Comparative persistence and adherence with newer anti-hyperglycemic agents to treat patients with type 2 diabetes in the United States

Objectives: Non-adherence and non-persistence to anti-hyperglycemic agents are associated with worse clinical and economic outcomes in patients with type 2 diabetes. This study evaluated treatment persistence and adherence across newer anti-hyperglycemic agents (canagliflozin, dapagliflozin, sitagliptin, saxagliptin, linagliptin, liraglutide, or exenatide).

Methods: This retrospective cohort study of Truven Health Analytics Marketscan databases included adult patients with type 2 diabetes whose first pharmacy claim for a newer anti-hyperglycemic agent was between February 1, 2014 and July 31, 2014. Treatment persistence and adherence were assessed for 12 months after the first claim (post-index). Persistence was defined as no gap ≥90 days between the end of one pharmacy claim and the start of the next pharmacy claim post-index. Adherence used two definitions: proportion of days covered (PDC) and medication possession ratio (MPR). Multivariable analyses of non-persistence (hazard ratios) and adherence (odds ratios) were adjusted for baseline demographics, drug cost, clinical characteristics, and other anti-hyperglycemic agents.

Results: A total of 11,961 patients met all study selection criteria. Persistence rates at 12 months were significantly greater (p?p?=?0.83; PDC?=?0.79) and canagliflozin 300?mg (MPR?=?0.92; PDC?=?0.81) were greater than for the other index anti-hyperglycemic agents (MPR?=?0.33–0.75; PDC?=?0.33–0.72). Consistent results for treatment persistence and adherence were observed in multivariable analyses that were adjusted baseline characteristics.

Conclusions: Canagliflozin was associated with better treatment persistence and treatment adherence compared with other anti-hyperglycemic agents in real-world settings.     

The cost-effectiveness of disease-modifying therapies for the treatment of relapsing-remitting multiple sclerosis

Background: The safety and efficacy of disease-modifying therapies (DMTs) for relapsing-remitting multiple sclerosis (RRMS) has been established; however, it is not clear which provides optimal value, given benefit-risk profiles and costs.

Aims: To compare the cost-effectiveness of current DMTs for patients with RRMS in the US.

Materials and methods: A Markov model predicting RRMS course following initiation of a DMT was created comparing outcomes (e.g. relapses, disease progression) and costs of natalizumab (NTZ), dimethyl fumarate (DMF), and peginterferon beta-1a (PEG) with fingolimod (FIN), glatiramer acetate (GA, 20?mg daily), and subcutaneous interferon beta-1a (IFN, 44?mcg), respectively, over 10 years. RRMS and secondary-progressive MS (SPMS) EDSS state transitions were predicted in 3-month cycles in which patients were at risk of death, relapse, or discontinuation. Upon DMT discontinuation, natural history progression and relapse rates were applied. Incremental cost-effectiveness ratios (ICERs) were estimated for the cost per relapse avoided, relapse-free years gained, progression avoided, and progression-free years gained. The impact of model parameters on outcomes was evaluated via one-way sensitivity analyses.

Results: Costs ranged from $561,177 (NTZ) to $616,251 (GA). NTZ, DMF, and PEG were dominant (less costly and more effective) compared to FIN, GA, and IFN, respectively, for all ICERs. Variability in drug costs and parameters that affected drug cost accrual (e.g. discontinuation rates and the decision to drop out after SPMS conversion) had a considerable impact on ICERs.

Limitations: Several simplifying assumptions were made that may represent potential limitations of this analysis (e.g. a constant treatment effect over time was assumed).

Conclusions: The results from this analysis suggest that the NTZ, DMF, and PEG are cost-effective DMT choices compared to FIN, GA, and IFN, respectively. The actual impact on a particular plan will vary based on drug pricing and other factors affecting drug cost accrual.     

Implications of Real-world Adherence on Cost-effectiveness Analysis in Multiple Sclerosis

Abstract

Objectives:

Adherence to medication is essential for optimal outcomes, especially for chronic diseases such as multiple sclerosis (MS). Studies in MS indicate that lower adherence is associated with an increased risk of relapse, hospitalization or emergency room (ER) visits, and higher medical costs. A previous investigation assessed the cost per relapse avoided for patients with MS receiving first-line disease modifying therapies (DMTs); however, the model assumed 100% adherence.

