Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study evaluated the cost-effectiveness of sequential treatment with romosozumab-to-alendronate compared to alendronate monotherapy and teriparatide-to-alendronate, in postmenopausal osteoporotic women from a Belgian healthcare perspective. Romosozumab-to-alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide-to-alendronate for osteoporotic women at high risk of fracture in Belgium. PURPOSE: This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. METHODS: A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. RESULTS: Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higher QALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. CONCLUSION: Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Therapeutic patterns and migraine disease burden in switchers of CGRP-targeted monoclonal antibodies - insights from the German NeuroTransData registry.

BACKGROUND: Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway have shown good efficacy in migraine prophylaxis. However, a subset of patients does not respond to the first mAb treatment and switches among the available mAbs. The goal of this study is to characterize the switching pattern of migraine patients treated with anti-CGRP(-receptor, -R) mAbs, and to describe the headache burden of those who did not switch, switched once, and switched twice. METHODS: This study used real world data from the NeuroTransData Cohort, a registry of migraine patients treated at outpatient neurology clinics across Germany. Patients who had received at least one anti-CGRP(-R) mAb were included. Headache diaries were collected at baseline and during treatment, along with quality of life measures every three months. Results were summarized for the subgroups of patients who did not switch and those with one and two switches. RESULTS: Of the 655 eligible patients, 479 did not switch, 135 switched once, 35 twice, and 6 three or more times. The ≥ 50% response rates for monthly migraine days were 64.7%, 50.7%, and 25.0% for the no switch, one switch, and two switches groups in their last treatment cycles, respectively. Quality of life measures improved for the no switch and one switch groups, but not for the two switches group. CONCLUSION: Patients who switched among anti-CGRP(-R) mAbs during the course of their treatment still benefited overall but to a lesser extent than those who did not switch. Treatment response in patients who switched twice was markedly lower compared to the no switch and one switch subgroup.

Expanded access to anticancer treatments from conversion to biosimilar pegfilgrastim-cbqv in US breast cancer patients.

Aim: To estimate cost-savings from conversion to biosimilar pegfilgrastim-cbqv that could be reallocated to provide budget-neutral expanded access to AC (doxorubicin/cyclophosphamide) and TCH (docetaxel/carboplatin/trastuzumab) in breast cancer (BC) patients. Methods: Simulation modeling in panels of 20,000 BC and 5000 HER2+ (HER2+ BC) patients, varying treatment duration (one-six cycles) and conversion rates (10-100%), to estimate cost-savings and additional AC and TCH treatment that could be provided. Results: In 20,000 patients, cost-savings of $1,083 per-patient per-cycle translate to $21,652,064 (one cycle) to $129,912,397 (six cycles). Savings range from $5,413,016 to $32,478,097, respectively, in the 5000-patient HER2+ BC panel. Conclusion: Conversion to pegfilgrastim-cbqv could save up to $130 million and provide more than 220,000 additional cycles of antineoplastic treatment on a budget-neutral basis to BC patients.

Lay abstract Pegfilgrastim is used to prevent low white blood cell count in patients receiving chemotherapy. Comparable to a generic version of a drug, a biosimilar is a follow-on version of a biologic treatment. We calculated the savings from using biosimilar pegfilgrastim in a hypothetical group of 20,000 patients with breast cancer receiving chemotherapy with AC (doxorubicin/cyclophosphamide). We then computed the number of additional doses of AC chemotherapy that could be purchased with those savings. We did the same for a group of 5000 HER2+ breast cancer patients treated with TCH (docetaxel/carboplatin/trastuzumab). Using biosimilar pegfilgrastim could save $1,083 per patient per cycle. If all patients were treated with biosimilar pegfilgrastim over six cycles, $129.9 million could be saved in the AC group and $32.5 million in the TCH group. This could provide 220,468 additional AC doses and 6981 TCH doses. Biosimilar pegfilgrastim can generate significant savings. These savings can be used to provide additional patients with chemotherapy cost-free.

Adverse Events of Thiopurine Therapy in Pediatric Inflammatory Bowel Disease and Correlations with Metabolites: A Cohort Study.

