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WHO adds cladribine, glatiramer acetate and rituximab to the MS EML

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Today, MS affects ~2.8 million people worldwide. Historically, it was believed that the prevalence of MS in African countries were very low. However, a new study argues that MS prevalence in Africa is likely underestimated due to a number of challenges (see below) including underreporting. According to the 2019 Global Study of Diseases, MS affects around 100 to 200 Africans per 100 000  population, compared to the global prevalence of 35.9 per 100 000 population.2,3,4

Vector of how MS affects the brain
As MS progresses, patients may become increasingly disabled, further impacting their mobility, ability to self-care, and overall independence. (Image from Shutterstock)

Interestingly, studies show that specific alleles (human leukocyte antigen (HLA) gene specifically within DRB1 [1503] gene) cause MS in African populations. Other risks in Africa include infection with the Epstein–Barr virus and lifestyle factors such as vitamin D deficiency, smoking, and obesity.3

How effective is MS managed in Africa?

Aderinto and colleagues state managing MS in Africa faces numerous challenges. These include:3

  • A lack of awareness and understanding of MS symptoms, which negatively affects early diagnosis and proper treatment.
  • Limited access to specialised healthcare, scarcity of neurologists, and inadequate infrastructure, including hospitals and clinics. Accurate diagnosis of MS is hindered by the varying availability of diagnostic tools, such as magnetic resonance imaging technologies.
  • Financial constraints, such as the high costs of medications, diagnostic tools, and treatments.
  • Sociocultural factors, including stigma, traditional beliefs, and a mistrust of modern medicine, contribute to delayed diagnosis, treatment adherence issues, and healthcare access problems. In many African cultures, disability is viewed negatively, resulting in social isolation and discrimination against MS patients.
  • Patients often travel long distances for testing, leading to both financial and time-related challenges.
  • The lack of support groups exacerbates these challenges, hindering emotional and psychological support for patients and their families.

What are the signs and symptoms of MS and how does it impact QoL?

Signs and symptoms include fatigue, muscle weakness, spasms, pain, numbness and tingling, balance issues (affecting mobility), visual disturbances (optic neuritis, causing inflammation of the optic nerve, can lead to vision loss or blurred vision, along with double vision and involuntary eye movements), bladder and bowel, as well as sexual dysfunctions.5

As MS progresses (see below), patients may become increasingly disabled, further impacting their mobility, ability to self-care, and overall independence. The declining physical abilities may necessitate the use of assistive devices or mobility aids.

MS not only affects patients’ physical abilities, but also have a profound effect on almost all other aspects of their lives. The cognitive effects of MS can lead to limited social participation, leading to feelings of isolation and loneliness. MS symptoms can interfere with work, potentially leading to unemployment or early retirement.5

Family dynamics may face strain as members become caregivers or adapt to changes in patients’ abilities. The costs of MS treatment, medications, and accessibility modifications can pose a substantial financial burden on individuals and families.5

According to Papathanasiou et al, cognitive dysfunction, fatigue (affecting 80% of patients living with MS and reported by 66% as the most disabling symptom), and depression are often overlooked by healthcare professionals. Cognitive dysfunction affects up to 65% of MS patients and impairs processing speed, memory, attention, executive functioning, and verbal fluency.6

Depression, prevalent in up to 50% of MS patients, significantly impacts quality of life (QoL). Suicidal rates are twice as high in patients living with MS compared to the general population. Clinicians are urged to regularly assess for depression in patients living with MS and ensure appropriate treatment.6

 Patients living with MS also exhibit high anxiety and stress levels due to uncertainties about the disease's course, its impact on daily life, and potential disability progression. Furthermore, the diagnosis of MS can be life-altering, prompting feelings of loss, grief, and uncertainty about the future.5

Progressive nature of MS

As mentioned, MS is a progressive disease that can be broadly classified into:

  • Relapsing-remitting MS (RRMS): Patients living with RRMS undergo periods of relapse or exacerbations, succeeded by periods of remission, where symptoms partially or completely improve.
  • Secondary progressive MS (SPMS): Following years of RRMS, some patients may transition to SPMS, characterised by a more consistent disease progression and fewer instances of remission.
  • Primary progressive MS (PPMS): PPMS entails a steady progression of symptoms from the disease's onset, lacking distinct relapses and remissions.
  • Progressive-relapsing MS (PRMS): PRMS, a less common subtype, involves a continuous progression of symptoms with sporadic relapses and remissions.

