Wan Ju Lee

Drugs Associated with Adverse Events in Children and Adolescents

To describe the suspected medications, types of reactions, and outcomes of adverse events (AEs) most commonly reported to the United States Food and Drug Administration (FDA) in children by age group.

Medication adherence and persistence over time with self-administered TNF-alpha inhibitors among young adult, middle-aged, and older patients with rheumatologic conditions

OBJECTIVE Self-injectable TNF inhibitors are increasingly used early in the chronic treatment of moderate to severe rheumatologic conditions. We estimated medication adherence/persistence over time following initiation in young adult and older adult patients with rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis. METHODS We conducted a retrospective cohort study of patients aged 18+ years newly initiating etanercept, adalimumab, certolizumab pegol, or golimumab using the Truven Health MarketScan Database between 2009 and 2013. Pharmacy dispensing data were used to calculate 12-month medication possession ratios (MPR) and determine adherence (MPR ≥ 0.80) for up to 3 years after starting therapy. Persistence over each 12-month interval was defined as not having a ≥92-day treatment gap. Multivariable generalized estimating equation models were used to calculate odds ratios (OR) and robust 95% confidence intervals (CI) for associations between patient characteristics and repeated adherence/persistence measures over time. RESULTS Among 53,477 new users, 14% were young adults (18-34 years), 49% middle-aged (35-54 years), and 37% older adults (55+ years). Overall, 37% of patients were adherent and 83% were persistent in the first year of therapy. The lowest adherence (17%) and persistence (70%) were observed among young adult patients by Year +3. Compared to older adults, middle-aged (OR = 0.73, 95% CI: 0.71-0.76) and young adults (OR = 0.50, 95% CI: 0.47-0.53) were less likely to be adherent. Higher Charlson comorbidity scores, hospitalizations, and emergency department visits were associated with non-adherence/non-persistence. CONCLUSIONS We observed low adherence to self-administered TNF inhibitors but most patients remained persistent over time. Further efforts to improve adherence in young adults and patients with greater comorbidity are needed.

Risk of serious bacterial infection associated with tumour necrosis factor-alpha inhibitors in children with juvenile idiopathic arthritis

Objectives TNF-α inhibitors (TNFIs) have a black box warning for increased risk of serious infection that was based on evidence from studies of adults. Evidence of the association is lacking for children. We aimed to examine the risk of infection posed by TNFIs compared with DMARDs in children with JIA. Methods We conducted a cohort study using the 2009-13 Truven MarketScan Commercial Claims and Encounters database. Children <16 years old with JIA who initiated monotherapy with TNFIs or DMARDs were identified and followed for occurrence of serious bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios for infection associated with TNFIs compared with DMARDs, adjusting for potential confounders with high-dimensional propensity scores and time-varying CS use. Results We identified 2013 DMARD initiators and 482 TNFI initiators with a mean follow-up of 255 and 307 days, respectively. We identified 18 and 11 patients with a serious infection in the DMARD and TNFI groups, resulting in crude rates of 1.28 (95% CI 0.76-2.02) and 2.72 (95%CI 1.36-4.86) per 100 person-years, respectively. In adjusted models, TNFIs were associated with an increased risk of serious bacterial infection compared with DMARDs (adjusted hazard ratio 2.72, 95% CI: 1.08, 6.86). Conclusion Use of TNFIs poses a higher risk of serious infection compared with DMARDs in children with JIA. Our analysis confirms the US Food and Drug Administration warning about TNFI-associated infection in children with JIA.

Polypharmacy and adherence to adjuvant endocrine therapy for breast cancer

PURPOSE Many patients with breast cancer are treated for other conditions and experience polypharmacy with multiple concurrent medications. Our aim was to evaluate polypharmacy in relation to adherence to adjuvant endocrine therapy (AET) in breast cancer. METHODS We conducted a retrospective cohort study of women with incident, invasive breast cancer initiating AET (tamoxifen, letrozole, anastrozole, exemestane) between 2009 and 2013 in the Truven Health MarketScan Database. Polypharmacy and pill burden were measured for commonly used concurrent medications, including lipid-lowering drugs, antihypertensives, oral diabetes medications, insulin analogs, antidepressants, anxiolytics/antipsychotics, and opioid-containing analgesics. Polypharmacy was defined as frequent use (three or more dispensings) of a given medication class and by pill burden (total dispensings). Medication possession ratios (MPR) were estimated for subsequent 12-month intervals. Multivariable generalized estimating equation models were used to calculate odds ratios (ORs) and robust 95% CIs for associations with AET adherence (MPR ≥ 0.80). RESULTS Among 40,009 women, 74% were adherent in year +1 and continued to have high mean adherence (MPR = 0.79) among those continuing AET through year +3. Increasing polypharmacy ( P < .001) and pill burden ( P < .001) were associated with greater adherence, but effects differed by medication class. Frequent use of lipid-lowering drugs (OR, 1.42; 95% CI, 1.36 to 1.49) and antihypertensives (OR, 1.15; 95% CI, 1.10 to 1.20) were associated with higher odds of adherence; frequent use of opioid-containing analgesics (OR, 0.80; 95% CI, 0.77 to 0.83), anxiolytics/antipsychotics (OR, 0.95; 95% CI, 0.91 to 0.99), antidepressants (OR, 0.85; 95% CI, 0.82 to 0.89), and insulin therapy (OR, 0.82; 95% CI, 0.72 to 0.95) were associated with lower odds of adherence. CONCLUSION Associations between polypharmacy and adherence in breast cancer may be better characterized by understanding specific classes of medications used concurrently. Comprehensive medication therapy management, including ongoing pain evaluation and psychoactive therapies, is warranted.

