Unmet Needs and Treatment of Relapsing-Remitting Multiple Sclerosis in Saudi Arabia: Focus on the Role of Ofatumumab.
B cells
Multiple sclerosis
Ofatumumab
Relapsing–remitting multiple sclerosis
Journal
Neurology and therapy
ISSN: 2193-8253
Titre abrégé: Neurol Ther
Pays: New Zealand
ID NLM: 101637818
Informations de publication
Date de publication:
Dec 2022
Dec 2022
Historique:
received:
06
07
2022
accepted:
17
08
2022
pubmed:
2
9
2022
medline:
2
9
2022
entrez:
1
9
2022
Statut:
ppublish
Résumé
Treatment-pattern data suggest that some patients with multiple sclerosis (MS) in the Kingdom of Saudi Arabia (KSA) may not be receiving optimal treatment. A virtual meeting of ten expert Saudi neurologists, held on October 23, 2020, discussed unmet needs in relapsing-remitting MS (RRMS), and the role of ofatumumab as a suitable treatment in the KSA. Multiple unmet needs were identified: poor quality of life, with high rates of depression and anxiety; a negative impact of MS on work ability; treatment choices that may compromise efficacy for safety or vice versa; inconvenient or complex dosage regimens; and limited access to patient education and support. Early use of highly effective disease-modifying treatments (DMTs) results in better patient outcomes than starting with less effective treatments and downstream escalation, but this strategy may be underutilized in the KSA. B cells are important in MS pathogenesis, and treatments targeting these may improve clinical outcomes. Ofatumumab differs from other B cell-depleting therapies, being a fully human monoclonal antibody that binds to CD20 at a completely separate site from the epitope bound by ocrelizumab, and being administered by subcutaneous injection. When compared with teriflunomide in two randomized, phase 3 clinical trials in patients with RRMS, ofatumumab was associated with significant reductions in annualized relapse rates, rates of confirmed disability worsening, and active lesions on magnetic resonance imaging. The incidence of adverse events, including serious infections, was similar with the two treatments. Ofatumumab is a valuable first- or second-line treatment option for RRMS in the KSA, particularly for patients who would benefit from highly effective DMTs early in the disease course, and for those who prefer the convenience of self-injection. Future research will clarify the position of ofatumumab in RRMS treatment, and comparative cost data may support the broad inclusion of ofatumumab in formularies across the KSA.
Identifiants
pubmed: 36048334
doi: 10.1007/s40120-022-00401-4
pii: 10.1007/s40120-022-00401-4
pmc: PMC9434517
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1457-1473Informations de copyright
© 2022. The Author(s).
Références
AlJumah M, Bunyan R, Al Otaibi H, et al. Rising prevalence of multiple sclerosis in Saudi Arabia, a descriptive study. BMC Neurol. 2020;20(1):49.
pubmed: 32035478
pmcid: 7007659
doi: 10.1186/s12883-020-1629-3
Etemadifar M, Nikanpour Y, Neshatfar A, Mansourian M, Fitzgerald S. Incidence and prevalence of multiple sclerosis in Persian Gulf area: a systematic review and meta-analysis. Mult Scler Relat Disord. 2020;40: 101959.
pubmed: 31991397
doi: 10.1016/j.msard.2020.101959
AlJumah M, Otaibi HA, Al Towaijri G, et al. Familial aggregation of multiple sclerosis: results from the national registry of the disease in Saudi Arabia. Mult Scler J Exp Transl Clin. 2020;6(4):2055217320960499.
pubmed: 33110617
pmcid: 7556172
Krieger SC, Sumowski J. New insights into multiple sclerosis clinical course from the topographical model and functional reserve. Neurol Clin. 2018;36(1):13–25.
pubmed: 29157394
doi: 10.1016/j.ncl.2017.08.003
Stuifbergen AK, Blozis SA, Harrison TC, Becker HA. Exercise, functional limitations, and quality of life: a longitudinal study of persons with multiple sclerosis. Arch Phys Med Rehabil. 2006;87(7):935–43.
