Attributed Medical Cost of Annual Multiple Sclerosis Relapses in Iran Related to Exposure of Ambient Air Particulate Matter

Document Type : Original Research Paper

Authors

1 Department of Toxicology and Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences Research Center (PSRC), Tehran University of Medical Sciences, Tehran, Iran

2 Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Pharmacoeconomics and Pharmaceutical Administration, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

4 Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran

6 Department of Research Methodology and Data Analysis, Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran

10.22059/poll.2025.385165.2642

Abstract

Multiple Sclerosis (MS) imposes a substantial burden on the healthcare system and society. In addition, air pollution has a high economic burden in terms of health impacts. There is growing evidence that associates the MS onset and relapse with environmental factors, including ambient air particulate matters (PM). The objective of this study was to estimate the additional direct medical costs of MS relapses related to PM exposure within a one-year timeframe in Iran. The cost of relapse management was estimated from the healthcare system perspective. Using the relevant relapse probabilities associated with PM reduction, the incremental total cost was estimated and reported as a saving cost from PM reduction. The calculated direct medical cost for managing mild relapses was 9.90 (US dollars) USD per episode, and the average costs for moderate and severe relapses were 115.17 and 515.48 USD per episode, respectively. In Iran, relapse management in relapsing-remitting MS (RRMS) patients was estimated to cost 5,365,896 USD per year. A reduction of PM per 10 μg/m³ could result in an average cost savings of 13.84 USD per RRMS patient in a given year and an average annual cost savings of 1,041,279 USD for all patients with RRMS, equal to a reduction of 19.40% of MS relapse management costs. These findings will assist policymakers in developing well-informed decisions to improve public health outcomes, including the quality of life of MS patients, besides decreasing healthcare costs.

