Patient characteristics, pain treatment patterns, and incidence of total joint replacement in a US population with osteoarthritis.

BACKGROUND: Currently available medications for chronic osteoarthritis pain are only moderately effective, and their use is limited in many patients because of serious adverse effects and contraindications. The primary surgical option for osteoarthritis is total joint replacement (TJR). The objectives of this study were to describe the treatment history of patients with osteoarthritis receiving prescription pain medications and/or intra-articular corticosteroid injections, and to estimate the incidence of TJR in these patients. METHODS: This retrospective, multicenter, cohort study utilized health plan administrative claims data (January 1, 2013, through December 31, 2019) of adult patients with osteoarthritis in the Innovation in Medical Evidence Development and Surveillance Distributed Database, a subset of the US FDA Sentinel Distributed Database. Patients were analyzed in two cohorts: those with prevalent use of "any pain medication" (prescription non-steroidal anti-inflammatory drugs [NSAIDs], opioids, and/or intra-articular corticosteroid injections) using only the first qualifying dispensing (index date); and those with prevalent use of "each specific pain medication class" with all qualifying treatment episodes identified. RESULTS: Among 1 992 670 prevalent users of "any pain medication", pain medications prescribed on the index date were NSAIDs (596 624 [29.9%] patients), opioids (1 161 806 [58.3%]), and intra-articular corticosteroids (323 459 [16.2%]). Further, 92 026 patients received multiple pain medications on the index date, including 71 632 (3.6%) receiving both NSAIDs and opioids. Altogether, 20.6% of patients used an NSAID at any time following an opioid index dispensing and 17.2% used an opioid following an NSAID index dispensing. The TJR incidence rates per 100 person-years (95% confidence interval [CI]) were 3.21 (95% CI: 3.20-3.23) in the "any pain medication" user cohort, and among those receiving "each specific pain medication class" were NSAIDs, 4.63 (95% CI: 4.58-4.67); opioids, 7.45 (95% CI: 7.40-7.49); and intra-articular corticosteroids, 8.05 (95% CI: 7.97-8.13). CONCLUSIONS: In patients treated with prescription medications for osteoarthritis pain, opioids were more commonly prescribed at index than NSAIDs and intra-articular corticosteroid injections. Of the pain medication classes examined, the incidence of TJR was highest in patients receiving intra-articular corticosteroids and lowest in patients receiving NSAIDs.

A cohort study of the risk of seizures in a pediatric population treated with atomoxetine or stimulant medications.

PURPOSE: Stimulant medications used for treating attention deficit hyperactivity disorder (ADHD) can be associated with an increased risk of seizures. Atomoxetine is a non-stimulant medication approved for treating ADHD. This retrospective cohort analysis evaluated risk of seizures among pediatric patients naïve to ADHD medication therapy, with exposure to atomoxetine relative to stimulant medications. METHODS: Among members of a large US health plan from 1/1/2003 to 12/31/2006, aged 6-17 years, we identified initiators of atomoxetine or stimulants with no evidence of prior study drug use. We created study cohorts using propensity score matching within 6-month calendar blocks. The outcome was a seizure event in the 6-month follow-up period verified through medical record review. Relative risks (RR) based on current use of each study drug adjusted for baseline covariates were calculated using Poisson regression. We estimated hazard ratios from Cox proportional hazards models for the comparison of atomoxetine to stimulants based on initial cohort assignment. RESULTS: We matched 13,398 initiators of atomoxetine to 13,322 initiators of stimulants. We identified 97 seizure events. After adjustment, current atomoxetine therapy was associated with a non-statistically significant 28% lower risk of seizure compared to current stimulant therapy (RR 0.72; 95%CI 0.37, 1.38). The adjusted RR of seizure with atomoxetine compared to stimulants based on initial cohort assignment was 0.90 (95%CI 0.54, 1.49). CONCLUSIONS: These results do not support an increase in the risk of seizure with atomoxetine therapy. The risk of seizure was not significantly different between pediatric patients taking atomoxetine compared with those taking stimulants.

The incidence of first provoked and unprovoked seizure in pediatric patients with and without psychiatric diagnoses.

PURPOSE: To estimate the rate of new-onset afebrile provoked and unprovoked seizure in a general pediatric population and subgroups of patients with and without psychiatric diagnoses other than attention deficit hyperactivity disorder (ADHD). METHODS: A retrospective cohort study of 133,440 pediatric patients, between the ages of 6 and 17 years, and without history of seizure or prior use of anticonvulsant medications, with follow-up during 2003. The data source for this study was Ingenix's research database containing pharmacy and medical claims for members of a large US-based managed care organization. The main outcome measure was new-onset nonfebrile seizure. Incidence rates of seizure and 95% confidence intervals (CI) were calculated and expressed as rates per 100,000 person-years. RESULTS: There were 132 new-onset provoked and unprovoked seizures in 78,423 person-years of follow-up among the general pediatric population sample. The incidence rate of seizure among the general pediatric population was 168 per 100,000 p-y (95% CI 141-200). The incidence rate of seizure among patients without psychiatric diagnoses was 149 per 100,000 p-y (95% CI 122-180). The incidence rate of seizure among patients with psychiatric diagnoses other than ADHD was 513 per 100,000 p-y (95% CI 273-878). There were increases in the incidence rates of seizure in all of the seizure risk factor groups, but this was more pronounced among males ages 6-12 with psychiatric diagnoses. CONCLUSIONS: The results of this study are consistent with previous reports showing that pediatric patients with psychiatric disorders have a higher incidence rate of seizure than the general pediatric population.

Perspectives on the use of data mining in pharmaco-vigilance.

In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmaco-vigilance. In 2003, a group of statisticians, pharmaco-epidemiologists and pharmaco-vigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods.In this paper, we provide an overview of: (i) the statistical and operational attributes of several currently used methods and their strengths and limitations; (ii) information about the characteristics of various postmarketing safety databases with which these tools can be deployed; (iii) analytical considerations for using safety data-mining methods and interpreting the results; and (iv) points to consider in integration of safety data mining with traditional pharmaco-vigilance methods. Perspectives from both the FDA and the industry are provided. Data mining is a potentially useful adjunct to traditional pharmaco-vigilance methods. The results of data mining should be viewed as hypothesis generating and should be evaluated in the context of other relevant data. The availability of a publicly accessible global safety database, which is updated on a frequent basis, would further enhance detection and communication about safety issues.