Kristen Johnson

Real-World Adherence and Persistence to Oral Disease-Modifying Therapies in Multiple Sclerosis Patients Over 1 Year

BACKGROUND Disease-modifying therapies (DMTs) are indicated to reduce relapse rates and slow disease progression for relapsing-remitting multiple sclerosis (MS) patients when taken as prescribed. Nonadherence or non-persistence in the real-world setting can lead to greater risk for negative clinical outcomes. Although previous research has demonstrated greater adherence and persistence to oral DMTs compared with injectable DMTs, comparisons among oral DMTs are lacking. OBJECTIVE To compare adherence, persistence, and time to discontinuation among MS patients newly prescribed the oral DMTs fingolimod, dimethyl fumarate, or teriflunomide. METHODS This retrospective study used MarketScan Commercial and Medicare Supplemental claims databases. MS patients with ≥ 1 claim for specified DMTs from April 1, 2013, to June 30, 2013, were identified. The index drug was defined as the first oral DMT within this period. To capture patients newly initiating index DMTs, patients could not have a claim for their index drugs in the previous 12 months. Baseline characteristics were described for patients in each treatment cohort. Adherence, as measured by medication possession ratio (MPR) and proportion of days covered (PDC); persistence (30-day gap allowed); and time to discontinuation over a 12-month follow-up period were compared across treatment cohorts. Adjusted logistic regression models were used to examine adherence, and Cox regression models estimated risk of discontinuation. RESULTS 1,498 patients newly initiated oral DMTs and met study inclusion criteria: fingolimod (n = 185), dimethyl fumarate (n = 1,160), and teriflunomide (n = 143). Patients were similar across most baseline characteristics, including region, relapse history, and health care resource utilization. Statistically significant differences were observed across the treatment cohorts for age, gender, previous injectable/infused DMT use, and comorbidities. Adherence and time to discontinuation were adjusted for age, gender, region, previous oral and injectable/infused DMT use, relapse history, and Charlson Comorbidity Index score. Relative to fingolimod patients, dimethyl fumarate and teriflunomide patients were significantly less likely to have an MPR ≥ 80% (OR = 0.18; 95% CI = 0.09-0.36; P < 0.001 and OR = 0.19; 95% CI = 0.08-0.42; P < 0.001, respectively). Similarly, relative to fingolimod patients, dimethyl fumarate and teriflunomide patients were significantly less likely to have PDC ≥ 80% (OR = 0.47; 95% CI = 0.33-0.67; P < 0.001 and OR = 0.37; 95% CI = 0.23-0.59; P < 0.001, respectively). Additionally, the HR for discontinuation was about 2 times greater for dimethyl fumarate (HR = 1.93; 95% CI = 1.44-2.59; P < 0.001) and teriflunomide patients (HR = 2.27; 95% CI = 1.57-3.28; P < 0.001) compared with fingolimod. CONCLUSIONS In a real-world setting, patients taking fingolimod had better adherence and persistence compared with patients taking other oral DMTs over 12 months. Coupled with clinical factors, medication adherence and persistence should be important considerations when determining coverage decisions for MS patients. DISCLOSURES This research was funded by Novartis Pharmaceuticals. Johnson, Lin, Ko, and Herrera are employed by Novartis Pharmaceuticals and own Novartis stock. Huanxue Zhou is employed by KMK Consulting, which provides consulting services to Novartis. Study concept and design were contributed by Johnson, Lin, Ko, and Herrera. Zhou collected the data, and data interpretation was performed by Johnson, Lin, Ko, and Herrera. All authors were involved in manuscript revision. The abstract for this study was presented at the AMCP Nexus 2015; October 26-29, 2015; Orlando, Florida.

Real-world persistence with fingolimod for the treatment of multiple sclerosis: A systematic review and meta-analysis

OBJECTIVE To systematically review reports of fingolimod persistence in the treatment of relapsing-remitting multiple sclerosis (RRMS) across data sources and practice settings, and to develop a consensus estimate of the 1-year real-world persistence rate. METHODS A systematic literature review was conducted (MEDLINE, EMBASE, and abstracts from selected conferences [2013-2015]) to identify observational studies reporting 1-year fingolimod persistence among adult patients with RRMS (sample size ≥50). A random-effects meta-analysis was performed to estimate a synthesized 1-year persistence rate and to assess heterogeneity across studies. RESULTS Of 527 publications identified, 25 real-world studies reporting 1-year fingolimod persistence rates were included. The studies included patients from different data sources (e.g., administrative claims, electronic medical records, or registries), used different definitions of persistence (e.g., based on prescriptions refills, patient report, or prescription orders), and spanned multiple geographic regions. Reported 1-year persistence rates ranged from 72%-100%, and exhibited statistical evidence of heterogeneity (I2 = 93% of the variability due to heterogeneity across studies). The consensus estimate of the 1-year persistence rate was 82% (95% confidence interval: 79%-85%). CONCLUSIONS Across heterogeneous study designs and patient populations found in real-world studies, the consensus 1-year fingolimod persistence rate exceeded 80%, consistent with persistence rates identified in the recently-completed trial, PREFERMS.

