Comparative effectiveness and safety of ozanimod versus other oral DMTs in relapsing-remitting multiple sclerosis: a synthesis of matching-adjusted indirect comparisons.

Background: Several oral disease-modifying therapies (DMTs) have been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis (RRMS). In the absence of head-to-head randomized data, matching-adjusted indirect comparisons (MAICs) can evaluate the comparative effectiveness and safety of ozanimod versus other oral DMTs in RRMS. Objectives: To synthesize results from the published MAICs of ozanimod and other oral DMTs for 2-year outcomes in RRMS. Methods: Published MAICs involving ozanimod for the treatment of RRMS were identified. Extracted data elements included efficacy [annualized relapse rate (ARR), confirmed disability progression (CDP), and brain volume loss] and safety [adverse events (AEs), serious AEs (SAEs), AEs leading to discontinuation, and infection] outcomes. Results: The four MAIC studies identified compared ozanimod with fingolimod, teriflunomide, dimethyl fumarate (DMF), and ponesimod. All comparisons were adjusted for differences in age, sex, relapses within the previous year, Expanded Disability Status Scale score, and percentage of patients with prior DMTs. Outcomes at 2 years were analyzed based on comparisons that lacked a common comparator arm. Ozanimod was associated with significantly lower ARR versus teriflunomide [ARR ratio (95% CI) 0.73 (0.62, 0.84) and DMF 0.80 (0.67, 0.97)], with no significant difference versus fingolimod or ponesimod. The proportions of patients treated with ozanimod or fingolimod had similar 3- and 6-month CDP. Compared with teriflunomide and DMF, ozanimod was associated with a significantly lower risk of 3-month CDP; 6-month CDP was comparable. Ozanimod was associated with significantly lower rates of any AE and AEs leading to discontinuation compared with the other oral DMTs evaluated. Ozanimod also had significantly lower rates of SAEs versus teriflunomide and DMF and lower rates of reported infection outcomes versus fingolimod and ponesimod. Conclusion: Compared with the other oral DMTs evaluated in MAICs, ozanimod was associated with a favorable safety profile and improved or comparable efficacy outcomes.

An indirect comparison of ozanimod vs other oral treatments in relapsing-remitting multiple sclerosis The many treatment options available for relapsing-remitting multiple sclerosis (RRMS) make treatment decisions difficult. While direct head-to-head treatment comparisons provide useful information, these studies are not available for every pair of treatments. Indirect comparisons of published study results can help fill that evidence gap. A technique called matching-adjusted indirect comparison (MAIC) offers a statistically robust way to compare safety/efficacy outcomes from different studies by accounting for important differences across the studies. We collected data from four MAIC studies that compared 2-year treatment outcomes in patients treated with ozanimod versus those treated with fingolimod, teriflunomide, dimethyl fumarate (DMF), or ponesimod. Each study accounted for differences in age, sex, relapses within the previous year, disability status, and previous therapy use. We found ozanimod was either better than or similar to other treatments based on the outcomes measured. The annual rate of RRMS relapse was lower for patients treated with ozanimod than for patients treated with teriflunomide or DMF and similar for patients treated with ponesimod or fingolimod. Ozanimod-treated patients saw their RRMS progress at rates similar to those treated with fingolimod at 3 and 6 months and teriflunomide and DMF at 6 months; RRMS was more likely to progress at 3 months in patients treated with teriflunomide and DMF versus those treated with ozanimod. Our analyses also found that patients treated with ozanimod had lower rates of side effects, including those serious enough to cause treatment discontinuation, compared with patients receiving other treatments. By comparing findings from existing MAIC studies, we found that patients with RRMS treated with ozanimod had fewer side effects and better or similar efficacy outcomes compared with patients who received other treatments for RRMS. These findings can potentially inform treatment decisions for patients with RRMS.

Real-World Treatment Patterns among Patients with Alopecia Areata in the USA: A Retrospective Claims Analysis.

Alopecia areata is an autoimmune disorder characterized by hair loss, for which there are few treatment options. This claims-based study characterized recent real-world treatment patterns among patients in the USA with alopecia areata, including the subtypes alopecia totalis and alopecia universalis, in the first year after diagnosis of an episode of alopecia areata. Approximately 5% of all patients (adults (age ≥ 18 years), n = 7,703; adolescents (age 12-17 years), n = 595) had alopecia totalis or alopecia universalis. Corticosteroids were the most common first-line (1L) and second-line (2L) treatments. The mean time from diagnosis of alopecia areata to initiation of 1L treatment was 2.2 days for adults and 2.6 days for adolescents; mean 1L duration was 76.9 and 64.3 days, respectively. For adults (57.5%) and adolescents (59.7%) with 2L therapy, the mean time from 1L discontinuation to 2L initiation was 57.2 and 53.6 days, respectively; the mean duration of 2L treatment was 55.5 and 50.1 days, respectively. More patients with vs without alopecia totalis or alopecia universalis initiated 2L therapy (adults: 71.9% vs 56.8%; adolescents: 71.4% vs 58.9%). The proportion of days covered during the first year post-diagnosis was 36.7% (adults) and 34.1% (adolescents). These results highlight the substantial disease burden of alopecia areata and a need for more effective treatments.

Avatrombopag treatment response in patients with immune thrombocytopenia: the REAL-AVA 1.0 study.