Methods:

Because real-world utilization patterns influence the actual effectiveness of medications, this analysis assessed the impact of real-world adherence from a US commercial payer perspective, using updated costs.

Results:

As was seen in the original study, in this revised model, fingolimod was associated with the lowest cost per relapse avoided ($90,566), followed by SC IFN β-1b (Extavia: $127,024), SC IFN β-1b (Betaseron: $137,492), SC IFN β-1a ($144,016), glatiramer acetate ($160,314), and IM IFN β-1a ($312,629). The model inputs that had the greatest impact on the results were adherence-adjusted relative relapse rate reduction (RRR) of fingolimod, the wholesale acquisition costs of fingolimod, and the average number of relapses in untreated patients with MS.

Limitations:

The estimates of DMT adherence are from a single claims database study of a large national pharmacy benefit manager that only measured adherence, not actual relapses, and the model does not incorporate manufacturer discounts and rebates, which are not publicly available.

Conclusion:

These results suggest that economic analyses of MS therapies should incorporate real-world adherence rates where available, rather than relying exclusively on trial-based efficacy estimates when considering the economic value of treatment alternatives, and that highly efficacious therapies with low adherence may yield real-world efficacy that is substantially lower than that observed in closely monitored clinical trials.     

The impact of persistence with therapy on inpatient admissions and emergency room visits in the US among patients with multiple sclerosis

Objective:

Disease-modifying therapy (DMT) for multiple sclerosis (MS) can reduce relapses and delay progression; however, poor adherence and persistence with DMT can result in sub-optimal outcomes. The associations between DMT adherence and persistence and inpatient admissions and emergency room (ER) visits were investigated.

Methods:

Patients with MS who initiated a DMT in a US administrative claims database were followed for 1 year. Persistence to initiated DMT was measured as the time from DMT initiation to discontinuation (a gap of >60 days without drug ‘on hand’) or end of 1-year follow-up. Adherence to initiated DMT was measured during the persistent period and was operationalized as the medication possession ratio (MPR). Patients with an MPR <0.80 were considered non-adherent. Claims during the 1-year follow-up period were evaluated for the presence of an all-cause inpatient admission or an ER visit. Adjusted odds ratios (AORs) for inpatient admission or ER visit comparing persistent vs non-persistent and adherent vs non-adherent patients were estimated using logistic regression models adjusted for patient characteristics.

Results:

The final sample included 16,218 patients. During the 1-year follow-up period, 35.3% of patients discontinued their initiated DMT and 13.9% were not adherent while on therapy. During that same period, 10.0% of patients had an inpatient admission and 24.9% had an ER visit. The likelihoods of inpatient admission and ER visit were significantly decreased in persistent patients (AOR [95% CI]?=?0.50 [0.45, 0.56] and 0.65 [0.60, 0.69], respectively) and in adherent patients (AOR [95% CI]?=?0.83 [0.71, 0.97] and 0.86 [0.77, 0.95], respectively).

Conclusions:

Persistence and adherence with initiated DMT are associated with decreased likelihoods of inpatient admission or ER visit, which may translate to improved clinical outcomes.     

Randomized,open-label study to evaluate patient-reported outcomes with fingolimod after changing from prior disease-modifying therapy for relapsing multiple sclerosis: EPOC study rationale and design

Abstract

Objective:

The study to Evaluate Patient OutComes, Safety, and Tolerability of Fingolimod (EPOC; NCT01216072) aimed to test the hypothesis that therapy change to oral Gilenya (Novartis AG, Stein, Switzerland) (fingolimod) improves patient-reported outcomes compared with standard-of-care disease-modifying therapy (DMT) in patients with relapsing multiple sclerosis; safety and tolerability were also assessed. This communication describes the study rationale and design.

Methods:

EPOC is a phase 4, open-label, multi-center study conducted in the US and Canada of patients with relapsing forms of multiple sclerosis who are candidates for therapy change. Therapy change eligibility was determined by the treating physician (US patients) or required an inadequate response to or poor tolerance for at least 1 MS therapy (Canadian patients). Patients were randomly assigned in a 3:1 ratio to 6 months of treatment with once-daily oral fingolimod 0.5?mg or standard-of-care DMTs. The primary study end-point was the change from baseline in treatment satisfaction as determined by the global satisfaction sub-scale of the Treatment Satisfaction Questionnaire for Medication. Secondary end-points included changes from baseline in perceived effectiveness and side-effects, and measures of activities of daily living, fatigue, depression, and quality-of-life. A 3-month open-label fingolimod extension was available for patients randomly assigned to the DMT group who successfully completed all study visits.