BACKGROUND: In the recent era of growing availability of biological agents, the role of thiopurines needs to be reassessed with the focus on toxicity. AIMS: We assessed the incidence and predictive factors of thiopurine-induced adverse events (AE) resulting in therapy cessation in pediatric inflammatory bowel disease (IBD), related to thiopurine metabolites and biochemical abnormalities, and determined overall drug survival. METHODS: We performed a retrospective, single-center study of children diagnosed with IBD between 2000 and 2019 and treated with thiopurine therapy. The incidence of AE and overall drug survival of thiopurines were evaluated using the Kaplan-Meier method. Correlations between thiopurine metabolites and biochemical tests were computed using Spearman's correlation coefficient. RESULTS: Of 391 patients with IBD, 233 patients (162 Crohn's disease, 62 ulcerative colitis, and 9 IBD-unclassified) were prescribed thiopurines (230 azathioprine and 3 mercaptopurine), of whom 50 patients (22%) discontinued treatment, at least temporary, due to thiopurine-induced AE (median follow-up 20.7 months). Twenty-six patients (52%) were rechallenged and 18 of them (70%) tolerated this. Sixteen patients (6%) switched to a second thiopurine agent after azathioprine intolerance and 10 of them (63%) tolerated this. No predictive factors for development of AE could be identified. Concentrations of 6-thioguanine nucleotides (6-TGN) were significantly correlated with white blood cell and neutrophil count, 6-methylmercaptopurine (6-MMP) concentrations with alanine aminotransferase and gamma-glutamyltranspeptidase. CONCLUSIONS: Approximately 20% of pediatric patients with IBD discontinued thiopurine treatment due to AE. A rechallenge or switch to mercaptopurine is an effective strategy after development of AE. Concentrations of 6-TGN and 6-MMP are associated with biochemical abnormalities.

Characteristics of patients with difficult-to-treat rheumatoid arthritis in clinical practice.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics of patients with difficult-to-treat RA (D2T RA) and the usefulness of switching to drugs with different modes of action in real-world. METHODS: We reviewed all consecutive patients with RA treated at Keio University Hospital between 2016 and 2017 with a definition of D2T RA. We analysed clinical characteristics and evaluated the usefulness of changing drugs according to mode of action. RESULTS: Among 1709 patients with RA, 173 (10.1%) were D2T RA. The reason for the D2T RA was multi-drug resistance in 59 patients (34.1%), comorbidity in 17 (9.8%), and socio-economic reasons in 97 (56.1%). The multi-drug-resistance group had significantly higher tender joint count and evaluator global assessment than the other groups, despite receiving the most intensive treatment. The comorbidity group showed a significantly older age and higher rheumatic disease comorbidity index. Although changing the drug to another with a different mode of action was useful, the proportion of patients who achieved remission or low disease activity decreased as the number of switches increased. CONCLUSION: Of the patients with RA, 10.1% were still difficult to treat in clinical practice, despite intensive treatment. Their characteristics were distinct by the reasons of D2T RA, which suggests the need for a personalized approach to D2T RA.

How Frequent Is Switching From an Initial Stimulant Family to the Alternative One in the Clinical Setting?: A Pilot Study of 49 Consecutively Referred Medication-Naive Adults With Attention-Deficit/Hyperactivity Disorder.

PURPOSE/BACKGROUND: This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants. METHODS/PROCEDURES: Subjects were 49 unmedicated adults (18-45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function-Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale-Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics. FINDINGS/RESULTS: Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment ("strugglers") was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance. IMPLICATIONS/CONCLUSIONS: Forty-one percent of medication-naive adults with ADHD initiating stimulant treatment required a switch from the initially prescribed stimulant family to the alternative one because of poor tolerability. Switching could not be adequately predicted by baseline demographic or clinical characteristics. These findings call for improved efforts to help identify predictors of response to stimulant treatment in adults with ADHD to avoid unnecessary delays in identifying a safe and effective treatment for these patients.

Effectiveness and Predictors of Discontinuation of Aripiprazole Long-acting Injection: A 12-Month Naturalistic Cohort Study.

