Comparative efficacy and incremental cost per responder of methotrexate versus apremilast for methotrexate-naïve patients with psoriasis.

BACKGROUND: To our knowledge, no clinical trials directly compare apremilast with methotrexate (the standard of care for initial systemic treatment of psoriasis). OBJECTIVE: We sought to compare apremilast's relative efficacy with that of methotrexate for moderate to severe psoriasis. METHODS: An anchor-based indirect comparison was conducted for 75% improvement in Psoriasis Area and Severity Index score from baseline to week 16 (PASI 75) rates for systemic-naïve patients from Efficacy and Safety Trial Evaluating the Effects of apreMilast in psoriasis (ESTEEM) 1 and 2 (apremilast vs placebo) and Comparative study of HumirA vs. Methotrexate vs Placebo In psOriasis patieNts (CHAMPION) (adalimumab vs methotrexate vs placebo) trials. The difference-in-difference in PASI 75 response rates was calculated as the difference between the ESTEEM apremilast and placebo rates and the CHAMPION methotrexate versus placebo rates. Number needed to treat and incremental drug cost per responder were also estimated. RESULTS: No statistically significant difference was found between apremilast and methotrexate in PASI 75 (risk difference 13.1%; 95% confidence interval -1.8% to 28.0%; P = .09). Number needed to treat with apremilast versus methotrexate to gain 1 additional PASI 75 responder was 7.6. Annual incremental drug cost of this responder was estimated at $187,888.33. LIMITATIONS: Few trials compare systemic-naïve patients. Only direct medication costs were considered. CONCLUSIONS: There was no statistical evidence of greater efficacy for apremilast versus methotrexate. The $187,888 incremental cost per PASI 75 may exceed what payers are willing to pay.

Clinical Outcomes and Health-Care Resource Use Associated With Reslizumab Treatment in Adults With Severe Eosinophilic Asthma in Real-World Practice.

BACKGROUND: Reslizumab, an anti-IL-5 monoclonal antibody, is indicated as add-on maintenance treatment for adults with severe eosinophilic asthma. RESEARCH QUESTION: What are the real-world outcomes associated with reslizumab use in patients with severe eosinophilic asthma in a US clinical practice? STUDY DESIGN AND METHODS: In this retrospective study, patient-level data from adults treated with reslizumab were obtained from center- and panel-based medical chart reviews. Eligible patients had available medical records and treatment history for ≥ 6 months before initiation of reslizumab treatment (index date) to ≥ 7 months after reslizumab initiation. The primary outcome was response to reslizumab treatment, based on clinical expert predefined definitions of response. Other outcomes included clinical asthma exacerbations (CAEs), use of maintenance oral corticosteroids (OCS), FEV1 percent predicted, Asthma Control Test (ACT) score, and health-care resource use (HRU). RESULTS: Medical charts were obtained for 215 patients. Most patients (58.6%) showed an excellent response, 16.3% showed a clinically meaningful response, 21.9% showed a partial response, and 3.3% were nonresponders or treatment failures. A significant reduction was observed in the proportion of patients experiencing a CAE in a 6-month period (from 86.0% to 40.5%; P < .001) and in the mean number of CAEs per patient (2.84 [SD, 2.41] vs 0.94 [SD, 1.86]) after reslizumab initiation. Improvements were observed in FEV1 percent predicted (65.1% [SD, 20.5%] vs 73.1% [SD, 23.1%]; P < .001) and in ACT scores (13.8 [SD, 4.2] vs 18.6 [SD, 4.0]; P < .001) before to after reslizumab initiation. Among patients using maintenance OCS at baseline, more than half discontinued use of these by approximately 10 months after reslizumab initiation. Significant reductions in asthma-related HRU were observed after reslizumab initiation. INTERPRETATION: In clinical practice, reslizumab may have been initiated in response to heavy symptom burden and CAEs. Reslizumab was associated with improved clinical and patient-reported outcomes and significant reductions in asthma-related HRU.

Association of antipsychotic treatment switching in patients with schizophrenia, bipolar, and major depressive disorders.

