Neetu Agashivala

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.

Direct and indirect cost burden associated with multiple sclerosis relapses: Excess costs of persons with MS and their spouse caregivers

BACKGROUND MS relapses are unpredictable and can be concerning to patients and their caregivers. OBJECTIVE To assess the direct and indirect cost burden associated with relapses of different severities in MS patients and with MS relapse frequency on spouse caregivers. METHODS Using a U.S. insurance claims and employee disability database (1999-2011), we studied adult MS patients (ICD-9-CM: 340.x) and their spouse caregivers. A previously published algorithm to identify relapses was used to stratify: (1) MS patients into cohorts of no, low/moderate, and high severity relapse based on the most severe relapse within one year of follow-up (if any); (2) caregivers into cohorts of no, less, and more frequent relapses based on the overall frequency of relapses of their spouse. Adjusted cost differences and 95% confidence intervals evaluating the yearly incremental costs at 12 months of follow-up (MS patients) and overall (caregivers) associated with relapses are reported. RESULTS Among the 9421 MS patients (N: no relapse=7686; low/moderate severity relapse=1220; high severity relapse=515) identified, both relapse cohorts incurred significantly higher annual incremental direct costs than the no relapse cohort (low/moderate severity=

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

8269 [6565-10,115]; high severity=

Cost-Effectiveness of Early Initiation of Fingolimod Versus Delayed Initiation After 1 Year of Intramuscular Interferon Beta-1a in Patients with Multiple Sclerosis

24,180 [20,263-28,482]) and indirect costs (low/moderate severity=

Impact of a switch to fingolimod versus staying on glatiramer acetate or beta interferons on patient- and physician-reported outcomes in relapsing multiple sclerosis: post hoc analyses of the EPOC trial

1429 [759-2147]; high severity=

Resource utilization, costs and treatment patterns of switching and discontinuing treatment of MS patients with high relapse activity

2714 [1468-4035]). More frequent relapses versus no relapse also translated into a significantly greater cost burden for caregivers (direct+indirect=

Treatment selection and experience in multiple sclerosis: survey of neurologists.

1725 [376-2885]) but less frequent relapses did not. CONCLUSIONS Relapse severity was significantly and increasingly associated with greater direct and indirect costs in MS patients. More frequent relapses also translated into a significant cost burden in spouse caregivers.

Patient perspectives on switching disease-modifying therapies in the NARCOMS registry

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.

First-dose effects of fingolimod after switching from injectable therapies in the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis

BACKGROUND Fingolimod is a once-daily orally administered disease-modifying therapy (DMT) indicated for treatment of relapsing forms of multiple sclerosis (MS) to reduce the frequency of clinical relapses and delay accumulation of physical disability. In the randomized, double-blind, phase 3 TRANSFORMS trial, 0.5 mg/d oral fingolimod substantially reduced relapse frequency when compared with IM interferon-β1a (IFN-β1a) at 12-months. In a 12-month, double-blind, extension phase of the TRANSFORMS study, patients assigned to receive fingolimod continued to receive the same dosage, whereas patients who originally received IM IFN-β1a were randomized to receive either 0.5 or 1.25 mg/d fingolimod. OBJECTIVE To investigate the cost-effectiveness of initiating fingolimod therapy early versus after 1 year of IFN-β1a therapy using TRANSFORMS study extension data. METHODS A Microsoft Excel-based model was used to calculate the cost per relapse avoided for 2 years with continuous treatment with fingolimod compared with first-year treatment with IM IFN-β1a and second-year treatment with fingolimod. One-way sensitivity analyses were conducted on key input variables to assess their effect on cost per relapse avoided. RESULTS The 2-year relapse rate in the early fingolimod arm was 0.23, and in the delayed fingolimod arm was 0.53. The cost per relapse avoided was