Treatment algorithm

According to Bisht and Mehra, substantial strides have been made in the treatment of MS over the past few decades. Several effective pharmacotherapies have been developed of which disease-modifying therapy (DMT) is the mainstay. DMTs are effective in preventing relapses, slowing disease progression, and addressing symptoms.5

Traditional DMTs, including interferons beta, glatiramer acetate, immunosuppressants and monoclonal antibodies (eg ocrelizumab, rituximab, natalizumab), target the immune system to diminish inflammation and suppress the immune response targeting the myelin sheath.5

The Middle East North Africa Committee for Treatment and Research in Multiple Sclerosis (MENACTRIMS) updated their treatment algorithm in 2023 (see Figure 1). A representative of the committee will share insights at the upcoming Neurological Association of South Africa Congress.7

According to the authors of the guideline, the diagnosis of MS relies on incorporating clinical and paraclinical findings to prove dissemination in space and time and exclude alternative diseases that can explain the findings at hand. The differential diagnostic workup should be guided by clinical and laboratory red flags to avoid unnecessary tests. Appropriate selection of MS therapies is critical to maximise patient benefit.7

In 2023, the World Health Organization (WHO) published the new editions of the Model Lists of Essential Medicines (EML) and Essential Medicines for Children, which include important new medicines that delay or slow the progression of MS. The WHO added cladribine, glatiramer acetate and rituximab to the EML, filling an important gap  given the large global burden of MS.2

Listing of these medicines as treatment options for MS with different routes of administration, different prices (with the availability of generics and biosimilars) and different recommended uses, is aimed at facilitating improved access to treatment for patients living with MS around the world, stated the body.2

The decision to support off-label use of rituximab is supported by strong evidence of its efficacy and safety for this indication. This recommendation, which is in line with previous recommendations by the WHO’s Expert Committee, could lead to major health benefits worldwide.2

Conclusion

The historical roots of MS can be traced back to Lidwina the Virgin. Today, ~2.8 million patients globally are living with MS. MS affects 100 to 200 people per 100 000 population in Africa. The effective management of MS on the continent faces numerous challenges, including limited awareness, healthcare access, and socio-cultural factors. The impact of MS extends beyond physical manifestations, impacting cognitive function, mental health, and overall QoL.

Figure 1: MENACTRIMS 2023 algorithm for the treatment of RRMS8

References

1. Orrell RW. Multiple Sclerosis: The History of a Disease. J R Soc Med, 2005.
2. World Health Organization. WHO endorses landmark public health decisions on Essential Medicines for Multiple Sclerosis. 2023. [Internet]. Available at: https://www.who.int/news/item/26-07-2023-who-endorses-landmark-public-health-decisions-on-essential-medicines-for-multiple-sclerosis
3. Aderinto N, Muili AO, Opanike J. Navigating the journey of multiple sclerosis management in Africa, overcoming hurdles and harnessing opportunities: a review. Ann Med Surg (Lond), 2023.
4. Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler, 2020.
5. Bisht C, Mehra D. Multiple Sclerosis: An Overview in 2023. Journal of Multiple Sclerosis, 2023.
6. Papathanasiou A, Saunders L, Sare G. Symptom management of patients with multiple sclerosis in primary care: focus on overlooked symptoms. Br J Gen Pract, 2021.
7. Yamout B, Al-Jumah M, Sahraian MA, et al. Consensus recommendations for diagnosis and treatment of Multiple Sclerosis: 2023 revision of the MENACTRIMS guidelines. Mult Scler Relat Disord, 2024.
8. MENACTRIMS. 2023 Algorithm for treatment of RRMS. 2023. [Internet]. Available at: https://menactrims.org/treatment-algorithm/

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