Raquel Lahoz

Relapse rates in patients with multiple sclerosis switching from interferon to fingolimod or glatiramer acetate: a US claims database study.

Background Approximately one-third of patients with multiple sclerosis (MS) are unresponsive to, or intolerant of, interferon (IFN) therapy, prompting a switch to other disease-modifying therapies. Clinical outcomes of switching therapy are unknown. This retrospective study assessed differences in relapse rates among patients with MS switching from IFN to fingolimod or glatiramer acetate (GA) in a real-world setting. Methods US administrative claims data from the PharMetrics Plus™ database were used to identify patients with MS who switched from IFN to fingolimod or GA between October 1, 2010 and March 31, 2012. Patients were matched 1∶1 using propensity scores within strata (number of pre-index relapses) on demographic (e.g. age and gender) and disease (e.g. timing of pre-index relapse, comorbidities and symptoms) characteristics. A claims-based algorithm was used to identify relapses while patients were persistent with therapy over 360 days post-switch. Differences in both the probability of experiencing a relapse and the annualized relapse rate (ARR) while persistent with therapy were assessed. Results The matched sample population contained 264 patients (n = 132 in each cohort). Before switching, 33.3% of patients in both cohorts had experienced at least one relapse. During the post-index persistence period, the proportion of patients with at least one relapse was lower in the fingolimod cohort (12.9%) than in the GA cohort (25.0%), and ARRs were lower with fingolimod (0.19) than with GA (0.51). Patients treated with fingolimod had a 59% lower probability of relapse (odds ratio, 0.41; 95% confidence interval [CI], 0.21–0.80; p = 0.0091) and 62% fewer relapses per year (rate ratio, 0.38; 95% CI, 0.21–0.68; p = 0.0013) compared with those treated with GA. Conclusions In a real-world setting, patients with MS who switched from IFNs to fingolimod were significantly less likely to experience relapses than those who switched to GA.

Persistence with and adherence to fingolimod compared with other disease-modifying therapies for the treatment of multiple sclerosis: a retrospective US claims database analysis

Abstract Objective: Achieving therapeutic goals in multiple sclerosis (MS) requires strict adherence to treatment schedules. This retrospective study analyzed persistence with, and adherence to, fingolimod compared with injectable/infusible disease-modifying therapies (DMTs) in patients with MS. Methods: Patients in the PharMetrics Plus™ US administrative claims database with at least one prescription for, or administration of, fingolimod, glatiramer acetate (GA), interferon (IFN), or natalizumab (index DMT) between October 1, 2010 and September 30, 2011 were included. Patients were naïve to index DMT (no claim in the previous 360 days) and had an MS diagnosis code within 360 days of the first index DMT prescription. Outcomes were persistence, risk of discontinuing index DMT (evaluated by a Cox proportional hazards model), adherence (measured using the medication possession ratio [MPR] and proportion of days covered [PDC] in patients with at least two index DMT prescriptions), and the risk of being non-adherent (MPR <80% and PDC <80%, assessed using a logistic regression model). Results: The study included 3750 patients (fingolimod, n = 889; GA, n = 1233; any IFN, n = 1341; natalizumab, n = 287). Discontinuation rates (fingolimod, 27.9%; GA, 39.5%; IFN, 43.7%; natalizumab, 39.5%; all p < 0.001) and risk of discontinuation were significantly higher (hazard ratios vs fingolimod [95% confidence interval]: GA, 1.75 [1.49–2.07]; IFN, 2.01 [1.71–2.37]; natalizumab, 1.53 [1.22–1.91]) for patients receiving other DMTs compared with fingolimod. The risk of being non-adherent was also lower for patients in the fingolimod cohort than the other treatment cohorts, irrespective of whether non-adherence was defined as MPR <80% (p < 0.05 for all) or PDC <80% (p < 0.05 for GA and IFN). Limitations: As with all studies assessing real-world treatment patterns it is unclear if medications were used as prescribed. Conclusions: In a real-world setting, persistence with, and adherence to, oral fingolimod was higher than for injectable and infusible DMTs.

