Social participation in patients with multiple sclerosis: correlations between disability and economic burden

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system causing various neurological symptoms, including motor, sensory, visual or cognitive troubles. MS primarily strikes adults between 18 and 45 years and has several forms of presentation [1]. 85% of patients have relapsing-remitting MS (RR-MS) with periods of defined relapse (with either fully recovery or residual deficit after recovery) and periods characterized by a lack of disease progression. Secondary progressive MS is an initial relapsing-remitting course followed by progression with or without occasional relapses (50% of RR-MS). In about 15% of cases, primary progressive MS is a gradual, nearly continuously worsening baseline with no distinct relapse. Consequences of MS progression can be clinically described with different scales or tools, but Expanded Disability Status Scale (EDSS) remains the most used outcome in worldwide neurological community, even if numerous shortcomings have been discussed [2]. Progressively, patients’ physical activities, ability to generate income [3] and social participation [4] can be restricted. From the beginning of the disease, MS significantly alters quality of life (QOL) [5, 6].

For over 15 years, clinical trials of various subcutaneously or intramuscularly immunomodulatory drugs have demonstrated a modest reduction in relapse rate and limited effects on disability progression, with a well-known long-term safety but a poor daily tolerability [1]. Recently, second-line treatments such as natalizumab [7] or fingolimod [8, 9] showed greater effects on relapse rate and convincingly on disease progression. However serious adverse events and long-term safety remain a concern with such drugs and require closed monitoring survey.

Treatment prices are an important vector of cost in MS, essentially in initial phases of the disease [10] and cost-effectiveness of all these drugs is questionable [11]. Economic evaluation is playing an increasing role in political decisions for resources allocation and health policies. In the current economic context with limited resources, national or international institutions need up-to-date economic burden studies and recommend assessment of patient-reported outcomes (PRO) as utilities in clinical trials [12, 13]. Utility is most often assessed by preference-based systems and through generic QOL measurement tools, like EuroQol (EQ5D-VAS), Short Form Health Survey (SF-6D) or Health Utilities Index III (HUI-III). Most studies in MS field have used EQ5D-VAS, in which explored dimensions have important link to mobility capacities [14]. However, several important domains of impairments or limitations, as cognition, vision and others, are poorly taken in count by these tools. Specific QOL scales are available for patients with MS, but these do not allow measuring utilities. Patient’s working capacity is well evaluated with loss of production in global burden studies, but others social disadvantages are only approached with utility scales.

Our hypothesis is that disability in MS and particularly social participation impairment should be better correlated with utility, MS-specific QOL and economic costs rather than health state described by an impairment scale as EDSS. If it was verified, this relationship could lead to an interesting tool for evaluation of health policy. Indeed, a health-promoting action that could correct functioning or social participation deficits could be economically recovered.

Our primary objective was to describe consequences for patients treated by natalizumab in term of disabilities and economic burden due to MS. In this study, disabilities covered impairments, activity limitations and social disadvantages, using EDSS and a measurement of autonomy and social participation. Secondary, we examined correlations between usual tools, as EDSS, MS-specific or generic QOL scales, and the "impact on participation and autonomy questionnaire" (IPA).

Among 70 eligible patients with diagnosis of MS and treatment by natalizumab in our centre, because of time-consuming interviews and a limited time available in this preliminary study, 42 were consecutively solicited. All patients being asked to participate accepted it, except one. Demographic and disease characteristics are presented in Table 1. Sex-ratio Male/Woman was 7/34 and mean age was 42.8 (SD 9.5) [23–72] years. Disease duration was 11.7 (SD 7.4) [2–40] years. EDSS score was 4.0 (SD 1.6) [1.5-7.0]. Demographic characteristics (age, sex, disease duration and EDSS) were not significantly different between participants and patients followed in our centre and treated with natalizumab, who were not included. Significant differences between groups for demographic and clinical data, utility, social participation and economic costs are reported in Table 1. For MS-specific QOL, only aggregated scores MSQOL-P and MSQOL-M are presented.

This study confirms that medico-economic costs due to MS increase with impairment measured by EDSS. Social participation evaluated by IPA questionnaire is altered in patients with MS. We found significant correlations between IPA and QOL (EQ5D-VAS or SEP-59). Association between QOL and EDSS was smaller (EQ5D-VAS) or absent. These results argue for a greater role of social participation than impairment itself (EDSS) to explain variations of QOL. Other while, moderate to strong correlations are evidenced between functional impairment (EDSS), social participation and economic costs.