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Alhussaini, A. R., Aljabri, M. R., Al-Harbi, Z. T., Abdulrahman Almohammadi, G., Al-Harbi, T. M., & Bashir, S. (2023). Air Pollution and Its Adverse Effects on the Central Nervous System. Cureus, 15(5), e38927. https://doi.org/10.7759/cureus.38927 
Amrhein, V., Greenland, S., & McShane, B. (2019). Scientists rise up against statistical significance. Nature, 567(7748), 305-307. https://doi.org/10.1038/d41586-019-00857-9 
Anderson, G. F., Reinhardt, U. E., Hussey, P. S., & Petrosyan, V. (2003). It’s the prices, stupid: why the United States is so different from other countries. Health Aff (Millwood), 22(3), 89-105. https://doi.org/10.1377/hlthaff.22.3.89 
Angelici, L., Piola, M., Cavalleri, T., Randi, G., Cortini, F., Bergamaschi, R., Baccarelli, A. A., Bertazzi, P. A., Pesatori, A. C., & Bollati, V. (2016). Effects of particulate matter exposure on multiple sclerosis hospital admission in Lombardy region, Italy. Environ Res, 145, 68-73. https://doi.org/10.1016/j.envres.2015.11.017 
Ashtari, F., Esmaeil, N., Mansourian, M., Poursafa, P., Mirmosayyeb, O., Barzegar, M., & Pourgheisari, H. (2018). An 8-year study of people with multiple sclerosis in Isfahan, Iran: Association between environmental air pollutants and severity of disease. J Neuroimmunol, 319, 106-111. https://doi.org/10.1016/j.jneuroim.2018.02.019 
Azami, M., YektaKooshali, M. H., Shohani, M., Khorshidi, A., & Mahmudi, L. (2019). Epidemiology of multiple sclerosis in Iran: A systematic review and meta-analysis. PLoS One, 14(4), e0214738. https://doi.org/10.1371/journal.pone.0214738 
Bergamaschi, R., Cortese, A., Pichiecchio, A., Berzolari, F. G., Borrelli, P., Mallucci, G., Bollati, V., Romani, A., Nosari, G., Villa, S., & Montomoli, C. (2018). Air pollution is associated to the multiple sclerosis inflammatory activity as measured by brain MRI. Mult Scler, 24(12), 1578-1584. https://doi.org/10.1177/1352458517726866 
Brandt, S. J., Perez, L., Künzli, N., Lurmann, F., & McConnell, R. (2012). Costs of childhood asthma due to traffic-related pollution in two California communities. Eur Respir J, 40(2), 363-370. https://doi.org/10.1183/09031936.00157811 
Casado, V., Martínez-Yélamos, S., Martínez-Yélamos, A., Carmona, O., Alonso, L., Romero, L., Moral, E., Gubieras, L., & Arbizu, T. (2006). Direct and indirect costs of Multiple Sclerosis in Baix Llobregat (Catalonia, Spain), according to disability. BMC Health Serv Res, 6, 143. https://doi.org/10.1186/1472-6963-6-143 
Cohen, A. J., Brauer, M., Burnett, R., Anderson, H. R., Frostad, J., Estep, K., Balakrishnan, K., Brunekreef, B., Dandona, L., Dandona, R., Feigin, V., Freedman, G., Hubbell, B., Jobling, A., Kan, H., Knibbs, L., Liu, Y., Martin, R., Morawska, L.,…Forouzanfar, M. H. (2017). Estimates and 25-year trends of the global burden of disease attributable to ambient air pollution: an analysis of data from the Global Burden of Diseases Study 2015. Lancet, 389(10082), 1907-1918. https://doi.org/10.1016/s0140-6736(17)30505-6 
Confavreux, C., & Compston, A. (2006). The natural history of multiple sclerosis. McAlpine’s Multiple Sclerosis, 183-272. https://doi.org/10.1016/b978-0-443-07271-0.50006-9 
El-Fadel, M., & Massoud, M. (2000). Particulate matter in urban areas: health-based economic assessment. Science of The Total Environment, 257(2), 133-146. https://doi.org/https://doi.org/10.1016/S0048-9697(00)00503-9 
Fattahi, N., Saeedi Moghaddam, S., Mohebi, F., Rezaei, N., Masinaei, M., Fateh, S. M., Soleymani Hassanlouei, E., Manoochehri, F., Fattahi, E., Sahraian, M. A., Moradi-Lakeh, M., Mokdad, A. H., Naghavi, M., & Farzadfar, F. (2021). Burden of multiple sclerosis in Iran from 1990 to 2017. BMC Neurol, 21(1), 400. https://doi.org/10.1186/s12883-021-02431-1 
Goodin, D. S., Reder, A. T., Bermel, R. A., Cutter, G. R., Fox, R. J., John, G. R., Lublin, F. D., Lucchinetti, C. F., Miller, A. E., Pelletier, D., Racke, M. K., Trapp, B. D., Vartanian, T., & Waubant, E. (2016). Relapses in multiple sclerosis: Relationship to disability. Mult Scler Relat Disord, 6, 10-20. https://doi.org/10.1016/j.msard.2015.09.002 