pubmed: 16813781
doi: 10.1016/j.apmr.2006.04.003
Antel J, Antel S, Caramanos Z, Arnold DL, Kuhlmann T. Primary progressive multiple sclerosis: part of the MS disease spectrum or separate disease entity? Acta Neuropathol. 2012;123(5):627–38.
pubmed: 22327362
doi: 10.1007/s00401-012-0953-0
Heydarpour P, Khoshkish S, Abtahi S, Moradi-Lakeh M, Sahraian MA. Multiple sclerosis epidemiology in Middle East and North Africa: a systematic review and meta-analysis. Neuroepidemiology. 2015;44(4):232–44.
pubmed: 26088327
doi: 10.1159/000431042
Nazish S, Shahid R, Zafar A, et al. Clinical presentations and phenotypic spectrum of multiple sclerosis at a university hospital in Saudi Arabia. J Clin Neurol. 2018;14(3):359–65.
pubmed: 29971975
pmcid: 6031989
doi: 10.3988/jcn.2018.14.3.359
Al-Abdullah MS, Siddiqui AF. Demographic and disease characteristics of multiple sclerosis in the Southwest Region of Saudi Arabia. Neurosciences (Riyadh). 2018;23(4):320–5.
doi: 10.17712/nsj.2018.4.20180235
Moradi N, Sharmin S, Malpas C, et al. Utilization of multiple sclerosis therapies in the Middle East over a decade: 2009–2018. CNS Drugs. 2021;35:1097–106.
pubmed: 34164782
doi: 10.1007/s40263-021-00833-w
Buc M. New biological agents in the treatment of multiple sclerosis. Bratisl Lek Listy. 2018;119(4):191–7.
pubmed: 29663814
Gensicke H, Leppert D, Yaldizli O, et al. Monoclonal antibodies and recombinant immunoglobulins for the treatment of multiple sclerosis. CNS Drugs. 2012;26(1):11–37.
pubmed: 22171583
doi: 10.2165/11596920-000000000-00000
He A, Merkel B, Brown JWL, et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020;19(4):307–16.
pubmed: 32199096
doi: 10.1016/S1474-4422(20)30067-3
Simonsen CS, Flemmen H, Broch L, et al. Early high efficacy treatment in multiple sclerosis is the best predictor of future disease activity over 1 and 2 years in a Norwegian population-based registry. Front Neurol. 2021;12: 693017.
pubmed: 34220694
pmcid: 8248666
doi: 10.3389/fneur.2021.693017
Algahtani HA, Shirah BH, Alzahrani FA, Abobaker HA, Alghanaim NA, Manlangit JS Jr. Quality of life among multiple sclerosis patients in Saudi Arabia. Neurosciences (Riyadh). 2017;22(4):261–6.
doi: 10.17712/nsj.2017.4.20170273
Alhazzani AA, Alqahtani MS, Alahmari MS, et al. Quality of life assessment among multiple sclerosis patients in Saudi Arabia. Neurosciences (Riyadh). 2018;23(2):140–7.
doi: 10.17712/nsj.2018.2.20170335
Goksel Karatepe A, Kaya T, Gunaydn R, Demirhan A, Ce P, Gedizlioglu M. Quality of life in patients with multiple sclerosis: the impact of depression, fatigue, and disability. Int J Rehabil Res. 2011;34(4):290–8.
pubmed: 21946317
doi: 10.1097/MRR.0b013e32834ad479
Miller A, Dishon S. Health-related quality of life in multiple sclerosis: the impact of disability, gender and employment status. Qual Life Res. 2006;15(2):259–71.
pubmed: 16468081
doi: 10.1007/s11136-005-0891-6
Zwibel HL, Smrtka J. Improving quality of life in multiple sclerosis: an unmet need. Am J Manag Care. 2011;17(Suppl 5):S139–45.
pubmed: 21761952
Hakim EA, Bakheit AM, Bryant TN, et al. The social impact of multiple sclerosis–a study of 305 patients and their relatives. Disabil Rehabil. 2000;22(6):288–93.
pubmed: 10864132
doi: 10.1080/096382800296755
Larocca NG. Impact of walking impairment in multiple sclerosis: perspectives of patients and care partners. Patient. 2011;4(3):189–201.
