Best Practices
The Multiple Sclerosis Centers of Excellence: A Model of Excellence in the VA
The MS Centers of Excellence at the VA improves the consistency and quality of care for veterans with MS.
Off-Label Use
Other potential ways to reduce DMT costs is to consider off-label treatments. The OLYMPUS trial studied off-label use of rituximab, an anti-CD20 antibody like ocrelizumab. It did not meet statistical significance for its primary endpoint; however, in a subgroup analysis, off-label use was found to be more effective in a population aged < 51 years.16 Other case reports and smaller scale studies also describe rituximab’s efficacy in MS.17,18 In 2018, the FDA approved the first rituximab biosimilar.19 Further competition from biosimilars likely will make rituximab an even more cost-effective choice when compared with ocrelizumab.
Alternate Dosing Regimens
Extended interval dosing of natalizumab has been studied, extending the standard infusion interval from every 4 weeks to 5- to 8-week intervals. One recent article compared these interval extensions and found that all extended intervals of up to 56 days did not increase new or enhancing lesions on MRI when compared with standard interval dosing.20 Another larger randomized trial is underway to evaluate efficacy and safety of extended interval dosing of natalizumab (NCT03689972). Utilization of this dosing may reduce natalizumab annual costs by up to 50%.
Safety Monitoring
DMF is an oral DMT on the VHA formulary with CFU. Since leukopenia is a known AE, baseline and quarterly monitoring of the complete blood count (CBC) is recommended for patients taking DMF. Additionally, DMF should be held if white blood cell count (WBC) falls below 2,000/mm3.21 There have been recent reports of death secondary to progressive multifocal leukoencephalopathy (PML) among European patients taking DMF.22-24 This has raised concerns about adherence to recommended CBC monitoring in veterans taking DMF. The association of DMF and leukopenia has been evident since early clinical trials.25 Leukopenia in immunocompromised patients increases the risk of PML.
In the long-term extension study ENDORSE, 6% to 7% of patients continuing DMF had WBC counts of 3.0×109/L compared with 7% to 10% in the new to DMF group.26 In addition 6% to 8% of patients continuing DMF had lymphocyte counts of 0.5×109/L, compared with 5% to 9% in the new to DMF group. The cases of PML occurred in patients who had low lymphocyte counts over an extended period with no adjustment to DMF therapy, such as holding the drug until WBC counts returned to normal levels or stopping the drug. Discussion and review within VHA resulted in the recommendation for quarterly WBC monitoring criteria.
PBM and VA Center for Medication Safety (MedSafe) conducted a medication usage evaluation (MUE) on adherence to the WBC monitoring set forth in the CFU. Data collection began in fourth quarter of fiscal year (FY) 2015 with the most recent reporting period of fourth quarter of FY 2017. The Medication Utilization Evaluation Tool tracks patients with no reported WBC in 90 days and WBC < 2,000/mm3. Over the reporting period, 20% to 23% of patients have not received appropriate quarterly monitoring. Additionally, there have been 4 cases where the WBC decreased below the threshold limit. To ensure safe and effective use of DMF, it is important to adhere to the monitoring requirements set forth in the CFU.