Aims: To evaluate the association of relapse and healthcare resource utilization in patients with schizophrenia (SZ), bipolar disorder (BD), or major depressive disorder (MDD) who switched antipsychotic medication versus those who did not.Materials and methods: Medicaid claims from six US states spanning six years were retrospectively analyzed for antipsychotic switching versus non-switching. For all patients with SZ, BD, or MDD, and for the subset of patients who also had ≥1 extrapyramidal symptoms (EPS) diagnosis at baseline, times to the following outcomes were analyzed: underlying disease relapse, other psychiatric relapse, all-cause emergency room (ER) visit, all-cause inpatient (IP) admission, and EPS diagnosis.Results: Switchers (N = 10,548) had a shorter time to disease relapse, other psychiatric relapse, IP admissions, ER visits, and EPS diagnosis (all, log-rank p < .001) than non-switchers (N = 31,644). Switchers reached the median for IP admission (21.50 months) vs non-switchers (not reached) and for ER visits (switchers, 9.07 months; non-switchers, 13.35 months). For disease relapse, other psychiatric relapse, and EPS diagnosis, <50% of patients had an event during the two-year study period. Subgroup analysis of those with ≥1 EPS diagnosis revealed similar associations.Limitations: Only association, not causation, may be inferred, and there may be differences between the patient groups in parameters not evaluated.Conclusions: These results show that disease and other psychiatric relapse, all-cause ER visits, IP admissions, and EPS diagnosis occurred earlier for patients who switched antipsychotics than for those who did not, suggesting that switching is associated with an increased risk of relapse in patients with SZ, BD, and MDD. This may be attributed to more-severely ill patients being less responsive than those with less-severe illness, which, in turn, may require more episodes of switching.

Economic Burden of Illness Among Commercially Insured Patients with Systemic Sclerosis with Interstitial Lung Disease in the USA: A Claims Data Analysis.

INTRODUCTION: Interstitial lung disease (ILD) is a common manifestation of scleroderma/systemic sclerosis (SSc). However, the direct and indirect economic burdens of SSc-ILD remain unclear. This study assessed and compared healthcare resource utilization (HRU), direct healthcare costs, work loss, and indirect costs between patients with SSc-ILD and matched controls with neither SSc nor ILD in the USA. METHODS: Data were obtained from a large US commercial claims database (2005-2015). Patients (at least 18 years old) had at least one SSc diagnosis in the inpatient (IP) or emergency room (ER) setting or at least two SSc diagnoses in another setting, and at least one diagnosis of ILD in the IP or ER setting or at least two diagnoses of ILD in another setting. Controls with neither SSc nor ILD were matched 5:1 to patients with SSc-ILD. Comparisons were conducted using Wilcoxon signed-rank and McNemar's tests and adjusted odds ratios (ORs) and incidence rate ratios (IRRs). RESULTS: A total of 479 SSc-ILD patients and 2395 matched controls were included (52 SSc-ILD patients and 260 matched controls for work loss and indirect cost analyses). Patients with SSc-ILD had significantly higher HRU and costs, IP admissions (adjusted IRR = 5.6), IP hospitalization days (adjusted IRR = 12.0), ER visits (adjusted IRR = 2.8), OP visits (adjusted IRR = 3.1), and days of work loss (adjusted IRR = 4.5). The adjusted difference in annual direct healthcare costs was $28,632 (SSc-ILD, $33,195; controls, $4562) and that in indirect costs was $4735 (SSc-ILD, $5640; controls, $906) (all p < 0.0001). CONCLUSION: SSc-ILD patients had significantly higher HRU, work loss, and direct and indirect costs compared to matched controls with neither SSc nor ILD. FUNDING: Boehringer Ingelheim Pharmaceuticals, Inc.

Economic Burden among Commercially Insured Patients with Systemic Sclerosis in the United States.