pubmed: 21766914
doi: 10.2165/11591150-000000000-00000
Boeschoten RE, Braamse AMJ, Beekman ATF, et al. Prevalence of depression and anxiety in multiple sclerosis: a systematic review and meta-analysis. J Neurol Sci. 2017;372:331–41.
pubmed: 28017241
doi: 10.1016/j.jns.2016.11.067
Schmidt S, Jostingmeyer P. Depression, fatigue and disability are independently associated with quality of life in patients with multiple sclerosis: results of a cross-sectional study. Mult Scler Relat Disord. 2019;35:262–9.
pubmed: 31437741
doi: 10.1016/j.msard.2019.07.029
Bahathig A, Alblowi MA, Alhilali AA, et al. The prevalence and association of depression and anxiety with multiple sclerosis in Riyadh, Saudi Arabia: a cross-sectional study. Cureus. 2020;12(12): e12389.
pubmed: 33532152
pmcid: 7845751
Alhussain H, Aldayel AA, Alenazi A, Alowain F. Multiple sclerosis patients in Saudi Arabia: prevalence of depression and its extent of severity. Cureus. 2020;12(2): e7005.
pubmed: 32206469
pmcid: 7077144
Abdulla FA, Albagmi FM, Al-Khamis FA. Factors that influence quality of life in patients with multiple sclerosis in Saudi Arabia. Disabil Rehabil. 2022;44(17):4775–83.
pubmed: 33966564
doi: 10.1080/09638288.2021.1919929
Gil-Gonzalez I, Martin-Rodriguez A, Conrad R, Perez-San-Gregorio MA. Quality of life in adults with multiple sclerosis: a systematic review. BMJ Open. 2020;10(11): e041249.
pubmed: 33257490
pmcid: 7705559
doi: 10.1136/bmjopen-2020-041249
Merkel B, Butzkueven H, Traboulsee AL, Havrdova E, Kalincik T. Timing of high-efficacy therapy in relapsing-remitting multiple sclerosis: a systematic review. Autoimmun Rev. 2017;16(6):658–65.
pubmed: 28428119
doi: 10.1016/j.autrev.2017.04.010
Binquet C, Quantin C, Le Teuff G, Pagliano JF, Abrahamowicz M, Moreau T. The prognostic value of initial relapses on the evolution of disability in patients with relapsing-remitting multiple sclerosis. Neuroepidemiology. 2006;27(1):45–54.
pubmed: 16825794
doi: 10.1159/000094380
Brown JWL, Coles A, Horakova D, et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA. 2019;321(2):175–87.
pubmed: 30644981
pmcid: 6439772
doi: 10.1001/jama.2018.20588
Johnson FR, Van Houtven G, Ozdemir S, et al. Multiple sclerosis patients’ benefit-risk preferences: serious adverse event risks versus treatment efficacy. J Neurol. 2009;256(4):554–62.
pubmed: 19444531
doi: 10.1007/s00415-009-0084-2
European Medicines Agency. Avonex (interferon beta-1a) summary of product characteristics. 2019. https://www.ema.europa.eu/en/documents/overview/avonex-epar-medicine-overview_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Betaferon (interferon beta-1b) summary of product characteristics. 2020. https://www.ema.europa.eu/en/documents/product-information/betaferon-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Extavia (interferon beta-1b) summary of product characteristics. 2020. https://www.ema.europa.eu/en/documents/product-information/extavia-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Tysabri (natalizumab) summary of product characteristics. 2020. https://www.ema.europa.eu/en/documents/product-information/tysabri-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Kesimpta (ofatumumab) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/kesimpta-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Ocrevus (ocrelizumab) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/ocrevus-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Rebif (interferon beta-1a) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/rebif-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Plegridy (pegylated interferon beta-1a) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/plegridy-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Tecfidera (dimethyl fumarate) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/tecfidera-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Mavenclad (cladribine) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/mavenclad-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Lemtrada (alemtuzumab) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/lemtrada-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Gilenya (fingolimod) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/gilenya-epar-product-information_en.pdf . Accessed 28 Aug 2021.
European Medicines Agency. Aubagio (teriflunomide) summary of product characteristics. 2021. https://www.ema.europa.eu/en/documents/product-information/aubagio-epar-product-information_en.pdf . Accessed 28 Aug 2021.
