Treatment patterns in multiple sclerosis: administrative claims analysis over 10 years.

OBJECTIVE: Treatment patterns for the MS disease-modifying therapies (DMT) have changed over time. The objective of this study was to examine and describe treatment patterns in MS over a 10-year period. METHODS: MS patients who filled a DMT prescription between January 1, 2001 and December 31, 2010 were identified from Clinformatics for DataMart affiliated with OptumInsight. Two cohorts were identified: those with a DMT prescription in 2003 and those with a DMT prescription in 2008. Treatment patterns were examined 2 years before and after the anchor prescriptions for each cohort. RESULTS: Comparing treatment patterns prior to the two anchor prescriptions, interferon-beta (IFNß)-1a IM (Avonex) and IFNß-1b (Betaseron) gained the most users in 2001-2003, while IFNß-1a IM and IFNß-1a SC (Rebif) gained the most users from 2006-2008. In the 2 years following the two anchor prescriptions, treatment patterns changed. From 2003-2005, 21.2% of IFNß-1a SC users and more than 15.0% of IFNß-1a IM and IFNß-1b users changed to another interferon or glatiramer acetate (GA; Copaxone), while 12.5% of GA users changed to an interferon, most often IFNß-1a SC. From 2008-2010 the largest proportion of changes from each of the interferons and natalizumab (NZ; Tysabri) were to GA, while those switching from GA were most often changed to IFNß-1a SC. Those with a 2008 anchor prescription for NZ were most often changed (57%) to GA. LIMITATIONS: In retrospective database analyses the presence of a claim for a filled prescription does not indicate that the drug was consumed, and reasons for changes in therapy are not available. The study design looking forward and backward from the anchor prescriptions may have contributed to differences in the proportion of patients seen with no observable change in DMT. Claims-based data are also constrained by coverage limitations that determine the data available and limit the generalizability of results to managed care patients. CONCLUSIONS: Changes in treatment patterns in the first half of the observation period were reflective of the addition of IFNß-1a SC to the market in 2002. Following the 2003 and 2008 anchor prescriptions there were differences in treatment patterns, with more IFNß-1a IM users being changed to IFNß-1a SC after the 2003 anchor DMT, and more of each of the interferons and NZ being changed to GA following the 2008 anchor DMT. With the introduction of oral therapies for MS, treatment patterns will again be impacted.

Burden of a multiple sclerosis relapse: the patient's perspective.

BACKGROUND: Relapses are a common feature of relapsing-remitting multiple sclerosis (RRMS) and increasing severity has been shown to be associated with higher healthcare costs, and to result in transient increases in disability. Increasing disability likely impacts work and leisure productivity, and lowers quality of life. OBJECTIVE: The objective of this study was to characterize from the patient's perspective the impact of a multiple sclerosis (MS) relapse in terms of the economic cost, work and leisure productivity, functional ability, and health-related quality of life (HR-QOL), for a sample of patients with RRMS in the US treated with immunomodulatory agents. METHODS: A cross-sectional, web-based, self-report survey was conducted among members of MSWatch.com, a patient support website now known as Copaxone.com. Qualified respondents in the US had been diagnosed with RRMS and were using an immunomodulatory agent. The survey captured costs of RRMS with questions about healthcare resource utilization, use of community services, and purchased alterations and assistive items related to MS. The Work and Leisure Impairment instrument and the EQ-5D were used to measure productivity losses and HR-QOL (health utility), respectively. The Goodin MS neurological impairment questionnaire was used to measure functional disability; questions were added about relapses in the past year. RESULTS: Of 711 qualified respondents, 67% reported having at least one relapse during the last year, with a mean of 2.2 ± 2.3 relapses/year. Respondents who experienced at least one relapse had significantly higher mean annual direct and indirect costs compared with those who did not experience a relapse ($US38 458 vs $US28 669; p = 0.0004) [year 2009 values]. Direct health-related costs accounted for the majority of the increased cost ($US5201; 53%) and were mainly due to increases in hospitalizations, medications, and ambulatory care. Indirect costs, including informal care and productivity loss, accounted for the additional 47% of increased cost ($US4588). Accounting for the mean number of relapses associated with these increased costs, the total economic cost of one relapse episode could be estimated at about $US4449, exclusive of intangible costs. The mean self-reported Expanded Disability Status Scale (EDSS) score, derived from the Goodin MS questionnaire, was significantly higher with relapse than with a clinically stable state (EDSS 4.3 vs 3.7; p < 0.0001), while the mean health utility score was significantly lower with relapse compared with a clinically stable state (0.66 vs 0.75; p = 0.0001). The value of these intangible costs of relapse can be estimated at $US5400. The overall burden (direct, indirect, and intangible costs) of one relapse in patients treated with immunomodulatory agents is therefore estimated conservatively at $US9849. CONCLUSIONS: This study shows that from a patient's perspective an MS relapse is associated with a significant increase in the economic costs as well as a decline in HR-QOL and functional ability.

