Inpatient Constipation Among Migraine Patients Prescribed Anti-calcitonin Gene-Related Peptide Monoclonal Antibodies and Standard of Care Antiepileptic Drugs: A Retrospective Cohort Study in a United States Electronic Health Record Database.

INTRODUCTION: Erenumab, an anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody (mAb), was approved by the US Food and Drug Administration in May 2018. Constipation with serious complications was added to the Warning and Precautions section in the erenumab Prescribing Information in October 2019 after events were observed during post-marketing surveillance. We aimed to assess and compare the risk of inpatient constipation, and, separately, inpatient constipation with serious complications, among patients with migraine treated with CGRP mAbs and standard of care antiepileptic drugs (AEDs). METHODS: Within Optum's Electronic Health Record Research Database, patients with migraine who initiated erenumab, other CGRP mAbs, and AEDs were identified from May 2018 through March 2020. Erenumab initiators were propensity score-matched separately to initiators of other CGRP mAbs and AEDs. Incident inpatient constipation events, and serious complications, were identified using multiple risk windows for outcome assessment (30-, 60-, 90-day risk windows, and all available follow-up). Odds ratios (ORs) were calculated comparing inpatient constipation risk among matched erenumab initiators relative to comparators. RESULTS: We identified 17,902 erenumab, 13,404 other CGRP mAb, and 49,497 AED initiators who met study criteria. Among matched initiators, the risk of inpatient constipation was 0.46% (95% confidence interval (CI) 0.35-0.60) for erenumab and 0.44% (95% CI 0.33-0.58) for other CGRP mAbs within the 90-day risk window, with a corresponding OR of 1.06 (95% CI 0.72-1.55). Among matched erenumab and AED initiators, inpatient constipation risk was 0.53% (95% CI 0.42-0.66) and 0.76% (95% CI 0.62-0.92), respectively, and the OR was 0.69 (95% CI 0.51-0.94). Few serious complications were observed. CONCLUSION: Patients initiating erenumab had similar risk of inpatient constipation within 90 days of treatment initiation versus patients initiating other CGRP mAbs, and lower risk versus patients initiating AEDs. These findings provide context to events observed during post-marketing surveillance.

Risk of cardiovascular and cerebrovascular events and mortality in patients with migraine receiving prophylactic treatments: An observational cohort study.

INTRODUCTION: This study quantified risks of cardiovascular, cerebrovascular, and mortality events among patients with migraine receiving prophylaxis. METHODS: Patients with migraine aged 18-65 years were identified from 2010 through 2015 within a United States administrative claims database. Topiramate initiators during follow-up were propensity score-matched separately to anticonvulsant, cardiovascular treatment, antidepressant, and other prophylactic treatment initiators. Incident outcomes were identified, and hazard ratios were calculated comparing outcome occurrence among topiramate initiators relative to each comparator. A case-control analysis was nested within the full migraine cohort, and odds ratios quantified the association between outcomes and use or non-use of individual prophylactic treatments (anticonvulsants, serotonin norepinephrine reuptake inhibitors, beta blockers, antihypertensives, tricyclic antidepressants, and other prophylactic treatments). RESULTS: The cohort included 119,243 patients with migraine. The matched topiramate initiators had a lower mortality risk versus antidepressant (hazard ratio: 0.44, 95% CI: 0.24, 0.83) and anticonvulsant initiators (hazard ratio: 0.45, 95% CI: 0.25, 0.84). In the case-control analysis, increased risks of several outcomes were observed with all prophylactic treatments relative to non-use of that treatment (odds ratios range from 1.54 to 7.90, and 95% CIs exclude 1.0) except for topiramate and calcium channel blockers. CONCLUSIONS: Although increased risks for several outcomes were observed with certain prophylactic treatments, the treatments other than topiramate likely represent markers for outcome risk factors that developed or progressed after cohort entry, rather than being a direct effect of the treatments. Factors including migraine severity, frequency, and other treatment indications should be considered in future migraine prophylactic treatment safety assessments.

