Characterizing the treatment patterns, medication burden, and patient demographics of older adults with major depressive disorder treated with antidepressants with or without selected comorbidities.

OBJECTIVE: Evaluate clinical characteristics, comorbidity burden, major depressive disorder (MDD)-related healthcare resource utilization (HCRU), medication burden, and antidepressant treatment (ADT) patterns among older adults with MDD with and without selected comorbidities. METHODS: Using Komodo's Healthcare Map claims data (1/1/2016-9/30/2022), patients with MDD (≥65 years) treated with ADTs were assessed 24 months preceding (baseline) and 12 months following (follow-up) first observed ADT prescription fill (index). Patients were separated into cohorts of those with ≥1 of 5 selected comorbidities and those without. Clinical characteristics, comorbidities, and MDD-related HCRU were assessed during baseline; treatment patterns were assessed during follow-up. Baseline and follow-up all-cause and comorbidity-specific medication burdens (mean prescription claims/month) were determined. RESULTS: Among the total cohort (N = 417,643), 97.1% had ≥1 of 5 selected comorbidities: hypertension (80.3%), hyperlipidemia (75.4%), diabetes (54.2%), anxiety disorder (39.0%), and chronic obstructive pulmonary disorder (19.5%). Baseline and follow-up all-cause medication burdens per month were 3.8 and 4.5 for patients with selected comorbidities and 1.7 and 2.3 for those without. During baseline, most patients (96.0% with selected comorbidities, 96.2% without) had ≥1 outpatient visit, and a numerically higher percentage of those with vs. without selected comorbidities had MDD-related emergency room (13.9% vs. 6.0%) and inpatient (13.5% vs. 4.1%) visits. The majority of both cohorts (61.0% with selected comorbidities, 59.5% without) underwent treatment pattern changes. CONCLUSION: This study highlights the medication burden and ADT patterns in older adults with MDD, assessing these outcomes among patients with and without comorbidities. Numerically higher medication burdens among those with selected comorbidities suggests future studies could investigate the impact of comorbidities on MDD-related care.

Real-World Treatment Patterns and Physician Preferences for Biologics in Moderate-to-Severe Inflammatory Bowel Disease: Retrospective Chart Review in Europe.

Background: With many options available for treating inflammatory bowel disease (IBD) in Europe, this study sought to characterize physician treatment preferences and real-world treatment patterns in patients with moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD). Methods: This was a retrospective, noninterventional, physician-administered study. Gastroenterologists and general practitioners (n = 348) in France, Germany, and the United Kingdom provided information on treatment preferences and extracted information from records of patients with moderate-to-severe UC (n = 587) or CD (n = 417) who had received biologic, biosimilar or Janus kinase inhibitor therapies (2014-2019) and had IBD-related medical history available 6 months before and after treatment initiation. Results: Physicians largely preferred infliximab and adalimumab or their biosimilars as first-line therapy for UC (originators, 65.8%; biosimilars, 26.1%) and CD (originators, 61.8%; biosimilars, 30.5%). Effectiveness was the most cited reason for treatment preference (92%-93% of physicians). Three-quarters of patients (UC, 75.8%; CD, 73.6%) received infliximab or adalimumab originators in the first line, with more patients receiving infliximab biosimilars than adalimumab biosimilars (12.4%-12.5% and 0.5%-4.1%, respectively, across UC and CD). Persistence was longer for first-line infliximab than adalimumab (UC, 26.6 vs 21.2 months; CD, 31.2 vs 26.7 months) and was generally shorter for their respective biosimilars. Nonbiologic treatments were used in combination with biologics in 14.1% (UC) and 11.5% (CD) of patients. Most patients received 1 biologic therapy (UC, 90.6%; CD, 83.2%); only 9.4% (UC) and 16.8% (CD) received a second biologic. Conclusions: Infliximab and adalimumab originators dominated first-line biologic therapy for moderate-to-severe UC and CD. Understanding real-world treatment patterns can help assess new treatment uptake and suggest opportunities for improving treatment.

The Risk Reduction of Accidental Exposure-Related Systemic Allergic Reactions Extrapolated Based on Food Challenge Data After 1 Year of Peanut Oral Immunotherapy.