PURPOSE/BACKGROUND: This study aimed to explore the discontinuation rate of aripiprazole long-acting injection (LAI) in a naturalistic clinical setting. METHODS/PROCEDURES: A retrospective cohort study of 1 year duration was conducted on the first 200 patients registered to receive aripiprazole LAI in Sussex, UK. Rate of discontinuation and the association of robustly recorded clinical variables with discontinuation or a new acute care episode were explored. FINDINGS/RESULTS: Of 200 registered, 173 patients initiated aripiprazole LAI and 40% discontinued this by 1 year. Mean discontinuation time was 18 weeks. The commonest discontinuation reason was "patient choice," independent of efficacy or adverse effects. Not having a diagnosis of schizophrenia spectrum was the only variable significantly associated with treatment continuation after 1 year. No single diagnostic group accounted for this, although a greater continuation rate was observed in those with bipolar disorder. Illness severity factors at baseline, including apparent treatment resistance, had no impact on later aripiprazole LAI discontinuation or on acute service use over the year. Medication-related variables had no identified impact on acute service use. IMPLICATIONS/CONCLUSIONS: This study supports the clinical utility of aripiprazole LAI for its licensed indications. The 1-year discontinuation rate is equivalent to that in reports of similarly designed studies of paliperidone LAI. Further exploration of nonmedication factors influencing LAI discontinuation is required. Preferential use of aripiprazole LAI over other medications may be supported due to fewer associated metabolic adverse effects.

Starting a new anti-seizure medication in drug-resistant epilepsy: Add-on or substitute?

OBJECTIVES: Randomized studies in drug-resistant epilepsy (DRE) typically involve addition of a new anti-seizure medication (ASM). However, in clinical practice, if the patient is already taking multiple ASMs, then substitution of one of the current ASMs commonly occurs, despite little evidence supporting this approach. METHODS: Longitudinal prospective study of seizure outcome after commencing a previously untried ASM in patients with DRE. Multivariable time-to-event and logistic regression models were used to evaluate outcomes by whether the new ASM was introduced by addition or substitution. RESULTS: A total of 816 ASM changes in 436 adult patients with DRE between 2010 and 2018 were analyzed. The new ASM was added on 407 (50.1%) occasions and substituted on 409 (49.9%). Mean patient follow-up was 3.2 years. Substitution was more likely if the new ASM was enzyme-inducing or in patients with a greater number of concurrent ASMs. ASM add-on was more likely if a γ-aminobutyric acid (GABA) agonist was introduced or if the patient had previously trialed a higher number of ASMs. The rate of discontinuation due to lack of tolerability was similar between the add-on and substitution groups. No difference between the add-on and substitution ASM introduction strategies was observed for the primary outcome of ≥50% seizure reduction at 12 months. SIGNIFICANCE: Adding or substituting a new ASM in DRE has the same influence on seizure outcomes. The findings confirm that ASM alterations in DRE can be individualized according to concurrent ASM therapy and patient characteristics.

Use of tramadol and other analgesics following media attention and risk minimization actions from regulators: a Danish nationwide drug utilization study.

PURPOSE: To describe the use of tramadol and other analgesics in Denmark focusing on the impact of media attention (June and December 2017) and regulatory actions (September 2017 and January 2018) on the use of tramadol. METHODS: Using nationwide registries, we identified all adults who filled a prescription for tramadol and other analgesics from 2014 to 2019. We described incidence rates, prevalence proportions, and total use of tramadol and other analgesics over time. We also described switching between analgesics, treatment duration, skewness in drug use, and doctor-shopping. RESULTS: From early 2017 until the end of 2019, total tramadol use decreased markedly while the use of morphine and oxycodone decreased slightly. The quarterly prevalence of tramadol use decreased from 32/1000 individuals in 2014 to 18/1000 at the end of 2019, dropping mainly at the time of media attention. Concomitantly, the quarterly prevalence increased for oxycodone (from 5.1 to 8.2) and morphine (from 8.5 to 9.8), mainly due to more short-term and sporadic users, and decreased for codeine (14 to 9.6). From 2014 to mid-2017, the incidence of tramadol use was stable (around 2.2/1000 person-months) but dropped in June 2017 to 1.7/1000, coinciding with the media attention. The incidence of tramadol use continued to decrease (to 1.1/1000 at the end of 2019). CONCLUSION: We identified a decline in tramadol use coinciding with the media attention in 2017 and continuing during regulatory actions. There was generally no evidence of unintended effects on the utilization of opioids related to the media attention and regulatory actions.

Is anticoagulation with bivalirudin comparable to heparin for pediatric extracorporeal life support? Results from a high-volume center.

