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image of Pharmacodynamics and Pharmacokinetics of Ublituximab Compared with Other Anti-CD20 Monoclonal Antibodies for Multiple Sclerosis Treatment
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Abstract

The therapeutic scenario for multiple sclerosis (MS) has expanded rapidly over the last few years. Among the available treatments, anti-CD20 monoclonal antibodies, including rituximab, ocrelizumab, ofatumumab, and ublituximab, have shown significant results in reducing disease activity and slowing progression, particularly in relapsing MS. The distinct mechanisms of action, including the pharmacokinetic and pharmacodynamic profiles as well as the immunogenicity of these drugs, require careful consideration to tailor treatment for individual patients. A comprehensive review of the literature was conducted by searching PubMed and evaluating key studies, trials, and congress abstracts related to the use of anti-CD20 monoclonal antibodies. The analysis focused on the pharmacokinetic and pharmacodynamic profiles, as well as the immunogenicity, of anti-CD20 therapies currently available, with particular emphasis on the recently approved ublituximab. Ocrelizumab is effective in both relapsing-remitting and primary-progressive MS, using antibody-dependent cellular cytotoxicity (ADCC) as its primary mechanism of action, with intravenous and subcutaneous administration options ensuring flexible treatment delivery. Ofatumumab depletes B-cells through enhanced complement-dependent cytotoxicity, offering convenient monthly subcutaneous self-administration. Ublituximab’s unique glycoengineered fragment crystallizable region enhances ADCC, resulting in rapid B-cell depletion and potentially improving its safety profile. Ublituximab allows for a shorter infusion time without requiring post-infusion monitoring after the second dose, provided there have been no prior reactions. Understanding the characteristics of different anti-CD20 monoclonal antibodies is critical for optimizing treatment, enhancing patient outcomes, and minimizing treatment burden. Ublituximab represents a promising option, offering a shorter infusion time and higher ADCC activity, which complements existing treatments such as ocrelizumab and ofatumumab.

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2025-11-04

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References

  1. Filippi M. Bar-Or A. Piehl F. Preziosa P. Solari A. Vukusic S. Rocca M.A. Multiple sclerosis. Nat. Rev. Dis. Primers 2018 4 1 43 10.1038/s41572‑018‑0041‑4 30410033
    [Google Scholar]
  2. Hauser S.L. Waubant E. Arnold D.L. Vollmer T. Antel J. Fox R.J. Bar-Or A. Panzara M. Sarkar N. Agarwal S. Langer-Gould A. Smith C.H. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N. Engl. J. Med. 2008 358 7 676 688 10.1056/NEJMoa0706383 18272891
    [Google Scholar]
  3. Montalban X. Hauser S.L. Kappos L. Arnold D.L. Bar-Or A. Comi G. de Seze J. Giovannoni G. Hartung H.P. Hemmer B. Lublin F. Rammohan K.W. Selmaj K. Traboulsee A. Sauter A. Masterman D. Fontoura P. Belachew S. Garren H. Mairon N. Chin P. Wolinsky J.S. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N. Engl. J. Med. 2017 376 3 209 220 10.1056/NEJMoa1606468 28002688
    [Google Scholar]