Medical chart validation of an algorithm for identifying multiple sclerosis relapse in healthcare claims.

OBJECTIVE: Relapse is a common measure of disease activity in relapsing-remitting multiple sclerosis (MS). The objective of this study was to test the content validity of an operational algorithm for detecting relapse in claims data. METHODS: A claims-based relapse detection algorithm was tested by comparing its detection rate over a 1-year period with relapses identified based on medical chart review. According to the algorithm, MS patients in a US healthcare claims database who had either (1) a primary claim for MS during hospitalization or (2) a corticosteroid claim following a MS-related outpatient visit were designated as having a relapse. Patient charts were examined for explicit indication of relapse or care suggestive of relapse. Positive and negative predictive values were calculated. RESULTS: Medical charts were reviewed for 300 MS patients, half of whom had a relapse according to the algorithm. The claims-based criteria correctly classified 67.3% of patients with relapses (positive predictive value) and 70.0% of patients without relapses (negative predictive value; kappa 0.373: p < 0.001). Alternative algorithms did not improve on the predictive value of the operational algorithm. Limitations of the algorithm include lack of differentiation between relapsing-remitting MS and other types, and that it does not incorporate measures of function and disability. CONCLUSIONS: The claims-based algorithm appeared to successfully detect moderate-to-severe MS relapse. This validated definition can be applied to future claims-based MS studies.

Glatiramer acetate and interferon beta-1a for intramuscular administration: a study of outcomes among multiple sclerosis intent-to-treat and persistent-use cohorts.

OBJECTIVE: To study outcomes of multiple sclerosis (MS) patients treated with either glatiramer acetate (Copaxone) or interferon beta-1a for once-weekly, intramuscular administration (Avonex). METHODS: An 'intent-to-treat' (ITT) cohort (n=1282) was established, consisting of patients diagnosed with MS who began therapy on either glatiramer acetate (GA) or intramuscular interferon beta-1a (IFN beta-1a-IM) and had continuous insurance coverage from 6 months before to 24 months after the date when they began taking the medication. A 'persistent use' (PU) cohort (n=639) was also constructed, consisting of individuals who, in addition to the criteria listed above, had a claim for GA or IFN beta-1a-IM within 28 days of the end of the 2-year post-period. Data were obtained from the i3 InVision Data Mart Database from July 2001 to June 2006. Multivariate regressions were used to examine both the 2-year total direct medical costs and the likelihood of relapse associated with the use of each of these alternative MS medications. A relapse was defined as either being hospitalized with a principal diagnosis of MS or having an outpatient visit with a MS diagnosis followed within 7 days by a claim for a corticosteroid. All regressions controlled a wide range of factors that may potentially affect outcomes. RESULTS: In the ITT cohort, patients who started therapy on GA had a significantly lower 2-year risk of relapse (10.01 vs. 5.18%; p=0.0034) as well as significantly lower 2-year total medical costs ($44,201 vs. $41,121; p=0.0294). In the PU cohort, patients who used GA also had a significantly lower 2-year risk of relapse (7.25 vs. 2.16%; p=0.0048) as well as significantly lower total medical costs ($67,744 vs. 63,714; p=0.0445). LIMITATIONS: The analyses relies on an administrative claims database of an insured population and hence, may not be generalizeable to other populations. In addition, such a database precludes measurement of lost work time, unemployment, caregiver burden or other costs associated with MS. CONCLUSIONS: Results from this study indicate that the use of GA is associated with significantly lower probability of relapse as well as significantly lower 2-year total direct medical costs than IFN beta-1a-IM.

Cost effectiveness of glatiramer acetate and natalizumab in relapsing-remitting multiple sclerosis.

