Risk Evaluation and Prediction of Cardiac Events among Azithromycin Users

In the last 30 years, over a billion azithromycin prescriptions have been dispensed since its approval in the US. The drug was once considered the safest macrolide, but ten years after its approval, evidence from case reports suggested a concern cardiac events and eath with its use. In three different studies, we measured the impact of the FDA warning in the use of azithromycin among high-risk patients, identified the baseline predictors of cardiac events among azithromycin users, and compared the risk of cardiac events with azithromycin and amoxicillin users. In the first study, we observed statistically lower prevalence rates of the cardiac risk factors after the FDA warning; however, the absolute prevalence remained similar before and after the warning. In the second study, we identified consistent predictors of the outcome, which included age, sex, history of syncope, cardiac dysrhythmias, non-specific chest pain, and presence of a concurrent QT-prolonging drug. From this list, we created a tool to ease the process of finding patients at a higher risk of cardiac events. In the third study, we evaluated the risk of cardiac events with azithromycin compared to amoxicillin. Using an active comparator, new user design in a large cohort of over 4 million episodes of azithromycin and amoxicillin, we found no increased risk of cardiac events with azithromycin. In sub-group analyses, the risk was 40% higher among patients prescribed concurrent QT-prolonging drugs. The finding of no increased risk was consistent across several other subgroup analyses. We used real-world data to measure the prevalence of cardiac risk factors before and after the FDA warning, quantified the predictors of cardiac risk factors, and evaluated the risk of cardiac risks with azithromycin compared to amoxicillin. We found that there was no change in prevalence of risk factors after the FDA warning, specific baseline patient characteristics put patients treated with azithromycin at a higher risk of cardiac events, and there was an increased risk of cardiac events with azithromycin compared to amoxicillin. Although the risk is rare, providers should avoid the use of QT-prolonging drugs with azithromycin. Future research should focus on examining the risk of cardiac deaths among azithromycin users

Indicators of suboptimal biologic therapy over time in patients with ulcerative colitis and Crohn's disease in the United States.

This study assessed the occurrence of indicators for suboptimal biologic therapy among ulcerative colitis (UC) and Crohn's disease (CD) patients over time in the United States (US). Data from a large US claims database (2005-2013) were used to retrospectively identify patients with diagnosed with either UC or CD who were new biologic users. Indicators of suboptimal biologic therapy included: dose escalation during the maintenance phase, discontinuation of the initial biologic, switch to another biologic within 90 days following the last day of supply of the initial biologic, augmentation with a non-biologic systemic therapy, UC- or CD-related surgery, UC- or CD-related urgent care, and development of fistula (for CD only). Kaplan-Meier analyses were used. A total of 1,699 UC and 4,569 CD patients were included. Among UC patients, 51.1% and 90.9% experienced ≥1 indicator of suboptimal biologic therapy within 6 months and 36 months of biologic therapy initiation, respectively. Among CD patients, 54.3% and 91.4% experienced ≥1 indicator of suboptimal biologic therapy within 6 and 36 months of biologic therapy initiation, respectively. For both UC and CD patients, the most frequent indicators of suboptimal biologic therapy were discontinuation, dose escalation and augmentation. In conclusion, this study found that the occurrence of suboptimal biologic therapy is common among patients with UC and CD, with approximately 90% of patients experiencing at least one indicator of suboptimal biologic therapy within 36 months of biologic treatment initiation

Variation in Care for Patients with Irritable Bowel Syndrome in the United States

Objectives Irritable bowel syndrome (IBS) affects nearly one in seven Americans. Significant national variations in care may exist, due to a current lack of standardized diagnosis and treatment algorithms; this can translate into a substantial additional economic burden. The study examines healthcare resource utilization in patients with IBS and in the subset of IBS patients with constipation (IBS-C) and analyzes the variation of IBS care for these patients across the United States (US). Methods Healthcare resource use (HRU), including gastrointestinal (GI) procedures and tests, all-cause and intestinal-related medical visits, GI specialist visits, and constipation or diarrhea pharmacy prescriptions for IBS patients enrolled in a large US administrative claims database (2001-2012) were analyzed for the 24-month period surrounding first diagnosis. Multivariate regression models, adjusting for age, gender, year of first diagnosis, insurance type, and Charlson comorbidity index, compared HRU across states (each state vs. the average of all other states). Results Of 201,322 IBS patients included, 77.2% were female. Mean age was 49.4 years. One in three patients had \u3e= 3 distinct GI medical procedures or diagnostic tests; 50.1% visited a GI specialist. Significant HRU differences were observed in individual states compared to the national average. IBS-C patients had more medical visits, procedures, and pharmacy prescriptions for constipation/diarrhea than IBS patients without constipation. Conclusions This study is the first to identify considerable regional variations in IBS healthcare across the US and to note a markedly higher HRU by IBS-C patients than by IBS patients without constipation. Identifying the reasons for these variations may improve quality of care and reduce the economic burden of IBS

Sample selection.

<p>[1] ICD-9 codes 556.xx; [2] ICD-9 codes 555.xx; [3] Biologic agents included adalimumab, certolizumab pegol, golimumab, infliximab, and natalizumab; [4] The index date was defined as the date of the first biologic prescription fill.</p

Factors associated with indicators of suboptimal therapy for UC and CD patients.

<p>Factors associated with indicators of suboptimal therapy for UC and CD patients.</p

Patient characteristics.

<p>Patient characteristics.</p

Assessment of corticosteroid-related quality of care measures for ulcerative colitis and Crohn’s disease in the United States: a claims data analysis

<p><b>Objective:</b> To evaluate corticosteroid (CS)-related quality of care indicators in patients with ulcerative colitis (UC) and Crohn’s disease (CD) in the US.</p> <p><b>Methods:</b> Adults diagnosed with UC or CD and prescription fills for an oral CS were identified from a large commercial US claims database (2005–2013). Quality indicators included prolonged CS use (≥60 days), use of CS-sparing therapy, and bone loss assessment. State-level variations in quality of care indicators were estimated using logistic regression models adjusting for age, gender, insurance plan type, and CD severity.</p> <p><b>Results:</b> Of the 25,063 UC and 22,155 CD patients receiving CS, 16.1% and 12.6%, respectively, were prolonged CS users. Among prolonged CS users, 52.5% of UC and 68.2% of CD patients used CS-sparing therapy. Bone loss assessment was observed in 11.0% of UC patients with prolonged CS use and 7.7% of newly diagnosed CD patients. Prolonged CS use was the lowest in Kentucky (odds ratio [OR] = 0.59) and the highest in Wisconsin (OR = 1.41) for UC patients; the lowest in North Carolina and New York (both OR = 0.71) and the highest in Utah (OR = 2.42) for CD patients. CS-sparing therapy use was the lowest in Delaware (OR = 0.42) and the highest in Michigan (OR = 0.83) for UC patients; it was significantly different only in South Carolina (OR = 0.57) for CD patients. Bone loss assessment rates were the highest in Arizona (OR = 1.83) for UC patients and were the lowest in Mississippi (OR = 0.52) and the highest in Texas (OR = 1.51) for CD patients.</p> <p><b>Limitations:</b> Information on disease severity was not available in the database.</p> <p><b>Conclusions:</b> Significant regional variations in all three quality indicators were observed across the US.</p