Does health-related quality of life evaluation in multiple sclerosis (MS) matter?
A review of labels of MS products approved by the EMA and the FDA
By Catherine Acquadro, MD, Mapi Research Trust, Lyon, France
(based on abstract submitted to the AAN 2016)
Background and Objectives
Multiple sclerosis (MS) is an autoimmune and inflammatory demyelinating disease of the central nervous system, often characterized by relapsing episodes of neurologic impairment followed by remissions (relapsing remitting MS). In about a third of MS patients, the disease evolves into a progressive course (progressive MS). The objective of this study was to evaluate how health-related quality of life (HRQL) was taken into consideration in the evaluation of MS products approved by the FDA and the EMA since 1995.
Methods
The websites of the FDA and the EMA were explored (December 2015) to identify all MS products approved. All labels and corresponding clinical reviews (FDA), summary of product characteristics (SmPC), and assessments reports (EMA) were manually retrieved and reviewed for HRQL evaluation.
Results
Twelve different products (11 INN) were approved: ten by both agencies, and two only by the FDA.
See Table 1.
*Extavia: The EMA application is an informed consent application of the Betaferon application; as for the FDA, no clinical studies have been done for this BLA (125290) as the sponsor has obtained a letter of authorization allowing the sponsor to reference the original Betaseron BLA (103471). Therefore Extavia was not included in the final count of products.
For the products approved by both agencies, the same clinical studies were submitted (except for alemtuzumab).
HRQL was evaluated in seven products. See Table 2.
- In only one case, HRQL evaluation was mentioned in the label (although negative), i.e., in the EMA SmPC of Betaferon [“In the open label follow-up phase, […] No benefit, attributable to immediate Betaferon in quality of life (as measured by FAMS – Functional Assessment of MS: Treatment Outcomes Index) was seen”]. There was no HRQL mention in the corresponding FDA label for the same product.
- In five products, HRQL was evaluated with generic measures (e.g., SF-36 or SF-12). In most cases, HRQL was considered as a tertiary/exploratory endpoint.
- In three products (alemtuzumab, natalizumab, and teriflunomide), statistical differences in HRQL endpoints were seen (measured by the FAMS and/or the SF-36), but not reported in labels/SmPCs. See Table 2.
- In most cases, reasons for not including data in the label were lack of statistical differences, no replication, or HRQL considered as a tertiary endpoint.
Conclusion
Health-related quality of life is not considered as a key endpoint in the evaluation of MS products. A patient-focused drug development initiative in MS could be helpful to identify what matters to the patients and their caregivers.