  4. Hauser S.L. Bar-Or A. Cohen J.A. Comi G. Correale J. Coyle P.K. Cross A.H. de Seze J. Leppert D. Montalban X. Selmaj K. Wiendl H. Kerloeguen C. Willi R. Li B. Kakarieka A. Tomic D. Goodyear A. Pingili R. Häring D.A. Ramanathan K. Merschhemke M. Kappos L. Ofatumumab versus teriflunomide in multiple sclerosis. N. Engl. J. Med. 2020 383 6 546 557 10.1056/NEJMoa1917246 32757523
    [Google Scholar]
  5. Margoni M. Preziosa P. Filippi M. Rocca M.A. Anti-CD20 therapies for multiple sclerosis: Current status and future perspectives. J. Neurol. 2022 269 3 1316 1334 10.1007/s00415‑021‑10744‑x 34382120
    [Google Scholar]
  6. Arneth B.M. Impact of B cells to the pathophysiology of multiple sclerosis. J. Neuroinflammation 2019 16 1 128 10.1186/s12974‑019‑1517‑1 31238945
    [Google Scholar]
  7. van Langelaar J. Rijvers, L.; Smolders, J.; van Luijn, M.M. B and T cells driving multiple sclerosis: Identity, mechanisms and potential triggers. Front. Immunol. 2020 11 760 10.3389/fimmu.2020.00760 32457742
    [Google Scholar]
  8. Machado-Santos J. Saji E. Tröscher A.R. Paunovic M. Liblau R. Gabriely G. Bien C.G. Bauer J. Lassmann H. The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells. Brain 2018 141 7 2066 2082 10.1093/brain/awy151 29873694
    [Google Scholar]
  9. Frischer J.M. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain 2009 132 Pt 5 1175 1189 10.1093/brain/awp070 19339255
    [Google Scholar]
  10. Magliozzi R. Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 2007 130 Pt 4 1089 1104 10.1093/brain/awm038 17438020
    [Google Scholar]
  11. Serafini B. Rosicarelli B. Magliozzi R. Stigliano E. Aloisi F. Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol. 2004 14 2 164 174 10.1111/j.1750‑3639.2004.tb00049.x 15193029
    [Google Scholar]
  12. de Sèze J. Maillart E. Gueguen A. Laplaud D.A. Michel L. Thouvenot E. Zephir H. Zimmer L. Biotti D. Liblau R. Anti-CD20 therapies in multiple sclerosis: From pathology to the clinic. Front. Immunol. 2023 14 1004795 10.3389/fimmu.2023.1004795 37033984
    [Google Scholar]
  13. Crickx E. Weill J.C. Reynaud C.A. Mahévas M. Anti-CD20–mediated B-cell depletion in autoimmune diseases: Successes, failures and future perspectives. Kidney Int. 2020 97 5 885 893 10.1016/j.kint.2019.12.025 32229095
    [Google Scholar]
  14. Baecher-Allan C. Kaskow B.J. Weiner H.L. Multiple sclerosis: Mechanisms and immunotherapy. Neuron 2018 97 4 742 768 10.1016/j.neuron.2018.01.021 29470968
    [Google Scholar]
  15. Pavlasova G. Mraz M. The regulation and function of CD20: An “enigma” of B-cell biology and targeted therapy. Haematologica 2020 105 6 1494 1506 10.3324/haematol.2019.243543 32482755
    [Google Scholar]
  16. Bubien J.K. Zhou L.J. Bell P.D. Frizzell R.A. Tedder T.F. Transfection of the CD20 cell surface molecule into ectopic cell types generates a Ca2+ conductance found constitutively in B lymphocytes. J. Cell Biol. 1993 121 5 1121 1132 10.1083/jcb.121.5.1121 7684739
    [Google Scholar]
  17. Walshe C.A. Beers S.A. French R.R. Chan C.H.T. Johnson P.W. Packham G.K. Glennie M.J. Cragg M.S. Induction of cytosolic calcium flux by CD20 is dependent upon B Cell antigen receptor signaling. J. Biol. Chem. 2008 283 25 16971 16984 10.1074/jbc.M708459200 18426802
    [Google Scholar]
  18. Kläsener K. Jellusova J. Andrieux G. Salzer U. Böhler C. Steiner S.N. Albinus J.B. Cavallari M. Süß B. Voll R.E. Boerries M. Wollscheid B. Reth M. CD20 as a gatekeeper of the resting state of human B cells. Proc. Natl. Acad. Sci. USA 2021 118 7 e2021342118 10.1073/pnas.2021342118 33563755