OBJECTIVE: To quantify healthcare resource utilization (HRU), work loss, and annual direct and indirect healthcare costs among patients with systemic sclerosis (SSc) compared to matched controls in the United States. METHODS: Data were obtained from a large US commercial claims database. Patients were ≥ 18 years old at the index date (first SSc diagnosis) and had ≥ 1 SSc diagnosis in the inpatient (IP) or emergency room (ER) setting, or ≥ 2 SSc diagnoses on 2 different dates in the outpatient (OP) setting between January 1, 2005, and March 31, 2015; continuous enrollment was required during the followup period (12 months after the index date). Individuals with no SSc diagnoses were matched 1:1 to patients with SSc. Wilcoxon signed-rank and McNemar tests were used for comparisons and regressions with generalized estimating equations for adjusted OR (aOR) and incidence rate ratios (IRR) between 2 cohorts. RESULTS: There were 2192 pairs of patients with SSc and matched controls included (mean age 57.6 yrs; 84.3% female); of these, 233 were eligible for work loss/indirect cost analyses. Compared to matched controls, patients with SSc had significantly higher HRU and costs during the 1-year followup period, IP admissions (adjusted IRR = 2.4), IP hospitalization days (adjusted IRR = 3.1), ER visits (adjusted IRR = 2.0), OP visits (adjusted IRR = 2.3), and days of work loss (adjusted IRR = 2.6). The adjusted difference in annual direct and indirect costs was US$12,820 and $3103, respectively (all p < 0.0001). CONCLUSION: Patients with SSc had a high direct and indirect economic burden postdiagnosis.

One-year and long-term molecular response to nilotinib and dasatinib for newly diagnosed chronic myeloid leukemia: a matching-adjusted indirect comparison.

BACKGROUND: Nilotinib and dasatinib have shown superior rates of molecular response (MR) compared to imatinib for the treatment of newly diagnosed chronic myeloid leukemia (CML) in chronic phase (CP). This study indirectly compares MR in patients taking nilotinib 300 mg bid with that in those taking dasatinib 100 mg qd by 12 months and through 48 months. METHODS: Patients in ENESTnd were re-weighted to match published baseline characteristics reported for DASISION using a propensity score model. After matching, differences in rates of major MR (MMR, measured as a 3 log reduction on the International Scale [IS]), MR(4.0) (4 log reduction on IS), and MR(4.5) (4.5 log reduction on IS) relative to imatinib were indirectly compared between nilotinib and dasatinib. Hazard ratios (HRs) were used to indirectly compare MR outcomes between nilotinib and dasatinib through 48 months of follow-up, while rate differences were used to compare progression to AP/BC between nilotinib and dasatinib by 48 months. RESULTS: After matching, rates of MR by 12 months were higher with nilotinib vs dasatinib by 11.7% for MMR (p = 0.045), 8.2% for MR(4.0) (p = 0.029), and 8.5% for MR(4.5) (p < 0.001). Higher rates of MMR (HR = 1.44, p = 0.018) and MR(4.0) (HR = 1.58, p = 0.013) achievement were maintained with nilotinib compared to dasatinib through 48 months of follow-up. No statistically significant differences were observed for MR(4.5) through 48 months or progression to AP/BC by 48 months. LIMITATIONS: LIMITATIONS include comparisons based solely on indirect evidence and HRs for MR(4.0) and MR(4.5) from the DASISION trial being extracted from cumulative incidence curves. CONCLUSIONS: This indirect comparison suggests that nilotinib is associated with higher rates of achieving MMR, MR(4.0), and MR(4.5) by 12 months compared to dasatinib for the treatment of newly diagnosed CML-CP. In addition, higher rates of MR achievement with nilotinib were also maintained through 48 months of follow-up.

Glycemic and Cholesterol Control Versus Single-Goal Control in US Veterans with Newly Diagnosed Type 2 Diabetes: A Retrospective Observational Study.

INTRODUCTION: A majority of patients with diabetes do not have levels of glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) under control, either individually or in combination. The objective was to assess the clinical benefits and patient characteristics associated with dual-goal achievement [HbA1c <7% (53 mmol/mol) and LDL-C <100 mg/dL] versus only LDL-C goal achievement in adults with newly diagnosed type 2 diabetes. METHODS: Newly diagnosed patients with ≥2 measures of LDL-C and HbA1c were identified in the South Central Veterans Affairs Health Care Network (01/2004-06/2010). The index date was the first HbA1c assessment within 3 months of the first type 2 diabetes diagnosis. Multivariate Cox proportional hazards models were used to assess the association between time-varying goal achievement and post-index microvascular and cardiovascular complications. Patient characteristics associated with dual-goal achievement in the 7-12 months post-index were identified using a logistic regression. RESULTS: The sample included 16,829 patients. Compared with LDL-C goal achievement, dual-goal achievement was associated with lower risk of microvascular complications [hazard ratio (95% confidence interval): 0.69 (0.63, 0.76)]. Other outcomes did not differ between those two groups. Characteristics associated with dual-goal achievement (44.2% of patients) include prior dual-goal achievement, older age, and use of lipid-lowering drugs. CONCLUSION: Dual-goal achievement in newly diagnosed type 2 diabetes is associated with a lower risk of microvascular complications versus only LDL-C goal achievement. Although dual-goal achievement rates are suboptimal, early and regular intervention will increase its likelihood. FUNDING: Daiichi Sankyo, Inc., Parsippany, NJ, USA.