Results:

Enrollment has been completed with 1053 patients; the patient population is generally older and has a longer duration of disease compared with populations from phase 3 studies of fingolimod.

Limitations:

Inclusion criteria selected for patients with a sub-optimal experience with a previous DMT, limiting the collection of data on therapy change in patients who were satisfied with their previous DMT.

Conclusions:

Results of the EPOC study are anticipated in early 2013 and will inform treatment selection by providing patient-centered data on therapy switch to fingolimod or standard-of-care DMTs.

Trial Registration:

ClinicalTrials.gov NCT01216072.     

Cost-effectiveness of natalizumab versus fingolimod for the treatment of relapsing multiple sclerosis

Abstract

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.     

Cost-minimization analysis of fingolimod compared with natalizumab for the treatment of relapsing–remitting multiple sclerosis in Sweden

Abstract

Background:

Fingolimod and natalizumab have the same European Union licence for the treatment of relapsing multiple sclerosis, and are considered by the Committee for Medicinal Products for Human Use (CHMP) to have broadly similar efficacy.

Objective:

A cost-minimization analysis was performed to compare differences in treatment costs between fingolimod and natalizumab from a societal perspective in Sweden.

Methods:

This analysis included costs associated with initiating and following treatment (physician visits and monitoring), continuing therapy (drugs and administration), and lost patient productivity and leisure time. Unit costs (in Swedish krona [SEK]) were based on regional data (median prices for physician visits and monitoring sessions). Natalizumab infusion costs were obtained from the national cost-per-patient database. Drug costs for both therapies were 15,651 SEK/28 days.

Results:

After 3 years, fingolimod use was associated with savings of 124,823?SEK/patient compared with natalizumab (total cost/patient: 566,718 SEK vs 691,542 SEK). Cost savings with fingolimod were 40,402 SEK/patient after 1 year and 301,730 SEK/patient after 10 years. Treatment with natalizumab was 18% more expensive than fingolimod therapy after 1 year and 23% more expensive after 10 years.

Limitations:

Based on the CHMP assessment, it was assumed that fingolimod and natalizumab have similar efficacy. The analysis was conducted for Sweden, and caution is needed in extrapolating the results to other countries.

Conclusion:

Fingolimod is cost-saving compared with natalizumab for the treatment of relapsing–remitting multiple sclerosis in Sweden.     

When does economic model type become a decisive factor in health technology appraisals? Learning from the expanding treatment options for relapsing–remitting multiple sclerosis

Objectives: Specific economic model types often become de facto standard for health technology appraisal over time. Markov and discrete event simulation (DES) models were compared to investigate the impact of innovative modeling on the cost-effectiveness of disease-modifying therapies (DMTs) in relapsing–remitting multiple sclerosis (RRMS). Fingolimod was compared to dimethyl fumarate (DMF; in highly active [HA] RRMS), alemtuzumab (in HA RRMS) and natalizumab (in rapidly evolving severe RRMS). Comparator DMTs were chosen to reflect different dosing regimens.

Materials and methods: Markov and DES models used have been published previously. Inputs were aligned in all relevant respects, with differences in the modeling of event-triggered attributes, such as relapse-related retreatment, which is inherently difficult with a memoryless Markov approach. Outcomes were compared, with and without different attributes.

Results: All results used list prices. For fingolimod and DMF, incremental cost-effectiveness ratios (ICERs) were comparable (Markov: £4206/quality-adjusted life year [QALY] gained versus DES: £3910/QALY gained). Deviations were observed when long-term adverse events (AEs) were incorporated in the DES (Markov: £25,412 saved/QALY lost, versus DES: £34,209 saved/QALY lost, fingolimod versus natalizumab; higher ICERs indicate greater cost-effectiveness). For fingolimod versus alemtuzumab, when relapse-triggered retreatment was included in the DES, large cost differences were observed (difference between incremental cost is £35,410 and QALY is 0.10).

