ABSTRACT
INTRODUCTION: Orthotopic liver transplantation has been used as a treatment for hereditary transthyretin-mediated (hATTR) amyloidosis, a rare, progressive, and multisystem disease. RESEARCH QUESTION: The objective is to evaluate survival outcomes post-liver transplantation in patients with hATTR amyloidosis in the United States and assess whether previously published prognostic factors of patient survival in hATTR amyloidosis are generalizable to the US population. DESIGN: This cohort study examined patients with hATTR amyloidosis undergoing liver transplant in the United States (N = 168) between March 2002 and March 2016 using data reported to the Organ Procurement and Transplantation Network (UNOS)/United Network for Organ Sharing (OPTN). RESULTS: A multivariable Cox hazards regression model showed among all factors tested, only modified body mass index (kg/m2 × g/L) at the time of transplant was significantly associated with survival. Higher modified BMI was associated with lower risk of death relative to a reference population (<600) with historically poor post-transplant outcomes. Patients with modified BMI 1000 to <1200 (hazard ratio [HR] = 0.27; 95% confidence interval [CI] = 0.10-0.73), 1200 to <1400 (HR = 0.20; 95% CI = 0.06-0.75), and ≥1400 (HR = 0.15; 95% CI = 0.04-0.61) exhibited improved adjusted 5-year post-transplant survival of 74%, 80%, and 85%, respectively, versus 33% in the reference population. DISCUSSION: The association between a higher modified BMI threshold at the time of transplant and improved post-transplant survival suggests that the previously published patient selection criterion for modified BMI may not be applicable to the US population.
Subject(s)
Amyloid Neuropathies, Familial/surgery , Body Mass Index , Liver Transplantation , Adult , Age Factors , Amyloid Neuropathies, Familial/mortality , Cohort Studies , Female , Heart Transplantation , Humans , Kaplan-Meier Estimate , Kidney Transplantation , Male , Middle Aged , Multivariate Analysis , Prognosis , Proportional Hazards Models , Prospective Studies , Survival Rate , United StatesSubject(s)
Amyloid Neuropathies, Familial , Polyneuropathies , Benzoxazoles , Humans , Prealbumin , RNA, Small InterferingABSTRACT
BACKGROUND: Hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) is a progressive, life-threatening disease. Until recently, tafamidis was the only approved pharmacotherapy. Patisiran significantly improved polyneuropathy and quality of life (QoL) in the phase III APOLLO trial. In the absence of direct comparisons, this analysis aimed to evaluate the comparative efficacy of tafamidis and patisiran in hATTR amyloidosis with polyneuropathy. RESEARCH DESIGN AND METHODS: Randomized controlled trial evidence for tafamidis was identified by systematic literature review. Indirect treatment comparisons were performed using the standard pairwise Bucher method for endpoints used in both APOLLO and the tafamidis Fx-005 trial: change from baseline in Neuropathy Impairment Score-lower limbs (NIS-LL), Norfolk QoL-Diabetic Neuropathy questionnaire (QoL-DN), NIS-LL response, and mBMI vs. placebo. Inter-trial population differences were assessed by sensitivity analysis. RESULTS: The base-case analysis (FAP Stage 1 APOLLO patients vs. intent-to-treat Fx-005 population) suggested patisiran had a greater treatment effect vs. tafamidis for all endpoints, with significant improvements in mean change in NIS-LL (-5.49) and QoL-DN (-13.10) from baseline to Month 18. Similar trends were observed in all sensitivity analyses. CONCLUSIONS: In the absence of direct comparisons, this analysis suggests patisiran has a greater treatment effect than tafamidis in patients with hATTR amyloidosis with polyneuropathy.