Background: Thrombopoietin-receptor agonists (TPO-RAs) are used to treat immune thrombocytopenia (ITP), a disorder characterized by prolonged low platelet counts (PCs) that pose a risk of serious bleeding episodes. Avatrombopag (AVA) is the most recently approved TPO-RA for the treatment of chronic ITP. A high proportion of patients responded to AVA in clinical trials, and treatment was well-tolerated; however, limited real-world effectiveness data have been reported to date. Objectives: To describe demographic and clinical characteristics, treatment patterns, and outcomes following the initiation of AVA in patients with ITP in the United States. Design: This is a retrospective study using administrative claims data from the Komodo Healthcare Map (1 February 2017 to 28 February 2022) linked with PC laboratory data. Methods: Patients with ⩾1 diagnosis of ITP, ⩾1 paid prescription for AVA (index date), and ⩾1 month of pharmacy coverage after AVA initiation were selected. Baseline characteristics and follow-up steroid, immunosuppressant, and rescue medication use were described. The percentage of patients achieving clinically meaningful PC thresholds (⩾30 × 109/l) were assessed among patients with ⩾1 PC following AVA initiation and prior to AVA discontinuation/switch (effectiveness subgroup). Results: A total of 205 patients met eligibility criteria and 49% reported TPO-RA use in the prior 6 months. Approximately 70% and 93% of patients did not require use of steroid or immunoglobulin rescue medication during follow-up, respectively. Among patients with concomitant steroid (n = 75) or immunosuppressant (n = 7) use at AVA initiation, 35% and 57% discontinued those treatments, respectively. Of the 21 patients in the effectiveness subgroup, 81% achieved clinically meaningful PC thresholds. Conclusion: A high proportion of evaluable patients with ITP in this real-world study achieved clinically meaningful PCs, without requiring rescue medication during AVA treatment, with many able to discontinue baseline concomitant steroid or immunosuppressant utilization. Despite limited availability of PC data, these results are consistent with results from the AVA pivotal clinical trials.

Burden of Illness and Treatment Patterns Among Patients With von Willebrand Disease in US Clinical Practice.

In this retrospective cohort study, data from an integrated US healthcare system containing both electronic medical record data and linked claims data (from 01/2004 to 12/2020) were used to evaluate the clinical burden, treatment patterns, and healthcare resource use (HRU) in patients with von Willebrand disease (VWD). Two patient cohorts were analyzed: the overall VWD population (n = 396) and a subset of these patients (n = 75) who were considered potentially eligible for prophylaxis treatment with von Willebrand factor (VWF) based on a history of severe and frequent bleeding. HRU (hospitalizations, outpatient visits, and emergency department visits) were measured in patients with linked claims data (n = 110, overall VWD patients; n = 23 potentially VWF-prophylaxis-eligible VWD patients). In general, patients with VWD experienced a substantial burden of bleeding events, comorbidities, and HRU. Patients with VWD who were considered potentially eligible for prophylaxis owing to severe and frequent bleeds suffered from a higher clinical burden and HRU than the overall VWD population, and thus may benefit from VWF prophylactic treatment. The findings from this study could help improve clinical outcomes and manage HRU for patients with VWD.

Benefits of Autoantibody Enrichment in Early Rheumatoid Arthritis: Analysis of Efficacy Outcomes in Four Pooled Abatacept Trials.

INTRODUCTION: The efficacy of abatacept is enhanced in anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF)-positive versus -negative patients with rheumatoid arthritis (RA). Four early RA abatacept trials were analyzed to understand the differential impact of abatacept among patients with SeroPositive Early and Active RA (SPEAR) compared to non-SPEAR patients. METHODS: Pooled patient-level data from AGREE, AMPLE, AVERT, and AVERT-2 were analyzed. Patients were classified as SPEAR if they were ACPA +, RF +, disease duration < 1 year, and Disease Activity Score-28 (DAS28) C-reactive protein (CRP) ≥ 3.2 at baseline; non-SPEAR otherwise. Outcomes included: American College of Rheumatology (ACR) 20/50/70 at week 24; mean change from baseline to week 24 for DAS28 (CRP), Simple Disease Activity Index (SDAI), ACR core components; DAS28 (CRP) and SDAI remission. Adjusted regression analyses among abatacept-treated patients compared SPEAR and non-SPEAR patients, and in full trial population estimating how the efficacy of abatacept versus comparators [adalimumab + methotrexate, methotrexate] was modified by SPEAR status. RESULTS: The study included 1400 SPEAR and 673 non-SPEAR patients; most were female (79.35%), white (77.38%), and with a mean age 49.26 (SD 12.86) years old. Around half with non-SPEAR were RF + and three-quarters ACPA +. Stronger improvements from baseline to week 24 were observed in almost all outcomes for abatacept-treated SPEAR versus non-SPEAR patients or versus SPEAR patients treated with comparators. Larger improvements were observed for SPEAR patients among the abatacept-treated population, and more strongly improved efficacy among SPEAR patients for abatacept than comparators. CONCLUSIONS: This analysis, including large patient numbers of early-RA abatacept trials, confirmed beneficial treatment effects of abatacept in patients with SPEAR versus non-SPEAR.

Real-world outcomes associated with vonoprazan-based versus proton pump inhibitor-based therapy for Helicobacter pylori infection in Japan.