Limitations: UK payer perspective, therefore societal approach was not considered. Resource utilization and utilities for both models were not derived from the subpopulations; as the focus is on model type, input limitations that apply to both models are less relevant.

Conclusions: Whilst no model can fully represent a disease, a DES allows an opportunity to include features excluded in a Markov structure. A DES may be more suitable for modeling in RRMS for health technology assessment purposes given the complexity of some DMTs. This analysis highlights the capabilities of different model structures to model event-triggered attributes.     

Cost-effectiveness of natalizumab vs fingolimod for the treatment of relapsing-remitting multiple sclerosis: analyses in Sweden

Abstract

Objective:

To assess the cost-effectiveness of natalizumab vs fingolimod over 2 years in relapsing-remitting multiple sclerosis (RRMS) patients and patients with rapidly evolving severe disease in Sweden.

Methods:

A decision analytic model was developed to estimate the incremental cost per relapse avoided of natalizumab and fingolimod from the perspective of the Swedish healthcare system. Modeled 2-year costs in Swedish kronor of treating RRMS patients included drug acquisition costs, administration and monitoring costs, and costs of treating MS relapses. Effectiveness was measured in terms of MS relapses avoided using data from the AFFIRM and FREEDOMS trials for all patients with RRMS and from post-hoc sub-group analyses for patients with rapidly evolving severe disease. Probabilistic sensitivity analyses were conducted to assess uncertainty.

Results:

The analysis showed that, in all patients with MS, treatment with fingolimod costs less (440,463 Kr vs 444,324 Kr), but treatment with natalizumab results in more relapses avoided (0.74 vs 0.59), resulting in an incremental cost-effectiveness ratio (ICER) of 25,448 Kr per relapse avoided. In patients with rapidly evolving severe disease, natalizumab dominated fingolimod. Results of the sensitivity analysis demonstrate the robustness of the model results. At a willingness-to-pay (WTP) threshold of 500,000 Kr per relapse avoided, natalizumab is cost-effective in >80% of simulations in both patient populations.

Limitations:

Limitations include absence of data from direct head-to-head studies comparing natalizumab and fingolimod, use of relapse rate reduction rather than sustained disability progression as the primary model outcome, assumption of 100% adherence to MS treatment, and exclusion of adverse event costs in the model.

Conclusions:

Natalizumab remains a cost-effective treatment option for patients with MS in Sweden. In the RRMS patient population, the incremental cost per relapse avoided is well below a 500,000 Kr WTP threshold per relapse avoided. In the rapidly evolving severe disease patient population, natalizumab dominates fingolimod.     

Comparison of utilization,cost, adherence,and hypoglycemia in patients with type 2 diabetes initiating rapid-acting insulin analog with prefilled pen versus vial/syringe

Abstract

Background:

Studies examining outcomes of different insulin delivery systems are limited. The objective of this study was to compare healthcare utilization, costs, adherence, and hypoglycemia rates in patients with type 2 diabetes mellitus (T2DM) initiating rapid-acting insulin analog (RAIA) using prefilled pen versus vial/syringe.

Methods:

A retrospective analysis was conducted using a US claims database (1/1/2007 to 12/31/2008). Inclusion criteria were: ≥18 years old, with T2DM, ≥12 months of continuous eligibility, and new to RAIA. Difference-in-difference analyses after propensity score matching were conducted to compare changes in outcomes from 6 months prior to and 6 months after initiating RAIA with a prefilled pen versus vial/syringe (Wilcoxon rank-sum test for costs and t-test for other outcomes). Categories of utilization and costs (2009 USD) included total and diabetes-related inpatient, outpatient, and emergency room. Adherence was measured by proportion of days covered (PDC). Hypoglycemia was identified using ICD-9-CM codes.

Results:

Baseline characteristics were similar between the prefilled pen (n?=?239) and vial/syringe (n?=?590) cohorts after matching. Adherence to RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (PDC: 54.6 vs. 45.2%, p?<?0.001). While the increase in diabetes-related pharmacy costs from before to after initiating RAIA was greater in the prefilled pen cohort than the vial/syringe cohort (+$900 vs. +$607, p?<?0.001), the prefilled pen cohort was associated with greater reductions in the total diabetes-related costs (–$235 vs. +$61, p?=?0.006) and the utilization of oral anti-hyperglycemic agents (–1.3 vs. –0.7, p?=?0.016). There were no significant differences in other outcomes.