Subject(s)
Amyloid Neuropathies, Familial/drug therapy , Benzoxazoles/therapeutic use , RNA, Small Interfering/therapeutic use , Humans , Polyneuropathies/drug therapy , Quality of Life , Randomized Controlled Trials as Topic , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Acute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. The aim of the present study was to qualitatively characterize the experience of patients with acute intermittent porphyria who have frequent attacks, as well as the impact of the disease on daily living. METHODS: Patients with acute intermittent porphyria who experience frequent attacks were recruited and took part in 2-h qualitative one-on-one interviews with a semi-structured guide. Interviews were anonymized, transcribed, and coded. The inductive coding approach targeted textual data related to acute intermittent porphyria attack symptoms, chronic symptoms, and the impact of the disease. Saturation analysis was conducted to assess whether the research elicited an adequate account of patients' experiences. RESULTS: In total, 19 patients with acute intermittent porphyria were interviewed (mean age 40 years; 79% female). Eighteen patients (95%) experienced both attack and chronic symptoms. Patients described attacks as the onset of unmanageable symptoms that generally lasted 3-5 days requiring hospitalization and/or treatment. Pain, nausea, and vomiting were considered key attack symptoms; pain, nausea, fatigue, and aspects of neuropathy (e.g., tingling and numbness) were considered key chronic symptoms. CONCLUSIONS: In this study population of acute intermittent porphyria with frequent attacks, most patients had symptoms during and between attacks. In these patients, acute intermittent porphyria appears to have acute exacerbations as well as chronic day-to-day manifestations, and is not just intermittent as its name implies. As a result, patients reported limitations in their ability to function across multiple domains of their lives on a regular basis and not just during acute attacks.
Subject(s)
Chronic Disease/psychology , Patients/psychology , Porphyria, Acute Intermittent/physiopathology , Porphyria, Acute Intermittent/psychology , Quality of Life/psychology , Adult , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
BACKGROUND: Multiple sclerosis (MS) patients experience lower health-related quality of life (HRQoL) than the general population. In clinical trials, natalizumab significantly improved HRQoL and reduced relapse rates and disability progression in patients with relapsing MS. In a 1-year analysis of patients included in the current study, HRQoL improvement occurred within 3 months of natalizumab initiation and continued for 1 year thereafter. However, natalizumab's long-term efficacy in improving HRQoL has not been studied. METHODS: In this longitudinal, observational, single-arm US study, HRQoL and treatment satisfaction were evaluated in MS patients receiving intravenous natalizumab 300 mg every 4 weeks in clinical settings. Patients completed surveys at baseline and every 6 months for 3 years and reported the following measures: Short Form-12 Version 2 (SF-12v2), Multiple Sclerosis Impact Scale (MSIS-29), and Treatment Satisfaction Questionnaire for Medication. RESULTS: In this study, 120 patients completed ≥3 years of natalizumab treatment. Significant HRQoL improvements were evident from baseline to year 3 by increases in SF-12v2 Physical Component Summary (PCS) and Mental Component Summary scores (P<0.01) and decreases in MSIS-29 physical and psychological scores (P<0.0001). Patients with less physical disability (baseline Disease Steps [DS] 0-2) had significant improvement from baseline to year 3 in SF-12v2 PCS (P<0.05) and MSIS-29 physical scores (P<0.05). Physical HRQoL outcomes in patients with baseline DS 3-6 remained stable over 3 years. Treatment satisfaction increased significantly from baseline to year 1 (P<0.0001) and was maintained in the following 2 years. CONCLUSION: Patients reported physical and psychological HRQoL improvements over 3 years of natalizumab treatment, supporting the long-term efficacy of natalizumab in real-world settings. Lower baseline disease activity and earlier treatment were related to better outcomes, indicating the importance of starting natalizumab early in the disease course. Treatment satisfaction increased after natalizumab initiation and remained high over 3 years of treatment.
ABSTRACT
The Early Mobility Impairment Questionnaire (EMIQ) was developed to facilitate early identification of mobility impairments in multiple sclerosis (MS) patients. We describe the initial development of the EMIQ with a focus on the psychometric evaluation of the questionnaire using classical and item response theory methods. The initial 20-item EMIQ was constructed by clinical specialists and qualitatively tested among people with MS and physicians via cognitive interviews. Data from an observational study was used to make additional updates to the instrument based on exploratory factor analysis (EFA) and item response theory (IRT) analysis, and psychometric analyses were performed to evaluate the reliability and validity of the final instrument's scores and screening properties (i.e., sensitivity and specificity). Based on qualitative interview analyses, a revised 15-item EMIQ was included in the observational study. EFA, IRT and item-to-item correlation analyses revealed redundant items which were removed leading to the final nine-item EMIQ. The nine-item EMIQ performed well with respect to: test-retest reliability (ICC = 0.858); internal consistency (α = 0.893); convergent validity; and known-groups methods for construct validity. A cut-point of 41 on the 0-to-100 scale resulted in sufficient sensitivity and specificity statistics for viably identifying patients with mobility impairment. The EMIQ is a content valid and psychometrically sound instrument for capturing MS patients' experience with mobility impairments in a clinical practice setting. Additional research is suggested to further confirm the EMIQ's screening properties over time.
