FOR US HEALTHCARE PROFESSIONALS
B CELLS & RMS
B cell illustration
B cell illustration
B cell illustration
B cell illustration
B cell illustration
B cell illustration
B cell illustration
B cell illustration

B-cell–targeting Treatments for RMS: Benefits & Concerns

Historically, multiple sclerosis (MS) was considered to be a T-cell–mediated disorder. However, accumulating evidence has revealed that B cells also play a critically important role in the disease process.1,2

B-cell–targeting Therapies

Today, many high-efficacy disease-modifying treatments (DMTs) for relapsing forms of MS either directly deplete B cells or block lymphocyte entry into the central nervous system.1-5 In contrast, other classes of DMTs for MS work by sequestering lymphocytes within the lymph nodes (S1P inhibitors) or by modulating the immune response (Nrf2 pathway inhibitors).1,6

B-cell Depletion as a Treatment Option

B-cell–depleting therapies have shown high efficacy in reducing relapse rates and disability progression, along with improved radiological outcomes.1,2,7 Because of their efficacy, these medications are considered for broad use in RMS, including in newly diagnosed patients.8 While these treatments offer the benefits of high efficacy, they are associated with certain trade-offs.1

B-cell Counts & Immunosuppression

B-cell–depleting treatments for relapsing multiple sclerosis (RMS) have been associated with increased rates of infections involving the respiratory tract, gastrointestinal tract, and urinary tract, as well as with reactivation of latent infections, such as tuberculosis, hepatitis, and herpes zoster. These infections can be serious or life-threatening.1,2,6,9 In addition, lower B-cell counts to the point of lymphopenia are a well-recognized possible side effect of DMTs that directly deplete B cells.3,10

Infection concerns are not limited to DMTs that directly target B cells. Like these high-efficacy treatments, medications for RMS that sequester lymphocytes in the lymph nodes or that modulate lymphocyte function can also raise the risk of infection. These types of treatments also are associated with an increased risk of herpes virus infection or reactivation, as well as the possibility of other opportunistic infections.11-14

Female doctor touching female patient's face
Download Infection Questionnaire
B cell illustration
B cell illustration

In MS management, immunosuppression can be a concern with healthcare providers and patients due to its association with an increased risk of infection and its potential impact on patients.10,15-20

B cell illustration

Your patients may have questions about how immunosuppression might lead them to:

  • Limit or avoid crowd-related social activities
  • Have concerns about being vaccinated20
  • Be anxious about the possibility of infections that their children could bring back from school or daycare
B cell illustration

Infection Risk is Among Treatment-related Considerations

A 2017 survey of patients (n = 129) with RMS documented their preference for DMT treatments with:

  • Greater efficacy
  • Lower out-of-pocket costs
  • Lower risk of respiratory infection
  • Lower risk of infections requiring hospitalization

In addition, oral medication was preferred over once- or twice-weekly injectable therapy.17

A subsequent, 2023 survey-based study of patient preferences (n = 817), reported patients ranking their preferences as18:

  • Relief of physical & cognitive fatigue & relapse prevention
  • Effects on MS progression
  • Immune system recovery time
  • Drug interactions
  • Monitoring visits

Both the nature and the likely duration of possible immunosuppression and infection risk merit discussion. These topics can be incorporated into the conversations with your patients as part of the shared decision-making process in MS treatment.

Treatment Timing & Duration of Related Immunosuppression

Among DMTs whose mechanism of action involves B-cell depletion to the point of lymphopenia, the duration of lymphopenia-related immunosuppression varies.3,10,21

For treatments in which lymphocyte counts generally return to the normal range between doses, the period of immunosuppression is transient rather than continuous.22 As a result, the heightened risk of treatment-associated infection is also transient. These DMTs can be classified as immune reconstitution therapies.22

Conversely, when the time to recovery of lymphocytes to normal range is longer than the dosing interval, patients remain in a continuous state of immunosuppression while on treatment.22

These aspects of therapy should be carefully considered by clinicians and patients.10,21

Immunosenescence & Older Patients

Aging can lead to a progressive and general decline in the functioning of physiologic systems, including the immune system. Immunologic changes affecting older patients can include a weakened immune response, chronic inflammation, and a heightened risk of autoimmune disease. Collectively, these changes are described as immunosenescence.23-25

When treating older patients with MS, there are important clinical considerations linked to immunosenescence. The qualitative and quantitative changes in the adaptive immune system that occur with aging can:

  • Diminish effectiveness of vaccines26,27
  • Lead to reactivation of latent viral and bacterial infections26
  • Weaken immune defense against respiratory infections, increasing the risk for common infections, such as influenza23,28
  • Impact incidence of malignancies in the elderly24,27,29

Most current DMTs for MS target the immune system. However, the mechanism, extent, and duration of their immunologic effects vary.1,30,31 These aspects of therapy are relevant in older adults whose ability to fight infection has been compromised by immunosenescence.32

Talk to your patients about the possibility of long-term immunosuppression risk & how this may affect them

Discover a treatment that offers non-continuous ​immunosuppression

DMT = disease-modifying therapy; Nrf2 = nuclear factor (erythroid-derived 2); RMS = relapsing multiple sclerosis; S1P = sphingosine-1-phosphate

REFERENCES:

