A pooled analysis of exenatide use and risk of acute pancreatitis.

OBJECTIVE: To estimate the association between exenatide BID use and acute pancreatitis across two claims-based studies. RESEARCH DESIGN AND METHODS: We pooled two cohort studies within separate commercial health insurance databases. We included initiators of exenatide BID and all other antihyperglycemic drugs without prior pancreatitis from 2005-2008. Poisson regression models provided rate ratios (RRs) and 95% confidence intervals (CIs) of the association of exenatide BID with acute pancreatitis adjusted for quintiles of propensity scores. MAIN OUTCOME MEASURES: Primary inpatient diagnoses of acute pancreatitis with correction for misclassification via a validation sub-study. RESULTS: There were 49,956 initiators of exenatide BID and 692,333 initiators of other antihyperglycemic drugs. Patients in the two studies were similar on many demographic and clinical characteristics. Exenatide BID initiators had a higher prevalence of diagnoses consistent with diabetes complications (e.g. peripheral neuropathy) and cardiovascular risk factors (e.g. hypertension). In both studies, current exenatide BID use was not associated with uncorrected outcomes of acute pancreatitis (pooled RR 1.0; CI 0.8-1.3). PPV correction resulted in a slightly higher point estimate for current use (pooled RR 1.3; CI 1.0-1.7) and past use (pooled RR 1.6; 95% CI 1.2-2.1). CONCLUSIONS: These data are consistent with little or no higher risk of acute pancreatitis associated with current exenatide BID use relative to nonuse. Although previous work identified non-causal mechanisms, an increased incidence of acute pancreatitis following cessation of treatment remains a possibility. Bias due to residual confounding or outcome misclassification may remain, and should be considered a potential explanation for these findings.

Stratum-specific positive predictive values of claims for acute pancreatitis among commercial health insurance plan enrollees with diabetes mellitus.

PURPOSE: To estimate the positive predictive value (PPV) of claims for acute pancreatitis among initiators of antihyperglycemic drugs in commercial health insurance claims data. METHODS: As part of a systematic study of the occurrence of acute pancreatitis among antihyperglycemic drug initiators (N=260,255) within a large US health insurer's claims database, we identified potential cases of acute pancreatitis and confirmed them through medical record review. Potential cases had an International Classification of Diseases, 9th revision diagnosis code for acute pancreatitis (577.0) associated with an inpatient or emergency department claim. We sought 860 medical records to confirm potential cases and received 585 (70%), which were reviewed by a clinical adjudication committee. We estimated the PPV and 95% confidence intervals (CI) of claims for these medical records and a subset that had the diagnosis code listed in the first position of an inpatient claim. RESULTS: The PPV was 0.50 (95% CI 0.44-0.53) for an acute pancreatitis diagnosis code in any position and 0.60 (95% CI 0.55-0.65) if in the first position of an inpatient claim. The estimated PPV varied across strata defined by patient characteristics and was generally lower within strata where potential risk factors for acute pancreatitis were present. CONCLUSIONS: These data indicate that health insurance claims-based identification of acute pancreatitis might overestimate actual cases and introduce appreciable bias, usually toward the null. Further case confirmation or relative risk correction may be necessary to address potential bias.

Risk of upper gastrointestinal complications associated with cyclooxygenase-2 selective and nonselective nonsteroidal antiinflammatory drugs.

STUDY OBJECTIVE: To estimate the risk of upper gastrointestinal complications associated with use of cyclooxygenase-2 (COX-2) selective (celecoxib and rofecoxib) and individual nonselective nonsteroidal antiinflammatory drugs (NSAIDs) compared with nonuse of these drugs. DESIGN: Nested case-control study. DATA SOURCE: Administrative health care databases of Saskatchewan, Canada. PATIENTS: Among a population of men and women aged 20-89 years who were covered by public health insurance with prescription drug benefits between November 15, 1999, and December 31, 2001, 726 case patients with first hospitalization for upper gastrointestinal complications (with validation of cases through review of hospital medical records) were confirmed from 1,054,532 person-years of follow-up, and 20,002 control patients were randomly selected from all eligible controls, frequency matched to cases on their index date (+/- 3 mo). MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between upper gastrointestinal complications and use of NSAIDs. Current rofecoxib and naproxen users had the highest risk for upper gastrointestinal complications with adjusted ORs of 3.6 (95% CI 2.2-5.7) and 3.4 (95% CI 1.8-6.7), respectively. No association was found between the risk of upper gastrointestinal complications and use of celecoxib (OR 1.1, 95% CI 0.7-1.8) or the use of diclofenac plus misoprostol (OR 0.7, 95% CI 0.3-1.8). A dose-response relationship was observed for rofecoxib and naproxen with ORs for high dose of 5.2 (95% CI 2.5-10.6) and 5.1 (95% CI 2.1-12.3), respectively. Short-term users of celecoxib and naproxen had a higher risk than long-term users, whereas among users of rofecoxib the risk was higher among long-term than short-term users. CONCLUSION: These findings support the variability of individual NSAIDs in the elevated risk of upper gastrointestinal complications. Our results suggest that the risk for rofecoxib is similar to that for naproxen. Celecoxib users appear to have a similar risk for upper gastrointestinal complications as nonusers; however, the risk may be increased at the start of treatment with celecoxib.