Real-world patterns of endocrine therapy for metastatic hormone-receptor-positive (HR+)/human epidermal growth factor receptor-2-negative (HER2-) breast cancer patients in the United States: 2002-2012.

OBJECTIVE: Clinical guidelines recommend that patients with HR+/HER2- metastatic breast cancer (mBC), the most prevalent mBC subtype, receive three lines of endocrine therapy (ET) prior to transitioning to chemotherapy (CT) in the absence of need for rapid response, symptomatic visceral disease, or suspected endocrine resistance. Little is known about real-world ET treatment patterns among HR+/HER2- mBC patients. RESEARCH DESIGN AND METHODS: Post-menopausal women with HR+/HER2- mBC were identified in the MarketScan databases (2002Q3-2012Q2). Patients were classified as receiving either ET or CT as their first therapy post-mBC diagnosis. Those receiving ET were studied further and stratified into three subgroups based on which of the following events occurred first: transition to CT, discontinuation of ET (90 days without evidence of ET), or end of data or insurance eligibility. MAIN OUTCOME MEASURES: Mean numbers of lines of ET and median durations of each line were summarized for the overall sample and subgroups. RESULTS: Among a total of 19,120 HR+/HER2- mBC patients, 11,545 (60%) initiated an ET; median follow-up time for these patients was 17 months. Seventy-four percent did not receive a second ET. The average patient received 1.36 lines of ET. Among patients with 2+ lines of ET, the duration of each subsequent line was significantly shorter than the previous line. RESULTS were similar in all subgroups. LIMITATIONS: Clinical characteristics and reasons for treatment choices are unavailable in claims data. CONCLUSIONS: Fewer than two thirds of patients initiated treatment for HR+/HER2- mBC with ET. Among those who did, most received only one line of ET before discontinuation or transition to CT. Patients who received multiple lines of ET experienced shorter durations of therapy with each line. Real-world treatment with ET falls short of the targets recommended by guidelines, representing unmet need for treatment options that improve the effectiveness of endocrine therapy.

Clinical and economic benefits associated with the achievement of both HbA1c and LDL cholesterol goals in veterans with type 2 diabetes.

OBJECTIVE: This study compared the clinical and economic benefits associated with dual-goal achievement, glycated hemoglobin (HbA1c)<7% (53 mmol/mol) and LDL cholesterol (LDL-C)<100 mg/dL, with achievement of only the LDL-C goal or only the HbA1c goal in veterans with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This retrospective cohort analysis evaluated electronic medical records (Veterans Integrated Service Network 16) in adult T2DM patients with two or more measurements of LDL-C and HbA1c between 1 January 2004 and 30 June 2010 (N=75,646). Cox proportional hazards models were used to compare microvascular and cardiovascular outcomes by goal achievement status; generalized linear regression models were used to assess diabetes-related resource utilization (hospitalization days and number of outpatient visits) and medical service costs. RESULTS: Relative to achievement of only the LDL-C goal, dual-goal achievement was associated with lower risk of microvascular complications (adjusted hazard ratio [aHR] 0.79), acute coronary syndrome (0.88), percutaneous coronary intervention (0.78), and coronary artery bypass graft (CABG) (0.74); it was also associated with fewer hospitalization days (adjusted incidence rate ratio [aIRR] 0.93) and outpatient visits (0.88), as well as lower diabetes-related annual medical costs (-$130.89). Compared with achievement of only the HbA1c goal, dual-goal achievement was associated with lower risk of the composite cardiovascular-related end point (aHR 0.87) and CABG (aHR 0.62), as well as fewer outpatient visits (aIRR 0.98). CONCLUSIONS: Achieving both HbA1c and LDL-C goals in diabetes care is associated with additional clinical and economic benefits, as compared with the achievement of either goal alone.