Activity restrictions, treatment and work disability among people with multiple sclerosis

Sammanfattning: Background: Multiple sclerosis (MS) is a disease that commonly occurs among individuals of working age. Its symptoms are heterogeneous and affect people with MS (PwMS) considerably in different aspects of their lives. Disease-modifying therapies (DMTs) have helped a lot in the improvement of health and work productivity. However, studies on the impact of MS in different facets of life as well as the long-term DMT use trends in relation to corresponding changes in work disability measures such as sickness absence and/or disability pension (SADP) as well as work ability are lacking. So, the present thesis aimed at increasing knowledge on activity restrictions, trends in disease-modifying therapy use, and associated work disability among PwMS in Sweden. Methods: In studies I and IV, data were collected in a cross-sectional survey among PwMS in Sweden in 2021. Among them, 4052 who responded to the questions on restrictions on the four domains of work, family, leisure activities, and contact with friends/acquaintances were included in the analysis. In study II, 1923 PwMS with MS onset during 2007-2010 were included in a longitudinal register-based study to assess the DMT use trajectories over 10 years and the associated trends in SADP days for over 11 years. A similar study was conducted in study III among 1395 PwMS with DMT start/decision time of 2014/2015 assessing DMT use trajectories for 5 years and the associated SADP days for 7 years (from two years before treatment start). In study IV, utilizing the same survey material as study I, a total of 4103 PwMS were included in the study of how DMT use and work ability are associated as well as the role of other factors. For the analyses, in study I, multinomial logistic regression analysis was performed to assess predictors of reporting restrictions in the work and private life domains. In study II and III, sequence analysis was used to describe the sequences of DMT use over the follow-up time and to identify clusters of DMT use. The factors associated with cluster belonging were assessed using multinomial regression analyses conducted in each study. In assessing the trends in SADP by cluster, generalized estimating equations (GEE) were used in study II while zero-inflated negative binomial regression analysis was conducted in study III. In study IV, linear regression analyses were conducted to assess the association between DMT use and work ability score (WAS) and the role of additional socio-demographic, clinical, and self-reported health variables. Results: About two-thirds of the 4052 PwMS in study I reported some form of restriction in the work (64.3%), family (61.3%), leisure activities (68.9%), and contact with friends/acquaintances (59.7%) domains. Tiredness/fatigue was the most-limiting symptom in half (49.5%) of the PwMS. Neurologically normal PwMS (expanded disability status scale (EDSS) score of zero) still reported restrictions in the four life domains ranging from 39.6% (friends/acquaintances) to 45.7% (leisure activities). Overall, older PwMS, women, those with lower levels of education, people with progressive forms of MS, with invisible limiting symptoms and higher EDSS scores had higher odds of restrictions in the work and private life domains. In study II, four clusters of DMT use trajectories were identified: long-term non-high-efficacy DMTs (38.6%), escalation to high-efficacy DMTs (31.2%), delayed start and escalation to high-efficacy DMTs (15.4%), and discontinued/ no DMT (14.2%). Younger ages, higher EDSS scores, progressive MS, and higher frequency of DMT switch were generally associated with being in clusters other than long-term-non-high-efficacy. The trends in SADP showed fewer mean SADP days among PwMS in the long-term non-high-efficacy DMT cluster than in the others about 9 years after MS onset. The GEE models on SADP trends showed comparable findings to the descriptive statistics. Similarly, in study III among 1395 PwMS also four clusters of DMT use trajectories were identified. These include long-term non-high-efficacy DMTs (34.6%), long-term high-efficacy DMTs (41%), escalation to high-efficacy DMTs (15.8%), and discontinued/no DMTs (8.5%) clusters. Progressive MS and higher EDSS scores were associated with the clusters other than the long-term non-high-efficacy one. Individuals in the long-term high-efficacy DMTs cluster had a higher likelihood of being on SADP. However, starting high-efficacy DMTs showed a larger decline in SADP days than other clusters. In study IV, among the 4103 PwMS, just over half reported good (37.0%) or excellent (16.3%) WAS. The association of DMT use and WAS showed that PwMS on non-high-efficacy DMTs had higher WAS than those on high-efficacy and those not on DMTs but explaining only 1.24% of the variation in WAS. Occupation, EDSS score, fatigue, and health-related quality of life (HRQoL) explained high proportions of the variance in WAS. Conclusions: The thesis showed that PwMS experience substantial levels of restrictions to their work and private lives, which were often associated with symptoms such as fatigue. Restrictions were also experienced among PwMS considered neurologically normal. The thesis also described long-term trajectories of DMT use and associated SADP days in two studies with different cohorts, showing the recent trend toward initiation of high-efficacy DMTs becoming more common. Trends of SADP days across clusters were stable and lower in the long-term non-high-efficacy DMTs cluster. Higher work ability was noted among PwMS on non-high-efficacy DMTs despite very low explanatory power. The important roles of occupation, disability, fatigue, and HRQoL were also observed.