Subject(s)
Movement Disorders/etiology , Multiple Sclerosis/complications , Multiple Sclerosis/diagnosis , Surveys and Questionnaires , Adult , Aged , Algorithms , Analysis of Variance , Disability Evaluation , Factor Analysis, Statistical , Female , Humans , Male , Middle Aged , Movement Disorders/diagnosis , Psychometrics , ROC Curve , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: Multiple sclerosis (MS) is a debilitating disease that negatively impacts patients' lives. OBJECTIVE: ENABLE assessed the effect of long-term prolonged-release (PR) fampridine (dalfampridine extended release in the United States) treatment on patient-perceived health impact in patients with MS with walking impairment. METHODS: ENABLE was a 48-week, open-label, Phase 4 study of PR-fampridine 10 mg twice daily. Patients who showed any improvement in Timed 25-Foot Walk walking speed at weeks 2 and 4 and any improvement in 12-item MS Walking Scale score at week 4 remained on treatment. The primary endpoint was change from baseline in 36-Item Short-Form Health Survey (SF-36) physical component summary (PCS) score. RESULTS: At week 4, 707/901 (78.5%) patients met the criteria to remain on treatment. Patients on treatment demonstrated significant and clinically meaningful improvements in SF-36 PCS scores from baseline (mean change (95% confidence interval)) to week 12 (4.30 (3.83, 4.78); p < 0.0001), week 24 (3.75 (3.23, 4.27); p < 0.0001), week 36 (3.46 (2.95, 3.97); p < 0.0001), and week 48 (3.24 (2.72, 3.77); p < 0.0001). Significant improvements from baseline were also demonstrated in secondary health measures in patients on treatment. CONCLUSION: PR-fampridine improved patient-perceived physical and psychological health impact of MS measured in a real-life setting.
Subject(s)
4-Aminopyridine/therapeutic use , Multiple Sclerosis/drug therapy , Patient Reported Outcome Measures , Potassium Channel Blockers/therapeutic use , 4-Aminopyridine/adverse effects , Adolescent , Adult , Aged , Australia , Delayed-Action Preparations , Disability Evaluation , Europe , Exercise Tolerance/drug effects , Female , Gait , Humans , Male , Middle Aged , Multiple Sclerosis/diagnosis , Multiple Sclerosis/physiopathology , Multiple Sclerosis/psychology , Potassium Channel Blockers/adverse effects , Quality of Life , Recovery of Function , Time Factors , Treatment Outcome , Walking , Young AdultABSTRACT
Multiple sclerosis (MS) has a significant impact on health-related quality of life (HRQoL) with symptoms adversely affecting many aspects of everyday living. BG-12 (dimethyl fumarate) demonstrated significant efficacy in the phase III studies DEFINE and CONFIRM in patients with relapsing-remitting MS. In CONFIRM, HRQoL was worse in patients with greater disability at baseline, and who relapsed during the study, and improved with BG-12 treatment. Mean Short Form-36 Physical Component Summary scores for BG-12 increased over 2 years and scores for placebo decreased. Coupled with clinical and neuroradiological benefits, these HRQoL results further support BG-12 as an effective oral treatment for relapsing MS.
Subject(s)
Fumarates/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Quality of Life , Adult , Dimethyl Fumarate , Double-Blind Method , Female , Humans , Male , Middle Aged , Surveys and Questionnaires , Treatment OutcomeABSTRACT
BACKGROUND: Oral BG-12 (dimethyl fumarate), approved for the treatment of the relapsing forms of MS, has demonstrated clinical efficacy with an acceptable safety profile in the Phase III "Determination of the Efficacy and Safety of Oral Fumarate in Relapsing-Remitting Multiple Sclerosis (RRMS)" (DEFINE) and "Comparator and an Oral Fumarate in RRMS" (CONFIRM) studies. OBJECTIVES: To evaluate the health-related quality of life (HRQoL) impairment that is associated with RRMS and to assess the effects of BG-12 on HRQoL in the DEFINE study. METHODS: Patients with RRMS were randomized to BG-12 240 mg twice (BID) or three times (TID) daily, or placebo, for 2 years. HRQoL was assessed by the Short Form-36 (SF-36), global assessment of well-being visual analog scale and the EuroQol-5D. RESULTS: In the 1237 patients from DEFINE, HRQoL impairment was greatest in patients who had higher disability scores and in those who had experienced relapse. Change in SF-36 physical component summary scores during 2 years' treatment significantly favored BG-12 over placebo (both doses: p < 0.001). We saw similar benefits in other measures of functioning and general well-being as early as Week 24. These benefits were maintained during the study. CONCLUSIONS: Our results add to evidence for a negative impact of RRMS on HRQoL and they demonstrate the benefits of BG-12 on HRQoL measures, which coupled with significant clinical efficacy, further support its use as a new treatment for RRMS.
