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OBJECTIVES: Bone marrow transplantation (BMT) is currently the only curative therapy available for patients with sickle cell disease (SCD), but clinical outcomes in routine care are not well understood. We describe the rates of vaso-occlusive crises (VOCs), transplant complications, and mortality in SCD patients after BMT. METHODS: A cohort study of SCD patients who underwent BMT was designed using US Medicaid claims data (2000-2013). RESULTS: A total of 204 SCD patients undergoing BMT were identified with a mean (SD) age of 10.6 (7.3) years, with 52.9% male and 67.6% African American. The overall VOC rate was 0.99 per person-year (95% CI: 0.91-1.07) over a median follow-up time of 2.1 years (IQR: 0.8-4.3 years). A total of 138 (67.6%) remained free of VOCs. The mortality rate was 1.7 (95% CI: 0.9-3.1) per 100 person-years, transplant-related complications occurred among 113 (55.4%) patients with an incidence rate of 38.2 (95% CI: 31.7-45.9) per 100 person-years, while 47 (23%) patients had GvHD with an incidence rate of 8.0 (95% CI: 6.0-10.7) per 100 person-years. CONCLUSION: Two thirds of the BMT recipients remained VOC-free over 2 years of follow-up, but transplant-related complications, including GvHD occurred with high frequency. This highlights a continuing unmet need for alternative curative interventions in SCD.
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Anemia Falciforme/epidemiologia , Anemia Falciforme/terapia , Transplante de Medula Óssea , Síndrome Torácica Aguda/epidemiologia , Síndrome Torácica Aguda/etiologia , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
To add to the limited existing evidence on clinical outcomes and healthcare use in sickle cell disease (SCD) among beneficiaries of the US Medicaid program, we conducted a cohort study using nationwide Medicaid claims data (2000-2013). Patients were included based on HbSS SCD diagnosis and followed until Medicaid disenrollment, death, bone marrow transplant, or end of data availability to assess vasoocclusive crises (VOC), emergency room (ER) visits, hospitalizations, outpatient visits, and blood transfusions. Annualized event rates (with 95% confidence intervals [CI]) were reported. The impact of VOCs on the risk of mortality was analyzed using a multivariable Cox model with VOC modeled as time-varying and updated annually. In a total of 44,033 SCD patients included with a mean (SD) age of 15.7 (13.6) years, the VOC rate (95% CI) was 3.71 (3.70-3.72) per person-year, with highest rate among patients 19-35 years who had ≥ 5 VOCs at baseline (13.20 [13.15-13.26]). Event rates (95% CI) per person per year for other outcomes were 2.97 (2.97-2.98) ER visits, 2.39 (2.38-2.40) hospitalizations, 5.80 (5.79-5.81) outpatient visits, and 0.91 (0.90-0.91) blood transfusions. A higher VOC burden in the preceding year was associated with an increased risk of mortality, with a hazard ratio (95% CI) of 1.26 (1.14-1.40) for 2-4 VOC vs. < 2 and 1.57 (1.41-1.74) for ≥ 5 VOC vs < 2. In conclusion, we documented a substantial burden of SCD in US Medicaid enrollees, especially during early adulthood and noted that ongoing burden of VOC is associated with mortality in these patients.
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Anemia Falciforme/mortalidade , Anemia Falciforme/terapia , Medicaid , Aceitação pelo Paciente de Cuidados de Saúde , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mortalidade , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
OBJECTIVES: The Psoriasis Symptom Inventory (PSI) is a patient-reported outcome instrument that measures the severity of psoriasis signs and symptoms. This study evaluated measurement properties of the PSI in patients with moderate to severe plaque psoriasis. METHODS: This secondary analysis used pooled data from a phase 3 brodalumab clinical trial (AMAGINE-1). Outcome measures included the PSI, Psoriasis Area and Severity Index (PASI), static Physician's Global Assessment (sPGA), psoriasis-affected body surface area, 36-item Short-Form Health Survey version 2, and the Dermatology Life Quality Index (DLQI). The PSI was evaluated for dimensionality, item performance, reliability (internal consistency and test-retest), construct validity, ability to detect change, and agreement between PSI response and response measures based on the PASI, sPGA, and DLQI. RESULTS: Results supported unidimensionality, good item fit, ordered responses, and PSI scoring. The PSI demonstrated reliability: baseline Cronbach's alpha ≥ 0.92 and intraclass correlation coefficients ≥ 0.95. Correlations between PSI total score and DLQI item 1 (r = 0.86), DLQI symptoms and feelings (r = 0.87), and 36-item Short-Form Health Survey version 2 bodily pain (r = -0.61) supported convergent validity. PSI scores differed significantly (P < 0.001) among severity groups based on the PASI (< 12/≥ 12), sPGA (0-1/2-3/4-5), body surface area (< 5%/5%-10%/> 10%), and DLQI (≤ 5/> 5) at weeks 8 and 12. At week 12, the PSI detected significant changes in severity based on PASI responses (< 50/50- < 75/≥ 75) and sPGA (0-1/≥ 2), and showed good agreement (k ≥ 0.66) between PSI response and PASI, sPGA, and DLQI responses. CONCLUSION: The PSI demonstrated excellent validity, reliability, and ability to detect change in the severity of psoriasis signs and symptoms.
