Sustained Benefits of a Multidomain Lifestyle Intervention in Multiple Sclerosis in the LIMS Study: A 24-Month Follow-Up

Background and Objectives – Multiple sclerosis (MS) often leads to physical, cognitive, and psychological impairments substantially affecting daily functioning and quality of life. Because current disease-modifying therapies do not fully prevent disease progression, interest has grown in the potential role of modifiable lifestyle factors. We evaluated (1) whether effects on patient-reported outcomes were sustained up to 24 months and (2) long-term changes in lifestyle behaviors after completion of the lifestyle in MS program. Methods – People with MS participated in a 3-month multimodal lifestyle program (i.e., Mediterranean-style diet, physical activity, and sleep and stress), followed by a 21-month maintenance phase. Patient-reported outcomes were assessed 3 months before the intervention, at baseline, postintervention, and after 6, 12, 18, and 24 months. The primary outcome was MS-related impact on daily functioning (MS Impact Scale–29 [MSIS-29]). Secondary outcomes included quality of life, general health, and MS-related symptoms. Longitudinal changes were analyzed using piecewise mixed-effects models, and individual-level change was evaluated using proportions exceeding the smallest detectable change (SDC). Results – In total, 659 participants were included (mean age 46 years, SD 11; 84% female). During the intervention phase, MSIS-29 physical and psychological scores significantly decreased by approximately 0.8 and 1.1 points per month, respectively, followed by attenuation during long-term follow-up. This was reflected by within-group changes of −2.7 (−3.7; –1.8) and −3.7 (−4.8; –1.6) points after the intervention and −0.8 (−1.7; 0.3) and −3.4 (−4.6; –2.3) point at month 24, remaining significantly improved or stable relative to baseline. Only a small proportion of participants exceeded the SDC for MSIS-29 (approximately 4%–7%). Trajectories were broadly similar across other patient-reported outcomes, with modest short-term improvements and subsequent stabilization. Most pronounced effects were found for dietary adherence and body mass index, which improved substantially during the intervention and remained partially sustained during follow-up. No significant changes were observed in physical activity adherence. Discussion – In this large, real-world study, a digital multimodal lifestyle intervention was associated with modest, mainly short-term improvements in patient-reported outcomes and more pronounced individual-level changes in dietary behavior and body composition. These findings support a complementary role for lifestyle interventions in long-term MS management. Trial Registration Information – The study was registered at ClinicalTrials.gov (Identifier: NCT05402501; classic.clinicaltrials.gov/ct2/show/NCT05402501).