Natalizumab treatment reduces fatigue in multiple sclerosis. Results from the TYNERGY trial; a study in the real life setting

Abstract

Fatigue is a significant symptom in multiple sclerosis (MS) patients. First-generation disease modifying therapies (DMTs) are at best moderately effective to improve fatigue. Observations from small cohorts have indicated that natalizumab, an antibody targeting VLA-4, may reduce MS-related fatigue. The TYNERGY study aimed to further evaluate the effects of natalizumab treatment on MS-related fatigue. In this one-armed clinical trial including 195 MS patients, natalizumab was prescribed in a real-life setting, and a validated questionnaire, the Fatigue Scale for Motor and Cognitive functions (FSMC), was used both before and after 12 months of treatment to evaluate a possible change in the fatigue experienced by the patients. In the treated cohort all measured variables, that is, fatigue score, quality of life, sleepiness, depression, cognition, and disability progression were improved from baseline (all p values<0.0001). Walking speed as measured by the six-minute walk-test also increased at month 12 (p = 0.0016). All patients were aware of the nature of the treatment agent, and of the study outcomes.

Conclusion: Natalizumab, as used in a real-life setting, might improve MS-related fatigue based on the results from this one-armed un-controlled stud. Also other parameters related to patients' quality of life seemed to improve with natalizumab treatment.

Trial registration: ClinicalTrials.gov NCT00884481.

Conflict of interest statement

Competing Interests: Anders Svenningsson has received unconditional research grants, travel support, and lecture honoraria from BiogenIdec AB, MerckSerono, BayerSchering A/G, Sanofi-Genzyme AB, and Baxter AB. Eva Falk is a BiogenIdec employee and holds stock in the company. Elisabeth G. Celius has received unconditional research grants, travel support and lecture honoraria from Biogen Idec, Novartis, MerckSerono, Teva, and Aventis. Siegrid Fuchs has received honoraria for scientific advisory boards and invited lectures for Biogen Idec, Merck Serono Bayer-Schering, Genzyme, and Novartis. Karen Schreiber has reiceved honoraria from BiogenIdec, Novartis, and Allergan. Sara Berkö is a BiogenIdec employee and holds stock in the company. Jennifer Sun is a BiogenIdec employee and holds stock in the company. Iris-Katharina Penner has received research grants from Bayer Switzerland AG and the Swiss Multiple Sclerosis Society and has received honoraria for serving as speaker at scientific meetings, consultant, and as member of scientific advisory boards for Actelion, Bayer Pharma AG, Biogen Idec, Merck Serono, Roche, and Teva Aventis. There are no patents, products in development, or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Flow diagram of the TYNERGY trial.

The CONSORT flow diagram model showing enrolment, follow-up, and data analysis was applied.

Figure 2. Patient reported fatigue at base line and during the 12 months of natalizumab treatment.

A validated questionnaire for MS, the Fatigue Scale for Motor and Cognitive functions (FSMC) allowing separate evaluations of motor and cognitive aspects of fatigue, was used. The total, motor and cognitive FSMC score at base line and month 3, 6, 9 and 12 are shown. Error bars = Standard Error of the Mean.