BACKGROUND: Disease-modifying drugs are a significant expenditure for treating multiple sclerosis. Natalizumab (NZ) has been shown to be effective in reducing relapses and disease progression. However, assessment of the cost effectiveness of NZ compared with other disease-modifying drugs in the presence of long-term data has been limited. OBJECTIVE: To assess the lifetime cost effectiveness from the US healthcare and societal perspectives of glatiramer acetate (GA) and NZ (both given with symptom management) relative to symptom management alone in patients with relapsing-remitting multiple sclerosis (RRMS) using evidence from long-term published studies. METHODS: A Markov model was developed with patients transitioning through health states based on Kurtzke's expanded disability status scale (EDSS). Patients were >/=18 years of age with RRMS, EDSS <6.0 and receiving treatment. Treatment effects were obtained from clinical trials for years 1 and 2 of therapy and long-term clinical assessments thereafter. Transitions were adjusted for discontinuation and persistent NZ antibodies. Patients incurred drug, other medical and lost worker productivity costs. Patient quality of life was considered in the form of utilities, which were taken from assessments of patients with MS. Costs were valued in 2007 $US, and costs and outcomes were discounted at 3% per annum. Various parameters and assumptions were tested in one-way sensitivity analyses, and scenario-based analyses were also performed. RESULTS: Remaining lifetime, direct medical costs for patients receiving GA or NZ versus symptom management were $US408 000, $US422 208 and $US341 436, respectively. Patients receiving GA or NZ benefited from increased years in EDSS 0.0-5.5 (1.18 and 1.09, respectively), years relapse-free (1.30 and 1.18) and QALYs (0.1341 and 0.1332). The incremental cost per QALY for GA or NZ compared with symptom management was $US496 222 and $US606 228, respectively, excluding lost worker productivity costs. GA was associated with a cost saving compared with NZ. The incremental cost per QALY results were sensitive to changes in time horizon, disease progression and drug costs. Improved QALYs for NZ were sensitive to changes in the clinical effect of NZ on disease progression and discontinuation over time. CONCLUSIONS: GA or NZ in RRMS patients is associated with increased benefits compared with symptom management, albeit at higher costs. Although year 1 and 2 disease progression and relapse rates were better for NZ than GA, long-term evidence may show GA to have similar, if not improved, clinical benefit.

Glatiramer acetate and interferon beta-1b: a study of outcomes among patients with multiple sclerosis.

INTRODUCTION: To study the medical cost and probability of relapse in patients with multiple sclerosis (MS) treated with either glatiramer acetate (GA) or interferon beta-1b (IFN beta.1b). METHODS: Data were obtained from the i3 InVision Data Mart Database from July 2001 to June 2006. We established an "intent-totreat" (ITT) cohort (n=842) of patients diagnosed with MS who began treatment with either GA or IFN beta-1b and had continuous insurance coverage from 6 months before to 2 years after the date when they began taking the medication. We also created a "continuous use" (CU) cohort (n=418) of individuals who, in addition to the criteria listed above, used either GA or IFN beta-1b within 28 days of the end of the 2-year postperiod. Using multivariate regressions, we examined both the 2-year total average direct medical costs and the likelihood of relapse within this period associated with the use of each of these MS medications. We defined relapse as being either hospitalization with a principal diagnosis of MS or having an outpatient visit with a diagnosis of MS and then prescribed steroids within a 7-day period. All regression analyses controlled for a wide range of factors that may potentially affect outcomes. RESULTS: In the ITT cohort, patients who started treatment with GA had a significantly lower 2-year estimated risk of relapse (13.54% vs. 5.31%; P=0.0006). In the CU cohort, patients who used GA also had a significantly lower 2-year estimated risk of relapse (10.91% vs. 2.09%; P=0.0018), as well as significantly lower average total medical costs ($53,157 vs. $48,130; P=0.0345). CONCLUSIONS: Results from this study indicate that users of GA have a significantly lower probability of 2-year relapse than users of IFN beta-1b. In addition, among continuous users, the 2-year total average direct medical costs are significantly lower for users of GA than for users of IFN beta-1b.

Glatiramer acetate versus interferon beta-1a for subcutaneous administration: comparison of outcomes among multiple sclerosis patients.

INTRODUCTION: We compared the outcomes of multiple sclerosis (MS) patients treated with either glatiramer acetate (GA) (Copaxone, Teva Pharmaceutical Industries, Israel) or interferon beta-1a for subcutaneous administration (IFN beta-1a-SC) (Rebif, Merck Serono, Switzerland). METHODS: Data were obtained from i3's Lab Rx Database from July 2001 to June 2006. We established an 'intent-to-treat' (ITT) cohort (n=845) of patients diagnosed with MS who began therapy on either GA (n=542) or IFN beta-1a-SC (n=303) and had continuous insurance coverage from 6 months before to 24 months after the date they began taking the medication. We also created a 'continuous use' (CU) cohort (n=410) of individuals who, in addition to the criteria listed above, used either GA or IFN beta-1a-SC within 28 days of the end of the 2-year-post period. Using multivariate regressions, we examined both the 2-year total direct medical costs and the likelihood of relapse associated with the use of these two MS medications. We defined relapse as either being hospitalised with a diagnosis of MS, or being diagnosed with MS during an outpatient visit and then prescribed steroids within a 7-day period. All regressions controlled a wide range of factors that have potentially affected outcomes. RESULTS: In the ITT cohort, patients who started therapy on GA had a significantly lower 2-year risk of relapse (5.92% versus 10.89%; P=0.0305), as well as significantly lower 2-year total medical costs (US$41,786 versus US$49,030; P=0.0002). In the CU cohort, patients who used GA also had a significantly lower 2-year risk of relapse (1.94% versus 9.09%; P=0.0049) and significantly lower total medical costs (US$45,213 versus US$57,311; P<0.0001). CONCLUSIONS: Results indicate that, compared with the use of IFN beta-1a-SC, use of GA is associated with significantly lower probability of relapse as well as significantly lower 2-year total direct medical costs. In addition, these results are more pronounced among patients defined as continuous users.