There is a paucity of data regarding the use of direct thrombin inhibitors such as bivalirudin for children on extracorporeal life support (ECLS). We sought to compare the outcomes of children on ECLS anticoagulated with bivalirudin versus heparin. Patients transitioned from heparin to bivalirudin were treated as a separate group. A single-institution, retrospective review of all consecutive children (neonate to 18 years) placed on ECLS in the cardiac or pediatric intensive care units was performed (June 2018-December 2019). Data collected included demographics, anticoagulation strategy, number of circuit interventions, blood product use on ECLS, survival to decannulation, and survival to discharge. Fifty-four children were placed on ECLS for a total of 56 runs. Demographics and venovenous versus venoarterial ECLS were similar. The bivalirudin group had longer median duration of support compared to the heparin group--11.0 days [IQR 6.2, 23.1] versus 3.3 days [2.1, 6.2], P < .001. Patients switched from heparin to bivalirudin had a similar duration of support (10.3 days [8.3, 18.3]) as those on bilvalirudin alone. However, there was no difference in red blood cell, fresh frozen plasma, or platelet transfusions. There was no difference in the number of circuit interventions, survival to decannulation or discharge. The freedom to first circuit intervention was longer with bivalirudin compared to heparin. Our data suggest that even with longer pediatric ECLS runs on bivalirudin, there were no differences in the outcomes between the heparin and bivalirudin groups, with longer freedom from first circuit intervention with bivalirudin. While this is the largest reported series comparing children on ECLS anticoagulated with heparin versus bivalirudin, larger studies are needed to determine the optimal anticoagulation strategy for this diverse and complicated group of children.

Psychiatric Medication Changes Associated With Increased Rate of Medical Readmissions in Patients With Serious Mental Illness.

ABSTRACT: To identify the impact of postdischarge psychiatric medication changes on general medical readmissions among patients with serious mental illness (SMI; bipolar disorder, major depressive disorder, and schizophrenia), claims from a 5% national sample of Medicare fee-for-service (FFS) beneficiaries hospitalized between 2013 and 2016 were studied. A total of 165,490 Medicare FFS beneficiaries with SMI 18 years or older with at least 1 year of continuous Medicare enrollment were identified. Within 30 days of discharge from index admission, 47.4% experienced a psychiatric medication change-including 75,892 beneficiaries experiencing a deletion and 55,713 experiencing an addition. After adjusting for potential confounders, those with a medication change experienced an 10% increase in the odds of 30-day readmission (odds ratio, 1.10; SE, 0.019; p < 0.001). Comorbid drug use disorder was also associated with an increased odds of readmission after controlling for other covariates. These findings suggest important factors that clinicians should be aware of when discharging patients with SMI.

Risk of metformin failure in the treatment of women with gestational diabetes.

OBJECTIVES: To estimate the metformin failure rate in women with gestational diabetes. METHODS: The study was designed as a retrospective cohort of women diagnosed with gestational diabetes by the 75 g 2 h oral glucose tolerance test. Women were placed into two groups: metformin success (107 patients not requiring insulin therapy) or metformin failure (15 patients requiring the addition of, or, transition to insulin). Primary outcome: rate of metformin failure. Secondary outcomes: maternal and neonatal factors. RESULTS: The failure rate of metformin was 15% (19/122 women) in the study. The failure group was more likely to have 3 abnormal values on a 2-h 75 g oral glucose tolerance test (37% (n=7/19) vs. 15% (n=15/103), p=0.02). Patients who failed had higher average fasting blood glucose levels on the glucose tolerance test as well as on pretreatment fasting finger stick values. Those who failed metformin were diagnosed with gestational diabetes and started on metformin earlier in gestation. CONCLUSIONS: Overall low rate of metformin failure in treatment of gestational diabetes.

Response to Propoxyphene Market Withdrawal: Analgesic Substitutes, Doses, and Adverse Events.

