Recent trends in disease-modifying therapy use and associated sickness absence and disability pension among people with multiple sclerosis in Sweden

Background: Disease-modifying therapies (DMTs) have led to improved health and work productivity among people with multiple sclerosis (PwMS). Objectives: To describe trajectories of recent DMT use and their association with sickness absence and/or disability pension (SADP) among PwMS in Sweden. Methods: A longitudinal register–based study was conducted among 1395 PwMS with treatment start in 2014/2015. While DMT use over 5 years was assessed using sequence analysis resulting in four clusters, a 7-year (Y−2 toY4) trend of SADP was analyzed using zero-inflated negative binomial regression. Results: Four clusters of DMT use trajectories were identified: long-term non-high-efficacy (483, 34.6%), long-term high-efficacy (572, 41%), escalation (221, 15.8%), and discontinuation (119, 8.5%). Progressive MS and higher expanded disability status scale scores were associated with the escalation, long-term high-efficacy, or discontinuation clusters. PwMS in the long-term high-efficacy and escalation clusters had higher likelihood of being on SADP. However, PwMS initiating high-efficacy DMTs demonstrated steeper decline in SADP than others. Conclusion: Using sequence analysis, this study showed recent DMT use trajectories among PwMS where initiation of high-efficacy DMTs has become more common. The trend of SADP was stable and lower in those using non-high-efficacy DMTs and larger improvements were shown in those initiating high-efficacy DMTs.


Sickness absence and disability pension
In this study, the data on SA included spells longer than 14 days to prevent bias in relation to unemployed individuals.Meanwhile for employed individuals, employers pay from the 2 nd to the 14 th day of SA, eligible unemployed individuals receive benefits from the SIA from the 2 nd day.
In Sweden, individuals aged 16+ years with income (a minimum of 24% of the annual price base amount) from work or unemployment benefits are eligible to SA benefits from the Social Insurance Agency (SIA).Furthermore, individuals aged 19-64 years with longterm/permanently reduced work capacity, despite the presence of previous income from work or not, are eligible to receive DP.Both SA and DP can be provided on a full or part-time basis (25%, 50% or 75%).SA and DP are paid out to cover about 80% and 64% of lost income, respectively, up to a certain level [1].

Comorbidity
Rx-Risk index identifies comorbidity through prescribed drugs.It was shown to be valid in predicting mortality and was also compared with another comorbidity measure [2,3].It has also been used in MS previously [4].; HC: Hubert's C a The ASW was among the main statistical criteria assessed in the study to determine quality of clusters using of its cut off points (ASW: 0.71-1.00:strong structure identified; 0.51-0.70:reasonable structure identified; 0.26-0.50:structure is weak and could be artificial.Try other algorithms; ≤0.25:no structure) [5,6].

Figure S1 .
Figure S1.Selection of people with multiple sclerosis included in the study [LISA: Longitudinal Integrated Database for Health Insurance and Labor Market Studies; PwMS: people with multiple sclerosis; MS: multiple sclerosis] [An individual might fulfil more than one exclusion criteria and the number of PwMS could appear more]

Figure S2 .
Figure S2.The ten most common sequences of disease-modifying therapies among the people with multiple sclerosis [The sequences of DMT use states shown here present the ten most frequent ones which account for about two-thirds (65.9%) of the total 1395.The total number of sequences (1 for each of the PwMS) are categorized in to the clusters as shown in the findings in the main text of the manuscript based on their similarity/dissimilarity.DMT: disease-modifying therapy]