Three disease-modifying therapies (DMTs) for multiple sclerosis are now part of the World Health Organization essential medicines list.
By Bassem Yamout1, Tomas Kalincik2,3, Joanna Laurson-Doube4, Bernhard Hemmer5,6, Shanthi Viswanathan7
On July 26, 2023, the World Health Organization (WHO) added three disease-modifying therapies (DMTs) for multiple sclerosis (MS) to its Essential Medicines List (EML) for the first time1. The list is an important tool for achieving universal health coverage, providing guidance to governments, health facilities, and procurers on priority medicines to tackle important public health conditions. The EML includes medicines on the basis of solid evidence for safety and efficacy. Inclusion of any medication in the WHO EML is expected to be associated with increased availability and reimbursement by governmental agencies. The WFN was one of the 15 organizations that endorsed the application to the WHO, submitted by Multiple Sclerosis International Federation and WHO Collaborating Centre Bologna.
With this decision, the WHO formally acknowledged MS as a global health concern as well as the critical importance of making MS treatments available in all health systems at all times. Although most approved MS therapies have been made available in many countries, people with MS living in certain regions of the world, especially in resource-limited settings, do not have access to much-needed therapies, which are either unavailable or unaffordable. In fact, around 70% of countries across the world report that people with MS face barriers accessing DMTs2. The WHO decision to include three MS therapies with different routes of administration, efficacy, and tolerability in their updated list will undoubtedly help increase access of people with MS to high-quality, cost-effective, and evidence-based treatments.
This decision was the culmination of two years of relentless efforts by the MS International Federation (MSIF) and its partner organizations, including several neurological academies, scientific societies, and the regional committees for Treatment and Research in MS (TRIMS). The MSIF set up two independent, multidisciplinary panels and started a comprehensive and rigorous review process in partnership with the WHO Collaborating Centre Bologna, and supported by the Cochrane MS group and McMaster GRADE Centre, both of which are internationally regarded as experts in the field of evidence-based reviews and decision-making3.
The WHO EML Committee decided to add rituximab, cladribine, and glatiramer acetate to the new EML4. Rituximab has been extensively used for treating MS patients especially in low/lower-middle income countries (LLMIC) due to its cost-effectiveness, but its off-label status has curtailed reimbursement by governmental and private insurance systems5. Its inclusion on the WHO EML should help in this respect. The decision to support off-label use of rituximab is supported by strong evidence of its efficacy and safety for this indication.
Dr. Deanna Saylor
“People with MS in lower-resourced settings, including most low- and middle-income countries, often face numerous challenges in their MS journeys. This starts with accessing the specialists and diagnostic tests, including MRIs, required to obtain their diagnosis, and continues with accessing effective treatments for their MS. As a result, people with MS in low- and middle-income countries often are untreated, undertreated, or have to expend significant personal resources in order to obtain treatment. Based on my own experience taking care of people with MS in Zambia, I am confident that if DMTs are available, treatment of MS is feasible, safe, and likely to be highly effective and result in good outcomes among people with MS in low- and middle-income countries.”
Dr. Deanna Saylor, clinical chair of the MSIF Essential Medicines Panel
Large-scale randomized controlled trials (e.g. DELIVER-MS and TREAT-MS) continue to study early use of high efficacy DMTs versus escalation treatment by treatment6,7. Nevertheless, studies have already suggested that early treatment with higher efficacy DMTs in patients with MS can lead to better outcomes compared to treatment initiation with low efficacy DMTs and escalating therapy only upon disease activity or progression8-12.
Intentionally, the treatments listed on the WHO EML are not categorized as first-, second-, or third-line treatments, but encourage clinicians and people with MS to determine the most appropriate course of treatment for the clinical and personal circumstances. Rituximab, cladribine, and glatiramer acetate represent different tiers of treatment effectiveness, modes of administration, and safety in pregnancy and breastfeeding. In particular, glatiramer acetate is known for its favorable safety profile in pregnancy and breastfeeding when compared with the two more potent listed therapies. Pregnancy is a particularly important clinical scenario due to high prevalence of MS in young women and more challenging access to family planning services in LMICs.
Countries can use the WHO decision to shift their treatment algorithms, allowing patients access to higher efficacy DMTs, e.g. rituximab, early in their disease course. Speaking from personal experience treating refugees in the Middle East, the use of rituximab, a high efficacy, safe, and low-cost DMT, made a considerable difference in the lives of people with MS that fled their country and had no means of affording any MS therapy13.
However, despite countries endorsing the concept of the EML over the years, implementing the list into local practice is variable and fraught with challenges, especially in LMICs. We should use this momentous decision to push forward the implementation of the WHO EML through coordinated efforts among national scientific and patient societies, international scientific, and health care organizations, frontline clinicians, and local policymakers.
Patients with MS cannot wait for decades to have this EML implemented: The time for action is now through the growing international momentum to improve care and access to treatment for multiple sclerosis.
1. Yamout is with the Neurology Institute, Harley Street Medical Centre, Abu Dhabi-UAE. 2. Kalincik is with the Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. 3. Laurson-Doube is with CORe, Department of Medicine, Melbourne, Australia.4. Hemmer is with Multiple Sclerosis International Federation, London, United Kingdom. 5. Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technische Universität München, Germany. 6. Munich Cluster for Systems Neurology (SyNergy), Germany. 7. Viswanathan is with Department of Neurology, Kuala Lumpur, Hospital, Malaysia.
References
1. WHO endorses landmark public health decisions on Essential Medicines for Multiple Sclerosis [Internet]. [cited 2023 Aug 1]. Available from: https://www.who.int/news/item/26-07-2023-who-endorses-landmark-public-health-decisions-on-essential-medicines-for-multiple-sclerosis
2. MS International Federation. Atlas of MS 2020 – Clinical management report [Internet]. 2020 [cited 2022 Dec 5]. Available from: https://pubmed.ncbi.nlm.nih.gov/35173808/
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