Costs of chronic obstructive pulmonary disease in relation to compliance with guidelines: a study in the primary care setting.

Background: The aim of this study was to analyse the economic impact of nonadherence to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines in patients with chronic obstructive pulmonary disease (COPD). Methods: A retrospective analysis was carried out on a claim database. Patients aged at least 40 years with a diagnosis of COPD were eligible for this analysis. Demographics, medical data and use of resources were collected and direct and indirect costs were analysed (from January 2008 to June 2009). A probabilistic multivariate sensitivity analysis of avoided costs was carried out. All results are presented in annualized form and costs are expressed in Euros (2009). Results: A total of 1365 patients were included, 79.5% were men. The mean age (±standard deviation) was 71.4 (±10.3) years, the mean forced expiratory volume in 1 s (FEV1) was 65.3% and they had a COPD history of 5.5 (±2.9) years. Patients were divided into an adherent group and a nonadherent group depending on whether therapeutic recommendations according to severity defined in the GOLD guidelines (2007) were followed. Patients in both groups were also classified as having stage II (FEV1 < 80% and < 50%) or stage III disease (FEV1 < 50% and ≥ 30%). The total annual drug cost per patient in the nonadherent group was €771.5 while it was only €426.4 for the adherent group. The average direct cost per patient per year in the nonadherent stage II group was €1465 (±971) and it rose to €2942 (±1918) for patients in the nonadherent group with stage III disease. The potential saving from the implementation of the GOLD guidelines in stage II COPD amounted to €758 per patient per year (68% saving on drug cost). In contrast, the cost for patients with stage III disease was higher in the adherent group versus the nonadherent group (€2468). Conclusions: The cost of COPD may vary according to compliance with the GOLD guidelines. The cost observed for patients with stage II disease is higher than expected in patients who adhere to treatment, but patients with stage III disease treated according to the GOLD guidelines had significantly higher treatment costs.

Mortality and comorbidities in patients with multiple sclerosis compared with a population without multiple sclerosis: An observational study using the US Department of Defense administrative claims database

BACKGROUND Data are limited for mortality and comorbidities in patients with multiple sclerosis (MS). OBJECTIVES Compare mortality rates and event rates for comorbidities in MS (n=15,684) and non-MS (n=78,420) cohorts from the US Department of Defense (DoD) database. METHODS Comorbidities and all-cause mortality were assessed using the database. Causes of death (CoDs) were assessed through linkage with the National Death Index. Cohorts were compared using mortality (MRR) and event (ERR) rate ratios. RESULTS All-cause mortality was 2.9-fold higher in the MS versus non-MS cohort (MRR, 95% confidence interval [CI]: 2.9, 2.7-3.2). Frequent CoDs in the MS versus non-MS cohort were infectious diseases (6.2, 4.2-9.4), diseases of the nervous (5.8, 3.7-9.0), respiratory (5.0, 3.9-6.4) and circulatory (2.1, 1.7-2.7) systems and suicide (2.6, 1.3-5.2). Comorbidities including sepsis (ERR, 95% CI: 5.7, 5.1-6.3), ischemic stroke (3.8, 3.5-4.2), attempted suicide (2.4, 1.3-4.5) and ulcerative colitis (2.0, 1.7-2.3), were higher in the MS versus non-MS cohort. The rate of cancers was also higher in the MS versus the non-MS cohort, including lymphoproliferative disorders (2.2, 1.9-2.6) and melanoma (1.7, 1.4-2.0). CONCLUSIONS Rates of mortality and several comorbidities are higher in the MS versus non-MS cohort. Early recognition and management of comorbidities may reduce premature mortality and improve quality of life in patients with MS.