Background: Japanese guidelines recommend triple therapy with vonoprazan or a proton pump inhibitor (PPI) in combination with antibiotics to treat Helicobacter pylori (H. pylori) infection. While studies have shown improved eradication rates and reduced costs with vonoprazan versus PPIs, there is little data describing healthcare resource use (HCRU) and treatment patterns. Objectives: To compare patients treated with a vonoprazan-based or PPI-based regimen for H. pylori infection in Japan in terms of their characteristics, HCRU, healthcare costs, clinical outcomes, and treatment patterns. Design: Retrospective matched cohort. Methods: We used data from the Japan Medical Data Center claims database (July 2014-January 2020) to identify adult patients with H. pylori infection and a first observed use of vonoprazan or a PPI in 2015 or later (index date). Patients prescribed a vonoprazan-based or a PPI-based regimen were matched 1:1 using propensity score matching. HCRU, healthcare costs, diagnostic tests, a proxy for H. pylori eradication (i.e. no triple therapy with amoxicillin in combination with metronidazole or clarithromycin >30 days after the index date), and second-line treatment were described during the 12-month follow-up period. Results: Among 25,389 matched pairs, vonoprazan-treated patients had fewer all-cause and H. pylori-related inpatient stays and outpatient visits than PPI-treated patients, resulting in lower all-cause healthcare costs [185,378 Japanese yen (JPY) versus 230,876 JPY, p < 0.001]. Over 80% of patients received a post-treatment test for H. pylori. Fewer vonoprazan-treated than PPI-treated patients subsequently received an additional triple regimen for H. pylori infection (7.1% versus 20.0%, p < 0.001) or a prescription for vonoprazan or a PPI as monotherapy (12.4% versus 26.4%, p < 0.001) between 31 days and 12 months after the index date. Conclusion: Patients with H. pylori infection who were treated with vonoprazan-based therapy had lower rates of subsequent H. pylori treatment, lower overall and H. pylori-related HCRU, and lower healthcare costs than patients treated with PPI-based therapy.

Association of Serum Calcium and Phosphate With Incident Cardiovascular Disease in Patients With Hypoparathyroidism.

The pathophysiological basis for the increased incidence of cardiovascular disease in patients with chronic hypoparathyroidism is poorly understood. To evaluate associations between levels of albumin-corrected serum calcium, serum phosphate, and calcium-phosphate product with the odds of developing cardiovascular events in patients with chronic hypoparathyroidism with ≥1 calcitriol prescription, we conducted a retrospective nested case-control study of patients who developed a cardiovascular event and matched controls without an event. The primary outcome was the instance of cardiovascular events. An electronic medical record database was used to identify 528 patients for the albumin-corrected serum calcium analysis and 200 patients for the serum phosphate and calcium-phosphate product analyses. Patients with ≥67% of albumin-corrected serum calcium measurements outside the study-defined 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) range had 1.9-fold higher odds of a cardiovascular event (adjusted odds ratio, 95% confidence interval 1.89, 1.10 to 3.25) compared with patients with <33% of calcium measurements outside the range. Likewise, patients with any serum phosphate measurements above 0.81 to 1.45 mmol/L (2.5 to 4.5 mg/100 ml) had 3.3-fold higher odds (3.26; 1.24 to 8.58), and those with any calcium-phosphate product measurements above 4.40 mmol2/L2 (55 mg2/dL2) had 4.8-fold higher odds of a cardiovascular event (95% confidence interval 1.36 to 16.81) compared with patients with no measurements above these ranges. In adult patients with chronic hypoparathyroidism, a cardiovascular event was more likely in those with a higher proportion of albumin-corrected serum calcium measurements outside 2.00 to 2.25 mmol/L (8.0 to 9.0 mg/100 ml) or any serum phosphate and any calcium-phosphate product measurements above the normal population range.

Patient characteristics associated with all-cause healthcare costs of alopecia areata in the United States.

Evidence on the factors of medical costs involved in the care of people with alopecia areata (AA) is limited, but mounting evidence points to significant variation in financial impact for patients with AA in the absence of effective treatments. This study explored drivers of medical costs among privately insured adults and adolescents with AA in the United States. The study found that patients of middle age (45­64 years), located in the Northeast region, with comprehensive health insurance, with greater extent of hair loss, or with other health disorders face greater all-cause medical costs. Adult females of young (18­44 years) and older (65+ years) age also faced greater costs on average. This research confirms high variability in the burden of AA, pointing to population subgroups that may be more affected by the disease and its commonly associated disorders.

Cost Per Relapse Avoided for Ozanimod Versus Other Selected Disease-Modifying Therapies for Relapsing-Remitting Multiple Sclerosis in the United States.

INTRODUCTION: This study assessed the cost-effectiveness of ozanimod compared with commonly used disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS). METHODS: Annualized relapse rate (ARR) and safety data were obtained from a network meta-analysis (NMA) of clinical trials of RRMS treatments including ozanimod, fingolimod, dimethyl fumarate, teriflunomide, interferon beta-1a, interferon beta-1b, and glatiramer acetate. ARR-related number needed to treat (NNT) relative to placebo and annual total MS-related healthcare costs was used to estimate the incremental annual cost per relapse avoided with ozanimod vs each DMT. ARR and adverse event (AE) data were combined with drug costs and healthcare costs to manage relapses and AEs in order to estimate annual cost savings with ozanimod vs other DMTs, assuming a 1 million USD fixed treatment budget. RESULTS: Treatment with ozanimod was associated with lower incremental annual healthcare costs to avoid a relapse, ranging from $843,684 vs interferon beta-1a (30 µg; 95% confidence interval [CI] - $1,431,619, - $255,749) to $72,847 (95% CI - $153,444, $7750) vs fingolimod. Compared with all other DMTs, ozanimod was associated with overall healthcare cost savings ranging from $8257 vs interferon beta-1a (30 µg) to $2178 vs fingolimod. Compared with oral DMTs, ozanimod was associated with annual cost savings of $6199 with teriflunomide 7 mg, $4737 with teriflunomide 14 mg, $2178 with fingolimod, and $2793 with dimethyl fumarate. CONCLUSION: Treatment with ozanimod was associated with substantial reductions in annual drug costs and total MS-related healthcare costs to avoid relapses compared with other DMTs. In the fixed-budget analysis, ozanimod demonstrated a favorable cost-effective profile relative to other DMTs.