Cost-effectiveness of four immunomodulatory therapies for relapsing-remitting multiple sclerosis: a Markov model based on long-term clinical data.

BACKGROUND: Before the introduction of the immunomodulatory therapies for multiple sclerosis (MS), treatment options for MS consisted of symptomatic management (physical therapy and pharmacological treatment for symptom management). Symptomatic management for MS has been supplemented in the past decade by 2 new classes of immunomodulatory therapies that have been approved as first-line treatments for relapsing-remitting multiple sclerosis (RRMS): subcutaneous glatiramer acetate (SC GA) and 3 beta-interferons: intramuscular interferon beta-1a (IM IFNbeta-1a), SC IFNbeta-1a, and SC IFNbeta-1b. OBJECTIVE: To estimate the economic outcomes of 5 treatment strategies: symptom management alone, symptom management combined with SC GA, IM IFNbeta1-a, SC IFNbeta1-a, or SC IFNbeta1-b in patients diagnosed with RRMS. METHODS: A literature-based Markov model was developed to assess the cost-effectiveness of 5 treatment strategies for managing a hypothetical cohort of patients diagnosed with RRMS in the United States--4 immunomodulatory drug therapies and symptom management alone. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS), a widely accepted scale for assessing RRMS (higher EDSS scores = increased disease severity). Baseline relapse and disease progression transition probabilities for symptom management were obtained from natural history studies. Treatment effects of the immunomodulatory therapies were estimated by applying a percentage reduction to the symptom management transition probabilities for relapse (27% reduction) and disease progression (30% reduction). Transition probabilities were subsequently adjusted to account for (1) the effects of neutralizing antibodies, specifically on relapse rates by assuming no additional therapy benefits after the second year of continuous therapy, and (2) treatment discontinuation. Therapy-specific data were obtained from clinical trials and long-term follow-up observational studies. Transitions among health states occurred in 1-month cycles for the lifetime of a patient. Costs (2005 US$) and outcomes were discounted at 3% annually. RESULTS: The incremental cost per quality-adjusted life-year for the 4 immunomodulatory therapies is $258,465, $303,968, $416,301, and $310,691 for SC GA, IM IFNbeta-1a, SC IFNbeta-1a, and SC IFNbeta-1b, respectively, compared with symptom management alone. Sensitivity analyses demonstrated that results were sensitive to changes in utilities, disease progression rates, time horizon, and immunomodulatory therapy cost. CONCLUSIONS: The pharmacoeconomic model determined that SC GA was the best strategy of the 4 immunomodulatory therapies used to manage MS and resulted in better outcomes than symptom management alone. Sensitivity analyses indicated that the model was sensitive to changes in a number of key parameters, and thus changes in these key parameters would likely influence the estimated cost-effectiveness results. Head-to-head randomized clinical trials comparing the immunomodulatory therapies for the treatment of MS are necessary to validate the projections from the pharmacoeconomic analyses, particularly since the results available today from the clinical trials do not account adequately for treatment dropouts.

Clinical and economic impact of glatiramer acetate versus beta interferon therapy among patients with multiple sclerosis in a managed care population.

OBJECTIVE: To examine the outcomes of use of glatiramer acetate (GA) versus beta interferons-1a (intramuscular) (1A) and -1b (1B) in patients with multiple sclerosis (MS) in a managed care setting. METHODS: Data were obtained from a national retrospective claims database from January 1996 to June 2001. Patients were followed from the first prescription for immunomodulatory therapy until plan disenrollment or end of study time frame. The incidence of all relapses (defined as hospitalization for MS or ambulatory visit followed by use of systemic corticosteroids) as well as utilization and costs of MS-related care were examined for each group. Data were adjusted for variable follow-up using survival techniques. RESULTS: A total of 8,457 patients receiving immunomodulatory therapy were included in the study cohort; follow-up averaged 17.3 months. Three quarters of patients were female; the mean age was 42.2 years. The risk of relapse (defined as number of new cases) at one year was significantly increased for the beta interferons relative to GA (hazard rates: 1.15 and 1.51 for 1A and 1B, respectively, P<0.01). Mean (+/- SD) costs of care also were reduced among GA patients ($9,522 [+/- $9,706] versus $9,957 [+/- $9,083] and $10,185 [+/- $9,526] for 1A and 1B, respectively). These findings persisted in multivariate analyses, controlling for differences in demographic characteristics and propensity scores for immunomodulatory therapy. CONCLUSIONS: Glatiramer acetate is associated with reductions in the incidence of relapse and costs of care relative to the beta interferons among this large group of managed care patients with MS.