    [Google Scholar]
  19. Ochs J. Nissimov N. Torke S. Freier M. Grondey K. Koch J. Klein M. Feldmann L. Gudd C. Bopp T. Häusser-Kinzel S. Weber M.S. Proinflammatory CD20+ T cells contribute to CNS-directed autoimmunity. Sci. Transl. Med. 2022 14 638 eabi4632 10.1126/scitranslmed.abi4632 35353539
    [Google Scholar]
  20. von Essen M.R. Hansen R.H. Højgaard C. Ammitzbøll C. Wiendl H. Sellebjerg F. Ofatumumab modulates inflammatory T cell responses and migratory potential in patients with multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2022 9 4 e200004 10.1212/NXI.0000000000200004 35672145
    [Google Scholar]
  21. Faissner S. Heitmann N. Plaza-Sirvent C. Trendelenburg P. Ceylan U. Motte J. Bessen C. Urlaub D. Watzl C. Overheu O. Reinacher-Schick A. Hellwig K. Pfaender S. Schmitz I. Gold R. Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination. Front. Immunol. 2022 13 980526 10.3389/fimmu.2022.980526 36119053
    [Google Scholar]
  22. Palanichamy A. Jahn S. Nickles D. Derstine M. Abounasr A. Hauser S.L. Baranzini S.E. Leppert D. von Büdingen H.C. Rituximab efficiently depletes increased CD20-expressing T cells in multiple sclerosis patients. J. Immunol. 2014 193 2 580 586 10.4049/jimmunol.1400118 24928997
    [Google Scholar]
  23. Gingele S. Jacobus T.L. Konen F.F. Hümmert M.W. Sühs K.W. Schwenkenbecher P. Ahlbrecht J. Möhn N. Müschen L.H. Bönig L. Alvermann S. Schmidt R.E. Stangel M. Jacobs R. Skripuletz T. Ocrelizumab depletes CD20+ T cells in multiple sclerosis patients. Cells 2018 8 1 12 10.3390/cells8010012 30597851
    [Google Scholar]
  24. Lovett-Racke A.E. Gormley M. Liu Y. Yang Y. Graham C. Wray S. Racke M.K. Shubin R. Twyman C. Alvarez E. Bass A. Eubanks J.L. Fox E. B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients. J. Neuroimmunol. 2019 332 187 197 10.1016/j.jneuroim.2019.04.017 31077854
    [Google Scholar]
  25. Margoni M. Preziosa P. Tortorella P. Filippi M. Rocca M.A. Does ocrelizumab limit multiple sclerosis progression? Current evidence from clinical, MRI, and fluid biomarkers. Neurotherapeutics 2022 19 4 1216 1228 10.1007/s13311‑022‑01252‑5 35668317
    [Google Scholar]
  26. Hauser S.L. Bar-Or A. Comi G. Giovannoni G. Hartung H.P. Hemmer B. Lublin F. Montalban X. Rammohan K.W. Selmaj K. Traboulsee A. Wolinsky J.S. Arnold D.L. Klingelschmitt G. Masterman D. Fontoura P. Belachew S. Chin P. Mairon N. Garren H. Kappos L. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N. Engl. J. Med. 2017 376 3 221 234 10.1056/NEJMoa1601277 28002679
    [Google Scholar]
  27. Hartung H-P. Berger T. Bermel R.A. Brochet B. Carroll W.M. Holmøy T. Karabudak R. Killestein J. Nos C. Patti F. Ross A.P. Vanopdenbosch L. Vollmer T. Buffels R. Garas M. Kadner K. Manfrini M. Wang Q. Freedman M.S. Shorter infusion time of ocrelizumab: Results from the randomized, double-blind ensemble plus substudy in patients with relapsing-remitting multiple sclerosis. Mult. Scler. Relat. Disord. 2020 46 102492 10.1016/j.msard.2020.102492 33039944
    [Google Scholar]
  28. Newsome S. Krzystanek E. Selmaj K. Goldstick L. Figueiredo C. Townsend B. Wolf C. Zecevic D. Giacobino C. Bortolami O. Shen Y-A. Kletzl H. Clinch S. Centonze D. OCARINA II, phase III study: Results of subcutaneous ocrelizumab administration in patients with multiple sclerosis (S31.006). Neurology 2024 102 7_supplement 1 3597 10.1212/WNL.0000000000205244
    [Google Scholar]
