The influence of disease-modifying therapy on hidden disability burden in people with newly diagnosed relapsing-remitting multiple sclerosis

Background: In addition to motor disability, hidden disability' such as depression, anxiety, fatigue, sleep disturbance, cognitive impairment and pain is a major complaint of people with multiple sclerosis. We explored changes in hidden disability burden in the early post-diagnostic period and examined the hypothesis that disease modifying therapies have a beneficial effect on hidden disability burden. Methods: Adults with recently diagnosed (< 6 months) relapsing-remitting multiple sclerosis (n = 440, mean age 37.4 +/- 10.4, 76% female), from a national multicentre cohort study (FutureMS) underwent testing with clinical and neuropsychological instruments as well as brain MRI at baseline and after 12-months. Disease modifying therapies were only started after baseline assessment and were classified into injectables (n = 70, interferons, glatiramer acetate), other DMTs (n = 215) and no DMT (n = 117, reference). Sensitivity analyses were undertaken using alternative classifications (disease modifying therapy vs none, and a 3-category system). We performed latent transition analysis with hidden disability burden as the latent variable including propensity score weights. Results: We identified three classes with low (58%), moderate (25%) and high (17%) hidden disability burden. 70% did not transition (unchanged, reference), 26% transitioned into a lower burden class (improvement) and 4% transitioned into a higher burden class (worsening). Median treatment duration was 11 months (IQR 9-12). Injectables [OR 1.3 (95%CIs 0.7, 2.3); P = 0.4] and other DMTs [OR 1.4 (95%CIs 0.9, 2.1); P = 0.2] were not associated with significant change in hidden disability burden in either direction (improvement or worsening). In the alternative 3-category classification, category 2 treatment (fingolimod, cladribine, n = 22) was associated with improvement [OR 4.3 (2.6, 7.0); P < 0.001]. Conclusion: Hidden disability was present in most newly diagnosed people with multiple sclerosis. The majority remained unchanged and approximately a quarter improved over the immediate post-diagnostic period. Disease modifying therapy had no significant influence on hidden disability burden in the study period of one year following diagnosis. The trend towards favourable outcomes with fingolimod and cladribine should be interpreted with caution due to the small sample size. Our exploratory data are observational, with scope for attendant biases, but highlight the need for further study including longer-term evaluation as well as randomised trials for non-motor disability.

Automated summary

In addition to motor disability, people with multiple sclerosis often experience hidden disabilities such as depression, anxiety, fatigue, sleep disturbances, cognitive impairment, and pain. This study explored the changes in hidden disability burden during the early post-diagnostic period and examined the effects of disease modifying therapies. The results showed that disease modifying therapies did not have a significant impact on hidden disability burden, although a small group of patients who received specific treatments did experience improvements.