Use of Tumor Necrosis Factor-Alpha Inhibitors in Children and Young Adults With Juvenile Idiopathic Arthritis or Rheumatoid Arthritis.

To characterize the use of tumor necrosis factor‐α inhibitors (TNFIs) in children with juvenile idiopathic arthritis (JIA) and young adults with rheumatoid arthritis (RA).

Top-down Versus Step-up Prescribing Strategies for Tumor Necrosis Factor Alpha Inhibitors in Children and Young Adults with Inflammatory Bowel Disease

Background:Early initiation of tumor necrosis factor-alpha inhibitor (TNFI) therapy for children and young adults with inflammatory bowel disease (IBD) is not well described. Methods:We conducted a retrospective cohort study of children and young adults (⩽24 yr) newly diagnosed with IBD using health insurance claims from 2009 to 2013. The conventional “step-up” approach was defined as TNFI initiation >30 days after first IBD medication prescription, whereas the “top-down” approach was defined as new TNFI prescription within 30 days of first IBD medication prescription. Switching rates, time to initiation, discontinuation, and adherence to TNFIs were compared between the 2 strategies. Results:A total of 11,962 IBD patients were identified. Among 3300 TNFI users, 1298 (39.3%) were treated with the top-down approach, whereas 2002 (60.7%) were treated with the step-up approach. Top-down approach use increased from 31.4% to 49.8% during the 5-year period, and under this approach, most patients were treated with TNFIs alone. Time to TNFI initiation was shorter for patients diagnosed in more recent years. Patients treated with the top-down strategy had lower rates of corticosteroid use (32.5% versus 94.2%) compared with step-up treatment but presented a higher rate of TNFI discontinuation. The 2 strategies both exhibited high adherence (mean proportion of days covered: 83.7%–95.4%). Conclusions:Early TNFI initiation increased over time for children and young adults with IBD and was related to lower rates of corticosteroid use compared with the conventional approach. However, the higher rate of TNFI discontinuation under the top-down approach requires further examination.

Using linked electronic data to validate algorithms for health outcomes in administrative databases.

The validity of algorithms used to identify health outcomes in claims-based and administrative data is critical to the reliability of findings from observational studies. The traditional approach to algorithm validation, using medical charts, is expensive and time-consuming. An alternative method is to link the claims data to an external, electronic data source that contains information allowing confirmation of the event of interest. In this paper, we describe this external linkage validation method and delineate important considerations to assess the feasibility and appropriateness of validating health outcomes using this approach. This framework can help investigators decide whether to pursue an external linkage validation method for identifying health outcomes in administrative/claims data.

Risk of Serious Bacterial Infection Associated with Tumor Necrosis Factor-Alpha Inhibitors in Children and Young Adults with Inflammatory Bowel Disease

Background Prior studies evaluating the relationship between tumor necrosis factor-alpha inhibitors (TNFI) and infection were conducted in adults and had conflicting findings. We sought to examine the risk of serious infection associated with TNFIs compared with nonbiologic immunomodulators in children and young adults with inflammatory bowel disease (IBD) and to compare the risk among individual TNFIs. Methods We conducted a cohort study using the Truven MarketScan Commercial Claims and Encounters database of patients age <30 years with a diagnosis of IBD who initiated treatment with a TNFI or immunomodulator (thiopurines or methotrexate) between 2009 and 2013. The outcome of interest was serious infection, defined as a nongastrointestinal bacterial infection requiring hospitalization. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for serious infection associated with TNFIs compared with immunomodulators. Results We identified 10,838 children and young adults with IBD; 236 and 192 cases of serious infection were observed in 4502 TNFI initiators (5.25/100 person-years) and 6336 immunomodulator initiators (3.59/100 person-years), respectively. Compared with immunomodulators, TNFIs were associated with a higher risk of serious infection (HR, 1.36; 95% CI, 1.08-1.72). Among TNFI users, certolizumab showed a 3.38-fold (95% CI, 2.25-5.09) increased risk vs infliximab, and subcutaneously administered TNFIs also exhibited a higher risk (HR, 1.34; 95% CI, 1.18-1.53) than intravenous TNFIs. Conclusions TNFIs pose a higher risk of serious infection compared with immunomodulators in children and young adults with IBD, and this risk differs among individual TNFIs and routes of administration.

Drugs Associated With Adverse Drug Events In Children: Analysis Of The United States Fda Adverse Event Reporting System Database

obtained from 1225 patients [709 male, 516 female]. The average age of the patients was found to be 56.8±0.5 years. The average number of medications prescribed was 10.6±0.2. 585 patients were found to be aged 60 years or more and 613 patients were in the age group 18-60 years. Out of the 1225 patients, 848 did not have any medication error. An error was noted on only in 377 patient profiles. The total number of medication errors was found to be 638. Of these, 597 were errors ‘with no harm’ and only 41 were errors ‘with harm’. Of these medication errors, drug interactions (DIs) were found to be leading the list with 50% of the medication errors. Cardiovascular agents contributed maximum to the DIs followed by anticoagulants and antimicrobial agents. Only 172 DIs had a moderate severity. DIs was followed by duplication of therapy (20%), incorrect interval (10%), monitoring error, incompleteness of prescription, omission error and overdosing, respectively. CONCLUSIONS: These results confirm that drug interaction continue to lead the list of medication errors in Indian tertiary health care settings. The study is ongoing to determine the interventions to reduce the errors.