  29. Steinman L. Fox E. Hartung H.P. Alvarez E. Qian P. Wray S. Robertson D. Huang D. Selmaj K. Wynn D. Cutter G. Mok K. Hsu Y. Xu Y. Weiss M.S. Bosco J.A. Power S.A. Lee L. Miskin H.P. Cree B.A.C. Ublituximab versus teriflunomide in relapsing multiple sclerosis. N. Engl. J. Med. 2022 387 8 704 714 10.1056/NEJMoa2201904 36001711
    [Google Scholar]
  30. Fox E. Lovett-Racke A.E. Gormley M. Liu Y. Petracca M. Cocozza S. Shubin R. Wray S. Weiss M.S. Bosco J.A. Power S.A. Mok K. Inglese M. A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis. Mult. Scler. 2021 27 3 420 429 10.1177/1352458520918375 32351164
    [Google Scholar]
  31. Boross P. Leusen J.H. Mechanisms of action of CD20 antibodies. Am. J. Cancer Res. 2012 2 6 676 690 23226614
    [Google Scholar]
  32. Klein C. Lammens A. Schäfer W. Georges G. Schwaiger M. Mössner E. Hopfner K.P. Umaña P. Niederfellner G. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. MAbs 2013 5 1 22 33 10.4161/mabs.22771 23211638
    [Google Scholar]
  33. Bar-Or A. O’Brien S.M. Sweeney M.L. Fox E.J. Cohen J.A. Clinical perspectives on the molecular and pharmacological attributes of Anti-CD20 therapies for multiple sclerosis. CNS Drugs 2021 35 9 985 997 10.1007/s40263‑021‑00843‑8 34370283
    [Google Scholar]
  34. Morschhauser F. Marlton P. Vitolo U. Lindén O. Seymour J.F. Crump M. Coiffier B. Foà R. Wassner E. Burger H.U. Brennan B. Mendila M. Results of a phase I/II study of ocrelizumab, a fully humanized anti-CD20 mAb, in patients with relapsed/refractory follicular lymphoma. Ann. Oncol. 2010 21 9 1870 1876 10.1093/annonc/mdq027 20157180
    [Google Scholar]
  35. Chisari C.G. Sgarlata E. Arena S. Toscano S. Luca M. Patti F. Rituximab for the treatment of multiple sclerosis: A review. J. Neurol. 2022 269 1 159 183 10.1007/s00415‑020‑10362‑z 33416999
    [Google Scholar]
  36. Taylor R.P. Lindorfer M.A. Immunotherapeutic mechanisms of anti-CD20 monoclonal antibodies. Curr. Opin. Immunol. 2008 20 4 444 449 10.1016/j.coi.2008.05.011 18585457
    [Google Scholar]
  37. Delgado S.R. Faissner S. Linker R.A. Rammohan K. Key characteristics of anti-CD20 monoclonal antibodies and clinical implications for multiple sclerosis treatment. J. Neurol. 2024 271 4 1515 1535 10.1007/s00415‑023‑12007‑3 37906325
    [Google Scholar]
  38. Teeling J.L. French R.R. Cragg M.S. van den Brakel J. Pluyter M. Huang H. Chan C. Parren P.W. Hack C.E. Dechant M. Valerius T. van de Winkel J.G. Glennie M.J. Characterization of new human CD20 monoclonal antibodies with potent cytolytic activity against non-Hodgkin lymphomas. Blood 2004 104 6 1793 1800 10.1182/blood‑2004‑01‑0039 15172969
    [Google Scholar]
  39. Pawluczkowycz A.W. Beurskens F.J. Beum P.V. Lindorfer M.A. van de Winkel J.G.J. Parren P.W.H.I. Taylor R.P. Binding of submaximal C1q promotes complement-dependent cytotoxicity (CDC) of B cells opsonized with anti-CD20 mAbs ofatumumab (OFA) or rituximab (RTX): Considerably higher levels of CDC are induced by OFA than by RTX. J. Immunol. 2009 183 1 749 758 10.4049/jimmunol.0900632 19535640
    [Google Scholar]
  40. Sellebjerg F. Blinkenberg M. Sorensen P.S. Anti-CD20 monoclonal antibodies for relapsing and progressive multiple sclerosis. CNS Drugs 2020 34 3 269 280 10.1007/s40263‑020‑00704‑w 31994023
    [Google Scholar]
  41. Torres J.B. Roodselaar J. Sealey M. Ziehn M. Bigaud M. Kneuer R. Leppert D. Weckbecker G. Cornelissen B. Anthony D.C. Distribution and efficacy of ofatumumab and ocrelizumab in humanized CD20 mice following subcutaneous or intravenous administration. Front. Immunol. 2022 13 814064 10.3389/fimmu.2022.814064 35967378