Trends in Prevalence and Incidence of Alopecia Areata, Alopecia Totalis, and Alopecia Universalis Among Adults and Children in a US Employer-Sponsored Insured Population.

Importance: Alopecia areata (AA) is characterized by nonscarring hair loss of the scalp, face, and/or body. Alopecia totalis (AT) and alopecia universalis (AU) involve complete loss of the scalp and body hair, respectively. The epidemiology of AA in the US remains unclear, having previously been extrapolated from older studies that were limited to specific geographic areas or clinical settings, or from self-reported data. Objective: To estimate the annual prevalence and incidence of AA and AT and/or AU (AT/AU) in the US. Design, Setting, and Participants: This retrospective, population-based cohort study was conducted from January 2016 to December 2019 and included enrollees in the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental databases and their dependents, with plan enrollment during each study calendar year and the year prior. Exposures: Prevalent cases were identified by 1 or more claims for AA or AT/AU (International Statistical Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM] codes L63.x, L63.0, L63.1) during each year of interest or the year prior. Incident cases were identified by 1 or more claims for AA or AT/AU during a specific year and no diagnosis the year prior. Main Outcomes and Measures: Annual incidence and prevalence rates were calculated and stratified by age, sex, and region. National employer-sponsored insurance population estimates were obtained using population-based weights. Results: Among eligible patients (2016: n = 18 368 [mean (SD) age, 40.6 (17.9) years; 12 295 women (66.9%)]; 2017: n = 14 372 [mean (SD) age, 39.6 (17.7) years; 9195 women (64.0%)]; 2018: n = 14 231 [mean (SD) age, 38.9 (17.3) years; 8998 women (63.2%)]; 2019: n = 13 455 [mean (SD) age, 39.1 (17.4) years; 8322 women (61.9%)]), AA prevalence increased from 0.199% (95% CI, 0.198%-0.200%) in 2016 to 0.222% (95% CI, 0.221%-0.223%) in 2019. Roughly 5% to 10% of prevalent and incident cases of AA were AT/AU. The prevalence of AT/AU increased from 0.012% (95% CI, 0.012%-0.013%) to 0.019% (95% CI, 0.018%-0.019%) from 2016 to 2019. Incidence of AA per 100 000 person-years ranged from 87.39 (95% CI, 86.84-87.96) in 2017 to 92.90 (95% CI, 92.35-93.45) in 2019. Incidence of AT/AU ranged from 7.09 (95% CI, 6.94-7.25) in 2017 to 8.92 (95% CI, 8.75-9.09) in 2016. Prevalence and incidence of AA and AT/AU were higher among female vs male individuals, adults vs children and adolescents, and in the Northeast vs other regions. Conclusions and Relevance: The results of this cohort study suggest that these recent AA prevalence and incidence estimates could help improve current understanding of the disease burden. Further research is warranted to elucidate subpopulation differences and trends in AA in the broader US population.

Comparative efficacy and safety of ozanimod and ponesimod for relapsing multiple sclerosis: A matching-adjusted indirect comparison.

BACKGROUND: Ozanimod and ponesimod are sphingosine 1-phosphate receptor modulators approved by the U.S. Food and Drug Administration for treatment of relapsing forms of multiple sclerosis (MS). Given that no head-to-head trials have assessed these two treatments, we performed a matching-adjusted indirect comparison (MAIC) to compare efficacy and safety outcomes between ozanimod and ponesimod for MS. METHODS: A MAIC compared efficacy and safety of ozanimod and ponesimod at 2 years. Outcomes included annualized relapse rate (ARR) and percentage change from baseline in brain volume loss (BVL) as well as rates of any treatment-emergent adverse events (TEAEs), serious adverse events (AEs), AEs leading to discontinuation, and other safety outcomes. Individual patient-level data were obtained for ozanimod from the RADIANCE-B trial, while aggregate-level patient data were obtained for ponesimod from the OPTIMUM trial. The MAIC was not anchored owing to lack of a common comparator across the two trials. The following characteristics were matched between the trials' populations: age, sex, time since MS symptom onset, relapses in prior year, Expanded Disability Status Scale score, disease-modifying therapies received in the prior 2 years, absence of gadolinium-enhancing T1 lesions, and percentage of patients from Eastern Europe. RESULTS: After matching, key baseline characteristics were balanced between patients receiving ozanimod and ponesimod. Compared with ponesimod, ozanimod had a numerically lower ARR (rate ratio: 0.80 [95% CI: 0.57, 1.10]) and was associated with a significant reduction in BVL (% change difference: 0.20 [95% CI: 0.05, 0.36]). Additionally, ozanimod was associated with a significantly lower risk of TEAEs (risk difference: -11.9% [95% CI: -16.8%, -7.0%]), AEs leading to discontinuation (-6.1% [95% CI: -8.9%, -3.4%]), and lymphocyte count <0.2 K/µL (-2.3% [95% CI: -4.2%, -0.5%]). There were no statistically significant differences in the other safety outcomes. CONCLUSION: The MAIC results suggest that, compared with ponesimod, ozanimod is more effective in preserving brain volume, is comparable in terms of reducing relapse rates, and has a favorable safety profile.