  1. Hauser SL, Cree BAC. Treatment of multiple sclerosis: a review. Am J Med. 2020;133:1380-1390.
  2. Mulero P, Midaglia L, Montalban X. Ocrelizumab: a new milestone in multiple sclerosis therapy. Ther Adv Neurol Disord. 2018;11:1-6.
  3. Bar-Or A, Grove RA, Austin DJ, et al. Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis: the MIRROR study. Neurology. 2018;90(20):e1805-e1814.
  4. Samjoo IA, Worthington E, Drudge C, et al. Efficacy classifications of modern therapies for multiple sclerosis. J Comp Effect Res. 2021;10(6):495-507.
  5. Giovannoni G, Comi G, Cook S, et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. New Engl J Med. 2010;362(5):416-426.
  6. Piehl F. Current and emerging disease-modulatory therapies and treatment targets for multiple sclerosis. J Intern Med. 2021;289(6):771-791.
  7. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus teriflunomide in multiple sclerosis. New Engl J Med. 2020;383(6):546-557.
  8. Freeman L, Longbrake EE, Coyle PK, et al. High-efficacy therapies for treatment-naïve individuals with relapsing-remitting multiple sclerosis. CNS Drugs. 2022;36(12):1285-1299.
  9. Havrdova E, Cohen JA, Horakova D, et al. Understanding the positive benefit:risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the Alemtuzumab Clinical Development Program. Ther Clin Risk Manag. 2017;13:1423-1437.
  10. Fox EJ, Buckle GJ, Singer B, et al. Lymphopenia and DMTs for relapsing forms of MS. Neurol Clin Pract. 2019;9(1):53-63.
  11. GILENYA [prescribing information]. Cambridge, MA: Novartis Pharmaceuticals Corporation; 2024.
  12. MAYZENT [prescribing information]. Cambridge, MA: Novartis Pharmaceuticals Corporation; 2024.
  13. TECFIDERA [prescribing information]. Cambridge, MA: Biogen; 2024.
  14. VUMERITY [prescribing information]. Cambridge, MA: Biogen; 2024.
  15. Cameron E, Rog D, McDonnell G, et al. Factors influencing multiple sclerosis disease-modifying treatment prescribing decisions in the United Kingdom: a qualitative interview study. Mult Scler Rel Disord. 2019;27:378-382.
  16. Mateen FJ, Rezzaei S, Alakel N, et al. Impact of COVID‑19 on U.S. and Canadian neurologists’ therapeutic approach to multiple sclerosis: a survey of knowledge, attitudes, and practices. J Neurol. 2020;267(12):3467-3475.
  17. Hincaple AL, Penm J, Burns CF. Factors associated with patient preferences for disease-modifying therapies in multiple sclerosis. J Manag Care Spec. 2017;23(8):822-830.
  18. Tervonen T, Fox RJ, Brooks A, et al. Treatment preferences in relation to fatigue of patients with relapsing multiple sclerosis: a discrete choice experiment. Mult Scler J Exp Transl Clin. 2023;9(1):1-11.
  19. Zecca C, Gobbi C. Long-term treatment with anti-CD20 monoclonal antibodies is untenable because of risk: yes. Mult Scler. 2022;28(8):1173-1175.
  20. Kim E, Haag A, Nguyen J, et al. Vaccination of multiple sclerosis patients during the COVID-19 era: novel insights into vaccine safety and immunogenicity. Mult Scler Relat Disord. 2022;67:104712.
  21. Comi G, Cook S, Giovannoni G, et al. Effect of cladribine tablets on lymphocyte reduction and repopulation dynamics in patients with relapsing multiple sclerosis. Mult Scler Relat Disord. 2019;29:168-174.
  22. Sorensen PS, Sellebjerg F. Pulsed immune reconstitution therapy in multiple sclerosis. Ther Adv Neurol Disord. 2019;12:1-16.
  23. Adamczyk-Sowa M, Nowak-Kiczmer M, Jaroszewicz J, et al. Immunosenescence and multiple sclerosis. Neuro Neurochir Pol. 2022;56(3):220-227.
  24. Aiello A, Farzaneh F, Candore G, et al. Immunosenescence and its hallmarks: how to oppose aging strategically? a review of potential options for therapeutic intervention. Front Immunol. 2019;(10):2247.
  25. Michaud M, Balardy L, Moulis G, et al. Proinflammatory cytokines, aging, and age-related diseases. J Am Med Dir Assoc. 2013;14(12):877-882.
  26. Pawelec G. Age and immunity: what is "immunosenescence"?. Exp Gerontol. 2018;105:4-9.
  27. Oh SJ, Lee JK, Shin OS. Aging and the immune system: the impact of immunosenescence on viral infection, immunity and vaccine immunogenicity. Immune Netw. 2019;19(6):e37.
  28. Li Y, Wang C, Peng M. Aging immune system and its correlation with liability to severe lung complications. Front Pub Health. 2021;9:735151.
  29. Aw D, Silva AB, Palmer DB. Immunosenescence: emerging challenges for an ageing population. Immunology. 2007;120(4):435-446.
  30. Giovannoni G. Disease-modifying treatments for early and advanced multiple sclerosis: a new treatment paradigm. Curr Opin Neurol. 2018;31(3):233-243.
  31. Rommer PS, Milo R, Han MH, et al. Immunological aspects of approved MS therapeutics. Front Immunol. 2019;10:1564.
  32. Graves JS, Krysko KM, Hua LH, et al. Ageing and multiple sclerosis. Lancet Neurol. 2023;22(1):66-77.