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Work ability in multiple sclerosis: the impact of immunomodulating treatments and adjusted working conditions
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease affecting the central nervous system (CNS) and is considered to be of autoimmune origin. The prevalence in Sweden is estimated to be about 1 in 500. The inflammation leads to demyelination as well as neurodegeneration and with time the patients often suffer from increasing neurological disability. The young age of onset makes MS one of the major causes of reduced ability to work in the Western society. Several factors in the disease affect the work ability. One important factor is ongoing inflammatory activity conferring risk to develop tissue damage and disability. Previous studies have indicated that fatigue, mobility and cognitive problems are the primary symptoms preventing individuals with MS to remain in employment. However, the possibility to adapt both tasks and the workplace, the possibility for sedentary work and flexible working hours also have great influence to keep the individual in employment.

The purpose of the thesis was to investigate how factors in the disease, immunomodulating treatments and work requirements influence the ability to work and study in people with MS.

Methods: A MS specific questionnaire was used in one retrospective and one prospective study to compare the work ability before and after start of the second-generation immunomodulating drug natalizumab. The number of working hours per week and the degree of sick leave before and after one year of treatment was calculated. The effect of disease-specific and workrelated factors on work ability was evaluated. The treatment effect on fatigue and walking ability was correlated to work ability. In addition, a healtheconomic calculation was performed to estimate the cost-benefit of the treatment. The degree of sickness absence was evaluated in a cross-sectional study of two MS-populations; one historical that never was exposed to immunomodulating drugs and the other consisted of individuals with MS that was diagnosed after the introduction of immunomodulating drugs. Furthermore, work ability was studied in two MS-populations, one southern and one northern cohort of Sweden, for the latter population more active immunomodulating treatment and work-promoting measures have been practiced. The data was collected using the instrument WAQ-MS. 

Results Paper I: After one year of treatment with natalizumab the average working hours per week had increased with 3.3 hours, corresponding to an economic value of 3216 euro per person per year. Paper II and III: After initiation of treatment with natalizumab, in an active phase of relapsing-remitting MS, the patients improved their working ability after one year from 31 % to 60 % (p<0.001) and reduced their sickness benefit correspondingly (p<0.001) in relation to their total employment rate. They also reported improved physical and cognitive ability in relation to their requirements. Short disease duration, younger age and lower Expanded Disability Status Scale (EDSS) grade at treatment onset predicted a positive effect on work ability and also improvement of walking ability correlated significantly with reduced sick leave. Paper IV: The proportion of individuals without any kind of sickness absence was higher in the MS population being exposed to disease modifying drugs compared to the unexposed population (66 % vs 38 %) (p<0.001). In addition, the proportion of patients with full-time sickness absence was higher in the unexposed compared to the exposed population (32 % vs 16 %) (p<0.001). The median EDSS was lower in the exposed compared to the unexposed MS population (p<0.001). Paper V: The proportion of MS patients who participated in the work force or studied was significantly higher in the northern cohort, where they had been exposed to more work promoting measures, compared with the southern cohort (p=0.022). MS patients in the northern cohort had significantly lower physical and cognitive requirements in their occupations, more adapted work conditions and could work more hours per week compared with the southern cohort. The EDSS level explained 12 % of the working ability in the northern cohort and 21 % in the southern cohort.

Conclusion Our results indicate that patients in the inflammatory phase of the disease may retain their work ability several years after disease onset if they are subjected to effective anti-inflammatory treatment regimens from disease onset. Furthermore, work ability may be additionally improved by adjusted working conditions even in the progressive phase of the disease. It is obvious that these results have implications in a socioeconomic perspective as well as for the individual patients as improved quality of life due to retained work-life participation. Long-term follow-up of our data is required to determine whether these positive effects are durable over longer time-periods.

Abstract [sv]

Bakgrund Multipel skleros (MS) är en kronisk inflammatorisk sjukdom i det centrala nervsystemet (CNS) och anses bero på en autoimmun attack mot nervbanor och nervceller i hjärna och ryggmärg. Prevalensen i Sverige uppskattas till ca 1 på 500. Sjukdomen debuterar ofta i 20-40 års åldern vilket gör MS till en av de främsta orsakerna till nedsatt arbetsförmåga och medför avsevärda ekonomiska konsekvenser såväl för individen som för samhället i stort. Det finns faktorer i sjukdomen som har stor påverkan på arbetsförmågan vid MS. En instabil sjukdom med återkommande inflammatorisk aktivitet kan resultera i vävnadsskador som medför olika typer och grader av funktionsnedsättning med nedsatt arbetsförmåga som följd. Studier har visat att fatigue, mobilitets- och kognitiva problem är primära symptom som hindrar personer med MS att arbeta. Faktorer som i sin tur ökar möjligheten att stanna kvar i arbetslivet är möjlighet till anpassade arbetsuppgifter och att arbeta i en anpassad arbetsmiljö med flexibla arbetstider.