The risk of chronic kidney disease development in adult patients with chronic hypoparathyroidism treated with rhPTH(1-84): A retrospective cohort study.

OBJECTIVE: This study assessed the risk of developing chronic kidney disease (CKD) and decline in estimated glomerular filtration rate (eGFR) over a period of up to 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1-84) (rhPTH[1-84]) compared with a historical control cohort of patients not treated with rhPTH(1-84). DESIGN: Retrospective cohort study of patients with chronic hypoparathyroidism treated with rhPTH(1-84) derived from the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309) and HEXT (NCT01199614, and its continuation study NCT02910466) clinical trials and a historical control cohort who did not receive PTH selected from an electronic medical record database. PATIENTS: One hundred and eighteen patients treated with rhPTH(1-84) and 497 patient controls. MEASUREMENTS: Incident CKD was defined as ≥2 eGFR measurements <60 ml/min/1.73 m2 ≥3 months apart during the study and a sustained eGFR decline of ≥30% from baseline. RESULTS: Over the 5-year period, Kaplan-Meier analyses showed that rhPTH(1-84)-treated patients had a significantly lower risk of developing CKD (log-rank p = .002) and a lower risk for a sustained eGFR decline ≥30% from baseline (log-rank p < .001) compared with patients in the control cohort. In adjusted analyses, patients in the rhPTH(1-84)-treated cohort had a 53% lower risk of developing CKD (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.25-0.87) and a 65% lower risk for sustained eGFR decline ≥30% from baseline (HR, 0.35; 95% CI, 0.13-0.89) compared with controls. CONCLUSIONS: Patients with chronic hypoparathyroidism treated with rhPTH(1-84) in long-term clinical trials had a significantly lower risk of developing CKD compared with patients in a historical control cohort not treated with rhPTH(1-84).

Five-Year Estimated Glomerular Filtration Rate in Adults with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study.

INTRODUCTION: Chronic hypoparathyroidism is associated with higher risk of developing chronic kidney disease compared with the general population. This study evaluated changes in estimated glomerular filtration rate (eGFR) over a 5-year period in adult patients with chronic hypoparathyroidism treated with recombinant parathyroid hormone (1-84), rhPTH(1-84), compared with a historical control cohort of patients who did not receive rhPTH(1-84). METHODS: This retrospective cohort study included patients with chronic hypoparathyroidism treated with rhPTH(1-84) in the REPLACE (NCT00732615), RELAY (NCT01268098), RACE (NCT01297309), and HEXT (NCT01199614 and continuation study NCT02910466) clinical trials. A historical control cohort who did not receive parathyroid hormone but who had enrollment criteria similar to those for the clinical trials was selected from the IBM® Explorys electronic medical record database (January 2007-August 2019). Outcomes of interest were the annual rate of change in eGFR from baseline (i.e., eGFR slope) and the predicted eGFR change from baseline at years 1 through 5. RESULTS: The study comprised 72 adult patients with chronic hypoparathyroidism treated with rhPTH(1-84) and 176 control patients who did not receive rhPTH(1-84). Over 5 years, eGFR remained stable in the rhPTH(1-84) cohort, whereas eGFR declined at a rate of 1.67 mL/min/1.73 m2 per year in the control cohort (P < 0.001 for eGFR slope in the control cohort). At 5 years, predicted eGFR in the rhPTH(1-84) cohort increased from baseline by 1.21 mL/min/1.73 m2, whereas eGFR in the control cohort declined by 10.36 mL/min/1.73 m2, after adjusting for baseline variables. The difference in eGFR slopes between the cohorts over 5 years was 1.37 mL/min/1.73 m2 per year (95% CI 0.62-2.13; P < 0.001). CONCLUSION: Long-term treatment with rhPTH(1-84) was associated with stable eGFR compared with eGFR decline in the controls not treated with rhPTH(1-84). Preservation of renal function conferred by rhPTH(1-84) may benefit patients with chronic hypoparathyroidism by reducing risk of long-term renal complications.

Healthcare Utilization and Costs Among US Adolescents With Alopecia Areata.

