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      Compliance to fingolimod and other disease modifying treatments in multiple sclerosis patients, a retrospective cohort study

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          Abstract

          Background

          Adherence to disease-modifying therapies (DMTs) results in the reduction of the number and severity of relapses and delays the progression of multiple sclerosis (MS). Patients with lower adherence rates experience more inpatient visits and higher MS-related medical costs. Fingolimod, the first oral DMT approved by the US Food and Drug Administration, may improve the access and compliance to MS treatment when compared to injectable DMTs.

          Methods

          This retrospective cohort study used pharmacy claims from Medco Health Solutions, Inc., of patients who initiated DMTs between October 2010 and February 2011. Initiation was defined as no prescription fills for the same DMT in the prior 12 months. Patients without a DMT prescription fill 12 months before the index date were considered naïve users. Compliance was measured via proportion of days covered (PDC) and medication possession ratio (MPR) for 12 months post-index. Discontinuation was defined as a ≥60-day gap of index DMT supply. Cox proportional hazard models compared time to discontinuation between cohorts.

          Results

          Of 1,891 MS patients (mean age: 45.7; female: 76.4%), 13.1% initiated fingolimod, 10.7% interferon beta-1b, 20.0% intramuscular interferon beta-1a, 18.8% subcutaneous interferon beta-1a, and 37.4% glatiramer acetate. Patients initiating fingolimod had highest average PDC and MPR in both experienced (fingolimod: mean PDC=0.83, 73.7% with PDC≥0.8; mean MPR=0.92, 90.5% with MPR≥0.8) and naïve DMT users (fingolimod: mean PDC=0.80, 66.7% with PDC≥0.8; mean MPR=0.90, 87.4% with MPR≥0.8). The proportion of patients discontinuing index DMT within 12 months was significantly lower for the fingolimod cohort (naïve: 31.3%; experienced: 25.7%). Adjusted results found that patients receiving self-injected DMTs discontinued significantly sooner than fingolimod users. This association was generally stronger in experienced DMT users.

          Conclusions

          Fingolimod initiators were more compliant, less likely to discontinue treatment, and discontinued later than patients who initiated self-injected DMT.

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          Most cited references16

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          The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis.

          most disease-modifying therapies (DMTs) for multiple sclerosis (MS) are self-injectable medications that must be taken on an ongoing basis to reduce disease activity. Thus, adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy. This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing-remitting MS. this was an observational, multicenter, multinational, phase 4 study. Patients and physicians received paper questionnaires regarding adherence to DMTs approved at the time of the study, including intramuscular interferon beta-1a (IFNβ-1a), subcutaneous IFNβ-1a, IFNβ-1b, and glatiramer acetate. Quality of life and cognition data also were collected. Multivariate analysis was conducted to identify factors associated with adherence to long-term DMTs. two thousand six hundred and forty-eight patients were studied, revealing an average treatment duration of 31 months. Seventy-five percent of patients (n = 1923) were adherent to therapy. The most common reasons for non-adherence were forgetting to administer the injection (50.2%) and other injection-related reasons (32.0%). Adherent patients reported better quality of life (P < 0.05) and fewer neuropsychological issues (P < 0.001) than non-adherent patients. Adherent patients had significantly shorter duration of disease (P < 0.001) and shorter duration of therapy (P = 0.005) than non-adherent patients. Women were more likely than men to adhere to treatment. identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy, thereby helping maximize the benefits of long-term DMTs.
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            Factors that influence adherence with disease-modifying therapy in MS.

            The complexity and cost of injection treatment can represent a formidable challenge for patients affected by a chronic illness, particularly those whose treatment is primarily preventative and only modestly effective on the more conspicuous symptomatic aspects of the disease process. The aim of this investigation was to identify which factors most influenced nonadherent behavior with the available disease-modifying injection therapies for multiple sclerosis (MS). A multicenter, observational (three-wave) study using surveys was developed and administered to patients with MS through the World Wide Web. Healthcare providers at 17 neurology clinics recruited patients for the study. A total of 798 patients responded to the baseline wave of the study (708 responded to all three waves). The nonadherence rates for all patients (missing one or more injections) across these waves remained relatively stable at 39%, 37%, and 36%, respectively. The most common reason participants listed for missing injections was that they simply forgot to administer the medication (58%). Other factors including injection-site reactions, quality of life, patients' perceptions on the injectable medications, hope, depression, and support were also assessed in relation to adherence. This study characterizes factors that are associated with failure to fully adhere with disease modifying injection therapy for MS and underscores the principles associated with optimizing adherence and its implications for effective treatment of the disease process in MS.
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              Impact of adherence to disease-modifying therapies on clinical and economic outcomes among patients with multiple sclerosis.

              Adherence to disease-modifying therapies (DMTs) is essential for the reduction of multiple sclerosis (MS) progression and relapse. However, only limited data currently exist on the impact of treatment adherence on MS-related clinical and economic outcomes in the real world setting. To assess the impact of treatment adherence on MS-related hospitalizations (inpatient [INP]), ER visits, MS relapses, and medical costs. Patients with ≥ 1 ICD-9-CM code for MS who received ≥ 1 DMT between July 1, 2004 and June 30, 2008 were identified using the administrative claims database. The first DMT received during the study period was defined as the index treatment and ≥ 6-month preindex and ≥ 12-month postindex continuous health-plan enrollment were required for inclusion. Adherence was assessed using the medication possession ratio (MPR); patients with MPR ≥ 80% were regarded as adherent. Multivariate analyses were used to evaluate the impact of adherence on MS-related outcomes after controlling for baseline demographic and clinical characteristics. In this cohort (n=2446), 59.6% of the patients were adherent to their DMT. Compared with the nonadherent group, adherent patients were significantly less likely to have MS-related INP (odds ratio [OR]: 0.63, 95% confidence interval [CI], 0.47-0.83) and MS relapses (OR: 0.71, 95% CI, 0.59-0.85). No significant difference was found in ER risk between adherent and nonadherent groups (8.4% vs. 10.5%, P=0.068, OR: 0.80, 95% CI: 0.60-1.07). On average, the adherent group incurred lower medical costs than the nonadherent group ($3380, 95% CI, $3046-$3750 vs. $4348, 95% CI, $3828-$4940, P=0.003). Treatment adherence is associated with better clinical and economic outcomes including lower risks for MS-related hospitalization, MS relapse, and less MS-related medical costs. Treatments that require infrequent administrations and have favorable adherence profiles may benefit patients who are unable to adhere to DMT therapies. Such treatments may be important in improving disease outcomes and may be suitable therapeutic candidates for the management of MS.
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                Author and article information

                Contributors
                Journal
                BMC Neurol
                BMC Neurol
                BMC Neurology
                BioMed Central
                1471-2377
                2013
                4 October 2013
                : 13
                : 138
                Affiliations
                [1 ]Novartis Pharmaceuticals Corporation, One Health Plaza, 07936, East Hanover, NJ USA
                [2 ]Evidera, 430 Bedford Street, Suite 300, 02420, Lexington, MA USA
                [3 ]Sweetwater Neurology, 10800 Parkside Drive Suite 202, 37934, Knoxville, TN USA
                Article
                1471-2377-13-138
                10.1186/1471-2377-13-138
                3851325
                24093542
                d8e64dff-4d25-4c85-9e58-23f500c5f443
                Copyright © 2013 Agashivala et al.; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 January 2013
                : 26 September 2013
                Categories
                Research Article

                Neurology
                multiple sclerosis,compliance,patient adherence,medication persistence,discontinuation,fingolimod

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