Limitations:

Claims databases do not provide optimal measures for adherence or T2DM severity, and only capture hypoglycemia events requiring clinical intervention.

Conclusion:

Initiating RAIA with a prefilled pen was associated with better adherence and greater reduction in total diabetes-related costs than a vial/syringe. There was no significant difference in total healthcare costs.     

Economic outcomes of exenatide vs liraglutide in type 2 diabetes patients in the United States: results from a retrospective claims database analysis

Abstract

Objective:

The safety and efficacy of the GLP-1 receptor agonists exenatide BID (exenatide) and liraglutide for treating type 2 diabetes mellitus (T2DM) have been established in clinical trials. Effective treatments may lower overall treatment costs. This study examined cost offsets and medication adherence for exenatide vs liraglutide in a large, managed care population in the US.

Methods:

This was a retrospective cohort analysis comprising adult patients with T2DM who initiated exenatide or liraglutide between 1/1/2010 and 6/30/2010 and had 6 months pre-index and post-index continuous eligibility. Patients were propensity score-matched to controls for baseline differences. Medication adherence was measured by proportion of days covered (PDC). Paired t-test and McNemar’s test were used to compare outcomes.

Results:

Matched exenatide and liraglutide cohorts (n?=?1347 pairs) had similar average total 6-month follow-up costs ($6688 vs $7346). However, exenatide patients had significantly lower mean pharmacy costs ($2925 vs $3272, p?<?0.001). Among liraglutide patients, patients receiving the 1.8?mg dose had significantly higher average total costs compared to those receiving the 1.2?mg dose ($8031 vs $6536, p?=?0.026), with higher mean pharmacy costs in the 1.8?mg cohort ($3935 vs $3146, p?<?0.001). There were no significant differences in inpatient or outpatient costs or medication adherence between groups (mean PDC: exenatide 56% vs liraglutide 57%, p?=?0.088).

Limitations:

The study assumed that all information needed for case classification and matching of cohorts was present and not differential across cohorts. The study did not control for covariates that were unavailable, such as HbA1c and duration of diabetes.

Conclusions:

Patients initiating exenatide vs liraglutide for T2DM had similar medication adherence and total healthcare costs; however, exenatide patients had significantly lower total pharmacy costs. Patients prescribed 1.8?mg liraglutide had significantly higher costs compared to those on 1.2?mg.     

Adherence,persistence, and inpatient utilization among adult schizophrenia patients using once-monthly versus twice-monthly long-acting atypical antipsychotics

Aims: This study compared healthcare resource utilization (HRU), healthcare costs, adherence, and persistence among adult patients with schizophrenia using once-monthly (OM) vs twice-monthly (TM) atypical long-acting injectable (LAI) antipsychotic (AP) therapy.

Materials and methods: A longitudinal retrospective cohort study was conducted using Medicaid claims data from six states. Patients initiated on aripiprazole or paliperidone palmitate were assigned to the OM cohort; risperidone-treated patients were assigned to the TM cohort. HRU and healthcare costs were assessed during the first 12 months following stabilization on the medication. Adherence was measured using the proportion of days covered (PDC) during the first year of follow-up. Persistence to the index medication was measured during the first 2 years following the index date. Comparison between the cohorts was achieved using multivariable generalized linear models, adjusting for demographic and clinical characteristics.

Results: Patients in the OM LAI cohort had lower inpatient HRU and medical costs when compared with patients in the TM cohort. Higher medical costs in the TM LAI cohort offset the higher pharmacy costs in the OM LAI cohort. Mean PDC during the first 12 months of follow-up was higher in the OM cohort than in the TM cohort (0.56 vs 0.50, p?<?.01). Median persistence was longer in the OM cohort than in the TM cohort (7.5 months vs 5.5 months), as was the hazard of discontinuing the index medication (hazard ratio?=?0.83, p?=?.01). Kaplan-Meier rates of persistence at 1 year were higher for OM patients than for TM patients (37.6% vs 29.6%, p?<?.01).

Limitations: This was a Medicaid sample with few aripiprazole LAI patients (5.4% of OM cohort). Medication use was inferred from pharmacy claims.

Conclusions: Among Medicaid patients in these six states, OM AP treatment was associated with lower HRU, better adherence and persistence, and similar total costs compared to patients on TM treatment.     