Syftet med avhandlingen var att undersöka hur faktorer i sjukdomen, immunomodulerande behandling och krav i arbetet påverkar förmågan att arbeta och studera vid MS.

Metoder I en retrospektiv respektive en prospektiv studie jämfördes arbetsförmåga före och efter starten av andra generationens immunomodulerande behandling med natalizumab. Antalet arbetstimmar per vecka och även graden av sjukskrivning före och efter 1 års behandling beräknades. Effekten av hur sjukdomsspecifika och arbetsrelaterade faktorer påverkade arbetsförmågan utvärderades. Behandlingens effekt på trötthet och gångförmåga ställdes i relation till arbetsförmågan. Dessutom gjordes en hälsoekonomisk beräkning för att uppskatta behandlingens produktionsvinst. Dessutom har en tvärsnittsstudie genomförts för att utvärdera graden av sjukfrånvaro i två MS-populationer, varav den ena har och den andra inte har haft tillgång till bromsläkemedel. Arbetsförmåga har även studerats i två MS-populationer där man undersökte hur arbetskraven och flexibilitetsmöjligheterna i arbetet har påverkat förmågan att arbeta i förhållande till olika EDSS grader. Data samlades in med hjälp av frågeformuläret WAQ-MS.

Resultat Arbete I: Efter ett års behandling med natalizumab hade arbetstiden per vecka i genomsnitt ökat med 3.3 timmar, vilket motsvarade ett ekonomiskt värde på 3216 euro per person och år. Arbete II och III: Efter start av behandling med natalizumab, i en immunologiskt aktiv skovvis MS, ökade arbetsförmågan från 31 % till 60 % (p<0.001) av arbetad tid per vecka och grad av sjukpenning minskade på motsvarande vis (p<0.001) i förhållande till anställningen. Patienterna skattade även att deras fysiska och kognitiva förmåga hade förbättrats i förhållande till deras krav i arbetet. Kort sjukdomsduration, ung ålder och lägre funktionsnedsättning enligt Expanded Disability Status Scale (EDSS) predikterade för positiv effekt på arbetsförmåga. Även förbättring av gångförmågan korrelerade signifikant med minskad sjukfrånvaro. Arbete IV: I MS populationen som hade exponerats för bromsläkemedel var andelen som inte hade någon form av sjukfrånvaro 66 % mot 38 % i den population som aldrig hade behandlats med bromsläkemedel (p<0.001). Dessutom hade andelen patienter med heltidssjukfrånvaro minskat från 32% till 16 % (p<0.001). Median EDSS var lägre i MS populationen som var exponerad för bromsläkemedel (p<0.001). Arbete V: I den norra MS-kohorten som hade haft tillgång till arbetsfrämjande åtgärder i större utsträckning, var signifikant större andel personer i arbete och i egna studier (p=0.022) än i den södra kohorten. De anställda i den norra kohorten hade signifikant lägre fysiska (p=0.002) och kognitiva (p=0.046) krav, större andel anpassade arbetsuppgifter (p=0.006) och kunde arbeta flera timmar per vecka (p=0.007) än motsvarande grupp i den södra kohorten. Arbetsförmåga kunde förklaras till 12 % av EDSS nivån i norra och 21 % i södra kohorten.

