Mahyar Etminan

Background: Estrogen-positive breast cancer (BC) makes up to 75% of all BC patients. With aromatase inhibitors (AIs) and tamoxifen considered mainstay therapies, several small cross-sectional studies have found an association between AI use and ocular adverse events, including dry eye disease (DED), but data on a head-to-head comparison between AIs and tamoxifen are scant. In this study we aim to quantify DED risk in women with BC taking AIs, compared to tamoxifen users. Methods: The IQVIA health claims database was the main data source. This database captures medical diagnoses, procedures, prescriptions, and demographic data on approximately 200 million United States residents. Using a retrospective, new-user, cohort design we identified all users of AIs or tamoxifen, from 2006 to 2020. Cohort members were followed to the first mutually exclusive outcome of DED defined by the first ICD 9th or 10th edition code or the use of a drug that is exclusively used to treat DED. Cox regression was used to estimate hazard ratios (HR), adjusting for confounders and risk factors. Subsequent analyses were conducted to test robustness of findings. Results: Our study included 6,177 and 4,239 patients taking AIs and tamoxifen, respectively. AI users had a mean age of 61.5 (± 16.8 years), whereas tamoxifen users had a mean age of 54.6 (± 12.6 years). The mean follow-up time was 17.5 months. The crude HR for DED with AI use was 1.41(95%CI: 1.07-1.86), compared to tamoxifen use. The adjusted HR for DED was 1.23(95%CI: 0.92-1.64). We found a positive duration response with AI use compared to tamoxifen use, with an adjusted HR for exposure of less than 6 months, 6-18 months, more than 18 months of, 1.34(0.91-1.97), 1.68(1.01-2.78), 1.77(0.82-3.83), respectively. Lastly, for participants older than 55, the HR was 1.07(95% CI:0.74-1.54), while for participants 55 or younger, the HR was 1.43(95% CI:0.88-2.31). Conclusion: Our study demonstrated an increased risk of DED among AI users compared to tamoxifen, although the estimates were mostly not precise. Given that most women with BC are either on AIs or tamoxifen, these findings need to be used for a more personalized risk-benefit assessment for each patient.

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Chronic Obstructive Pulmonary Disease (COPD) is a common chronic disease of the airways responsible for significant burden to the patient and health-care systems. Pharmacotherapy is a cornerstone of COPD management. We aimed at evaluating population-level trends of filled inhaled prescriptions over the time course of COPD and their agreement with guidelines. Further, inhaled medications have potential side effects that are not sufficiently investigated. We aimed to examine the association between use of long-acting or short-acting muscarinic antagonists (LAMA and SAMA) and the risk of acute angle-closure glaucoma (AACG) in COPD. We used administrative health databases in British Columbia, Canada to create a cohort of COPD patients. We quantified inhaled medication prescriptions within each year of follow-up, and documented their trends over the time course of COPD. Using generalized linear models, we investigated the association between the frequent exacerbator status and filling a prescription after a physician visit. To assess AACG risk, a case-control study was nested within this cohort. All cases of AACG followed by laser iridotomy were obtained and matched to controls by age, sex, and calendar time. The exposure to LAMA/SAMA was categorized into three levels: current use (≥ 1 prescription of LAMA or SAMA during the last 30 days), new use (initiated medication in the last 30 days), and past use (≥ 1 prescription in 6 months to 30 days before AACG). Conditional logistic regression models were used to estimate the rate ratio (RR) of AACG controlling for confounders.The most common medication class in COPD incident cohort during the first year of diagnosis was inhaled corticosteroids (ICS, used by 49.9%). We documented low utilization of monotherapies (specifically LAMA) and high utilization of combination therapies (particularly containing ICS). Moreover, specialists were less likely to consider exacerbation history in the choice of therapies compared with general practitioners. In the safety study, 92 cases were matched to 460 controls. We demonstrated that the use of inhaled muscarinic antagonists in a COPD population, regardless of dose and timing, does not appear to affect the risk of AACG (adjusted RR:1.14, 95%CI [0.64 to 2.01], p=0.65). Results remained consistent in sensitivity analyses.

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Background: Glaucoma is a chronic, progressive disease that affects over 60 million people worldwide and can lead to either partial or complete vision loss. Similarly, migraines are one of the most prevalent and disabling conditions worldwide. Recent case studies and reports to the Food and Drug Administration have alluded to a link between triptans and an acute angle closure glaucoma (AACG) attack; a true ophthalmic emergency. Given that triptans are a highly prescribed medication, we sought to examine the risk of triptan induced AACG. Methods: We undertook a nested case-control study. We had access to a random sample of 9,053,240 patients from 2006-2016. Cases were identified by their first diagnosis of AACG. A risk-set of controls matched by age, sex, calendar time, and follow-up time were constructed. Our manner of control selection has shown to generate odds ratios that are close approximations of the risk ratios (RR). RRs for a positive control (topiramate) and negative control (ranitidine) were also calculated. Study drug use was defined as those with a prescription within 7 (current), 14 (recent), and 30 days (past) and any use of the drug within 1 year (0-365 days) prior to the index date. Results: There were 1,307 cases and 13,070 controls. The adjusted RR for those with any use of triptans was 1.09 (95%CI: 0.56-1.82). The adjusted RR for current, recent, and past use for triptans was 1.37 (95% CI 0.31-6.09), 1.16 (95% CI 0.35-3.92), and 1.19 (95% CI 0.50-2.81) respectively. The adjusted RR for current, recent, past use, and any use for topiramate was 4.44 (95% CI 0.80-24.64), 12.86 (95% CI 5.10-32.42), 6.52 (95% CI 3.34-12.71), and 3.77 (95% CI 2.29-6.20) respectively. The adjusted RR for current, recent, past use, and any use for ranitidine was 0.66 (95% CI 0.08-5.24), 0.39 (95% CI 0.05-2.91), 0.18 (95% CI 0.02-1.28), and 0.79 (95% CI 0.43-1.44) respectively. Conclusion: Although a significantly increased risk was not found for triptan induced AACG, we cannot exclude the existence of this risk due to presence of wide confidence intervals. Therefore, alerting patients on the risk of AACG with triptan use is not currently indicated.

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