Background: Alopecia areata (AA) is an autoimmune disease of hair loss affecting people of all ages. Alopecia totalis (AT) and universalis (AU) involve scalp and total body hair loss, respectively. AA significantly affects quality of life, but evidence on the economic burden in adolescents is limited. Objectives: To assess healthcare resource utilization (HCRU) and all-cause direct healthcare costs, including out-of-pocket (OOP) costs, of US adolescents with AA. Methods: IBM MarketScan® Commercial and Medicare databases were used to identify patients aged 12-17 years with ≥2 claims with AA/AT/AU diagnosis (prevalent cases), from October 1, 2015, to March 31, 2018, enrolled for ≥12 months before and after the first AA diagnosis (index). Patients were matched 1:3 to non-AA controls on index year, demographics, plan type, and Charlson Comorbidity Index. Per patient per year HCRU and costs were compared post-index. Results: Patients comprised 130 AT/AU adolescents and 1105 non-AT/AU adolescents (53.8% female; mean age, 14.6 years). Post-index, AT/AU vs controls had more outpatient (14.5 vs 7.1) and dermatologist (3.6 vs 0.3) visits, higher mean plan costs ($9397 vs $2267), including medical ($7480 vs $1780) and pharmacy ($1918 vs $487) costs, and higher OOP costs ($2081 vs $751) (all P<.001). The non-AT/AU cohort vs controls had more outpatient (11.6 vs 8.0) and dermatologist (3.4 vs 0.4) visits, higher mean plan costs ($7587 vs $4496), and higher OOP costs ($1579 vs $805) (all P<.001). Discussion: This large-sample, real-world analysis found that adolescents with prevalent AA had significantly higher HCRU and all-cause costs than matched controls. The greater burden was driven by more frequent outpatient visits, and higher payer medical and pharmacy costs in comparison with controls. Oral corticosteroid use was higher among patients with AT/AU; topical and injectable corticosteroid use was higher for non-AT/AU. Although the data preclude the identification of AA-attributable costs, the matched-control design allows an estimation of incremental all-cause costs associated with AA. Conclusions: Adolescents with AA incurred substantial incremental healthcare costs, with greater costs incurred among those with AT/AU. Study findings suggest that AA incurs costs as a medical condition with a high burden on adolescent patients and health plans.

Lower Risk of Cardiovascular Events in Adult Patients with Chronic Hypoparathyroidism Treated with rhPTH(1-84): A Retrospective Cohort Study.

INTRODUCTION: Patients with chronic hypoparathyroidism are at increased risk of cardiovascular disease. This study evaluated the risk of developing cardiovascular conditions over a period of 5 years in adult patients with chronic hypoparathyroidism treated with recombinant human parathyroid hormone (1-84), rhPTH(1-84), compared with a historical control cohort of patients not treated with rhPTH(1-84). METHODS: This retrospective cohort study comprised patients with chronic hypoparathyroidism treated with rhPTH(1-84) in the REPLACE (NCT00732615), RELAY (NCT01268098), and RACE (NCT01297309) clinical trials, and controls selected from the IBM® Explorys electronic medical record database (January 2007-August 2019) who did not receive parathyroid hormone but who had enrollment criteria similar to those for the clinical trials. Cardiovascular outcomes were the first diagnosis of cerebrovascular, coronary artery, peripheral vascular disease, or heart failure during the study period. RESULTS: We evaluated 113 adult patients with chronic hypoparathyroidism treated with rhPTH(1-84) and 618 control patients who did not receive rhPTH(1-84). Over the 5-year follow-up period, 3.5% of patients (n = 4) in the rhPTH(1-84) cohort had a cardiovascular event compared with 16.3% (n = 101) in the control cohort. Kaplan-Meier analysis demonstrated that patients in the rhPTH(1-84) cohort had lower risk of experiencing a cardiovascular event compared with patients in the control cohort (P = 0.005). Multivariable analyses adjusted for baseline variables showed that patients in the rhPTH(1-84) cohort had 75% lower risk for a cardiovascular event compared with patients in the control cohort (adjusted hazard ratio, 0.25 [95% CI 0.08-0.81]; P = 0.020). CONCLUSION: Long-term treatment with rhPTH(1-84) was associated with a lower risk of incident cardiovascular conditions compared with conventional therapy in patients with chronic hypoparathyroidism. Previous studies demonstrated that mineral homeostasis was maintained with lower use of calcium and active vitamin D when rhPTH(1-84) was added to conventional therapy. Future studies are needed to understand whether improved regulation of mineral homeostasis conferred by rhPTH(1-84) may provide long-term cardiovascular benefits to patients with chronic hypoparathyroidism.

Direct health care costs associated with COVID-19 in the United States.

BACKGROUND: Data on the real-world health care burden of COVID-19 in the United States are limited. OBJECTIVE: To compare health care resource use (HRU), direct health care costs, and long-term COVID-19-related complications between patients with vs patients without COVID-19 diagnoses. METHODS: Using IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental and Coordination of Benefits administrative claims databases (January 1, 2018, to March 1, 2021), this retrospective, matched cohort study compared patients with a recorded COVID-19 diagnosis to control subjects with no recorded diagnosis for COVID-19, personal history of COVID-19, or pneumonia due to COVID-19. To capture typical health care utilization, the control group was analyzed in 2019 (prepandemic); their index date was assigned as 1 year before the index date (first observed COVID-19 diagnosis) of their matched COVID-19 patient. All patients had continuous health plan coverage for at least 6 months pre-index (baseline) and at least 6 months post-index (allowing censoring during month 6). Separately for commercial and Medicare cohorts, COVID-19 and control patients were matched 1:1 using propensity scores, number of followup months, and indicator of age 18 years or older. During each month of the 6-month follow-up, all-cause HRU, health care costs, and COVID-19-related complications were compared between patients with COVID-19 and controls. RESULTS: After matching COVID-19 and control patients 1:1, a total of 150,731 commercial matched pairs and 1,862 Medicare matched pairs were retained; baseline characteristics were similar between patients with COVID-19 and controls. Patients with COVID-19 and controls had mean ages of 38.9 and 39.7 years in the commercial cohort and 74.3 and 75.3 years in the Medicare cohort, respectively. In month 1 of follow-up, patients with COVID-19 relative to controls were significantly more likely to have at least 1 inpatient admission (commercial: 6.9% vs 0.5%; Medicare: 29.1% vs 1.3%; both P < 0.001) and at least 1 emergency department visit (commercial: 37.3% vs 3.4%; Medicare: 26.2% vs 4.1%; both P < 0.001). Total health care costs in month 1 were significantly higher among patients with COVID-19 than controls (mean differences: $3,706 for commercial; $10,595 for Medicare; both P < 0.001), driven by inpatient costs. Though the incremental HRU and cost burden of COVID-19 decreased over time, patients with COVID-19 continued to have significantly higher total costs through month 5 (all P < 0.001 for both commercial and Medicare). During follow-up, patients with COVID-19 had significantly higher rates of complications than controls (commercial: 52.8% vs 29.0% with any; Medicare: 74.5% vs 47.9% with any; both P < 0.001), most commonly cough, dyspnea, and fatigue. CONCLUSIONS: COVID-19 was associated with significant economic and clinical burden, both in the short-term and over 6 months following diagnosis. DISCLOSURES: Jessica K DeMartino is an employee of Janssen Scientific Affairs, LLC. Elyse Swallow, Debbie Goldschmidt, Karen Yang, Marta Viola, Tyler Radtke, and Noam Kirson are employees of Analysis Group, Inc., which has received consulting fees from Janssen Scientific Affairs, LLC. This study was funded by Janssen Scientific Affairs, LLC. The sponsor was involved in the study design, interpretation of the results, manuscript review, and the decision to publish the article.