OBJECTIVE: Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we compared drug receipts and outcomes among propoxyphene users before and aftermarket withdrawal. STUDY DESIGN: Using OptumLabs data, we studied 3 populations: commercial, Medicare Advantage (MA) aged (age 65+ y) and MA disabled (age below 65 y) enrollees. The exposed enrollees received propoxyphene in the 3 months before market withdrawal (n=13,622); historical controls (unexposed) received propoxyphene 1 year earlier (n=9971). Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures. PRINCIPAL FINDINGS: Aged MA enrollees illustrate the experience of all 3 populations examined. Following the market withdrawal, propoxyphene users in the exposed cohort experienced an abrupt decline of 69% in average daily MME, compared with a 14% decline in the unexposed. Opioids were discontinued by 34% of the exposed cohort and 18% of the unexposed. Tramadol and hydrocodone were the most common opioids substituted for propoxyphene. The proportion of each group receiving ≥4 g of prescription acetaminophen per day decreased from 12% to 2% in the exposed group but increased from 6% to 8% among the unexposed. Adverse events were rare and not significantly different in exposed versus unexposed groups. CONCLUSIONS: After propoxyphene market withdrawal, many individuals experienced abrupt discontinuation of opioids. Policymakers might consider supporting appropriate treatment transitions and monitoring responses following drug withdrawals.

Serial biologic therapies in psoriasis patients: A 12-year, single-center, retrospective observational study.

BACKGROUND: Biologic therapy for psoriasis is effective but not always long-lasting and sometimes needs to be switched. OBJECTIVE: We aimed to evaluate the drug survival (ie, the time from initiation to discontinuation) of each biologic and the factors affecting survival to identify better switching strategies and improve drug survival. METHODS: In total, 195 psoriasis patients treated in our unit during 2006-2018 were retrospectively observed. Descriptive statistical analyses and logistic regression models were performed. Kaplan-Meier survival curves and multivariate Cox models adjusted for confounding variables were used to estimate and compare drug survival. RESULTS: Overall, 90.6% of patients achieved an ≥75% reduction in their baseline Psoriasis Area and Severity Index score. In 2018, the most frequently used biologic was ustekinumab (47/169, 27.8%). Patients with higher baseline Psoriasis Area and Severity Index scores were more likely to be switched (P = .0399, odds ratio 1.08). In naive patients, ustekinumab showed longer drug survival (>7.0 years), but in biologic-experienced patients, we found no significant differences in drug survival. Previous biologic therapies increased the need for switching (P = .014, hazard ratio 1.20). Switching between biologic classes yielded longer drug survival than switching within biologic classes (P = .003, hazard ratio 0.48). LIMITATIONS: As a single-center, retrospective real-life study, the data were not perfectly homogeneous. CONCLUSION: Switching between biologic classes might increase drug survival but retrospective studies designed ad hoc are needed to confirm this better switching strategy.

Comparison of real-world treatment patterns among patients with psoriasis prescribed ixekizumab or secukinumab.

BACKGROUND: Real-world data on treatment patterns associated with use of interleukin-17A inhibitors in psoriasis are lacking. OBJECTIVE: To compare treatment patterns between ixekizumab or secukinumab users in clinical practice. METHODS: A retrospective cohort study included patients with psoriasis aged ≥18 years treated with ixekizumab or secukinumab between March 1, 2016, and May 31, 2018 in IBM MarketScan (IBM Corp, Armonk, NY) databases. Inverse probability of treatment weighting and multivariable models were used to address cohort imbalances and estimate the risks of nonpersistence (60-day gap), discontinuation (≥90-day gap), switching, and the odds of adherence. RESULTS: The study monitored 645 ixekizumab users for 13.7 months and 1152 secukinumab users for 16.3 months. Ixekizumab users showed higher persistence rate (54.8% vs 45.1%, P < .001) and lower discontinuation rate (37.8% vs 47.5%, P < .001) than secukinumab. After multivariable adjustment, ixekizumab users had lower risks of nonpersistence (hazard ratio, 0.82; 95% confidence interval, 0.71-0.95) and discontinuation (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96), and higher odds of high adherence to treatment measured by a medication possession ratio ≥80% (hazard ratio, 1.31; 95% confidence interval, 1.07-1.60). The risk of switching was similar between cohorts. LIMITATIONS: Disease severity and clinical outcomes were unavailable. CONCLUSION: Ixekizumab users demonstrated longer drug persistence, lower discontinuation rate and risk of discontinuation, higher likelihood of adherence, and similar risk of switching compared with secukinumab users in clinical practices.

Steroid variability in pediatric inpatient asthmatics: survey on provider preferences of dexamethasone versus prednisone.