Effectiveness and Tolerability of Therapy With Once-Weekly Exenatide Versus Basal Insulin Among Injectable-Naive Patients With Type 2 Diabetes in a Real-World Setting in the United States.

A propensity-matched cohort study compared injectable-naive patients with type 2 diabetes initiating exenatide once weekly (EQW) or basal insulin (BI), from 2012 through 2015, within a U.S. electronic health record database. A1C and weight were obtained as observed or multiply imputed values at baseline and quarterly for 1 year (Q1-Q4). Hypoglycemia and gastrointestinal symptoms were identified using diagnostic codes and clinical notes. EQW (n = 2,008) and BI (n = 4,016) cohorts were comparable at baseline (mean A1C and weight: EQW, 8.3% and 107.5 kg, respectively; BI, 8.5% and 107.9 kg, respectively). A1C declined in Q2: -0.69 and -0.50 percentage points for EQW and BI, respectively, with little further change in year 1. The EQW cohort lost 0.9 kg in Q1 and 1.9 kg by the end of the year; no weight change was observed in the BI cohort. Among EQW and BI cohorts, 25.9% and 14.3% achieved both glycemic control and weight loss, respectively. In the EQW and BI cohorts, the incidence of hypoglycemia per 1,000 person-years was 52.5 and 65.7, respectively. The incidence of nausea was greater among EQW relative to BI initiators (relative rate 1.18). EQW offers an advantage compared to BI in achieving glycemic control and weight loss and a lower incidence of hypoglycemia, but is associated with greater risk of gastrointestinal symptoms.

Tolerability and Effectiveness of Exenatide Once Weekly Relative to Basal Insulin Among Type 2 Diabetes Patients of Different Races in Routine Care.

INTRODUCTION: Analyses of efficacy and tolerability of pharmacologic interventions are based on clinical trials that often include predominately white populations, in part because of challenges associated with recruitment and retention of racial/ethnically diverse study populations. Using real-world electronic health record (EHR) data, we sought to evaluate the tolerability and effectiveness of exenatide once weekly (EQW), overall and relative to basal insulin (BI), according to race. METHODS: Patients with type 2 diabetes initiating EQW or BI between 2012 and 2015 were selected from the Optum EHR Research Database, a system pooling data from dozens of hospitals throughout the US. Measures of HbA1c, weight, and body mass index (BMI) were summarized at initiation and quarterly in the first year afterwards. Occurrences of gastrointestinal (GI) symptoms and hypoglycemia were identified by diagnostic codes and clinical notes, and incidence rates (IR) and relative rates (RR) were calculated. RESULTS: Overall, 4907 white patients (mean age = 57 years) and 454 African American patients (mean age = 53 years) were included. The percent change in HbA1c from initiation through 9-12 months was similar for white and African American patients [EQW-White: -6.89 (95% CI: -8.29, -5.50), EQW-African American: -5.99 (95% CI: -10.33, -1.65), BI-White: -4.68 (95% CI: -5.51, -3.86), BI-African American: -3.11 (95% CI: -5.37, -0.85)]. For EQW, percent change in weight was -1.73 (95% CI: -2.45, -1.02) for white patients and -1.11 (95% CI: -3.02, -0.81) for African American patients. No weight loss was observed among BI initiators. Relative to BI initiators, EQW initiators had lower rates of hypoglycemia [White RR: 0.82 (95% CI: 0.66, 1.01), African American RR: 0.59 (95% CI: 0.26, 1.34)]. GI symptoms were increased in white EQW initiators. CONCLUSIONS: Treatment with EQW, relative to BI, was associated with larger reductions in HbA1c and weight and reduced risk of hypoglycemia, effects that were not different for white and African American patients. FUNDING: AstraZeneca, Gothenburg, Sweden.