Slutsats Våra resultat visar att patienter som är i den inflammatoriska fasen av sjukdomen kan behålla sin arbetsförmåga flera år efter sjukdomsdebut, om de behandlas med effektiva bromsläkemedel från sjukdomsdebut. Vidare kan möjligheten att stanna kvar i arbete förbättras genom flexibla och anpassade arbetsförhållanden, även i den progressiva fasen då funktionsnedsättningen ofta är mer uttalad. Det är uppenbart att dessa resultat får konsekvenser i såväl ett samhällsekonomiskt som livskvalitets perspektiv. Långsiktig uppföljning av våra data krävs för att avgöra om dessa positiva effekter är hållbara över längre tidsperioder.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2015. , 52 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1724
National Category
Neurology
Identifiers
URN: urn:nbn:se:umu:diva-102974ISBN: 978-91-7601-282-6 (print)OAI: oai:DiVA.org:umu-102974DiVA: diva2:811718
Public defence
2015-06-03, Hörsal D Unod T9, byggnad 1D, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2015-05-13 Created: 2015-05-12 Last updated: 2015-05-20Bibliographically approved
List of papers
1. Effect of treatment with natalizumab on ability to work in people with multiple sclerosis: productivity gain based on direct measurement of work capacity before and after 1 year of treatment
Open this publication in new window or tab >>Effect of treatment with natalizumab on ability to work in people with multiple sclerosis: productivity gain based on direct measurement of work capacity before and after 1 year of treatment
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2011 (English)In: BioDrugs, ISSN 1173-8804, E-ISSN 1179-190X, Vol. 25, no 5, 299-306 p.Article in journal (Refereed) Published
Abstract [en]

Background: Sweden is a high endemic region for multiple sclerosis (MS), a neurologic disorder characterized by repeated inflammatory episodes affecting the CNS. The disease has its peak age of onset at approximately 30 years and affects women twice as often as men. The young age of onset makes MS one of the major causes of reduced capacity to work due to neurologic disease in Western society. Natalizumab (Tysabri(R)) is among the new generation of biologic drugs for the treatment of MS. Clinical studies have demonstrated that natalizumab is an effective treatment for preventing relapses and inflammatory activity.

Objective: The aim of the study was to estimate the monetary value of treatment with natalizumab on the ability to work in patients with MS in Sweden, based on a direct measurement of weekly hours worked before and after 1 year of treatment with natalizumab.

Methods: A sample of patients, consisting of all patients who had started treatment with natalizumab during the period June 2007 May 2008, was identified through the Swedish Multiple Sclerosis Register (SMSreg). Data about sex, age, disease severity, and disease duration were collected from the register. Data about type of work and work capacity (number of hours worked per week) were collected retrospectively through a postal questionnaire. The average hours worked per week was estimated at baseline (2 weeks before treatment started) and at follow-up (50 weeks after treatment started), and the change was assigned an economic value using the human capital approach.

Results: This study showed that after 50 weeks of treatment with natalizumab, people with MS increased their productivity by 3.3 hours per week on average (p<0.01), which corresponded to an economic value of 3216 per person per year (year 2007 values). A shorter duration of illness or being 25-35 years old was significantly associated with a greater productivity gain (p = 0.025 and p = 0.002, respectively). Conclusion: A shorter duration of illness and a lower age at the start of treatment were significantly associated with a greater productivity gain after 50 weeks of treatment with natalizumab, which indicates that it is more beneficial to initiate efficient therapy early in patients with MS.

Place, publisher, year, edition, pages
Auckland: ADIS International, 2011
National Category
Cancer and Oncology Immunology Pharmacology and Toxicology
Identifiers
urn:nbn:se:umu:diva-49622 (URN)000296040300003 ()
Available from: 2011-11-18 Created: 2011-11-14 Last updated: 2017-12-08Bibliographically approved
2. Improved ability to work after one year of natalizumab treatment in multiple sclerosis. Analysis of disease-specific and work-related factors that influence the effect of treatment
Open this publication in new window or tab >>Improved ability to work after one year of natalizumab treatment in multiple sclerosis. Analysis of disease-specific and work-related factors that influence the effect of treatment
2013 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 5, 622-630 p.Article in journal (Refereed) Published
Abstract [en]

Background: Multiple sclerosis (MS) constitutes one of the major diseases that leads to neurological impairment and as a consequence also reduces ability to work. Objectives: The purpose of this study was to analyze possible effects on work ability resulting from highly active anti-inflammatory treatment in MS. Methods: We analyzed the effects of introducing an anti-inflammatory treatment, natalizumab, in MS, on factors related to work ability. This was done through a comprehensive questionnaire distributed to all patients in Sweden starting on natalizumab treatment between June 2007 and May 2008, identified via the Swedish National MS registry. Results: MS patients who were receiving sickness benefit and were treated with natalizumab approximately doubled their working ability in relation to their total employment rate. We also documented a significant improvement of their ability to cope with work-related requirements after one year of natalizumab treatment, an improvement which was independent of the previous level of employment. Predictors of a positive effect on work ability were short disease duration, younger age and lower Expanded Disability Status Scale (EDSS) grade at treatment onset. Conclusions: Our data support the notion that early inflammatory control in MS is essential to preserve a healthy state in MS that counteracts the negative consequences of the disease both at a personal and at a societal level.