    [Google Scholar]
  42. Pereira N.A. Chan K.F. Lin P.C. Song Z. The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity. MAbs 2018 10 5 693 711 10.1080/19420862.2018.1466767 29733746
    [Google Scholar]
  43. Bowles J.A. Weiner G.J. CD16 polymorphisms and NK activation induced by monoclonal antibody-coated target cells. J. Immunol. Methods 2005 304 1-2 88 99 10.1016/j.jim.2005.06.018 16109421
    [Google Scholar]
  44. Koene H.R. Kleijer M. Algra J. Roos D. von dem Borne A.E. de Haas M. Fc gammaRIIIa-158V/F polymorphism influences the binding of IgG by natural killer cell Fc gammaRIIIa, independently of the Fc gammaRIIIa-48L/R/H phenotype. Blood 1997 90 3 1109 1114 9242542
    [Google Scholar]
  45. Wu J. Edberg J.C. Redecha P.B. Bansal V. Guyre P.M. Coleman K. Salmon J.E. Kimberly R.P. A novel polymorphism of FcgammaRIIIa (CD16) alters receptor function and predisposes to autoimmune disease. J. Clin. Invest. 1997 100 5 1059 1070 10.1172/JCI119616 9276722
    [Google Scholar]
  46. Mahaweni N.M. Olieslagers T.I. Rivas I.O. Molenbroeck S.J.J. Groeneweg M. Bos G.M.J. Tilanus M.G.J. Voorter C.E.M. Wieten L. A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism. Sci. Rep. 2018 8 1 15983 10.1038/s41598‑018‑34258‑1 30374078
    [Google Scholar]
  47. Congy-Jolivet N. Bolzec A. Ternant D. Ohresser M. Watier H. Thibault G. Fc gamma RIIIa expression is not increased on natural killer cells expressing the Fc gamma RIIIa-158V allotype. Cancer Res. 2008 68 4 976 980 10.1158/0008‑5472.CAN‑07‑6523 18281470
    [Google Scholar]
  48. Cartron G. Dacheux L. Salles G. Solal-Celigny P. Bardos P. Colombat P. Watier H. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor FcγRIIIa gene. Blood 2002 99 3 754 758 10.1182/blood.V99.3.754 11806974
    [Google Scholar]
  49. Kaifu T. Nakamura A. Polymorphisms of immunoglobulin receptors and the effects on clinical outcome in cancer immunotherapy and other immune diseases: A general review. Int. Immunol. 2017 29 7 319 325 10.1093/intimm/dxx041 28910969
    [Google Scholar]
  50. Gogesch P. Dudek S. van Zandbergen G. Waibler Z. Anzaghe M. The role of Fc receptors on the effectiveness of therapeutic monoclonal antibodies. Int. J. Mol. Sci. 2021 22 16 8947 10.3390/ijms22168947 34445651
    [Google Scholar]
  51. Zhong M. van der Walt A. Campagna M.P. Stankovich J. Butzkueven H. Jokubaitis V. The pharmacogenetics of rituximab: Potential implications for anti-CD20 therapies in multiple sclerosis. Neurotherapeutics 2020 17 4 1768 1784 10.1007/s13311‑020‑00950‑2 33058021
    [Google Scholar]
  52. Kim S.H. Jeong I.H. Hyun J.W. Joung A. Jo H.J. Hwang S.H. Yun S. Joo J. Kim H.J. Treatment outcomes with rituximab in 100 patients with Neuromyelitis optica. JAMA Neurol. 2015 72 9 989 995 10.1001/jamaneurol.2015.1276 26167726
    [Google Scholar]
  53. Quartuccio L. Fabris M. Pontarini E. Salvin S. Zabotti A. Benucci M. Manfredi M. Biasi D. Ravagnani V. Atzeni F. Sarzi-Puttini P. Morassi P. Fischetti F. Tomietto P. Bazzichi L. Saracco M. Pellerito R. Cimmino M. Schiavon F. Carraro V. Semeraro A. Caporali R. Cavagna L. Bortolotti R. Paolazzi G. Govoni M. Bombardieri S. De Vita S. The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumatoid arthritis: Results of an Italian multicentre study. Ann. Rheum. Dis. 2014 73 4 716 721 10.1136/annrheumdis‑2012‑202435 23505228