Objective: Our hospital's pediatric Emergency Department (ED) began using dexamethasone for treating asthma exacerbations after ED studies showed non-inferiority of dexamethasone compared to prednisone. However, providers have not reached consensus on optimal inpatient steroid regimen. This study evaluates provider preference for inpatient steroid treatment.Methods: A survey was distributed to providers who care for inpatient pediatric asthmatics. Respondents answered questions about steroid choice and timing. Data were summarized as percentages; bivariate comparisons were analyzed with Pearson's chi-squared test.Results: Ninety-two providers completed the survey (60% response rate). When patients received dexamethasone in the ED, subsequent inpatient management was variable: 44% continued dexamethasone, 14% switched to prednisone, 2% said no additional steroids, and 40% said it depended on the scenario. Hospitalists were more likely to continue dexamethasone than pulmonologists (61% and 15%, respectively; p < .001). Factors that influenced providers to switch to prednisone in the inpatient setting included severity of exacerbation (73%) and asthma history (47%). Fifty-one percent felt uncomfortable using dexamethasone because of "minimal data to support [its] use inpatient." In case-based questions, 28% selected dexamethasone dosing intervals outside the recommended range. Thirteen percent reported experiencing errors in clinical practice.Conclusions: Use of dexamethasone in the ED for asthma exacerbations has led to uncertainty in inpatient steroid prescribing practices. Providers often revert to prednisone, especially in severe asthma exacerbations, possibly due to experience with prednisone and limited research on dexamethasone in the inpatient setting. Further research comparing the effectiveness of dexamethasone to prednisone in inpatient asthmatic children with various severities of illness is needed.

Impact of protocol change on individual factors related to course of adverse reactions to chemotherapy for breast cancer.

PURPOSE: Asthenia, myalgia, arthralgia, mucositis, abdominal pain, diarrhea, and neutropenia are adverse reactions commonly reported by women undergoing chemotherapy. Traditional approaches do not take into account the effect that chemotherapeutic changes and variable interactions can cause in adverse reactions. We aimed to identify the impact of the change of a chemotherapy protocol within the same treatment in profiles associated with adverse reactions. METHODS: A total of 166 women admitted to the Brazilian National Institute of Cancer (INCA) were followed. Polymorphisms, clinical variables, and FAC-D protocols (3 cycles of cyclophosphamide, 5-fluorouracil, and doxorubicin followed by 3 cycles of docetaxel) composed the set of independent variables analyzed. Reaction levels were recorded at the end of each chemotherapy cycle via interviews. Marginal models were fitted. RESULTS: The results of marginal models for non-hematological reactions revealed that the docetaxel phase was associated with increased reaction levels compared with the FAC phase. In addition, the set of factors associated with the reactions changed in each protocol. The post-menopausal status was related to high levels of asthenia in docetaxel protocol whereas CYP2B6 polymorphism (rs3745274) was related to high levels in FAC protocol. Regarding the docetaxel phase, high levels of abdominal pain and mucositis were related to CBR3 gene (rs8133052) polymorphism and diabetes respectively. CONCLUSION: The results suggest the need for monitoring non-hematological reactions during the docetaxel phase of FAC-D treatment. The factors related to more severe reactions depend on the chemotherapy protocol used.

Biologic Use Patterns and Predictors for Non-persistence and Switching of Biologics in Patients with Inflammatory Bowel Disease: A Nationwide Population-Based Study.

BACKGROUND: Data on real-life patterns of biologic use for inflammatory bowel disease (IBD) are scarce. AIMS: We aimed to examine the patterns of biologic use and the factors associated with non-persistence and switching of biologics in Korean IBD patients. METHODS: Using National Health Insurance claims, we collected data on patients who were diagnosed with IBD and exposed to biologics between 2010 and 2016. RESULTS: Among 1838 patients with Crohn's disease (CD), 1237 and 601 started with infliximab and adalimumab, respectively. Among 1125 patients with ulcerative colitis (UC), 774, 294, and 57 initiated infliximab, adalimumab, and golimumab, respectively. Rates of non-persistence and switching were higher in UC than in CD. One- and 3-year non-persistence rates were 14.2% and 26.5% in CD and 35.4% and 53.4% in UC, respectively. One- and 3-year switching rates were 3.7% and 10.1% in CD and 15.6% and 22.0% in UC, respectively. In both CD and UC, infliximab and adalimumab initiators showed similar persistence rates, whereas adalimumab initiators had a higher risk of switching than infliximab initiators. In UC, golimumab initiators had a higher risk of non-persistence and switching than infliximab initiators. Steroid use at biologic initiation was associated with an increased risk of non-persistence and switching in both CD and UC. UC patients who started biologic treatment at tertiary hospitals were more likely to continue treatment than those who started at general hospitals/community hospitals/clinics. CONCLUSIONS: In real-world clinical practice settings, discontinuation of biologics occurred frequently in IBD patients, and switching of biologics was common in UC patients.