Subject(s)
Fumarates/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Quality of Life , Adult , Dimethyl Fumarate , Double-Blind Method , Female , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
OBJECTIVE: Currently, direct comparative evidence or head-to-head data between BG-12 (dimethyl fumarate) and other disease-modifying treatments (DMTs) is limited. This study is a systematic review and data synthesis of published randomized clinical trials comparing the efficacy and safety of existing DMTs to BG-12 for relapsing-remitting multiple sclerosis (RRMS). METHODS: A systematic review was conducted by searching MEDLINE, EMBASE, and the Cochrane Library for English-language publications from 1 January 1960 to 15 November 2012. Clinicaltrials.gov, metaRegister of Controlled Trials, and conference proceedings from relevant annual symposia were also hand searched. Two independent reviewers collected and extracted data, with discrepancies reconciled by a third reviewer. Included studies were randomized controlled trials (RCTs) of DMTs (interferon [IFN] beta-1a, IFN beta-1b, glatiramer acetate [GA], BG-12, fingolimod, natalizumab, and teriflunomide) in adults with RRMS. Mixed treatment comparisons were conducted to derive the relative effect size for the included treatments. Annualized relapse rate (ARR), disability progression, and safety outcomes were assessed. RESULTS: BG-12 240 mg twice a day (BID) significantly reduces ARR compared to placebo (rate ratio: 0.529 [95% CI: 0.451-0.620]), IFNs (0.76 [95% CI: 0.639-0.904]), GA (0.795 [95% CI: 0.668-0.947]), and teriflunomide 7 mg and 14 mg (0.769 [95% CI: 0.610-0.970] and 0.775 [95% CI: 0.614-0.979]), and does not show a significant difference when compared to fingolimod. Only natalizumab was significantly superior to BG-12 in reducing ARR. BG-12 also demonstrated favorable results for disability and safety outcomes. CONCLUSION: Based on indirect comparison, BG-12 offers an effective oral treatment option for patients with RRMS with an overall promising efficacy and safety profile compared to currently approved DMTs. Key limitations of the systematic review were the large heterogeneity in patients enrolled and the variability in the definition of outcomes in included trials.
Subject(s)
Fumarates/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Crotonates/therapeutic use , Dimethyl Fumarate , Disease Progression , Fingolimod Hydrochloride , Fumarates/adverse effects , Humans , Hydroxybutyrates , Interferon beta-1a , Interferon beta-1b , Interferon-beta/therapeutic use , Natalizumab , Nitriles , Propylene Glycols/therapeutic use , Randomized Controlled Trials as Topic , Recurrence , Sphingosine/analogs & derivatives , Sphingosine/therapeutic use , Toluidines/therapeutic useABSTRACT
BACKGROUND: Natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals) significantly reduces the relapse rate and disability progression, and improves health-related quality of life (HRQoL), in patients with relapsing-remitting multiple sclerosis. We investigated the impact of natalizumab on patient-reported outcomes (PROs) in a real-world setting. METHODS: PRO data were collected from patients enrolled in a longitudinal real-world study using validated measures administered as surveys before the patients initiated natalizumab treatment and after the 3rd, 6th, and 12th monthly infusion. HRQoL, ability to carry out daily activities, disability level, and impact on cognitive functioning and fatigue were assessed. RESULTS: A total of 333 patients completed 12 months of assessments. After 12 months of natalizumab treatment, 69% to 88% of patients reported a positive outcome (either an improvement or no further decline) in all PRO measures assessed. Significant improvements in general and disease-specific HRQoL were observed after three infusions, both with physical (p < .01) and psychological (p < .001) measures, and were sustained after 12 infusions (all p < .001). The impact of multiple sclerosis on cognitive functioning and fatigue was significantly reduced (both p < .001 after 3 and 12 infusions). CONCLUSIONS: PRO measures were improved with natalizumab in a real-world setting. The improvements were observed as early as after 3 months and sustained over a 12-month period. The improvements in PROs show that, in clinical practice, the clinical benefits of natalizumab are translated into patient-reported benefits.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Multiple Sclerosis/drug therapy , Outcome Assessment, Health Care , Self Report , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , NatalizumabABSTRACT
INTRODUCTION: There are no published data on patient adherence to, and persistence with, disease-modifying therapies (DMT) for multiple sclerosis (MS) after one immunomodulatory failure. The present study compares secondline DMT adherence and persistence among patients with MS. METHODS: Patients with MS initiating a second-line treatment with natalizumab, intramuscular interferon beta-1a (i.m.-IFNß-1a), subcutaneous (s.c.) IFNß-1a, interferon beta-1b (IFNß-1b), and glatiramer acetate (GA) from January 1, 2006 to October 4, 2008 were identified from a retrospective claims database associated with a large US health plan. Adherence was measured with medication possession ratio (MPR); adherence indicated MPR ≥ 0.80. Persistence was measured as time until a minimum 60-day gap in second-line therapy. Adherence and persistence were modeled with logistic and Cox proportional hazard regressions, respectively. RESULTS: The study population comprised 1381 patients. Multivariate analysis showed that the odds of adherence were significantly higher in the natalizumab cohort compared with all other second-line cohorts. The natalizumab cohort was more likely to be persistent compared with the i.m.-IFNß-1a and IFNß-1b cohorts. CONCLUSION: The natalizumab cohort was more adherent compared with the other second-line DMT cohorts, likely due in large part to active physician involvement and monitoring. Adherence to DMT, even after first-line failure, is critical to achieving optimal therapeutic benefit.
Subject(s)
Immunologic Factors/therapeutic use , Medication Adherence , Multiple Sclerosis/drug therapy , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Female , Glatiramer Acetate , Humans , Injections, Intramuscular , Injections, Subcutaneous , Insurance Claim Review , Interferon beta-1a , Interferon beta-1b , Interferon-beta/therapeutic use , Male , Natalizumab , Peptides/therapeutic use , Proportional Hazards Models , Treatment FailureABSTRACT
BACKGROUND: With the addition of new agents for the treatment of multiple sclerosis (MS) (e.g., fingolimod), there is a need to evaluate the relative value of newer therapies in terms of cost and effectiveness, given healthcare resource constraints in the United States. OBJECTIVE: To assess the cost-effectiveness of natalizumab vs fingolimod in patients with relapsing MS. METHODS: A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from a US managed care payer perspective. Two-year costs of treating patients with MS included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided (data from AFFIRM and FREEDOMS trials). One-way and probabilistic sensitivity analyses were conducted to assess uncertainty. RESULTS: Mean 2-year estimated treatment costs were $86,461 (natalizumab) and $98,748 (fingolimod). Patients receiving natalizumab had a mean of 0.74 relapses avoided per 2 years vs 0.59 for fingolimod. Natalizumab dominated fingolimod in the incremental cost-effectiveness analysis, as it was less costly and more effective in reducing relapses. One-way sensitivity analysis showed the results of the model were robust to changes in drug acquisition costs, administration costs, and costs of treating MS relapses. Probabilistic sensitivity analysis showed natalizumab was cost-effective 95.1% of the time, at a willingness-to-pay (WTP) threshold of $0 per relapse avoided, increasing to 96.3% of the time at a WTP threshold of $50,000 per relapse avoided. LIMITATIONS: Absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as primary model outcome, assumption of 100% adherence to MS treatment, and not capturing adverse event costs in the model. CONCLUSIONS: Natalizumab dominates fingolimod in terms of incremental cost per relapse avoided, as it is less costly and more effective.