Hospitalization rates in patients switched from oral anti-psychotics to aripiprazole once-monthly: final efficacy analysis

Abstract

Objective:

To compare hospitalization rates in patients with schizophrenia treated prospectively with aripiprazole once-monthly 400?mg (AOM 400; an extended-release injectable suspension) vs the same patients’ retrospective rates with their prior oral anti-psychotic therapy.

Research design and methods:

Multi-center, open-label, mirror-image, naturalistic study in a community setting in North America. Patients who required a change in treatment and/or would benefit from long-acting injectable anti-psychotic therapy were treated prospectively for 6 months with AOM 400. Retrospective data on hospitalization rates were obtained.

Clinical trial registration:

ClinicalTrials.gov: NCT01432444.

Main outcome measures:

The proportion of patients with ≥1 psychiatric inpatient hospitalization with oral anti-psychotic therapy examined retrospectively (months –4 to –1 before oral conversion) and after switching to AOM 400 (months 4–6 after initiating AOM 400).

Results:

Psychiatric hospitalization rates were significantly lower when patients were treated with AOM 400 compared with oral anti-psychotic therapy both in the 3-month primary efficacy sample (2.7% [n?=?9/336] vs 27.1% [n?=?91/336], respectively; p?<?0.0001) and in the total sample (6-month prospective rate: 8.8% [n?=?38/433] vs 6-month retrospective rate: 38.1% [n?=?165/433]; p?<?0.0001). Discontinuations due to adverse events (AEs) during cross-titration were lower in patients cross-titrated on oral aripiprazole for >1 and <4 weeks (2.9% [n?=?7/239]) compared with patients cross-titrated for ≤1 week (10.4% [n?=?5/48]). The most common treatment-emergent AEs during the prospective treatment phase were insomnia (6.7% [n?=?29/431]) and akathisia (6.5% [n?=?28/431]). Patient-rated injection-site pain decreased from the first injection to the last visit.

Conclusions:

In a community setting, patients with schizophrenia demonstrated significantly lower psychiatric hospitalization rates after switching from their prior oral anti-psychotic therapy to AOM 400. Patients served as their own control, and thus an active control group was not included in this study. Confounding factors, such as insurance coverage and availability of hospital beds, were not examined here and deserve further consideration.     

Fingolimod reduces direct medical costs compared to natalizumab in patients with relapsing–remitting multiple sclerosis in The Netherlands

Abstract

Objective:

To assess the costs of oral treatment with Gilenya® (fingolimod) compared to intravenous infusion of Tysabri® (natalizumab) in patients with relapsing–remitting multiple sclerosis (RRMS) in The Netherlands.

Methods:

A cost-minimization analysis was used to compare both treatments. The following cost categories were distinguished: drug acquisition costs, administration costs, and monitoring costs. Costs were discounted at 4%, and incremental model results were presented over a 1, 2, 5, and 10 year time horizon. The robustness of the results was determined by means of a number of deterministic univariate sensitivity analyses. Additionally, a break-even analysis was carried out to determine at which natalizumab infusion costs a cost-neutral outcome would be obtained.

Results:

Comparing fingolimod to natalizumab, the model predicted discounted incremental costs of ?€2966 (95% CI: ?€4209; ?€1801), ?€6240 (95% CI: ?€8800; ?€3879), ?€15,328 (95% CI: ?€21,539; ?€9692), and ?€28,287 (95% CI: ?€39,661; ?€17,955) over a 1, 2, 5, and 10-year time horizon, respectively. These predictions were most sensitive to changes in the costs of natalizumab infusion. Changing these costs of €255 within a range from €165–364 per infusion resulted in cost savings varying from €4031 to €8923 after 2 years. The additional break-even analysis showed that infusion costs—including aseptic preparation of the natalizumab solution—needed to be as low as the respective costs of €94 and €80 to obtain a cost neutral result after 2 and 10 years.

Limitations:

Neither treatment discontinuation and subsequent re-initiation nor patient compliance were taken into account. As a consequence of the applied cost-minimization technique, only direct medical costs were included.

Conclusion:

The present analysis showed that treatment with fingolimod resulted in considerable cost savings compared to natalizumab: starting at €2966 in the first year, increasing to a total of €28,287 after 10 years per RRMS patient in the Netherlands.