    [Google Scholar]
  54. Cui L. Jiao J. Zhang Y. Wang R. Peng D. Jiao Y. Zhang W. FCGR3A-V158F gene polymorphism: A potential predictor for rituximab dosing optimization in Chinese patients with neuromyelitis optica spectrum disorder. Mult. Scler. Relat. Disord. 2024 86 105600 10.1016/j.msard.2024.105600 38579568
    [Google Scholar]
  55. Robinson J.I. Md Yusof M.Y. Davies V. Wild D. Morgan M. Taylor J.C. El-Sherbiny Y. Morris D.L. Liu L. Rawstron A.C. Buch M.H. Plant D. Cordell H.J. Isaacs J.D. Bruce I.N. Emery P. Barton A. Vyse T.J. Barrett J.H. Vital E.M. Morgan A.W. Comprehensive genetic and functional analyses of Fc gamma receptors influence on response to rituximab therapy for autoimmunity. EBioMedicine 2022 86 104343 10.1016/j.ebiom.2022.104343 36371989
    [Google Scholar]
  56. Foley J.F. Ublituximab after transitioning from a different disease-modifying therapy: Updates from the ENHANCE study. Mult. Scler. J. 2024 30 3_suppl. 10.1177/13524585241269219
    [Google Scholar]
  57. Hawker K. O’Connor P. Freedman M.S. Calabresi P.A. Antel J. Simon J. Hauser S. Waubant E. Vollmer T. Panitch H. Zhang J. Chin P. Smith C.H. Rituximab in patients with primary progressive multiple sclerosis: Results of a randomized double-blind placebo-controlled multicenter trial. Ann. Neurol. 2009 66 4 460 471 10.1002/ana.21867 19847908
    [Google Scholar]
  58. Kira J. Nakahara J. Sazonov D.V. Kurosawa T. Tsumiyama I. Willi R. Zalesak M. Pingili R. Häring D.A. Ramanathan K. Kieseier B.C. Merschhemke M. Su W. Saida T. Effect of ofatumumab versus placebo in relapsing multiple sclerosis patients from Japan and Russia: Phase 2 APOLITOS study. Mult. Scler. 2022 28 8 1229 1238 10.1177/13524585211055934 34787005
    [Google Scholar]
  59. Bar-Or A. Grove R.A. Austin D.J. Tolson J.M. VanMeter S.A. Lewis E.W. Derosier F.J. Lopez M.C. Kavanagh S.T. Miller A.E. Sorensen P.S. Subcutaneous ofatumumab in patients with relapsing-remitting multiple sclerosis. Neurology 2018 90 20 e1805 e1814 10.1212/WNL.0000000000005516 29695594
    [Google Scholar]
  60. Sorensen P.S. Lisby S. Grove R. Derosier F. Shackelford S. Havrdova E. Drulovic J. Filippi M. Safety and efficacy of ofatumumab in relapsing-remitting multiple sclerosis. Neurology 2014 82 7 573 581 10.1212/WNL.0000000000000125 24453078
    [Google Scholar]
  61. Bar-Or A. Calabresi P.A.J. Arnold D. Markowitz C. Shafer S. Kasper L.H. Waubant E. Gazda S. Fox R.J. Panzara M. Sarkar N. Agarwal S. Smith C.H. Rituximab in relapsing-remitting multiple sclerosis: A 72-week, open-label, phase I trial. Ann. Neurol. 2008 63 3 395 400 10.1002/ana.21363 18383069
    [Google Scholar]
  62. Bar-Or A. Wiendl H. Montalban X. Alvarez E. Davydovskaya M. Delgado S.R. Evdoshenko E.P. Giedraitiene N. Gross-Paju K. Haldre S. Herrman C.E. Izquierdo G. Karelis G. Leutmezer F. Mares M. Meca-Lallana J.E. Mickeviciene D. Nicholas J. Robertson D.S. Sazonov D.V. Sharlin K. Sundaram B. Totolyan N. Vachova M. Valis M. Bagger M. Häring D.A. Ludwig I. Willi R. Zalesak M. Su W. Merschhemke M. Fox E.J. Rapid and sustained B-cell depletion with subcutaneous ofatumumab in relapsing multiple sclerosis: APLIOS, a randomized phase-2 study. Mult. Scler. 2022 28 6 910 924 10.1177/13524585211044479 34605319
    [Google Scholar]
