Combination Therapy Best for MS Fatigue

Research results presented at the Americas Committee for Treatment & Research in Multiple Sclerosis (ACTRIMS) Forum 2023 show that although cognitive behavioral therapy (CBT), modafinil (Provigil; Teva Pharmacueticals USA, Inc, Parsippany-Troy Hills, NJ), and a combination of the 2 therapies each provide relief from fatigue from multiple sclerosis (MS), combination therapy was associated more frequently with perceived global benefits.

The randomized, pragmatic COMBO-MS trial (NCT03621761) compared CBT, modafinil, and a combination of both therapies on MS fatigue relief. The 336 study participants who reported fatigue were randomized (1:1:1) to receive telephone-based CBT (n=114), modafinil (n=114), or both (n=108) for 12 weeks. Fatigue impact (Modified Fatigue Impact Scale, MFIS) was assessed at baseline and 12 weeks. The researchers also assessed potential effect modifiers, including depression (Patient Health Questionnaire-8 score), sleep (Sleep Hygiene Index scores, Epworth Sleepiness Scale, sleep duration, and known/suspected obstructive sleep apnea), disability level (self-reported Expanded Disability Status Scale), and MS subtype. Treatment effect on change in MFIS score was assessed with multiple linear regression models. Patient Global Impression of Change (PGIC) score, a self-report measure of overall change in activity, symptoms, and quality of life, also was assessed.

At 12 weeks, CBT, modafinil, and combination therapy each were associated with statistically significant and clinically meaningful MFIS score reductions of greater than 1 SD: 15.2 (SD=11.9), 16.9 (SD=15.9), and 17.3 (SD=16.2), respectively, without differences between groups. More than 2/3 of participants in each group saw at least a 10-point reduction in overall MFIS score. Mean PGIC score, however, was higher for combination therapy (M=5.1 ± 1.6) compared to CBT (M=4.7 ± 1.6, P=.07) or modafinil (M=4.5 ± 1.7, P<.01). Both CBT and modafinil were well-tolerated with infrequent discontinuation.