US Food and Drug Administration. Copaxone (glatiramer acetate injection), for subcutaneous use. Prescribing information. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/020622s110lbl.pdf . Accessed 28 Aug 2021.
Remington G, Rodriguez Y, Logan D, Williamson C, Treadaway K. Facilitating medication adherence in patients with multiple sclerosis. Int J MS Care. 2013;15(1):36–45.
pubmed: 24453761
pmcid: 3883032
doi: 10.7224/1537-2073.2011-038
Correale J, Marrodan M, Ysrraelit MC. Mechanisms of neurodegeneration and axonal dysfunction in progressive multiple sclerosis. Biomedicines. 2019;7(1):14.
pmcid: 6466454
doi: 10.3390/biomedicines7010014
Schoonheim MM, Geurts JJ, Barkhof F. The limits of functional reorganization in multiple sclerosis. Neurology. 2010;74(16):1246–7.
pubmed: 20404304
doi: 10.1212/WNL.0b013e3181db9957
Giovannoni G, Butzkueven H, Dhib-Jalbut S, et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord. 2016;9(Suppl 1):S5–48.
pubmed: 27640924
doi: 10.1016/j.msard.2016.07.003
Kern DM, Cepeda MS. Treatment patterns and comorbid burden of patients newly diagnosed with multiple sclerosis in the United States. BMC Neurol. 2020;20(1):296.
pubmed: 32781983
pmcid: 7418327
doi: 10.1186/s12883-020-01882-2
Kavaliunas A, Manouchehrinia A, Stawiarz L, et al. Importance of early treatment initiation in the clinical course of multiple sclerosis. Mult Scler. 2017;23(9):1233–40.
pubmed: 27754943
doi: 10.1177/1352458516675039
Stankiewicz JM, Weiner HL. An argument for broad use of high efficacy treatments in early multiple sclerosis. Neurol Neuroimmunol Neuroinflamm. 2020;7(1): e636.
pubmed: 31757815
doi: 10.1212/NXI.0000000000000636
Franciotta D, Salvetti M, Lolli F, Serafini B, Aloisi F. B cells and multiple sclerosis. Lancet Neurol. 2008;7(9):852–8.
pubmed: 18703007
doi: 10.1016/S1474-4422(08)70192-3
Reindl M, Linington C, Brehm U, et al. Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study. Brain. 1999;122(Pt 11):2047–56.
pubmed: 10545390
doi: 10.1093/brain/122.11.2047
Disanto G, Morahan JM, Barnett MH, Giovannoni G, Ramagopalan SV. The evidence for a role of B cells in multiple sclerosis. Neurology. 2012;78(11):823–32.
pubmed: 22411958
pmcid: 3304944
doi: 10.1212/WNL.0b013e318249f6f0
Krumbholz M, Derfuss T, Hohlfeld R, Meinl E. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol. 2012;8(11):613–23.
pubmed: 23045237
doi: 10.1038/nrneurol.2012.203
Howell OW, Reeves CA, Nicholas R, et al. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain. 2011;134(Pt 9):2755–71.
pubmed: 21840891
doi: 10.1093/brain/awr182
Molnarfi N, Schulze-Topphoff U, Weber MS, et al. MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies. J Exp Med. 2013;210(13):2921–37.
pubmed: 24323356
pmcid: 3865476
doi: 10.1084/jem.20130699
Oliver AR, Lyon GM, Ruddle NH. Rat and human myelin oligodendrocyte glycoproteins induce experimental autoimmune encephalomyelitis by different mechanisms in C57BL/6 mice. J Immunol. 2003;171(1):462–8.
pubmed: 12817031
doi: 10.4049/jimmunol.171.1.462
Hauser SL, Bar-Or A, Comi G, et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221–34.
pubmed: 28002679
doi: 10.1056/NEJMoa1601277
Hauser SL, Waubant E, Arnold DL, et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008;358(7):676–88.
pubmed: 18272891
doi: 10.1056/NEJMoa0706383
Montalban X, Hauser SL, Kappos L, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209–20.