  63. Saida T. Nakahara J. Sazonov D.V. Kurosawa T. Tsumiyama I. Willi R. Zalesak M. Pingili R. Häring D.A. Ramanathan K. Su W. Kira J. Sustained efficacy of ofatumumab in relapsing multiple sclerosis patients: Results from extended treatment in the phase 2 APOLITOS study (2032). Neurology 2021 96 15_supplement 2032 10.1212/WNL.96.15_supplement.2032
    [Google Scholar]
  64. Cotchett K.R. Dittel B.N. Obeidat A.Z. Comparison of the efficacy and safety of anti-CD20 B cells depleting drugs in multiple sclerosis. Mult. Scler. Relat. Disord. 2021 49 102787 10.1016/j.msard.2021.102787 33516134
    [Google Scholar]
  65. Yu H. Graham G. David O.J. Kahn J.M. Savelieva M. Pigeolet E. Das Gupta A. Pingili R. Willi R. Ramanathan K. Kieseier B.C. Häring D.A. Bagger M. Sørensen S.P. Population pharmacokinetic–B cell modeling for ofatumumab in patients with relapsing multiple sclerosis. CNS Drugs 2022 36 3 283 300 10.1007/s40263‑021‑00895‑w 35233753
    [Google Scholar]
  66. Ellrichmann G. Bolz J. Peschke M. Duscha A. Hellwig K. Lee D.H. Linker R.A. Gold R. Haghikia A. Peripheral CD19 + B-cell counts and infusion intervals as a surrogate for long-term B-cell depleting therapy in multiple sclerosis and neuromyelitis optica/neuromyelitis optica spectrum disorders. J. Neurol. 2019 266 1 57 67 10.1007/s00415‑018‑9092‑4 30377816
    [Google Scholar]
  67. Hauser S.L. Kappos L. Bar-Or A. Wiendl H. Paling D. Williams M. Gold R. Chan A. Milo R. Das Gupta A. Karlsson G. Sullivan R. Graham G. Merschhemke M. Häring D.A. Vermersch P. The development of ofatumumab, a fully human anti-CD20 monoclonal antibody for practical use in relapsing multiple sclerosis treatment. Neurol. Ther. 2023 12 5 1491 1515 10.1007/s40120‑023‑00518‑0 37450172
    [Google Scholar]
  68. Monteiro I. Nicolella V. Fiorenza M. Novarella F. Carotenuto A. Lanzillo R. Mauriello L. Scalia G. Castaldo G. Terracciano D. Brescia Morra V. Moccia M. The ocrelizumab wearing-off phenomenon is associated with reduced immunomodulatory response and increased neuroaxonal damage in multiple sclerosis. J. Neurol. 2024 271 8 5012 5024 10.1007/s00415‑024‑12434‑w 38777960
    [Google Scholar]
  69. Bai S. Jorga K. Xin Y. Jin D. Zheng Y. Damico-Beyer L.A. Gupta M. Tang M. Allison D.E. Lu D. Zhang Y. Joshi A. Dresser M.J. A guide to rational dosing of monoclonal antibodies. Clin. Pharmacokinet. 2012 51 2 119 135 10.2165/11596370‑000000000‑00000 22257150
    [Google Scholar]
  70. Gibiansky E. Petry C. Mercier F. Günther A. Herman A. Kappos L. Hauser S. Yamamoto Y. Wang Q. Model F. Kletzl H. Ocrelizumab in relapsing and primary progressive multiple sclerosis: Pharmacokinetic and pharmacodynamic analyses of OPERA I, OPERA II and ORATORIO. Br. J. Clin. Pharmacol. 2021 87 6 2511 2520 10.1111/bcp.14658 33202059
    [Google Scholar]
  71. Turner B. Cree B.A.C. Kappos L. Montalban X. Papeix C. Wolinsky J.S. Buffels R. Fiore D. Garren H. Han J. Hauser S.L. Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis. J. Neurol. 2019 266 5 1182 1193 10.1007/s00415‑019‑09248‑6 30820738
    [Google Scholar]
  72. Gärtner J. Hauser S.L. Bar-Or A. Montalban X. Cohen J.A. Cross A.H. Deiva K. Ganjgahi H. Häring D.A. Li B. Pingili R. Ramanathan K. Su W. Willi R. Kieseier B. Kappos L. Efficacy and safety of ofatumumab in recently diagnosed, treatment-naive patients with multiple sclerosis: Results from ASCLEPIOS I and II. Mult. Scler. 2022 28 10 1562 1575 10.1177/13524585221078825 35266417
    [Google Scholar]
