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Supplements Best Practices for Natalizumab Utilization in the Treatment of Multiple Sclerosis
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John Foley, MD
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Quantifying the Role of Natalizumab in Health and Economic Outcomes in Multiple Sclerosis
David W. Brandes, MS, MD, FAAN; Fadia T. Shaya, PhD, MPH; and Michael W. Pill, PharmD

Quantifying the Role of Natalizumab in Health and Economic Outcomes in Multiple Sclerosis

David W. Brandes, MS, MD, FAAN; Fadia T. Shaya, PhD, MPH; and Michael W. Pill, PharmD
Natalizumab treatment has similarly been associated with improvements in cognition. Preliminary results from an ongoing study were recently presented by Stephenson et al.16 Among 186 patients with MS enrolled in the TOUCH (Tysabri Outreach: Unified Commitment to Health) Prescribing Program, natalizumab was associated with a significant improvement in cognitive function, as measured by the 6-question Medical Outcomes Study Cognitive Functioning scale (baseline score 24.63 ± 8.50; third infusion score 27.04 ± 7.06 [P <.001]). Also, after only 3 months of treatment, natalizumab was associated with significantly less fatigue as measured by the Modified Fatigue Impact Scale (baseline score 12.72 ± 4.35; third infusion score 10.38 ± 4.83 [P <.001]). Other studies have reported reductions in fatigue following natalizumab treatment.17

The Multiple Sclerosis Functional Composite (MSFC) score is a brief measure of functional capacity that examines ambulation, upper extremity function, and cognitive function with one validated test of each function. In the phase 3 AFFIRM study, natalizumab was associated with a 33% relative reduction in the cumulative probability of MSFC Progression-20 (defined as worsening from baseline on scores for at least 1 MSFC component by 20%) (HR , 0.67; 95% CI , 0.52-0.86; P = .002).18 The improvement in MSFC scores in this study was driven primarily by improved function in cognition and upper extremity assessments.

Overall, natalizumab has been associated with improvements in various aspects of quality of life by providing physical, cognitive, and psychological benefits in patients with MS. How these improvements lead to lower direct or indirect medical costs is only now being studied.

Impact of Natalizumab on Economic Outcomes

Economic Models

To date, available economic studies on natalizumab are limited to mostly budget impact models that quantify the cost of a drug for managed care payers. Chiao and Meyer developed both a cost-effectiveness and budget impact model to address the cost-effectiveness of natalizumab versus other DMTs and the impact of natalizumab on US payers.19 In their model, a hypothetical plan population of 1 million members was used, with an estimated 592 of those members having relapsing MS requiring natalizumab or another DMT.19 The model inputs were drug acquisition costs (wholesale acquisition costs), costs of drug administration and monitoring, costs of treating relapses, anticipated reduction in relapse rates after 2 years of therapy, and estimated market utilization of natalizumab. Outcomes included total 2-year costs of therapy per patient, costs per relapse avoided for each treatment, and overall 2-year costs to the health plan and per-member per-month costs (all costs adjusted to 2008 dollar amounts). The results of this study were very interesting. The 2-year cost of therapy was highest for natalizumab (natalizumab, $72,120; intramuscular [IM] interferon [IF N] beta-1a, $56,790; IFN beta-1b, $56,773; subcutaneous [SC] IFN beta-1a, $58,538; and glatiramer acetate [GA], $57,180). However, the cost per relapse avoided was dramatically lower for natalizumab compared with the other DMTs (natalizumab, $56,594; IFN beta-1b, $87,791; IM IFN beta-1a, $93,306; SC IFN beta-1a, $96,178; and GA, $103,665) because natalizumab was associated with half as many relapses as the other treatments (Table 1).19