Patients’ perception of social participation in our study was comparable with the results described in UK validation study of IPA [18]. The biggest change of IPA scores was present between the 2 groups with EDSS range of 0–3.5 and 4.0-5.5 for the following domains of IPA: autonomy indoors, family role, autonomy outdoors and work and education. The known shift of utility, which occurs when patients live a transition of EDSS score in the range of 1.0-3.0 to 3.5-5.5 [14, 23], seems to be similar for these domains of IPA. Groups’ stratification was based on ability to walk. So walking impairment could explain a part of this shift. Outcomes, as EDSS, EQ-5D and probably IPA and MSQOL-P, are all sensitive to walking impairment. In an other hand, IPA domain on social life and relationships was significantly altered for the group of patients with EDSS ≥ 6 in comparison with patients which had unlimited walking ability. Stability of the majority of IPA domains between the two groups with higher EDSS scores is questionable and interesting. We can hypothesize with cautious that a part of the increasing economic costs with EDSS worsening can be justify by the relative preservation of social participation. Social support and informal care could help patient to maintain some activities and a relative social participation level. On the other hand, coping mechanisms can influence the individuals’ perception of their own quality or life and social participation. Acceptance of disease could participate to limit worsening of QOL or perception of participation, when disability due to MS has progressed. But a larger study is necessary to conclude on these hypotheses.

Correlations between IPA and QOL are found in this study, in particular with generic utility (EQ-5D). An other preliminary study previously showed similar associations between specific activities like physical and leisure/recreation activities and QOL in patients with MS [24]. However some domains of IPA are not or less correlated to P- and M-MSQOL. But others factors as depression, fatigue, pain, social support, living area, religiosity, which are not lightened by our data, would probably contribute to variations of MSQOL-M [25]. In this context, IPA domain on social life and relationships was expected to be more correlated to MSQOL-M, but it was not verified in our study. Kierkegaard and colleagues recently observed that some manual dexterity, cognition and walking tests could be used as predictive factors of participation limitations [4]. Previous researches with the NARCOMS registry have incriminated the earliest mobility impairment in indirect costs’ increasing, activities of daily living, socio-economic status and utility’s declining [26, 27]. Indirect costs (mostly productivity losses) driven by working ability and early retirement are often considered as the most important factor to explain global cost increasing with MS progression [10, 28]. In this study, the post-hoc analysis confirmed that ability to maintain employment is an important outcome and could be considered as a good marker of well-being. Economically, patients who have a job still contribute to the Gross Domestic Product of their country. So, direct costs due to MS are at least partly neutralized by their economic contribution.

The mean overall cost of MS seems increased in comparison of previous studies. This observation is explained mostly by the high cost of natalizumab. Noteworthy, this study did not aim to evaluate a cost/benefit ratio for this treatment. The calculated global burden is similar in proportion to previous French and international data [6, 10, 29], usually collected by postal questionnaires and therefore weakened by inherent biases. In France, Kobelt and colleagues conducted the larger costs’ evaluation in 2007. Excluding disease-modifying drugs’ cost, estimated global burden in 2007 (39353+/-39790 EUR) is close with our results (38622 +/- 33374 EUR). Utility values (EQ5D-VAS) are also very similar with a mean value to 0.52 (SD 0.29) in 2007 compared to 0.52 (SD 0.28) in this study [29].

International Conference on Disability Outcomes in MS on May 2011 underlines how wider assessments of function are potentially useful and could be acceptable by regulators [2]. Global measures of disability should be used as adjunct to or replace MS-specific outcomes depend on the purpose of the study. Regulation agencies such as FDA in USA, NICE in UK or HAS in France recommend evaluating utility by generic measures of QOL related to health status in economic analysis of health cares (such as EQ5D-VAS, SF-6D or HUI-III). These generic tools allow comparison of a disease to another to facilitate decision-making, but these do not capture several important areas for pwMS. This may lead to an underestimation of the impact of disability in patients [30]. In "cost-utility" or "cost of illness" studies, utility which is mostly expressed like Quality-adjusted life years (QALYs), is used as a comparator outcome to economic costs driven by clinical factors like relapse rates and disease progression. QALYs measures both quantity (mortality) and quality (morbidity) of life. It reflects the relative desirability or value of the health states that are described by changes in lifestyle of patient including pain, anxiety, social functioning and ability to continue activities of daily living (including leisure). In the conventional approach, ratio between global economic costs and QALY (Costs/QALY) needs to be as small as possible and first objective of a healthcare action is to maximize utility. However using QALY method is still very controversial, particularly in population concerned with disability [31]. According to theory developed by Amartya Sen and others [32, 33], the level of wellbeing of a person with disabilities is less affected by changes in health status than the effect of these changes on its functionings and ultimately on their social participation [34]. Tools that explore social participation and quality of life share some common elements [35]. In the definition of QOL by the World Health Organisation, QOL can be seen as consequence of the bio-psycho-social model defined in the International Classification of Functioning, Disability and Health (ICF). So the level of social participation could influence quality of life, but it does not exactly measure the same concept. In accordance with our results, we propose that social participation measure is a complementary outcome, which highlights different concepts than QOL level.

From a small sample of pwMS, links between progression of the disease (EDSS), generic QOL, social participation and economic costs seem obvious and consistent with previous national economic data. Moderate to strong correlations of social participation with health status (EDSS), QOL, utility and economic costs encourage exploring better these links in larger cohort.