Improving employment outcomes for people with multiple sclerosis

Multiple sclerosis (MS) is a chronic neurodegenerative disease, with a mean age of onset between 30-40 years. Due to disease-related impairments, people with MS often experience difficulties in maintaining employment. This thesis aims to investigate factors associated with employment outcomes in people with MS, including MS symptoms, comorbidities, and the effects of disease modifying therapies (DMTs). The Australian Multiple Sclerosis Longitudinal Study (AMSLS) is the data platform used for the studies presented in this thesis. The AMSLS, established in 2002, is an ongoing survey-based longitudinal research project. Currently it has around 3,000 active participants who have been shown to be representative of Australians with MS. This thesis used data from several AMSLS surveys that were conducted in 2015 and 2016. The first analytical study quantified MS-related work productivity loss, that comes from both absenteeism (time absent from work) and presenteeism (reduced work productivity while at work), and then compared factors associated with labour force participation and total MS-related work productivity loss. The study found that work productivity loss due to presenteeism was three times higher than that from absenteeism. Multivariable analyses showed that work productivity was determined most strongly by MS symptoms, particularly 'fatigue and cognitive symptoms' and 'pain and sensory symptoms', while older age, and lower education level were also predictive of not being in the labour force. The second study assessed the prevalence of 30 comorbidities and the impact of these comorbidities on employment outcomes in a working-aged MS cohort. Building on the first study, the possible mediation effects of symptom severity on the associations between comorbidities and employment outcomes were also examined. The study found that among the Australian working-aged MS population, comorbidities were very common (90% with ‚Äöv¢‚Ä¢1 morbidity) and many limit people's activities. Comorbidities showed a dose-dependent association with more MS-related work productivity loss and a higher likelihood of not working, and these effects were mainly mediated through symptom severity. The third study compared the effects of different DMTs used in the previous 5 years on improvements in work attendance, amount of work (working hours) and work productivity of people with MS. The study showed that those who used higher efficacy DMTs (e.g. fingolimod and natalizumab) were 2‚Äö-3 times more likely to report improvements in the three employment outcomes compared to those who used classical injectable DMTs (˜í‚â§-interferons and glatiramer acetate). Natalizumab was associated with superior beneficial effects on patient-reported employment outcomes than fingolimod. The last study evaluated risk factors of leaving employment due to MS, and whether the risk of leaving employment has changed differentially between people with relapsing-remitting MS (RRMS, for whom DMTs have been available) and people with primary progressive MS (PPMS, for whom DMTs have not been available during the study period) over the recent several decades in Australia. The study found that being male, having progressive MS, having a lower education level and being of an older age at diagnosis were associated with a higher sub-distribution hazard of leaving employment. Compared to the period before 2012, the sub-distribution hazard of leaving employment due to MS during 2012-2016 was reduced by 43% (sHR 0.57, 95% CI 0.41 to 0.80) for people with RRMS, while no significant reduction was seen for people with PPMS (sHR 1.31,95% CI: 0.74 to 2.33). Such differential changes seem to coincide with the increased usage of high efficacy DMTs in Australia. In summary, for the first time, the thesis quantified MS-related work productivity loss due to presenteeism, and the findings highlight the importance of presenteeism being included in employment outcomes in MS research. The dominance of the severity of symptoms as predictors of both work participation and productivity loss emphasises the need for improved management of symptoms to improve employment outcomes. In addition, optimal and simultaneous management of comorbidities may be a viable strategy to reduce MS symptom severity, which in turn could improve employment outcomes. More importantly, I provide the first evidence of the direct comparative effectiveness of multiple DMTs for MS using employment measures as outcomes. The last two studies show that DMTs may have important beneficial effects on the work life of people with MS.