Kobelt et al used a Markov model to compare drug efficacy and costs with natalizumab and other DMTs.20 Data from the AFFIRM study (n = 942) and the Stockholm MS registry (n = 512) were assessed. Total costs (2005 values) over a 20-year period were similar in the 2 groups (natalizumab, €609,850 [or $762,313]; other DMTs, €613,680 [or $767,100]).20 The study also determined that when only direct healthcare costs were included, the cost per quality-adjusted life-year (QALY) gained with natalizumab was €38,145 ($47,682).21

A British cost-effectiveness analysis examined the pharmacoeconomics of natalizumab versus standard DMT therapy in patients with highly active relapsing-remitting MS. At a willingness-to-pay threshold of £30,000 ($37,500) per QALY, the probability of natalizumab being cost-effective from a societal perspective compared with other agents was greater than 89%.21 This model included indirect costs to society, such as loss of productivity, which is common in patients with highly active relapsing-remitting MS. Therefore, the model may be closer to real-world observations, as patients and society make numerous financial adjustments as the symptoms of MS progress.

Finally, a US economic model study compared natalizumab with GA and took into account medical costs, nonmedical costs (eg, devices and investments to adapt living conditions), and informal care by family and friends.22 The model predicted that the incremental cost per QALY for natalizumab was $606,228 (2007 dollars) (vs $496,222 for patients receiving GA).22 The 10- to 20-fold increase in financial burden calculated in this model (compared with the above studies) was attributed to differences in utilities used for QALY calculations. This latter study illustrates the strong need to clarify the cost of care for MS patients and the need for additional real-world data.

Real-World Observational Data23

In addition to the above budget models, real-world observational data are available on the financial impact of natalizumab. Below is a summary of recent retrospective medical and pharmacy claims data obtained from a large US-based database. This study did not consider nonmedical costs associated with MS but does provide an excellent assessment of cost to the payer.


Data were obtained from the IM S/PharMetrics Integrated Patient-Centric Database, which contains medical and pharmaceutical claims for more than 55 million unique patients from 75 health plans across the United States. This database includes both inpatient and outpatient diagnoses (in International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] format) and procedures (in ICD-9-CM, Current Procedural Terminology, and Health Care Financing Administration Common Procedure Coding System formats), as well as community and mail-order pharmacy claims; available data for pharmacy claims are based primarily on National Drug Code and Common Procedure Coding System drug codes. Only health plans submitting data for all of their members are included in the database. Data submissions were subjected to a series of data quality checks to ensure a standardized format and minimize error rates. Only patients diagnosed with MS and who started natalizumab during 2006 or 2007 and continued therapy through 2008 were included in this analysis. All studied patients had 3 full years of eligibility and contribution of claims data. Charges and utilization of medical services and prescription drugs were identified and captured using the Episode Treatment Groups software.



As shown in Table 2, the mean age of patients was 44 years and the majority was female. Table 3 shows changes in pharmacotherapy over the 3-year period. The percentage of patients requiring medications for relief of MS-related symptoms (eg, corticosteroids, benzodiazepines, antispastics) decreased from 2007 to 2008. A total of 45% of patients maintained sole use of natalizumab in 2007 (ie, no other DMTs); by 2008, that percentage increased to 94% (data not shown).


Total expenditures are shown in Table 4. In 2008, the year in which natalizumab was the sole DMT for most patients, outpatient costs decreased, as did the number of emergency department visits and hospitalizations due to MS. Offsetting this, pharmacy expenditures increased.



While the time frame used in this study limits definitive conclusions, it does provide a unique opportunity to examine changes in expenditures when patients switch medications. Interestingly, the switch to natalizumab was associated with a decrease in costly emergency department visits and hospitalizations. This pattern was observed in a previous study using 2005/2006 data for other DMTs in which pharmacy costs rose while inpatient and outpatient costs declined.24 Patients appropriate for treatment with natalizumab, however, generally have greater disease severity. In this study, the severity of MS was not provided. Future studies that detail MS severity as well as the economic and physical changes that result from longterm natalizumab therapy are warranted.



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