  73. Martin S.J. Guenette M. Oh J. Evaluating the therapeutic potential of ublituximab in the treatment of MS: Design, development and place in therapy. Drug Des. Devel. Ther. 2024 18 3025 3042 10.2147/DDDT.S388410 39050801
    [Google Scholar]
  74. Lamb Y.N. Ocrelizumab: A review in multiple sclerosis. Drugs 2022 82 3 323 334 10.1007/s40265‑022‑01672‑9 35192158
    [Google Scholar]
  75. Kang C. Blair H.A. Ofatumumab: A review in relapsing forms of multiple sclerosis. Drugs 2022 82 1 55 62 10.1007/s40265‑021‑01650‑7 34897575
    [Google Scholar]
  76. Lehmann-Horn K. Kinzel S. Feldmann L. Radelfahr F. Hemmer B. Traffehn S. Bernard C.C.A. Stadelmann C. Brück W. Weber M.S. Intrathecal anti‐ CD 20 efficiently depletes meningeal B cells in CNS autoimmunity. Ann. Clin. Transl. Neurol. 2014 1 7 490 496 10.1002/acn3.71 25356419
    [Google Scholar]
  77. Hauser S.L. Bar-Or A. Weber M.S. Kletzl H. Günther A. Manfrini M. Model F. Mercier F. Petry C. Wing Q. Koendgen H. Smith T. Kappos L. Association of higher ocrelizumab exposure with reduced disability progression in multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 2023 10 2 e200094 10.1212/NXI.0000000000200094 36792367
    [Google Scholar]
  78. Viola M. Sequeira J. Seiça R. Veiga F. Serra J. Santos A.C. Ribeiro A.J. Subcutaneous delivery of monoclonal antibodies: How do we get there? J. Control. Release 2018 286 301 314 10.1016/j.jconrel.2018.08.001 30077735
    [Google Scholar]
  79. Fox E. Steinman L. Hartung H-P. Alvarez E. Qian P. Wray S. Robertson D. Huang D.R. Selmaj K. Wynn D. Weiss M.S. Bosco J.A. Power S.A. Mok K. Lee L. Cree B. Infusion-related reactions (IRRs) with ublituximab in patients with relapsing multiple sclerosis (RMS): Post Hoc analyses from the phase 3 ULTIMATE I and II studies (P6-4.010). Neurology 2022 98 18_supplement 1017 10.1212/WNL.98.18_supplement.1017
    [Google Scholar]
  80. Alvarez S.L. Fox E. Neutralizing antibodies and antidrug antibodies in the Ublituximab Phase 3 ULTIMATE I and II studies in relapsing multiple sclerosis. Mult. Scler. J. 2022 28 1 suppl.
    [Google Scholar]
  81. Dunn N. Juto A. Ryner M. Manouchehrinia A. Piccoli L. Fink K. Piehl F. Fogdell-Hahn A. Rituximab in multiple sclerosis: Frequency and clinical relevance of anti-drug antibodies. Mult. Scler. 2018 24 9 1224 1233 10.1177/1352458517720044 28762877
    [Google Scholar]
  82. Holmøy T. Fogdell-Hahn A. Svenningsson A. Serum sickness following rituximab therapy in multiple sclerosis. Neurol. Clin. Pract. 2019 9 6 519 521 10.1212/CPJ.0000000000000685 32042497
    [Google Scholar]
  83. Moreira Ferreira V.F. Kimbrough D.J. Stankiewicz J.M. A possible case of serum sickness after ocrelizumab infusion. Mult. Scler. 2021 27 1 155 158 10.1177/1352458520910486 32427524
    [Google Scholar]
/content/journals/cn/10.2174/011570159X392955250815095236
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Pharmacodynamics and Pharmacokinetics of Ublituximab Compared with Other Anti-CD20 Monoclonal Antibodies for Multiple Sclerosis Treatment
Bentham Science Publishers ; https://doi.org/10.2174/011570159X392955250815095236
/content/journals/cn/10.2174/011570159X392955250815095236
/content/journals/cn/10.2174/011570159X392955250815095236
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  • Article Type:     Review Article
Keywords: anti-CD20 therapy ; ocrelizumab ; disease-modifying therapy ; ublituximab ; ofatumumab ; multiple sclerosis ; B cells

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