Keyword
Multiple sclerosis, work ability, biological drugs, natalizumab
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-72707 (URN)10.1177/1352458512461391 (DOI)000318253100016 ()
Available from: 2013-06-10 Created: 2013-06-10 Last updated: 2017-12-06Bibliographically approved
3. Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial
Open this publication in new window or tab >>Reduced sick leave in multiple sclerosis after one year of natalizumab treatment. A prospective ad hoc analysis of the TYNERGY trial
2014 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 8, 1095-1101 p.Article in journal (Refereed) Published
Abstract [en]

Background: In a retrospective study, we have previously shown that work ability was improved after the initiation of natalizumab treatment in relapsing remitting multiple sclerosis (RRMS). In another prospective trial (TYNERGY) the effect on MS-related fatigue was evaluated after 12 months of treatment with natalizumab. A comprehensive Capacity for Work Questionnaire (CWQ) was used to collect data regarding number of working hours and sickness absence. The predefined intention-to-treat analysis regarding work ability did not, however, show significant results.

Objectives: The objective of this paper is to assess the amount of sick leave in RRMS before and after one year of natalizumab treatment and correlate it to fatigue and walking ability.

Methods: This is a post-hoc analysis of the complete data from the CWQ used in the TYNERGY trial. Results: MS patients receiving sickness benefit before start of treatment reduced their sickness benefit by an absolute change of 33% after one year of natalizunnab treatment. Younger age and improvement of walking ability correlated significantly with reduction of sick leave.

Conclusions: This ad-hoc analysis of prospectively collected data supported our previous retrospective study and thus indicates a positive relationship between natalizumab treatment and improvement in work ability.

Place, publisher, year, edition, pages
Sage Publications, 2014
Keyword
Multiple sclerosis, work ability, fatigue, motor fatigue, walking distance, biological drugs, natalizumab
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-91757 (URN)10.1177/1352458513517590 (DOI)000338819400012 ()
Available from: 2014-08-19 Created: 2014-08-15 Last updated: 2017-12-05Bibliographically approved
4. Improved work ability in a contemporary MS population compared with a historic non-treated MS population in the same geographic area of Sweden
Open this publication in new window or tab >>Improved work ability in a contemporary MS population compared with a historic non-treated MS population in the same geographic area of Sweden
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2015 (English)In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 1Article in journal (Refereed) Published
Abstract [en]

Background Multiple sclerosis (MS) often causes a reduced ability to work. Improved disease control as well as adjustment of working conditions may improve work ability in MS.

Objectives The objective of this article is to compare the degree of sickness absence in two MS populations that either have or have not received disease-modifying drug (DMD) treatments or active work-promoting measures.

Methods We investigated the occurrence of sickness absence in MS patients living in Västerbotten County, Sweden, in 2013, in which the majority of MS patients receive DMD treatment. The result was compared with a previous survey in the same area during a period when no DMD was available and no work-promoting measures for MS patients were practiced.

Results The proportion of MS patients active in the labor market or studying increased from 38% to 70% in the contemporary compared with the historic population (p < 0.001). The proportion of MS patients with a full-time disability pension decreased from 27% to 12% (p < 0.001). There was a significant decrease of sickness absence in several individual EDSS grades.

Conclusions Our data indicate that treatment with DMDs combined with active work-promoting measures lead to improved work ability in MS.

National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-102972 (URN)
Available from: 2015-05-12 Created: 2015-05-12 Last updated: 2017-12-04Bibliographically approved
5. The impact of adjusted work conditions on the working ability, measured with Work Ability Questionnaire - Multiple Sclerosis (WAQ–MS)
Open this publication in new window or tab >>The impact of adjusted work conditions on the working ability, measured with Work Ability Questionnaire - Multiple Sclerosis (WAQ–MS)
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(English)Manuscript (preprint) (Other academic)
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-102973 (URN)
Available from: 2015-05-12 Created: 2015-05-12 Last updated: 2015-05-13

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