Subject(s)
Antibodies, Monoclonal, Humanized/economics , Health Care Costs/trends , Immunosuppressive Agents/economics , Multiple Sclerosis/drug therapy , Multiple Sclerosis/prevention & control , Propylene Glycols/economics , Sphingosine/analogs & derivatives , Antibodies, Monoclonal, Humanized/therapeutic use , Cost-Benefit Analysis , Fingolimod Hydrochloride , Humans , Immunosuppressive Agents/therapeutic use , Natalizumab , Propylene Glycols/therapeutic use , Recurrence , Sphingosine/economics , Sphingosine/therapeutic use , United StatesABSTRACT
PURPOSE: To compare adherence and persistence among patients with multiple sclerosis (MS) initiated on disease-modifying therapy (DMTs), including intramuscular (IM) interferon beta-1a (IFNß-1a), subcutaneous (SC) IFNß-1a, IFNß-1b, or glatiramer acetate (GA). METHODS: MS patients initiated on IM-IFNß-1a, SC-IFNß-1a, IFNß-1b, or GA between January 1, 2000 and January 2, 2008 were identified from a retrospective claims database study associated with a large US health plan. The date of DMT initiation was the index date; patients were observed for 6 months before and 12-36 months after the index date. Adherence to the index DMT was measured with a medication possession ratio (MPR), the proportion of days patients possessed their index DMTs; MPR ≥ 0.80 was considered adherent. Persistence was time in days from index date until the earlier of a minimum 60-day gap in DMT therapy or the last DMT claim during follow-up. Adherence and persistence were modeled with logistic and Cox proportional hazard regressions, respectively. RESULTS: The study population comprised 6,680 patients in the DMT cohorts: IM-IFNß-1a (N = 2,305, 34.5%); IFNß-1b (N = 894, 13.4%); GA (N = 2,270, 34.0%); and SC-IFNß-1a (N = 1,211, 18.1%). The IM-IFNß-1a cohort had significantly higher regression-adjusted odds of adherence relative to the other cohorts: 52.4% higher odds versus the IFNß-1b cohort (OR = 0.656, CI = 0.561-0.768); 33.5% higher odds versus the GA cohort (OR = 0.749, CI = 0.665-0.844); and 20.6% higher odds versus the SC-IFNß-1a cohort (OR = 0.829, CI = 0.719-0.957). There were no consistent differences in persistence between the cohorts. CONCLUSION: IM-IFNß-1a patients had significantly higher odds of adherence compared with other DMT cohorts, possibly attributable to IM-IFNß-1a's less frequent dosing schedule. The benefits of adherence may include better quality of life, lower risk of relapse, and fewer hospitalizations and emergency visits, making adherence a critical component of MS management.
ABSTRACT
BACKGROUND: 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. OBJECTIVE: To assess the impact of treatment adherence on MS-related hospitalizations (inpatient [INP]), ER visits, MS relapses, and medical costs. DESIGN/METHODS: 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. RESULTS: 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). CONCLUSION: 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.
Subject(s)
Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Medication Adherence , Multiple Sclerosis/drug therapy , Peptides/therapeutic use , Adult , Female , Glatiramer Acetate , Health Care Costs , Humans , Male , Multivariate Analysis , Patient Admission/statistics & numerical data , Recurrence , Retrospective Studies , Treatment Outcome , United StatesABSTRACT
OBJECTIVE: : To assess multiple sclerosis (MS) patients' experience with natalizumab (TYSABRI, Biogen Idec, Inc. and Elan Pharmaceuticals, Inc.) in a clinical practice setting. METHODS: : MS patients who were enrolled in the TOUCH (TYSABRI Outreach Unified Commitment to Health) prescribing program and who had received their third natalizumab infusion participated in this study. Patient-reported measures included an overall quality-of-life (QOL) assessment, an adapted version of the Multiple Sclerosis Impact Scale-29 (MSIS-29), and pre-/post-disease level and functional status scores. MSIS-29 responses were modified to measure patient-perceived change since initiating natalizumab. Paired t-tests assessed pre-/post- changes in disease level and functional status, where negative change indicated improvement. RESULTS: : Results from 451 patients in this study indicated that 73% were female and, on average, were diagnosed with MS >11 years previously. Almost all (96%) patients had used one or more MS drugs prior to natalizumab initiation. After receiving natalizumab, 97% of all patients reported an improvement or remained stable in their overall QOL. Despite the short treatment duration, there were significant improvements (mean ± SD change) in disease level (-0.26 ± 0.99, paired t-test = 5.47; p < 0.001) and functional status (-0.33 ± 0.73, paired t-test = 9.40; p < 0.001) scores. More than 80% of patients reported an improvement in one or more MSIS-29 physical items. The physical item on the adapted MSIS-29 with the highest reported improvement (58%) was 'the ability to do physically demanding tasks'. The physical item with the lowest reported improvement (32%) was 'problems using transport'. CONCLUSION: : Overall, the experiences of MS patients with natalizumab were positive in a clinical practice setting. Patients reported improvements in overall QOL, ambulation and functional status as early as after three natalizumab infusions. While preliminary, these early results are suggestive of a beneficial effect of natalizumab in patients with MS and warrant further long-term investigation of the impact of this treatment on patient outcomes.