Comparative effectiveness of fingolimod versus interferons or glatiramer acetate for relapse rates in multiple sclerosis: a retrospective US claims database analysis

Abstract Objective: Disease-modifying therapies, such as fingolimod, interferon (IFN) and glatiramer acetate (GA), have differing effects on relapse rates in patients with multiple sclerosis (MS), but little is known about the real-world differences in relapse rates with these treatments. This retrospective study assessed relapse rates in patients with active MS initiating fingolimod, IFN or GA therapy in a real-world setting. Methods: Using administrative claims data from the US PharMetrics Plus database, we identified previously treated and untreated patients with MS who initiated fingolimod, IFN or GA treatment between 1 October 2010 and 31 March 2011 and had experienced a relapse in the previous year. A claims-based algorithm was used to identify relapses over the persistence period in patients with 540 days of post-index continuous enrolment. A logistic regression model assessed the probability of having at least one relapse and a generalized linear model estimated differences in annualized relapse rates (ARRs). Results: The study enrolled 525 patients (fingolimod, n = 128; combined IFN/GA cohort, n = 397) of the 31,041 initially identified. Similar findings for fingolimod and IFN/GA were observed for the unadjusted proportion of patients experiencing relapses (31.3% vs. 34.0%, respectively; p = 0.5653) and ARRs (0.50 vs. 0.55, respectively) while persistent to treatment. After adjusting for baseline differences, fingolimod was associated with a 52% reduction in the probability of having a relapse (odds ratio, 0.48; 95% confidence interval [CI], 0.28–0.84; p = 0.0097) and a 50% reduction in ARR (rate ratio, 0.50; 95% CI, 0.34–0.75; p = 0.0006) compared with IFN/GA. Limitations: Identification of relapses is based on the claims in the database rather than on a clinical assessment. Conclusions: In a real-world setting, fingolimod was shown to be associated with significantly lower relapse rates than IFN/GA in patients with MS who had a history of relapses.

Healthcare resource use and relapses with fingolimod versus natalizumab for treating multiple sclerosis: a retrospective US claims database analysis

Abstract Objective: Healthcare resource utilization in patients with multiple sclerosis (MS) is linked to relapses and disease progression. This retrospective cohort database analysis compared healthcare resource use and proxy measures of relapse outcomes in patients with active disease who switched to fingolimod or natalizumab. Methods: Using administrative claims data from the US PharMetrics Plus database, we identified patients with an MS diagnosis and a claim for fingolimod or natalizumab between 1 October 2010 and 30 June 2012 (index period) who had experienced a relapse (identified using a claims-based algorithm) and used other disease-modifying therapies (DMTs) in the previous year. Patients in the fingolimod and natalizumab cohorts were propensity score matched (1:1). MS-related inpatient stays, corticosteroid use and the proportion of patients experiencing claims-based relapses were assessed in the pre-index and post-index persistence periods. Time to first claims-based relapse in the post-index persistence period was assessed using a Kaplan–Meier curve. Results: The study included 623 unmatched patients (299 and 324 patients in the fingolimod and natalizumab cohorts, respectively) and 370 matched patients (185 in each cohort). In the matched analysis, MS-related inpatient stays and corticosteroid use were similar in the fingolimod and natalizumab cohorts during the post-index persistence period, and were significantly reduced versus the pre-index period (p < 0.01). A similar proportion of patients in the fingolimod and natalizumab cohorts were free from claims-based relapses in the persistence period (68.1% and 68.6%, respectively). There was no significant difference in the likelihood of experiencing a claims-based relapse (p = 0.8696). Limitation: Identification of relapses is based on database claims rather than on clinical assessment. Conclusions: In analyses of patients with MS with a history of relapse and DMT use, fingolimod and natalizumab reduce healthcare resource utilization and have similar effectiveness in a real-world setting.

Expanding the use of administrative claims databases in conducting clinical real-world evidence studies in multiple sclerosis.