The impact of disease-modifying therapy access barriers on multiple sclerosis patients: A mixed methods study. (Preprint)

Background In the United States, people with relapsing-remitting multiple sclerosis (RRMS) can face difficulty accessing disease-modifying therapies (DMTs) because of insurance, pharmacy, or provider policies. These barriers have been associated with poor adherence and negative health outcomes. Objective The goals of this study were to describe the overall occurrence of difficulties and delays associated with gaining access to DMTs among people with RRMS, to assess DMT adherence during periods of reduced access, and to contextualize the patients’ journey from receipt of a prescription for DMT to obtaining and taking their medication when faced with access barriers. Methods We recruited US-based adults self-reporting RRMS from a Web-based health data-sharing social network, PatientsLikeMe. Individuals were invited to complete a Web-based survey if they reported a diagnosis of RRMS and were prescribed a DMT for MS. Follow-up phone interviews were conducted with 10 respondents who reported experiencing an MS-related relapse during the time they had experienced challenges accessing DMTs. Results Among 507 survey completers, nearly half were either currently experiencing an issue related to DMT assess or had difficulty accessing a DMT in the past (233/507, 46.0%). The most frequently reported reasons for access difficulty were authorization requirements by insurance companies (past issues: 78/182, 42.9%; current issues: 9/42, 21%) and high out-of-pocket costs (past issues: 54/182, 29.7%; current issues: 13/42, 31%). About half (20/39, 51%) of participants with current access issues and over a third (68/165, 41.2%) of those with past issues went without their medication until they could access their prescribed DMT. Relapses were reported during periods of reduced DMT access for almost half (56/118, 47.5%) of those with past issues and nearly half (22/45, 49%) of those with current issues. Resolving access issues involved multiple stakeholder agents often coordinated in a patient-led effort. Among those who had resolved issues, about half (57/119, 47.9%) reported that doctors or office staff were involved, under half (48/119, 40.3%) were involved themselves, and about a third (39/119, 32.8%) reported the drug manufacturer was involved in resolving the issue. Follow-up interviews revealed that the financial burden associated with obtaining a prescribed DMT led to nonadherence. Additionally, participants felt that DMT treatment delays and stress associated with obtaining the DMT triggered relapses or worsened their MS. Conclusions This study expands current research by using a patient-centered, mixed-methods approach to describe barriers to MS treatment, the process to resolve barriers, and the perceived impact of treatment barriers on outcomes. Issues related to DMT access occur frequently, with individuals often serving as their own agents when navigating access difficulties to obtain their medication(s). Support for resolution of DMT access is needed to prevent undue stress and nonadherence.

Health care costs and comorbidities for patients with inclusion body myositis

Abstract Objective: This study identifies the health care costs and utilization, as well as comorbidities, in a Medicare population of inclusion body myositis (IBM) patients. Methods: Medicare patients aged ≥65 years with a diagnosis claim for IBM were identified and matched to a cohort of non-IBM patients based on age, sex, race, calendar year and census region. Generalized linear models were used to estimate health care costs and utilization during the follow-up period. Results: The prevalence of IBM in this population, aged ≥65 years, was 83.7 cases per 1 million patients. Mean 1 year costs for the IBM cohort (N = 361) were

Adherence, persistence, and discontinuation among Hispanic and African American patients with multiple sclerosis treated with fingolimod or glatiramer acetate

44,838 compared to

Real-World Durability of Long-Term Relapse Rates Among Patients with Multiple Sclerosis Receiving Fingolimod Therapy: A Retrospective US Claims Database Analysis (P3.074)

10,182 for the matched non-IBM cohort (N = 1805), an excess of

Comparison of Baseline Characteristics of Glatiramer Acetate Versus Fingolimod in Multiple Sclerosis Patients on Brain Volume, Cognition and Neuro-QOL Outcomes: Preliminary Analysis of a Longitudinal Observational Study (P6.170)

34,656. IBM was significantly associated with multiple unsuspected comorbidities, including hypertension (66% vs. 22%), hyperlipidemia (47% vs. 18%) and myocardial infarction (13% vs. 2%) (all p < .0001). Conclusions: IBM patients utilize more health care resources and incur higher health care costs than patients without IBM. Furthermore, IBM patients were more likely to have multiple comorbidities, including cardiovascular risk factors and events, muscle and joint pain, and pulmonary complications compared to those without IBM. Limitations: The presence of a diagnosis code for a condition on a medical claim does not necessarily indicate the presence of the disease condition because the diagnosis code could be incorrectly entered in the database. Clinical and disease-specific parameters were not available in the claims data. Additionally, due to the observational study design, the analysis may be affected by unobserved differences between patients.

Real World Relapse Rates of Glatiramer Acetate Patients Switching to Fingolimod or Interferon Beta-1a Versus Remaining on Glatiramer Acetate (P6.181)

Abstract Objective: Few studies have examined compliance to disease-modifying therapies (DMTs) for multiple sclerosis (MS) in minority populations. This study compared adherence, discontinuation, and persistence for fingolimod (FTY) and glatiramer acetate (GA) initiators among Hispanic and African American patients with MS. Methods: This retrospective claims data study examined Hispanic and African American adults with MS who initiated FTY or GA between September 1, 2010 and June 30, 2014. Outcomes (adherence, discontinuation, and persistence) were analyzed descriptively and with multivariable models, comparing FTY and GA cohorts within racial/ethnic groups. Adherence was assessed using medication possession ratio (MPR) and proportion of days covered (PDC). Results: There were 171 patients in the Hispanic group (62 FTY, 109 GA) and 210 in the African American group (71 FTY, 139 GA). A larger proportion of GA initiators than FTY initiators were treatment-naïve; other baseline characteristics were similar between cohorts. Hispanic FTY initiators had greater mean MPR, PDC, and persistence and less discontinuation than GA initiators. African American FTY initiators had greater mean PDC than GA initiators; other outcomes favored FTY but were not statistically significant. Multivariable analysis results were consistent with the unadjusted results, but differences between treatment cohorts were not statistically significant. Conclusions: Hispanic and African American patients with MS who initiated FTY had higher adherence than those who initiated GA, similar to the general MS population. These findings suggest that adherence should be considered in DMT selection, and racial/ethnic variations in MS disease course may not be primarily attributable to differences in DMT compliance.