INTRODUCTION: The phase 3 trial PALISADE, comparing peanut (Arachis hypogaea) allergen powder-dnfp (PTAH) oral immunotherapy versus placebo in peanut-allergic children, reported that a significantly higher percentage of PTAH-treated participants tolerated higher doses of peanut protein after 1 year of treatment. This study used PALISADE data to estimate the reduction in the risk of systemic allergic reaction (SAR) after accidental exposure following 1 year of PTAH treatment. METHODS: Participants (aged 4-17 years) enrolled in PALISADE were included. Parametric interval-censoring survival analysis with the maximum likelihood estimation was used to construct a real-world distribution of peanut protein exposure using lifetime SAR history and highest tolerated dose (HTD) from a double-blind, placebo-controlled food challenge conducted at baseline. The SAR risk reduction was extrapolated using the exposure distribution and the HTD were collected at baseline and trial exit for PTAH- and placebo-treated participants. RESULTS: Assuming a maximum peanut protein intake of 1500 mg, participants were estimated to have < 1% probability of ingesting > 0.01 mg during daily life. The mean annual SAR risk at trial entry was 9.25-9.98%. At trial exit, the relative SAR risk reduction following accidental exposure was 94.9% for PTAH versus 6.4% for placebo. For PTAH-treated participants with exit HTD of 600 or 1000 mg without dose-limiting symptoms, the SAR risk reduction increased to 97.2%. The result was consistent in the sensitivity analysis across different parametric distributions. CONCLUSION: Oral immunotherapy with PTAH is expected to result in a substantially greater reduction in risk of SAR following accidental exposure compared to placebo among children with peanut allergy.

Health-care resource utilization associated with peanut allergy management under allergen avoidance among commercially insured individuals.

Background: Until recently, the standard approach to care for individuals with peanut allergy (PA) was limited to allergen avoidance and treatment of reactions with emergency medicines. Objectives: To assess health-care resource utilization (HRU) and costs associated with PA management under allergen avoidance and to identify risk factors associated with peanut reactions that resulted in inpatient (IP) and/or emergency department (ED) visits. Methods: Privately insured individuals with PA diagnosis codes were identified from a large U.S. administrative claims data base (January 1, 1999, to March 31, 2017). PA-related HRU, indicated by a PA diagnosis and/or diagnostic procedure codes and by epinephrine autoinjectors (EAI) prescription fills in medical and pharmacy claims, respectively, and all-cause costs were described per patient-year (PPY). Risk factors associated with peanut reactions in an IP and/or ED setting were identified by using a multivariable logistic regression model. Results: A total of 86,483 patient-years from 14,136 individuals with PA were included. At the patient-year level, 28.1% were ages 0-3 years, 43.6% were ages 4-11 years, 13.7% were ages 12-17 years, and 14.5% were ages ≥ 18 years; 35.6% had PA-related outpatient visits; 50.6% had EAI fills; and 2.4% had PA-related IP and/or ED visits PPY. Younger individuals had more PA-related outpatient visits and EAI fills, with peak intensive use at ages 4-11 years. The proportion of individuals with PA-related IP and/or ED visits was highest among those aged ≥ 18 years. Mean all-cause costs were $3084 PPY; individuals with PA-related IP and/or ED visits incurred $8902 PPY ($17,451 for those with one or more IP visits). Risk factors associated with peanut reactions that resulted in IP and/or ED visits included young adults (odds ratio [OR] 3.19 [95% confidence interval {CI}, 2.66-3.83]), previous peanut reaction(s) (OR 1.66 [95% CI, 1.23-2.24]), asthma (OR 1.33 [95% CI, 1.18-1.51]), and male sex (OR 1.14 [95% CI, 1.01-1.28]). Conclusion: Individuals with PA and under allergen avoidance had significant HRU that varied across all age groups, with more PA-related outpatient visits during preschool and/or school age and PA-related urgent care among adults. Individuals with previous peanut reaction(s), asthma, and males had a higher risk of peanut reactions that resulted in IP and/or ED visits.

Heterogeneity in Parent Preferences for Peanut Desensitization Therapy.

BACKGROUND: Recently developed peanut desensitization treatment reduces the incidence of allergic reactions, the anxiety associated with the risk of accidental exposure, and the burden of precautionary behavior. Eliciting parent preferences for tradeoffs involving treatment effectiveness, tolerability, costs, and convenience quantifies the burden of juvenile peanut allergy and the perceived value of peanut desensitization therapies. OBJECTIVE: To understand heterogeneity in parents' treatment preferences and the role of personal characteristics in explaining differences. METHODS: An Internet-based, discrete-choice experiment survey was administered to a national sample of 500 parents of children aged 4 to 17 years with peanut allergy to quantify parents' preferences for peanut desensitization therapies for their children. Latent-class, mixed-logit analysis estimated relative importance coefficients for groups of participants with distinctly different preferences. RESULTS: Parents' choice patterns fell into 1 of 4 preference subgroups: (1) Cost-sensitive, (2) Protreatment (but Side-Effect-Averse), (3) Trader, and (4) Inconsistent. Mode of administration had little relative importance across all subgroups. Characteristics associated with belonging to a given preference subgroup included parent age, child age, income, parent perception of child risk and ability to manage allergic reactions, past allergic reactions, and changes in precautionary behaviors posttreatment. CONCLUSIONS: We found distinct differences in parent preferences for tradeoffs involving effectiveness, tolerability, and costs of peanut desensitization treatments. Parents' treatment preferences help quantify the burden of juvenile peanut allergy and the perceived value of new therapies. Such information can inform patient-centric clinical and regulatory decision making.