Hawton, A., & Green, C. (2016). Health Utilities for Multiple Sclerosis. Value Health, 19(4), 460-468. https://doi.org/10.1016/j.jval.2016.01.002 
Heydarpour, P., Amini, H., Khoshkish, S., Seidkhani, H., Sahraian, M. A., & Yunesian, M. (2014). Potential impact of air pollution on multiple sclerosis in Tehran, Iran. Neuroepidemiology, 43(3-4), 233-238. https://doi.org/10.1159/000368553 
Huygens, S., & Versteegh, M. (2021). Modeling the Cost-Utility of Treatment Sequences for Multiple Sclerosis. Value Health, 24(11), 1612-1619. https://doi.org/10.1016/j.jval.2021.05.020 
Jeanjean, M., Bind, M. A., Roux, J., Ongagna, J. C., de Sèze, J., Bard, D., & Leray, E. (2018). Ozone, NO(2) and PM(10) are associated with the occurrence of multiple sclerosis relapses. Evidence from seasonal multi-pollutant analyses. Environ Res, 163, 43-52. https://doi.org/10.1016/j.envres.2018.01.040 
Kalincik, T. (2015). Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review. Neuroepidemiology, 44(4), 199-214. https://doi.org/10.1159/000382130 
Karimzadegan, H., Rahmatian, M., Farhud, D., & Yunesian, M. (2008). Economic Valuation of Air Pollution Health Im‌pacts in the Tehran Area, Iran. . Iran J Public Health, 37, 20-30. 
Kent, D. M., Rothwell, P. M., Ioannidis, J. P., Altman, D. G., & Hayward, R. A. (2010). Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal. Trials, 11, 85. https://doi.org/10.1186/1745-6215-11-85 
Kister, I., Chamot, E., Salter, A. R., Cutter, G. R., Bacon, T. E., & Herbert, J. (2013). Disability in multiple sclerosis: a reference for patients and clinicians. Neurology, 80(11), 1018-1024. https://doi.org/10.1212/WNL.0b013e3182872855 
Lorenzoni, L., & Dougherty, S. (2022). Understanding Differences in Health Care Spending: A Comparative Study of Prices and Volumes Across OECD Countries. Health Serv Insights, 15, 11786329221109755. https://doi.org/10.1177/11786329221109755 
Lotfi, F., Mansourian, M., Mirmoayyeb, O., Najdaghi, S., Shaygannejad, V., & Esmaeil, N. (2022). Association of Exposure to Particulate Matters and Multiple Sclerosis: A Systematic Review and Meta-Analysis. Neuroimmunomodulation, 29(1), 21-27. https://doi.org/10.1159/000516559 
Lublin, F. D., Coetzee, T., Cohen, J. A., Marrie, R. A., & Thompson, A. J. (2020). The 2013 clinical course descriptors for multiple sclerosis: A clarification. Neurology, 94(24), 1088-1092. https://doi.org/10.1212/wnl.0000000000009636 
McShane, B. B., Gal, D., Gelman, A., Robert, C., & Tackett, J. L. (2019). Abandon Statistical Significance. The American Statistician, 73(sup1), 235-245. https://doi.org/10.1080/00031305.2018.1527253 
Mehrpour, M., Shams-Hosseini, N. S., Rezaali, S., Sahraiian, M. A., & Taki, S. (2013). Effect of Air Pollutant Markers on Multiple Sclerosis Relapses. Iran J Public Health, 42(10), 1167-1173. 
Mirmosayyeb, O., Shaygannejad, V., Bagherieh, S., Hosseinabadi, A. M., & Ghajarzadeh, M. (2022). Prevalence of multiple sclerosis (MS) in Iran: a systematic review and meta-analysis. Neurol Sci, 43(1), 233-241. https://doi.org/10.1007/s10072-021-05750-w 
Mosadeghrad, A. M., Abbasi, M., & Heydari, M. (2022). Evaluation of Iran’s Health Financing System [Research]. Journal of School of Public Health and Institute of Public Health Research, 20(2), 111-132. http://sjsph.tums.ac.ir/article-1-6134-en.html 
Naddafi, K., Mesdaghinia, A., Abtahi, M., Hassanvand, M., & Saeedi, R. (2019). A review of studies on burden of disease attributable to environmental risk factors in Iran: achievements, limitations and future plans [Review Article]. Iranian Journal of Health and Environment, 12(2), 319-350. http://ijhe.tums.ac.ir/article-1-6257-en.html 
Nicholas, J., Zhou, H., & Deshpande, C. (2021). Annual Cost Burden by Level of Relapse Severity in Patients with Multiple Sclerosis. Adv Ther, 38(1), 758-771. https://doi.org/10.1007/s12325-020-01570-0 
O’Brien, J. A., Ward, A. J., Patrick, A. R., & Caro, J. (2003). Cost of managing an episode of relapse in multiple sclerosis in the United States. BMC Health Serv Res, 3(1), 17. https://doi.org/10.1186/1472-6963-3-17 