All-cause health care resource utilization and costs among adults with alopecia areata: A retrospective claims database study in the United States.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder characterized by hair loss. Patients may present with hair loss of the scalp, eyelashes, eyebrows, and/or body. Alopecia totalis (AT), total scalp hair loss, or alopecia universalis (AU), total body hair loss, are extensive forms. Although the impact of AA on quality of life is understood, evidence of its economic burden is limited. A better understanding of the all-cause health care costs for health plans and patients with AA is critical to comprehend disease burden. OBJECTIVE: To evaluate all-cause health care resource utilization and direct health care costs in US adults with AA with or without AT or AU, vs matched control subjects. METHODS: Patients (≥ 18 years) with AA with no less than 2 claims of AA at diagnosis (October 31, 2015, to March 3, 2018) were identified in the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental databases. Patients were enrolled no less than 12 months before and after first diagnosis (index). Patients were grouped according to AT or AU status (AT/AU group) or AA without AT/AU (non-AT/AU group) and matched 1:3 to control subjects without AA/AT/AU. Summary statistics were calculated for demographic and clinical characteristics at baseline and follow-up. RESULTS: At baseline, there were 14,972 adult patients with AA and 44,916 control subjects. Of patients with AA, 1,250 and 13,722 were in the AT/AU and non-AT/AU groups, respectively. A significantly greater proportion of patients with AA had atopic and autoimmune comorbidities vs control subjects. After index, patients with AA used significantly more corticosteroid treatments (injectable/oral/topical) than control subjects. A greater mean number of annual outpatient and dermatologist visits was observed for both AA groups vs control subjects (outpatient visits: AT/AU group: 17.8 vs 11.8; non-AT/AU group: 15.4 vs 11.2; dermatologist visits: AT/AU group: 3.4 vs 0.4; non-AT/AU group: 3.4 vs 0.4; P < 0.001 for all). Mean total all-cause medical and pharmacy costs (2018 US$) were higher in both AA groups vs control subjects (AT/AU group: $18,988 vs $11,030; non-AT/AU group: $13,686 vs $9,336; P < 0.001 for both). Patient out-of-pocket costs were higher for AA vs control subjects (AT/AU group: $2,685 vs $1,457; non-AT/AU group: $2,223 vs $1,341; P < 0.001 for both). CONCLUSIONS: Compared with control subjects, patients with AA are more likely to have atopic and autoimmune comorbidities, to use corticosteroids, and to make outpatient visits. Patients with AA have greater all-cause medical (including pharmacy) and out-of-pocket costs. The difference in total medical costs for patients with AT/AU vs control subjects is higher than the difference for patients with non-AT/AU vs control subjects. DISCLOSURES: This study was sponsored by Pfizer Inc. Pfizer Inc was involved in the study design; collection, analysis, and interpretation of data; writing of the report; and the decision to submit this report for publication. A. Mostaghimi reports consulting fees from Pfizer Inc, Concert, Lilly, AbbVie, hims, and Digital Diagnostics; reports equity from Lucid and hims; and is an associate editor at JAMA Dermatology. K. Gandhi, M. Ray, and V. Sikirica are former employees of Pfizer Inc and held stock and/or stock options with Pfizer Inc at the time of writing. N. Done, W. Gao, C. Carley, T. Wang, and E. Swallow are employees of Analysis Group, Inc, a consultancy that received payment from Pfizer Inc for participation in this analysis.

The societal economic value of COVID-19 vaccines in the United States.