pubmed: 28002688
doi: 10.1056/NEJMoa1606468
Sorensen PS, Lisby S, Grove R, et al. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis: a phase 2 study. Neurology. 2014;82(7):573–81.
pubmed: 24453078
doi: 10.1212/WNL.0000000000000125
Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus teriflunomide in multiple sclerosis. N Engl J Med. 2020;383(6):546–57.
pubmed: 32757523
doi: 10.1056/NEJMoa1917246
Ginaldi L, De Martinis M, D’Ostilio A, Marini L, Quaglino D. Changes in antigen expression on B lymphocytes during HIV infection. Pathobiology. 1998;66(1):17–23.
pubmed: 9577962
doi: 10.1159/000027990
Ginaldi L, De Martinis M, Matutes E, Farahat N, Morilla R, Catovsky D. Levels of expression of CD19 and CD20 in chronic B cell leukaemias. J Clin Pathol. 1998;51(5):364–9.
pubmed: 9708202
pmcid: 500695
doi: 10.1136/jcp.51.5.364
Florou D, Katsara M, Feehan J, Dardiotis E, Apostolopoulos V. Anti-CD20 agents for multiple sclerosis: spotlight on ocrelizumab and ofatumumab. Brain Sci. 2020;10(10):758.
pmcid: 7589300
doi: 10.3390/brainsci10100758
Cragg MS, Walshe CA, Ivanov AO, Glennie MJ. The biology of CD20 and its potential as a target for mAb therapy. Curr Dir Autoimmun. 2005;8:140–74.
pubmed: 15564720
doi: 10.1159/000082102
Hawker K, O’Connor P, Freedman MS, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66(4):460–71.
pubmed: 19847908
doi: 10.1002/ana.21867
Naegelin Y, Naegelin P, von Felten S, et al. Association of rituximab treatment with disability progression among patients with secondary progressive multiple sclerosis. JAMA Neurol. 2019;76(3):274–81.
pubmed: 30615019
pmcid: 6439730
doi: 10.1001/jamaneurol.2018.4239
Klein C, Lammens A, Schafer W, et al. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs. 2013;5(1):22–33.
pubmed: 23211638
pmcid: 3564883
doi: 10.4161/mabs.22771
Touil I, Perrot C, Elain G, Weckbecker G. Ofatumumab and ocrelizumab differentially induced human primary B-cell lysis by complement-dependent cytotoxicity [abstract LB325]. Mult Scler J. 2019;25(Suppl 1):162–3.
Teeling JL, Mackus WJ, Wiegman LJ, et al. The biological activity of human CD20 monoclonal antibodies is linked to unique epitopes on CD20. J Immunol. 2006;177(1):362–71.
pubmed: 16785532
doi: 10.4049/jimmunol.177.1.362
Wiendl H, Hauser SL, Bar-Or A et al., editors. Effect of ofatumumab on B-cell depletion and efficacy outcomes: subgroup analysis from the pooled phase 3 ASCLEPIOS I and II trials [abstract EPR3101 plus poster]. 6th Congress of the European Academy of Neurology; 2020 May 23–26; Virtual meeting.
Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab vs teriflunomide in relapsing multiple sclerosis: analysis of No Evidence of Disease Activity (NEDA-3) from ASCLEPIOS I and II trials [abstract LB62]. Eur J Neurol. 2020;27(Suppl 1):1289–90.
de Seze J, Bar-Or A, Correale J, et al. Effect of ofatumumab on serum immunoglobulin levels and infection risk in relapsing multiple sclerosis patients from the phase 3 ASCLEPIOS I and II trials [abstract LB82]. Eur J Neurol. 2020;27(Suppl 1):1295–6.
Hauser SL, Cross AH, Winthrop K, et al. Safety experience with continued exposure to ofatumumab in patients with relapsing forms of multiple sclerosis for up to 3.5 years. Mult Scler. 2022;28(10):1576–90.
pubmed: 35229668
pmcid: 9330270
doi: 10.1177/13524585221079731
Hauser SL, Cross AH, Winthrop K, et al. Long-term safety of ofatumumab in patients with relapsing multiple sclerosis (S14.004). Neurology. 2022;98(18 Supplement):2481.