Economic burden of peanut allergy in pediatric patients with evidence of reactions to peanuts in the United States.

BACKGROUND: The economic burden of food allergy is large; however, costs specific to individuals with peanut allergy experiencing reactions to peanuts remain to be evaluated. As the prevalence of peanut allergy continues to increase in children, a better understanding of the cost of care is warranted. OBJECTIVE: To assess the cost of care of peanut allergy among privately insured and Medicaid-insured pediatric patients in the United States. METHODS: This retrospective matched-cohort study included patients aged 4-17 years from the Optum Health Care Solutions and Medicaid Claims databases (January 1, 2007-March 31, 2017). Patients were classified into 2 cohorts: peanut allergy (with peanut allergy diagnosis codes and reactions triggering health care resource utilization [HRU]) and peanut allergy-free (no peanut allergy diagnosis codes in claims). Peanut allergy patients were matched 1:10 to peanut allergy-free patients based on baseline covariates. Comorbidities including anxiety and depression, HRU, and direct health care costs were compared between cohorts and reported for both perspectives separately. RESULTS: Compared with peanut allergy-free patients (n = 30,840 privately insured; n = 12,450 Medicaid), peanut allergy patients (n = 3,084 privately insured; n = 1,245 Medicaid) had higher prevalence of asthma, atopic dermatitis/eczema, other food allergies, allergic rhinitis, depression, and anxiety (all P < 0.01). Peanut allergy patients had higher HRU per patient per year (PPPY), including 90% more emergency department visits among both privately insured and Medicaid patients (P < 0.01) and higher direct health care costs PPPY, with incremental costs of $2,247 total or $1,712 excluding asthma-related costs for privately insured patients and $2,845 total or $1,844 excluding asthma-related costs for Medicaid patients (all P < 0.01). CONCLUSIONS: Pediatric patients in the United States with peanut allergy and reactions triggering HRU had significantly higher comorbidity burdens, HRU, and direct health care costs, regardless of asthma-related costs, versus those without peanut allergy. DISCLOSURES: This study was funded by Aimmune Therapeutics, a Nestlé Health Science company. The study sponsor was involved in several aspects of the research including the study design, the interpretation of data, the writing of the manuscript, and the decision to submit the manuscript for publication. Yu and Tilles are employees of Aimmune Therapeutics, a Nestlé Health Science company. Robison and Norrett were employees of Aimmune Therapeutics at the time this study was conducted. Blaiss, Meadows, and Hass provided paid consulting services to Aimmune Therapeutics. Guerin and Latremouille-Viau are employees of Analysis Group, a consulting company that provided paid consulting services to Aimmune Therapeutics. Parts of the results were presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting held March 25-28, 2019, in San Diego, CA, and at the ISPOR Annual Meeting held May 18-22, 2019, in New Orleans, LA.

Is Easier Better Than Harder? An Experiment on Choice Experiments for Benefit-Risk Tradeoff Preferences.

OBJECTIVES: To test the convergent validity of simple and more complex study designs in a discrete-choice experiment (DCE) of multiple sclerosis (MS) treatment preferences. METHODS: Five hundred US adults with MS completed an online DCE survey. Respondents answered 8 choice questions with pairs of constructed MS treatment profiles defined by delays in problems with walking, delays in problems with cognition, thyroid disorders, and 10-y risks of kidney failure and serious brain infection (i.e., progressive multifocal leukoencephalopathy [PML]). Four hundred respondents completed choice questions using 4 levels for all attributes, except thyroid disorders with 3 levels. One hundred respondents completed choice questions using only the 2 extreme attribute levels of the 4-level version. Random-parameters logit models were used to estimate choice-model parameters. RESULTS: Respondents viewing the 4-level and 2-level versions agreed on the relative importance of the 3 most important attributes: cognition, walking, and PML. Respondents viewing the 4-level version indicated much stronger disutility for a 0% to 0.5% increase in kidney-failure risk than those viewing the 2-level version where the risk for kidney failure increased from 0% to 3%. Otherwise, utilities for other 4-level attributes were approximately linear but with significantly steeper slopes (except for cognition) than the 2-level estimates, indicating that attributes were perceived as more important as the number of levels increased. CONCLUSIONS: Although the relative importance of some attributes was similar, the 2-level and 4-level versions generally failed to demonstrate convergent validity. If the study goal is attribute rankings, a 2-level version could be adequate. If goals include quantifying tradeoffs among attribute levels, more complex designs can help respondents discriminate among attribute levels. Reductions in measurement error using fewer attribute levels appear to have come at the expense of less discriminating evaluations.

