Improvement in Fatigue during Natalizumab Treatment is Linked to Improvement in Depression and Day-Time Sleepiness

Abstract

Background: Fatigue is a frequent symptom in multiple sclerosis (MS) and often interrelated with depression and sleep disorders making symptomatic treatment decisions difficult. In the single-arm, observational phase IV TYNERGY study, relapsing-remitting MS patients showed a clinically meaningful decrease in fatigue over 1 year of treatment with natalizumab.

Objective: To evaluate whether fatigue improvement might be directly linked to improved depression and day-time sleepiness.

Methods: Patients were assessed regarding fatigue, depression, and day-time sleepiness. The relation between changes of the two latter symptoms and changes in fatigue was analyzed.

Results: After 1 year of natalizumab treatment, the majority of patients (>92%) remained stable or improved in total, motor, and cognitive fatigue. Proportion of patients without depression increased by 17% while proportions of mildly depressed patients or patients with potential major depression decreased by 5 and 12%, respectively. Proportion of patients classified as not being sleepy increased by 13% while proportions of sleepy and very sleepy patients decreased by 11 and 2%, respectively. Most importantly, improved depression and sleepiness were significantly related to improved fatigue.

Conclusion: Our findings highlight the importance of patient-reported outcomes in identifying potential benefits of drug treatment beyond its well-established effects on disease activity and disability progression.

Keywords: depression; fatigue; multiple sclerosis; sleepiness; treatment response.

Figures

Figure 1

Changes from baseline in total, motor, and cognitive FSMC scores. *P < 0.001 across status groups (worsened, stable, improved). Worsened = shift to higher fatigue classification; stable = no change in fatigue classification; improved = shift to lower fatigue classification.

Figure 2

Depression status at baseline and at 1 year of follow-up.

Figure 3

CES-D score change in patients with worsened, stable, and improved FSMC total, motor, and cognitive scores. P value is for comparison across subgroups of worsened, stable, and improved.

Figure 4

Degree of sleepiness at baseline and at 1 year of follow-up.

Figure 5

ESS-score change in patients with worsened, stable, and improved FSMC total, motor, and cognitive scores. P value is for comparison across subgroups of worsened, stable, and improved.