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Anticorpos Monoclonais/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Psoríase/fisiopatologia , Qualidade de Vida , Adulto , Anticorpos Monoclonais Humanizados , Ensaios Clínicos Fase III como Assunto , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
PURPOSE: To assess the variation in the interpretation of common verbal descriptors (VDs) used in response scales and examine factors associated with those interpretations. METHODS: Subjects were recruited through MediGuard and they assigned interpretation scores (11-point scale; 0 = lowest possible, 10 = highest possible) to five common sets of VDs: set one (none, mild, moderate, severe, very severe); set two (never, rarely, sometimes, often, always); set three (poor, fair, good, very good, excellent); set four (not at all, a little bit, moderately, quite a bit, extremely); and set five (not at all, a little bit, somewhat, quite a bit, very much). One-sample test for proportions and T-tests examined equality of proportions (anchors) and means scores (non-anchors) with the fixed intervals (0.0, 2.5, 5.0, 7.5, and 10.0). Ordinal regression examined adjusted associations between demographic/clinical factors and VD scores. RESULTS: Of the 350 subjects, 68 % were females and mean (SD) age was 56.9 (12.1). Two sets had two VDs with mean (95 % CI) scores not different than the fixed intervals. Set one had mild = 2.50 (2.33; 2.66) and moderate = 5.01 (4.89; 5.13) with 98.8 % (97.3 %; 100 %) assigning none = 0. Set five had a little bit = 2.35 (2.17; 2.53) and quite a bit = 7.65 (7.43; 7.87) with 95.0 % (95 % CI 91.7; 98.2) assigning not at all = 0. Significant associations (p ≤ 0.05) included age and education with somewhat and income and comorbidities with very severe. Age, sex, and education showed associations with other VDs albeit in nonsignificant models. CONCLUSIONS: Sets one and five yielded data closest to the fixed intervals. Demographic and clinical factors are associated with the interpretation of some VDs and should be adjusted for in analyses of non-randomized data.
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Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
INTRODUCTION: Despite new therapies for relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), treatments with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents continue to be commonly used. METHODS: This retrospective study utilized longitudinal data from 4226 real-world electronic health records to characterize outcomes in patients with R/R DLBCL. Eligible patients were diagnosed with DLBCL between January 2010 and March 2022 and had R/R disease treated with ≥ 1 prior systemic line of therapy (LOT), including ≥ 1 anti-CD20-containing regimen. RESULTS: A total of 573 patients treated with ≥ 1 prior LOT were included (31.2% and 13.4% with ≥ 2 and ≥ 3 prior LOTs, respectively). Median duration of follow-up was 7.7 months. Most patients (57.1%) were male; mean standard deviation (SD) age was 63 (14.7) years. Overall and complete response rates (95% confidence interval (CI) were 52% (48-56) and 23% (19-27). Median duration of response and duration of complete response were 3.5 and 18.4 months. Median progression-free and overall survival (95% CI) was 3.0 (2.8-3.3) and 12.9 (10.1-16.9) months, respectively. Patients with a higher number of prior LOTs, primary refractoriness, refractoriness to last LOT, refractoriness to last anti-CD20-containing regimen, and prior CAR T exposure had worse outcomes (i.e., challenging-to-treat R/R DLBCL) compared with those without these characteristics. CONCLUSIONS: Outcomes in patients with R/R DLBCL treated with chemotherapy, single-agent rituximab/obinutuzumab, single-agent lenalidomide, or combinations of these agents remain poor, especially for those with challenging-to-treat R/R DLBCL. These findings underscore the unmet need for new, safe, and effective therapies, especially for challenging-to-treat R/R DLBCL populations.
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Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Rituximab/uso terapêutico , Lenalidomida/uso terapêutico , Estudos Retrospectivos , Padrão de Cuidado , Linfoma não Hodgkin/tratamento farmacológico , Resultado do Tratamento , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Análise de Dados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: Patient-reported outcomes were evaluated in EPCORE NHL-1 in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with epcoritamab monotherapy (NCT03625037). MATERIALS AND METHODS: Adults with R/R CD20+ LBCL and ≥2 prior systemic antilymphoma therapies, including anti-CD20, completed the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) and EQ-5D-3L. A subgroup of patients provided additional feedback in one-on-one qualitative interviews. FACT-Lym and EQ-5D-3L score changes from baseline (CFB) to cycle 9 or end of treatment were interpreted using published minimally important differences (MID). RESULTS: In total, 157 patients (88.5% with diffuse LBCL) were treated (median age, 64 years). In total, 70.7% had ≥3 prior treatments, 61.1% had primary refractory disease, and 82.8% were refractory to last systemic therapy. FACT-Lym scores exceeded MID thresholds: mean (SD) CFB were 4.4 (15.2), MID 3.0 to 7.0 (FACT-General); 5.9 (7.6), MID 2.9 to 5.4 (FACT-Lymphoma subscale); 8.4 (15.2), MID 5.5 to 11.0 (FACT-Trial Outcome Index); 10.3 (20.2), MID 6.5 to 11.2 (FACT-Lym total score). EQ-5D-3L index scores, 0.09 (0.20), MID 0.08, and EQ-VAS scores, 16.6 (22.8), MID 7.0, improved. In 20 qualitative interviews, 88.2% reported symptom improvements; 80.0% were "very satisfied" or "satisfied" with epcoritamab. CONCLUSIONS: R/R LBCL patients reported consistent, clinically meaningful improvements in symptoms and HRQoL and satisfaction with epcoritamab.
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Antineoplásicos , Linfoma de Células B , Linfoma , Adulto , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Medidas de Resultados Relatados pelo PacienteRESUMO
This study used COTA de-identified data (2010-2021) of patients in the US to explore outcomes of novel therapies in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in real-world settings. Demographics, clinical characteristics, and clinical outcomes of patients with R/R DLBCL who received novel treatments including chimeric antigen receptor T-cell (CAR T) therapy and tafasitamab- or polatuzumab-based therapies were evaluated. Overall, 175 patients with R/R DLBCL were analyzed; 73, 69, and 27 received CAR T therapy, polatuzumab-based regimens, and tafasitamab-based regimens, respectively. In patients who had ≥1 prior lines of therapy (i.e. starting second-line or later therapy; 2 L+), CAR T, polatuzumab-based regimens, and tafasitamab-based regimens achieved a median overall survival of 26.5, 7.8, and 6.3 months, respectively. Outcomes were particularly poor for patients with relapse following CAR T, indicating that polatuzumab- and tafasitamab-based regimens in 2 L + R/R DLBCL have suboptimal outcomes in the real world. Additional treatment options are needed.
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OBJECTIVE: To assess patients' information needs regarding drug-drug interactions (DDIs) to inform patient DDI education resources. DESIGN: Cross-sectional study. SETTING: Online (United States in May 2011). PARTICIPANTS: Registered users of an online medication monitoring service (MediGuard). INTERVENTION: Online questionnaire. MAIN OUTCOME MEASURE: Participants' information needs regarding DDIs and perceived importance of questions related to detecting and preventing harm from DDIs. RESULTS: Characteristics of the 100 surveyed participants were as follows: 57% women, 88% white, 96% non-Hispanic, 71% retired, mean (±SD) age 65.2 ± 9.7 years (range 35-86). The number of prescription medications ranged from 2 to 22 (median 7) and the number of over-the-counter (OTC) medications from 1 to 10 (4). The most common concerns cited by participants were identification of interacting medications, seriousness of DDIs, interactions with OTC medications, interactions with foods, exacerbating comorbidities, short- and long-term adverse effects, signs and frequency of DDIs, and how to minimize adverse effects. Statistically significant differences based on gender, number of prescriptions, and number of OTC medications were observed in rankings of the importance of some DDI questions ( P < 0.05). CONCLUSION: Patient-centered DDI education programs should consider addressing the seriousness of DDIs, the effect of DDIs on comorbidities, and interactions with OTC medications and foods and determining methods for identifying, minimizing, and managing DDIs.
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Interações Medicamentosas , Medicamentos sem Prescrição/efeitos adversos , Educação de Pacientes como Assunto/métodos , Medicamentos sob Prescrição/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Monitoramento de Medicamentos , Feminino , Interações Alimento-Droga , Humanos , Internet , Masculino , Pessoa de Meia-Idade , Medicamentos sem Prescrição/administração & dosagem , Medicamentos sob Prescrição/administração & dosagem , Fatores Sexuais , Inquéritos e Questionários , Estados UnidosRESUMO
Aim: To evaluate trials of systemic therapies in transplant-ineligible or -experienced, relapsed/refractory diffuse large-B cell lymphoma and the impact of patient characteristics on overall response rate (ORR). Patients & methods: Systematically reviewed multiple databases through 22 July 2021. Analyzed variations in patient characteristics and their relationship with ORR across trials. Results: Among 17 included trials, key patient characteristics varied substantially: primary refractory (0-69%), refractory to last line of therapy (LOT) (12-100%), ≥2 prior LOTs (14-100%), ≥3 prior LOTs (0-64%), IPI ≥3 (23-73%), tumor stage III/IV (50-90%) and median age (56-74 years). ORRs varied substantially (25-83%), correlating with these characteristics. Conclusion: Differences in patient characteristics significantly contribute to the variability in ORR across these trials and should be considered when contextualizing efficacy data.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Pessoa de Meia-Idade , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/uso terapêuticoRESUMO
BACKGROUND: Prevalence is reflective of disease incidence and survival, and defined as the number of patients living with active disease. In diseases such as diffuse large B-cell lymphoma (DLBCL) with treatments with curative potential, a proportion of patients are cured, leading to a need for accurate, contemporary estimates of DLBCL prevalence to gauge the impact of the rapidly emerging treatment landscape. METHODS: Data from Surveillance, Epidemiology, and End Results (SEER) from 2000-2018 were utilized to develop an epidemiological model of incidence, survival, and cure, to estimate the current prevalent DLBCL population requiring active management in the United States (US). A variety of estimates were explored regarding cure rate and timing, based on a companion analysis of MarketScan data for treatment patterns and survival in incident DLBCL patients, and conditional survival analysis of SEER data. RESULTS: Across scenarios, with estimated cure ranging from 52.8% and 68.9%, and timing of cure ranging from 1 and 20 years post diagnosis, the estimated prevalence ranged from 63,883 to 142,889. With an assumption of no cure, estimated prevalence was 179,475. DISCUSSION: Prevalence estimates of DLBCL varied almost 3-fold, depending on specific cure adjustments made. Further understanding of DLBCL prevalence, for newly diagnosed and relapsed and/or refractory disease, is important to characterize the impact of emerging treatment options and related health care burden.
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Modelos Epidemiológicos , Linfoma Difuso de Grandes Células B , Estados Unidos/epidemiologia , Humanos , Programa de SEER , Prevalência , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/diagnóstico , Análise de SobrevidaRESUMO
PURPOSE: To examine whether the move from the multidimensional SF-36 patient-reported outcome measure to the single-index preference-based SF-6D entails a loss in discriminative and evaluative properties, the magnitude of that loss and whether it matters. METHODS: Retrospective analysis of data from studies that used the SF-36 and the derived SF-6D. The discriminative and evaluative properties of the two measures were compared by calculating effect size (ES), standardized response mean (SRM), and relative validity (RV) statistics using the SF-6D as the reference. RESULTS: Data were available from seven studies and 8,522 subjects. At least one SF-36 scale was always more sensitive than the index. Cross-sectional pooled results showed that physical functioning (RV = 0.19 and ES = 0.13) and PCS (RV = 0.18 and ES = 0.13) were generally most sensitive compared to the index (RV = 0.16 and ES = 0.12). Longitudinal pooled results showed that PCS (RV = 0.20), MCS (RV = 0.17), general health (RV = 0.18), and social functioning (RV = 0.17) were generally more sensitive than the index (RV = 0.14) based on RVs. Longitudinal pooled SRMs were all very small in magnitude. CONCLUSION: No scale/dimension consistently had the largest RV, ES, or SRM across all conditions studied. Moving from the SF-36 to SF-6D entails losses of a small magnitude in discriminative and evaluative properties.
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Nível de Saúde , Qualidade de Vida , Inquéritos e Questionários/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino UnidoRESUMO
OBJECTIVES: The aim was to estimate the impact of TNF inhibitor (TNFi) exposure on radiographic disease progression in US Veterans with RA during the first year after initiating therapy. METHODS: This historical longitudinal cohort design used clinical and claims data to evaluate radiographic progression after initiation of TNFi. US Veterans with RA initiating TNFi treatment (index date), ≥ 6 months pre-index and ≥ 12 months post-index VA enrolment/activity, and initial (6 months pre-index to 30 days post-index) and follow-up (10-18 months post-index) bilateral hand radiographs were eligible. The cumulative TNFi exposure and change in modified Sharp score (MSS) between initial and follow-up radiographs were calculated. The percentage of patients with clinically meaningful change in MSS (≥ 5) for each month of exposure was assessed using a longitudinal marginal structural model with inverse probability of treatment weights. Mean values and CIs were generated using 1000 bootstrapped samples. RESULTS: For 246 eligible patients, the mean (s.d.) age was 58 (11) years; 81% were male. The mean (s.d.) initial MSS was 19.6 (33.4) (range 0-214). The mean change (s.d.) in MSS was 0.3 (3.6) (median 0, range -19 to 22). Patients with the greatest exposure had the least radiographic progression for both crude and adjusted model analyses. Adjusted rates of MSS change ≥ 5 points (95% CI) were 10.6% (9.8%, 11.4%) for patients with 3 months of exposure compared with 5.4% (5.1%, 5.7%) for patients with 12 months of exposure. CONCLUSION: One-year changes in radiographic progression were small. Patients with the greatest cumulative TNFi exposure experienced the least progression.
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Introduction: It is challenging to identify health state utilities associated with psoriasis because generic preference-based measures may not capture the impact of dermatological symptoms. The Psoriasis Area Severity Index (PASI) is one of the most commonly used psoriasis rating scales in clinical trials. The purpose of this study was to develop a utility scoring algorithm for the PASI. Methods: Forty health states were developed based on PASI scores of 40 clinical trial patients. Health states were valued in time trade-off interviews with UK general population participants. Regression models were conducted to crosswalk from PASI scores to utilities (e.g. OLS linear, random effects, mean, robust, spline, quadratic). Results: A total of 245 participants completed utility interviews (51.4% female; mean age = 45.3 years). Models predicting utility based on the four PASI location scores (head, upper limbs, trunk, lower limbs) had better fit/accuracy (e.g. R2, mean absolute error [MAE]) than models using the PASI total score. Head/upper limb scores were more strongly associated with utility than trunk/lower limb. The recommended model is the OLS linear model based on the four PASI location scores (R2 = 0.13; MAE = 0.03). An alternative is recommended for situations when it is necessary to estimate utility based on the PASI total score. Conclusions: The derived scoring algorithm may be used to estimate utilities based on PASI scores of any treatment group with psoriasis. Because the PASI is commonly used in psoriasis clinical trials, this scoring algorithm greatly expands options for quantifying treatment outcomes in cost-effectiveness analyses of psoriasis therapies. Results indicate that psoriasis of the head/upper limbs could be more important than trunk/lower limbs, suggesting reconsideration of the standard PASI scoring approach.
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Psoríase/psicologia , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adulto , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Preferência do Paciente , Adulto JovemRESUMO
INTRODUCTION: Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. METHOD: Longitudinal data were examined from the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry. Linear regression modeled the effect of biologic exposure on changes in disease activity (Disease Activity Score-28 with C-reactive protein [DAS28-CRP]), functional status (modified Health Assessment Questionnaire [mHAQ]), and RA severity (Routine Assessment of Patient Index Data [RAPID3]). Biologic exposure was the ratio of time on a biologic relative to time participating in the BRASS cohort. RESULTS: The analysis included 1395 RA patients, 82.3% female, with 6783 unique study visits from 2003 to 2015. At the patient's first visit, mean (SD) age was 56.3 (14.2) years and mean (SD) duration of RA was 12.7 (11.9) years. Average follow-up duration was 5.59 years (range, 1-13). Over time, DAS28-CRP, mHAQ, and RAPID3 scores decreased as the biologic exposure ratio increased. In repeated measures regression models, increased biologic exposure was significantly associated with decreased DAS28-CRP score (ß = - 0.647; P < 0.001), decreased mHAQ score (ß = - 0.096; P < 0.001), and decreased RAPID3 score (ß = - 0.724; P < 0.001) during follow-up. Methotrexate use at baseline predicted decreased DAS28-CRP, mHAQ, and RAPID3 scores during follow-up. Biologic use at baseline predicted increased DAS28-CRP or mHAQ during follow-up. CONCLUSIONS: Increased biologic exposure is associated with decreased disease activity, function impairment, and RA severity. Future studies should examine whether earlier initiation of biologics improves patient outcomes in RA. TRIAL REGISTRATION: ClinicalTrials.gov , NCT01793103 Key Points ⢠Biologics effectively manage symptoms and disease activity in rheumatoid arthritis (RA), but their long-term effects remain unclear. ⢠In this analysis of longitudinal annual population samples of 1395 RA patients in the Brigham and Women's Rheumatoid Arthritis Sequential Study (BRASS) registry, disease activity, function, and severity scores improved as time on biologic therapy increased. ⢠In repeated measures regression models, time on biologic therapy was a significant predictor of improved outcomes for disease activity, function, and RA severity. ⢠Further studies should examine whether earlier initiation of biologics limits the long-term effect of inflammation on RA outcomes.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Sistema de Registros , Adulto , Idoso , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
INTRODUCTION: Clinical outcomes data on BRAF-mutated non-small cell lung cancer (NSCLC) patients treated in routine practice is limited. To address this gap, we described treatment patterns and survival in a cohort of these patients evaluated/treated at 7 US academic cancer centers during 2009-2016. METHODS: This was a retrospective chart review. Patients with BRAF V600-mutated metastatic NSCLC were selected. Current/previous participants in BRAF-related trials were excluded. Onset of metastatic NSCLC defined a patient's index date, which had to occur ≥6 months before the chart review date. Analyses were descriptive, including Kaplan-Meier analyses for overall survival (OS). RESULTS: The study included 72 patients. At index, median age (range) was 65 (44-90) years; 61.1% were female. Fifty-two patients received ≥1 line of systemic therapy for metastatic disease. Platinum-based doublet chemotherapy was the most common first-line (1 L) regimen (76.9% of 1 l recipients); no patient received 1 l targeted therapy (TT) with a BRAF/MEK inhibitor. In total, 20 patients received TT in any treatment line (2 l or later). At time of review, 38 patients were deceased. Median (95%CI) OS from index for all patients was 31.0 (14.5, 63.8) months. Median (95%CI) OS was 56.5 (13.4, 89.1) months from index for TT recipients and 27.2 (10.6, 64.6) months in patients not treated with TT. CONCLUSION: Survival time in BRAF V600-mutated metastatic NSCLC patients studied here was higher than expected based on indirect comparisons with historical NSCLC cohorts for whom no oncogenic driver (BRAF or otherwise) was present. TT recipients had a numerically longer OS from metastatic onset than patients receiving usual care, further highlighting the importance of TT in BRAF V600-mutant NSCLC.
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Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Mutação , Padrões de Prática Médica , Proteínas Proto-Oncogênicas B-raf/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Tomada de Decisão Clínica , Terapia Combinada , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: The aim of the current study was to assess the economic impact of using next-generation sequencing (NGS) versus single-gene testing strategies among patients with metastatic non-small-cell lung cancer (mNSCLC) from the perspective of the Centers for Medicare & Medicaid Services (CMS) and US commercial payers. METHODS: A decision analytic model considered patients who were newly diagnosed with mNSCLC who received programmed death ligand 1 and genomic alteration tests-EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1-using upfront NGS (all alterations tested simultaneously plus KRAS), sequential testing (sequence of single-gene tests), exclusionary testing (KRAS plus sequential testing), and hotspot panels (EGFR, ALK, ROS1, and BRAF tested simultaneously plus single-gene tests or NGS for MET, HER2, RET, and NTRK1). Model outcomes for each strategy were time-to-test results, the proportion of patients identified harboring alterations with or without US Food and Drug Administration-approved therapies, and total testing costs. A budget impact analysis assessed the economic effects of increasing the proportion of NGS-tested patients. RESULTS: In a hypothetical 1,000,000-member health plan, 2,066 Medicare-insured patients and 156 commercially insured patients were estimated to have mNSCLC and to be eligible for testing. Time-to-test results were 2.0 weeks for NGS and the hotspot panel, faster than exclusionary and sequential testing by 2.7 and 2.8 weeks, respectively. NGS was associated with cost savings for both CMS ($1,393,678; $1,530,869; and $2,140,795 less than exclusionary, sequential testing, and hotspot panels, respectively) and commercial payers ($3,809; $127,402; and $250,842 less than exclusionary, sequential testing, and hotspot panels, respectively). Increasing the proportion of NGS-tested patients translated into substantial cost savings for both CMS and commercial payers. CONCLUSION: Use of upfront NGS testing in patients with mNSCLC was associated with substantial cost savings and shorter time-to-test results for both CMS and commercial payers.
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OBJECTIVES: To estimate total costs among patients with rheumatoid arthritis (RA) who persisted on or switched from newly initiated biologic therapy. STUDY DESIGN: A retrospective claims database analysis. METHODS: This analysis included adults in the HealthCore Integrated Research Database with RA who initiated treatment with a biologic for RA (abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab, rituximab, or tocilizumab) between January 2009 and November 2014. Total healthcare costs (plan- and patient-paid) were estimated for 1 year post index. Treatment persistence was defined as no discontinuation (ie, no refill gap >45 days) and no biologic switch. RESULTS: Of 7468 patients, 45.2% persisted on the index biologic for at least 1 year without a refill gap and 16.7% switched to another biologic in the first year; other patients discontinued the index biologic (23.2%) or restarted after a refill gap (15.0%). Mean 1-year total healthcare costs per patient were $41,901 (95% CI, $40,855-$42,947) among persistent patients and $44,244 (95% CI, $40,820-$47,668) among switchers. In a multivariable analysis of all patients, switchers had 5% higher postindex costs on average than persistent patients (exp(ß) = 1.05; 95% CI, 1.01-1.08), and etanercept had the lowest postindex costs (exp(ß) ranged from 1.03 to 1.51 for other biologics relative to etanercept). CONCLUSIONS: Patients with RA who switched biologic therapy incurred higher 1-year total postswitch healthcare costs compared with patients who were persistent on the index biologic. Healthcare costs were lowest for patients who started on etanercept, particularly those who persisted on etanercept.
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Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Custos de Cuidados de Saúde , Adesão à Medicação/estatística & dados numéricos , Adulto , Antirreumáticos/economia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/economia , Produtos Biológicos/economia , Estudos de Coortes , Análise Custo-Benefício , Substituição de Medicamentos , Feminino , Humanos , Revisão da Utilização de Seguros/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Estados UnidosRESUMO
Objective: To describe patient characteristics, treatment patterns, healthcare resource utilization (HRU), and costs among patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) receiving ceritinib in second or later line of therapy. Methods: Adult patients with NSCLC receiving ceritinib were identified from two large US claims databases (2006-2015). Patient characteristics, comorbidity profile, treatment patterns prior to ceritinib, and ceritinib dosing patterns were described. All-cause, HRU, and costs incurred during the observation period after ceritinib initiation were reported per patient per six months. Results: One hundred sixty-four patients were included (mean age 54.2 years, 57.3% female); the majority had metastatic disease (94.5%) and the average Charlson Comorbidity Index was 7.6. 150 (91.5%) patients received crizotinib prior to ceritinib - average crizotinib duration was 10.2 months and time between crizotinib discontinuation and ceritinib initiation was 2.1 months (median= 0; 25th-75th percentile= 0-0.8). Most patients (73.8%) initiated ceritinib on the recommended dose (750 mg) and maintained the dose until the end of the observation period (mean of 7.4 months) or ceritinib discontinuation; 61 (37.2%) patients discontinued ceritinib during the observation period. A total of 76 (46.3%) patients had at least one inpatient admission during the observation period after ceritinib initiation. Mean total healthcare cost per patient per six months was $111,468. Conclusions: Patients with ALK-positive NSCLC receiving ceritinib had a high comorbidity burden and generally started ceritinib on the recommended dose quickly after crizotinib discontinuation. Medical costs accounted for nearly a half of the total healthcare costs.