Abstract Objective: Administrative claims databases provide a wealth of data for assessing the effect of treatments in clinical practice. Our aim was to propose methodology for real-world studies in multiple sclerosis (MS) using these databases. Research design and methods: In three large US administrative claims databases: MarketScan, PharMetrics Plus and Department of Defense (DoD), patients with MS were selected using an algorithm identified in the published literature and refined for accuracy. Algorithms for detecting newly diagnosed (‘incident’) MS cases were also refined and tested. Methodology based on resource and treatment use was developed to differentiate between relapses with and without hospitalization. Results: When various patient selection criteria were applied to the MarketScan database, an algorithm requiring two MS diagnoses at least 30 days apart was identified as the preferred method of selecting patient cohorts. Attempts to detect incident MS cases were confounded by the limited continuous enrollment of patients in these databases. Relapse detection algorithms identified similar proportions of patients in the MarketScan and PharMetrics Plus databases experiencing relapses with (2% in both databases) and without (15–20%) hospitalization in the 1 year follow-up period, providing findings in the range of those in the published literature. Limitation: Additional validation of the algorithms proposed here would increase their credibility. Conclusions: The methods suggested in this study offer a good foundation for performing real-world research in MS using administrative claims databases, potentially allowing evidence from different studies to be compared and combined more systematically than in current research practice.

Relación entre variables clínicas y terapéuticas y calidad de vida relacionada con la salud en pacientes con hipertensión arterial: estudio MINICHAL

Fundamento y objetivo: Evaluar, mediante el cuestionario de calidad de vida relacionada con la salud (CVRS) MINICHAL, la influencia de las variables sociodemograficas, clinicas y terapeuticas en la calidad de vida relacionada con la salud de los pacientes hipertensos. Pacientes y metodo: Estudio observacional, prospectivo y multicentrico en pacientes hipertensos que iniciaban o modificaban tratamiento antihipertensivo. Se realizaron tres visitas, una basal y dos de seguimiento (una al mes y otra a los 6 meses). En ellas se registraron las variables sociodemograficas, clinicas y terapeuticas, y se aplicaron los cuestionarios validados de CVRS MINICHAL, la version espanola del Indice de Bienestar Psicologico y una pregunta sobre el cambio en el estado de salud general con el objetivo de evaluar la influencia sobre la CVRS de dichas variables sociodemograficas, clinicas y terapeuticas. Resultados: Se evaluo a un total de 736 pacientes hipertensos. En el analisis multivariante, el sexo femenino, el numero de enfermedades concomitantes, el grado de hipertension arterial, el grado de afeccion organica y el nivel educativo fueron las variables que se mostraron relacionadas con la CVRS. Se observo una mejoria de la CVRS tras 6 meses de intensificacion del tratamiento, apreciandose una correlacion positiva entre grado de reduccion de presion arterial y de frecuencia cardiaca y mejora en la CVRS, especialmente en la dimension de «Estado de animo». Conclusiones: En los pacientes hipertensos, el mejor control de la presion arterial incide favorablemente sobre la CVRS. Ademas, ciertas caracteristicas de los pacientes se correlacionan negativamente con la CVRS, por lo que la intervencion terapeutica debe estar especialmente dirigida a corregir los factores modificables.

Concepto e instrumentos

Unidad Docente de Medicina de Familia y Universidad Jaime I, Castellón, España Universidad Jaime I, Castellón, España Departamento de Investigación Clı́nica, Lilly, Madrid, España Economı́a de la Salud, Medtronic, Madrid, España Investigación de Resultados en Salud, Novartis, Barcelona, España Departamento de Psicologı́a de la Salud, Universidad de Alicante, Alicante, España Disponible en Internet el 29 de abril de 2009

Concept and tools [Concepto e instrumentos]

Unidad Docente de Medicina de Familia y Universidad Jaime I, Castellón, España Universidad Jaime I, Castellón, España Departamento de Investigación Clı́nica, Lilly, Madrid, España Economı́a de la Salud, Medtronic, Madrid, España Investigación de Resultados en Salud, Novartis, Barcelona, España Departamento de Psicologı́a de la Salud, Universidad de Alicante, Alicante, España Disponible en Internet el 29 de abril de 2009