O’Connell, K., Kelly, S. B., Fogarty, E., Duggan, M., Buckley, L., Hutchinson, M., McGuigan, C., & Tubridy, N. (2014). Economic costs associated with an MS relapse. Mult Scler Relat Disord, 3(6), 678-683. https://doi.org/10.1016/j.msard.2014.09.002 
Oh, J., Vidal-Jordana, A., & Montalban, X. (2018). Multiple sclerosis: clinical aspects. Curr Opin Neurol, 31(6), 752-759. https://doi.org/10.1097/wco.0000000000000622 
Oikonen, M., Laaksonen, M., Laippala, P., Oksaranta, O., Lilius, E. M., Lindgren, S., Rantio-Lehtimäki, A., Anttinen, A., Koski, K., & Erälinna, J. P. (2003). Ambient air quality and occurrence of multiple sclerosis relapse. Neuroepidemiology, 22(1), 95-99. https://doi.org/10.1159/000067108 
Orlewska, E. (2006). Economic burden of multiple sclerosis: what can we learn from cost-of-illness studies? Expert Rev Pharmacoecon Outcomes Res, 6(2), 145-154. https://doi.org/10.1586/14737167.6.2.145 
Orme, M., Kerrigan, J., Tyas, D., Russell, N., & Nixon, R. (2007). The effect of disease, functional status, and relapses on the utility of people with multiple sclerosis in the UK. Value Health, 10(1), 54-60. https://doi.org/10.1111/j.1524-4733.2006.00144.x 
Papanicolas, I., Woskie, L. R., & Jha, A. K. (2018). Health Care Spending in the United States and Other High-Income Countries. JAMA, 319(10), 1024-1039. https://doi.org/10.1001/jama.2018.1150 
Prüss-Ustün, A., Bonjour, S., & Corvalán, C. (2008). The impact of the environment on health by country: a meta-synthesis. Environ Health, 7, 7. https://doi.org/10.1186/1476-069x-7-7 
Prüss-Ustün, A., & Corvalán, C. (2007). How much disease burden can be prevented by environmental interventions? Epidemiology, 18(1), 167-178. https://doi.org/10.1097/01.ede.0000239647.26389.80 
Repovic, P., & Lublin, F. D. (2011). Treatment of Multiple Sclerosis Exacerbations. Neurologic Clinics, 29(2), 389-400. https://doi.org/https://doi.org/10.1016/j.ncl.2010.12.012 
Roux, J., Bard, D., Le Pabic, E., Segala, C., Reis, J., Ongagna, J. C., de Sèze, J., & Leray, E. (2017). Air pollution by particulate matter PM(10) may trigger multiple sclerosis relapses. Environ Res, 156, 404-410. https://doi.org/10.1016/j.envres.2017.03.049 
Safari, Z., Fouladi-Fard, R., Vahedian, M., Mahmoudian, M. H., Rahbar, A., & Fiore, M. (2022). Health impact assessment and evaluation of economic costs attributed to PM2.5 air pollution using BenMAP-CE. International Journal of Biometeorology, 66(9), 1891-1902. https://doi.org/10.1007/s00484-022-02330-1 
Stenager, E. (2019). A global perspective on the burden of multiple sclerosis. Lancet Neurol, 18(3), 227-228. https://doi.org/10.1016/s1474-4422(18)30498-8 
Taghizadeh, F., Mokhtarani, B., & Rahmanian, N. (2023). Air pollution in Iran: The current status and potential solutions. Environmental Monitoring and Assessment, 195(6), 737. https://doi.org/10.1007/s10661-023-11296-5 
Tang, C., Li, Q. R., Mao, Y. M., Xia, Y. R., Guo, H. S., Wang, J. P., Shuai, Z. W., & Ye, D. Q. (2021). Association between ambient air pollution and multiple sclerosis: a systemic review and meta-analysis. Environ Sci Pollut Res Int, 28(41), 58142-58153. https://doi.org/10.1007/s11356-021-14577-z 
Torabipour, A., Asl, Z. A., Majdinasab, N., Ghasemzadeh, R., Tabesh, H., & Arab, M. (2014). A study on the direct and indirect costs of multiple sclerosis based on expanded disability status scale score in khuzestan, iran. Int J Prev Med, 5(9), 1131-1138. 
Tremlett, H., Zhao, Y., Rieckmann, P., & Hutchinson, M. (2010). New perspectives in the natural history of multiple sclerosis. Neurology, 74(24), 2004-2015. https://doi.org/10.1212/WNL.0b013e3181e3973f 
Vollmer, T. (2007). The natural history of relapses in multiple sclerosis. J Neurol Sci, 256 Suppl 1, S5-13. https://doi.org/10.1016/j.jns.2007.01.065 
Yamout, B., Al-Jumah, M., Sahraian, M. A., Almalik, Y., Khaburi, J. A., Shalaby, N., Aljarallah, S., Bohlega, S., Dahdaleh, M., Almahdawi, A., Khoury, S. J., Koussa, S., Slassi, E., Daoudi, S., Aref, H., Mrabet, S., Zeineddine, M., Zakaria, M., Inshasi, J.,…Alroughani, R. (2024). Consensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelines. Mult Scler Relat Disord, 83, 105435. https://doi.org/10.1016/j.msard.2024.105435