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AIMS: To assess the time to BRAF testing, compare the characteristics of tested vs not-tested patients, and describe the costs for sequential vs next-generation sequencing (NGS) BRAF testing. METHODS: Patients diagnosed with lung cancer after December 1, 2013 were identified from two US claims databases; their characteristics were assessed during the 12 months before diagnosis (index date). Testing modalities were analyzed from the index date to end of continuous health plan enrollment or data availability (December 2015), based on combinations of Current Procedural Terminology (CPT) procedure codes. Time to BRAF testing was assessed using Kaplan-Meier analysis. Costs were analyzed from a payer's perspective. RESULTS: A total of 28,011 patients newly-diagnosed with lung cancer were identified. Of them, 1,260 (4.5%) were tested for BRAF: 3.2% and 4.2% were tested at 6 and 12 months, respectively, after the index date. Compared to non-tested patients, tested patients were younger (58.3 vs 65.3 years; p < .001), had a lower Charlson Comorbidity Index (2.8 vs 2.9; p = .005), and a higher proportion had metastases (70.9% vs 43.4%; p < .001). In 76.0% of cases, BRAF was tested along with KRAS. BRAF was tested using NGS in 6.6% of cases. The average reimbursed amounts for the 10 most common CPT code combinations were $207-$2,074. Using the average costs of individual mutation tests, the total cost of sequential testing comprising KRAS, EGFR, ALK, ROS1, and BRAF tests was $3,763 ($464, $696, $1,070, $1,127, and $406, respectively), that of NGS was $2,860. LIMITATIONS: Claims data did not include BRAF test results. CONCLUSIONS: Among patients newly-diagnosed with lung cancer, 4.5% were tested for BRAF. Tested patients were younger and had a lower comorbidity burden, but more advanced disease. While reimbursed amounts varied greatly based on combinations of testing procedures, NGS testing was associated with cost savings compared to sequential testing of individual mutations.
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Carcinoma Pulmonar de Células não Pequenas/genética , Sequenciamento de Nucleotídeos em Larga Escala/economia , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas B-raf/genética , Fatores Etários , Idoso , Quinase do Linfoma Anaplásico , Carcinoma Pulmonar de Células não Pequenas/economia , Carcinoma Pulmonar de Células não Pequenas/patologia , Comorbidade , Análise Custo-Benefício , Receptores ErbB/genética , Feminino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Revisão da Utilização de Seguros , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/economia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Receptores Proteína Tirosina Quinases/genética , Estudos Retrospectivos , Fatores de Tempo , Estados UnidosRESUMO
OBJECTIVES: To evaluate adherence to newly initiated biologic disease-modifying antirheumatic drugs (bDMARDs) in effectively treated patients with rheumatoid arthritis (RA). STUDY DESIGN: Retrospective cohort study of administrative claims data (IMS PharMetrics Plus) for services incurred from July 1, 2008, to December 31, 2014. METHODS: Data from patients with RA aged 18 to 64 years with continuous enrollment for at least 30 months and initiating abatacept, adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab were analyzed. Treatment effectiveness was determined using a validated algorithm. Outcomes included adherence rates (proportion of days covered ≥80%) for 1 year and 2 years, year 2 adherence among patients effectively and noneffectively treated in year 1, year 2 adherence predictors, and year 2 costs and cost predictors. RESULTS: Across 10,374 patients, adherence rates were 46% for year 1 and 34% for 2 years; rates were lowest for golimumab and highest for infliximab. In year 1, 3076 (29.7%) patients were considered effectively treated. Year 2 adherence was 59% in effectively treated patients, 32% in patients who failed any effectiveness criteria, and 12% in patients who failed only the adherence criterion. Intravenous bDMARDs, older age, male sex, Northeast region, commercial payer, prior DMARD use, index year 2010 or later, and lower preindex all-cause costs each predicted better adherence. Adjusted year 2 all-cause and RA-related costs were $39,425 and $22,123, respectively, for effectively treated patients and $25,313 and $9250 for noneffectively treated patients. Cost predictors included effective treatment, region, payer, and index year. CONCLUSIONS: Adherence to the first bDMARD was suboptimal even in effectively treated patients, suggesting opportunities to improve adherence in patients with RA initiating biologics.