Health-related quality-of-life evaluation of crohn disease patients after receiving natalizumab therapy.

Crohn disease (CD) is a chronic inflammatory condition without a permanent medical cure and commonly requiring a lifetime of care. This article discusses the impact of natalizumab induction and maintenance therapy on the health-related quality of life (HRQoL) of CD patients. Two natalizumab phase III studies were evaluated: the Efficacy of Natalizumab in Crohn's Disease Response and Remission (ENCORE) study evaluated the HRQoL of CD patients during 12 weeks of natalizumab induction therapy, and the Evaluation of Natalizumab As Continuous Therapy (ENACT-2) trial evaluated the effect of natalizumab maintenance therapy on HRQoL for a period of 48 weeks past a 12-week induction period (ENACT-1). HRQoL assessments were made with the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Short Form-36 (SF-36). In the ENCORE study, induction therapy with natalizumab was demonstrated to significantly increase HRQoL scores at 12 weeks when compared with patients on placebo. During the ENACT-2 trial, IBDQ and SF-36 scale scores of patients who responded to natalizumab induction remained stable whereas those on placebo worsened. At week 60, the mean change from baseline on all scales of the IBDQ and the SF-36 were significantly higher for those who continued to receive natalizumab as compared to those who received placebo (p

Adverse events associated with common therapy regimens for moderate-to-severe Crohn's disease.

OBJECTIVES: We sought to determine whether treatment with steroids, immunosuppressives (ISs), and anti-tumor necrosis factor (TNF) agents is associated with an increased risk of adverse events in patients with Crohn's disease (CD). METHODS: This study analyzed claims from patients with CD and controls without CD from the United States with private insurance (2002-2005). Patients were classified by treatment with steroids, ISs, anti-TNF agents, combinations of two or three, and none of these medications. Follow-up adverse events in patients with CD and controls were compared across different treatment categories and are presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Within the CD patients, a subset analysis examined the relationship between therapies and outcomes. RESULTS: A total of 22,310 patients with CD (8,581 longitudinal cohort cases) and 111,550 controls were identified. Compared with the controls, CD patients had higher rate ratios for all pre-specified events. Within the CD patient population subgroup, monotherapy with steroids, ISs, or anti-TNF agents was associated with an increased risk of tuberculosis (TB) (HR 2.7; 95% CI, 1.0-7.3), candidiasis (HR 2.7; 95% CI, 1.8-4.0), herpes zoster (HR 1.7; 95% CI, 1.0-2.7), sepsis (HR 1.3; 95% CI, 1.1-1.5), demyelinating conditions (HR 3.2; 95% CI, 1.5-6.9), and cervical dysplasia (HR 1.5; 95% CI, 1.2-2.0) as compared with patients not receiving these medications. The use of two or three of these medications further increased these risks: TB (HR 7.4; 95% CI, 2.1-26.3), candidiasis (HR 3.8; 95% CI, 2.0-7.6), herpes zoster (HR 3.7; 95% CI, 1.8-7.5), sepsis (HR 1.6; 95% CI, 1.2-2.1), and cervical dysplasia (HR 1.8; 95% CI, 1.1-3.0). CONCLUSIONS: Treatment with steroids, ISs, or anti-TNF agents singly and in combination in patients with CD is associated with increased risks of infection, demyelinating disorders, and cervical dysplasia.

Multiple sclerosis patients' benefit-risk preferences: serious adverse event risks versus treatment efficacy.

OBJECTIVE: The aim of this study is to estimate the willingness of multiple sclerosis (MS) patients to accept life-threatening adverse event risks in exchange for improvements in their MS related health outcomes. METHODS: MS patients completed a survey questionnaire that included a series of choice-format conjoint tradeoff tasks. Patients chose hypothetical treatments from pairs of treatment alternatives with varying levels of clinical efficacy and associated risks. RESULTS: Among the 651 patients who completed the survey, delay in years to disability progression was the most important factor in treatment preferences. In return for decreases in relapse rates from 4 to 1 and increases in delay in progression from 3 to 5 years, patients were willing to accept a 0.38% annual risk of death or disability from PML, a 0.39% annual risk of death from liver failure or a 0.48% annual risk of death from leukemia. CONCLUSIONS: Medical interventions carry risks of adverse outcomes that must be evaluated against their clinical benefits. Most MS patients indicated they are willing to accept risks in exchange for clinical efficacy. Patient preferences for potential benefits and risks can assist in decision-making.

Health-related quality of life in multiple sclerosis: effects of natalizumab.

OBJECTIVE: To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. METHODS: HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300 mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-beta-1a) plus natalizumab 300 mg (n = 589), or IFN-beta-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. RESULTS: Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. INTERPRETATION: HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab.