanoprost and ≥65 years of age between January 2012 - December 2018.

For study inclusion, patients should not have been exposed to any other pharmacological treatment of glaucoma prior to latanoprost. Patients were followed for 1 year from the date of the first redeemed prescription of latanoprost and only those still on latanoprost at the end of the first-year follow-up period were included in the final study population. At the end of the first year of follow-up, those included in the final population were assigned to 3 different cohorts: (1) switchers, (2) non-switchers, and (3) preservative-free latanoprost users.

In the analysis, the primary outcome was adherence and persistence to latanoprost treatment within 1 year from the index date. Selected comorbidities including sex, age, and equalized income were used as covariates. Cox regression models calculated the hazard ratio (HR) or latanoprost discontinuation for the 3 cohorts, with the non-switchers’ cohort chosen as the reference level, in both adjusted and unadjusted analyses.

A total of 10,014 patients were included in the study population, with 2321 identified as non-switchers, 6396 as switchers, and 1297 as preservative-free latanoprost users. The mean age of the population was 75.4 years and 55% were women. Upon analysis, the study found non-switchers experienced statistically significant lower adherence (proportion of days covered [PDC], 92%) than switchers (PDC, 96%; P <.001) and preservative-free latanoprost users (PDC, 99%; P <.001).

Users of preservative-free latanoprost were found to be more adherent compared to both switchers (P <.001) and non-switchers (P <.001). Additionally, when comparing non-switchers with switchers, switchers were statistically more adherent (P <.001). Regarding persistence, the 1-year cumulative incidences show statistically significant differences in discontinuation among the 3 cohorts (P <.0001), with preservative-free latanoprost being the cohort with the lowest risk of discontinuation.

The analysis indicated switchers had a 53% lower risk of treatment discontinuation, compared to the reference group, within 1 year following the first redemption of latanoprost in both unadjusted (HR, 0.47; 95% CI, 0.41 - 0.53; P <.001) and adjusted (HR, 0.47; 95% CI, 0.42 - 0.53; P <.001) analyses. Additionally, compared to non-switchers, preservative-free latanoprost users had a 78% lower risk of treatment discontinuation in both unadjusted (HR, 0.22; 95% CI, 0.17 - 0.28; P <.001) and adjusted (HR, 0.22; 95% CI, 0.17 - 0.29; P <.001) analyses.

Kolko and colleagues noted the main limitation of their findings is the lack of information on the “real use” of retrieved prescriptions, noting the national registry can only report the extent to which medication prescriptions are redeemed.

“Researchers cannot obtain information on whether a patient is acting by the prescribed range and dose of a dosing regimen,” investigators wrote. “Therefore, we had a strong assumption in our study, or rather that a redeemed prescription was used by the patient and that patients exhibiting higher PDCs were more likely to take the medication as prescribed.”

References

1. Amiri, D., Sessa, M., Andersen, M. & Kolko, M. (2023) Persistence and adherence with Latanoprost: A Danish register- based cohort study in older patients with glaucoma. Acta Ophthalmologica, 00, 1–7. Available from: https://doi.org/10.1111/aos.15715
2. Johannesdottir, S.A., Horváth-Puhó, E., Ehrenstein, V., Schmidt, M., Pedersen, L. & Sørensen, H.T. (2012) Existing data sources for clinical epidemiology: the Danish National Database of reimbursed prescriptions. Clinical Epidemiology, 4, 303–313