Drug switching in the Netherlands: a cohort study of 20 active substances.

BACKGROUND: For a patient, drug switches are not desirable (either between a brand-name drug and a generic drug, or between two generic drugs of the same active substance). Research into the causes of drug switches, and related adverse drug reactions, is hampered by the absence of quantitative data on drug switches. METHODS: We describe the frequency of drug switches in the Netherlands for a selection of active substances. A retrospective cohort study was conducted using the Drug Information System of the National Health Care Institute in the Netherlands. We studied the Dutch patient population from mid-2009 to 2016. The selection of active substances (n = 20) was made based on a report by Lareb, the Netherlands Pharmacovigilance Centre, on adverse drug reactions related to drug switching, and we used qualitative and quantitative descriptive analyses. A drug switch is defined as the replacement of a patient's prescribed drug with a similar drug from a different manufacturer. RESULTS: We identified 23.8 million drug switches on a total of 206 million (11.6%) similar drug dispenses. The frequency of drug switches demonstrated a yearly peak in the period from January to March. In some months, for atorvastatin, losartan, pantoprazole, and irbesartan, more than 60% of similar drug dispenses were drug switches. Most drug switches (80.3%) were between two generic drugs, and 0.12% of these involved a drug from a European parallel import. The proportion of drug switches between two brand-name drugs decreased from 14.5 to 5.53% during our study period, and of these, 86.5% involved a drug from a European parallel import. CONCLUSIONS: Drug switching is common in the Netherlands, and most of the drug switches we studied are between generic drugs. The observed annual peak of drug switches is most likely explained by a specific Dutch reimbursement policy. Not only are the data valuable as is, but they also serve as a first step towards elucidating the reasons for the occurrence of these drug switches. In addition, these data can be used to put into perspective the adverse drug reactions associated with drug switching.

Body composition is associated with risk of toxicity-induced modifications of treatment in women with stage I-IIIB breast cancer receiving chemotherapy.

PURPOSE: Initial dose of chemotherapy is planned based on body surface area, which does not take body composition into account. We studied the association between fat mass (kg and relative to total body weight) as well as lean mass (kg and relative to total body weight) and toxicity-induced modifications of treatment in breast cancer patients receiving chemotherapy. METHODS: In an observational study among 172 breast cancer patients (stage I-IIIB) in the Netherlands, we assessed body composition using dual-energy X-ray scans. Information on toxicity-induced modifications of treatment, defined as dose reductions, cycle delays, regimen switches, or premature termination of chemotherapy, was abstracted from medical records. Adjusted hazard ratios and 95% confidence intervals (95% CI) were calculated to assess associations between body composition and the risk of toxicity-induced modifications of treatment. RESULTS: In total, 95 out of 172 (55%) patients experienced toxicity-induced modifications of treatment. Higher absolute and relative fat mass were associated with higher risk of these modifications (HR 1.14 per 5 kg; 95% CI 1.04-1.25 and HR 1.21 per 5%; 95% CI 1.05-1.38, respectively). A higher relative lean mass was associated with a lower risk of modifications (HR 0.83 per 5%; 95% CI 0.72-0.96). There was no association between absolute lean mass and risk of toxicity-induced modifications of treatment. CONCLUSIONS: A higher absolute and a higher relative fat mass was associated with an increased risk of toxicity-induced modifications of treatment. Absolute lean mass was not associated with risk of these treatment modifications, while higher relative lean mass associated with lower risk of modifications. These data suggest that total fat mass importantly determines the risk of toxicities during chemotherapy in breast cancer patients.