Digital Lifestyle App Levidex Fails to Meet Primary End Point for Early MS in POWER@MS1 Trial

Nicole Krause, PhD

(Credit: University Medical Center Hamburg–Eppendorf)

Newly published findings from the randomized controlled POWER@MS1 trial (NCT03968172) assessing Levidex showed that the cognitive behavioral therapy-based, personalized digital application did not differ from a nonpersonalized psychoeducational application “dexilev” in its effects on inflammatory disease activity in newly diagnosed patients with multiple sclerosis (MS). Overall, use of this personalized lifestyle app failed to meet its combined primary end point of T2 lesions and new relapses.¹

Among 234 patients with MS in the study, researchers reported no difference between the intervention group (IG; n = 115) and control group (CG; n = 119) in the time to the first relapse and/or new T2 lesion (ITT analysis, HR, 0.91; 95% CI, 0.66-1.27; P = .596). Over the follow-up period, authors noted an average of 2.3 (SD, 4.4) new T2 lesions in the IG vs 2.2 (SD, 4.4) new T2 lesions in the CG. Additionally, there were no between-group differences among untreated patients with MS (HR, 1.08; 95% CI, 0.64-1.82; P = .78) and highly adherent participants (HR, 1.25 95% CI, 0.82-1.92; P = .298).

“This pragmatic RCT did not meet its ambitious primary end point. Additional personal support might induce more pronounced behavior change and possibly have a greater impact on MS disease activity, but such potential advantages remain to be demonstrated, and they must be weighed against the higher costs and limited scalability of person-delivered treatments, compared to fully automated digital interventions,” lead author Nicole Krause, PhD, public health scientist in Department of Neurology at University Medical Center Hamburg–Eppendorf, and colleagues wrote.¹ “Nevertheless, the study shows that close clinical and MRI follow-up in the first years after diagnosis and extensive lifestyle information is appreciated and adhered to by people recently diagnosed with MS.”

The trial enrolled participants between July 2019 to April 2022 from 20 study centers in Germany and followed up until April 2023. Neurologists determined physical impairment of the participants using the Expanded Disability Status Scale (EDSS).² Researchers analyzed that combined primary endpoint, new T2 lesion and/or relapse, using Cox proportional hazards regression. Key secondary end points of the trial included self-reported quality of life (QoL), measured by Hamburg Quality of Life in MS Scale (HAQUAMS)³, and health behavior, measured by the Hospital Anxiety and Depression Scale (HADS).

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Out of the total number of randomized patients with MS from the study, 90% completed follow-up surveys (n = 211). Even though the core study period was 12 months, researchers invited early recruited participants to remain in the study. The study excluded 1 participant from primary outcome analyses because of missing MRI data following randomization.

All told, participants in the IG with access to levidex perceived the program as more convincing (OR, 2.80; 95% CI, 1.64-4.76; P <.001), had a higher expectation regarding a positive effect on their condition (OR, 2.72; 95% CI, 1.57-4.71, P <.001) and were more likely to recommend the program to a friend with similar problems (OR, 4.70; 95% CI, 2.46-8.97; P <.001) compared with CG participants at 4 weeks. At 3-months post randomization, authors noted that risk knowledge was higher in the CG (HR, −0.52; 95% CI, −0.93 to −0.10; P = .015); however, the difference of 4.2 versus 4.7 points out of 10 was marginal. In addition, diet quality was reported higher in the IG 3 months post randomization compared with those in the CG (HR, 0.43; 95% CI, 0.14-0.72; P = .004).

In subgroup analyses, participants with lower QoL (HAQUAMS score at least 2; HR, 1.02; 95% CI, 0.54- 1.92; P = .96), higher physical impairment (EDSS at least 2; HR, 0.9; 95% CI, 0.47-1.72; P = .75) and moderate to severe symptoms of anxiety (HADS-A, score 8–17; HR, 0.97; 95%-CI, 0.54-1.73; P = .91) or depression (HADS-D, score 8–16; HR, 0.25; 95% CI, 0.06-1.05; P = .06) displayed no effect on the primary end point. Combining all cut-offs, authors detected no effect on the primary end point (HR, 1.06; 95% CI, 0.68-1.64; P = .81). In terms of safety, no adverse events or harms, beyond psychological impact, were anticipated and reported during study conduct.

REFERENCES
1. Krause N, Derad C, von Glasenapp B, et al. Digital lifestyle management application (levidex) for empowerment and health behaviour change in early multiple sclerosis - Results of the randomised controlled POWER@MS1 trial. Mult Scler. Published online August 12, 2025. doi:10.1177/13524585251356410
2. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452. doi:10.1212/wnl.33.11.1444
3. Gold SM, Heesen C, Schulz H, et al. Disease specific quality of life instruments in multiple sclerosis: validation of the Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS). Mult Scler. 2001;7(2):119-130. doi:10.1177/135245850100700208
4. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361-370. doi:10.1111/j.1600-0447.1983.tb09716.x