AIMS: The COVID-19 pandemic has claimed the lives of more than 800,000 people in the United States (US) and has been estimated to carry a societal cost of $16 trillion over the next decade. The availability of COVID-19 vaccines has had a profound effect on the trajectory of the pandemic, with wide-ranging benefits. We aimed to estimate the total societal economic value generated in the US from COVID-19 vaccines. METHODS: We developed a population-based economic model informed by existing data and literature to estimate the total societal value generated from COVID-19 vaccines by avoiding COVID-19 infections as well as resuming social and economic activity more quickly. To do this, we separately estimated the value generated from life years saved, healthcare costs avoided, quality of life gained, and US gross domestic product (GDP) gained under a range of plausible assumptions. RESULTS: Findings from our base case analysis suggest that from their launch in December 2020, COVID-19 vaccines were projected to generate $5.0 trillion in societal economic value for the US from avoided COVID-19 infections and resuming unrestricted social and economic activity more quickly. Our scenario analyses suggest that the value could range between $1.8 and $9.9 trillion. Our model indicates that the most substantial sources of value are derived from reduction in prevalence of depression ($1.9 trillion), gains to US GDP ($1.4 trillion), and lives saved from fewer COVID-19 infections ($1.0 trillion). LIMITATIONS: Constructed as a projection from December 2020, our model does not account for the Delta or future variants, nor does it account for improvements in COVID-19 treatment. CONCLUSIONS: The magnitude of economic benefit from vaccination highlights the need for coordinated policy decisions to support continued widespread vaccine uptake in the US.

Real-world migraine-related healthcare resource utilization and costs associated with improved vs. worsened/stable migraine: a panel-based chart review in France, Germany, Italy, and Spain.

OBJECTIVE: To estimate the migraine-related healthcare resource utilization (HRU) and costs among patients with improved vs. worsened/stable migraine. METHODS: This was a follow-up to a retrospective, panel-based chart review conducted in France, Germany, Italy, and Spain among a panel of physicians (neurologists, headache specialists, and pain specialists) who agreed to participate in patient studies and had treated ≥10 migraine patients in 2017. Eligible physicians extracted data for up to five adults with ≥4 monthly migraine days (MMDs) who initiated a preventive treatment on or after 1 January 2013 and received physician care for ≥6 months after the date of the most recent preventive treatment initiation (index date). Based on the trajectory of migraine severity from the 1-month pre-index period to the 6-month post-index period, cohorts were classified as improved (converting from chronic to episodic or from chronic/episodic to <4 MMDs) or stable/worsened (remaining chronic/episodic or transforming from episodic to chronic) migraine. Migraine-related HRU and costs (2017 €) during the 6-month post-index period were compared between patients with improved vs. stable/worsened migraine. RESULTS: Overall, 470 patient charts were analyzed, with 339 classified as improved migraine and 131 classified as stable/worsened migraine. After adjusting for within-physician correlation, country, sex, and presence of comorbidities before the index date, the improved migraine cohort had significantly fewer migraine-related physician office visits (-0.81; p < .001), emergency room/accident & emergency (ER/A&E) visits (-0.67; p < .001), and hospitalizations (-0.12; p < .001) in the 6-month post-index period vs. the stable/worsened migraine cohort. Consistent with HRU patterns, the adjusted migraine-related costs for physician office visits (-€42.23; p < .05), hospitalizations (-€215.56; p < .05), and total costs (-€396.81; p < .01) in the 6-month post-index period were significantly reduced for the improved migraine cohort vs. the stable/worsened migraine cohort. CONCLUSIONS: Over a 6-month period following initiation of preventive migraine treatment, patients with improved migraine had significantly lower migraine-related HRU and costs than those with stable/worsened migraine.

Risk of Cardiovascular Conditions in Patients with Chronic Hypoparathyroidism: A Retrospective Cohort Study.

INTRODUCTION: In patients with chronic hypoparathyroidism disordered calcium homeostasis has been associated with risk of cardiovascular diseases, including cardiomyopathy, congestive heart failure, and arrhythmia; however, larger-scale studies are needed to examine these risks. This study evaluated the risk of cardiovascular conditions among patients with chronic hypoparathyroidism. METHODS: Adults with and without chronic hypoparathyroidism were selected from a medical insurance claims database in the USA from January 2007 to June 2017, and were followed for up to 5 years. Associations between chronic hypoparathyroidism and incident atrial fibrillation (AF), tachyarrhythmia, myocardial infarction (MI), coronary artery disease (CAD), heart failure (HF), stroke, cerebrovascular disease, peripheral vascular disease (PVD), and a combined cardiovascular endpoint of cerebrovascular disease, CAD, HF, and PVD were compared between cohorts using Kaplan-Meier analyses and unadjusted and adjusted Cox proportional hazards models. RESULTS: In 8097 patients with chronic hypoparathyroidism compared with 40,485 patients without, respectively, mean ± SD ages were 58.6 ± 16.3 and 47.3 ± 18.0 years, 76.2% and 54.4% were female, and 19.4% and 9.5% had the combination of cardiovascular findings at baseline. In adjusted analyses, patients with chronic hypoparathyroidism had significantly higher risk (adjusted hazard ratio and 95% confidence interval) of incident AF (1.72; 1.51-1.97), tachyarrhythmia (1.68; 1.32-2.14), MI (1.18; 1.01-1.38), CAD (1.39; 1.26-1.54), HF (1.64; 1.46-1.84), stroke (1.45; 1.31-1.62), cerebrovascular disease (1.48; 1.34-1.62), PVD (1.66; 1.51-1.81), and combined cardiovascular endpoint (1.63; 1.52-1.75), all P < 0.001 except P = 0.036 for MI, compared with patients without chronic hypoparathyroidism. CONCLUSIONS: This large retrospective cohort study showed that chronic hypoparathyroidism was associated with increased risk of incident cardiovascular conditions and arrhythmias. Results should be evaluated in light of limitations inherent to claims database analyses. Further studies are warranted to investigate reasons for these risks and to develop strategies for reducing cardiovascular conditions in patients with chronic hypoparathyroidism.