„Today” is different out of the yesterday’s and tomorrow’s perspective – time in SM Review article
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Published:
Jun 30, 2022
Keywords:
multiple sclerosis, progression independent relapse activity, relapse-associated worsening, Bruton tyrosine kinase inhibitors, pharmacovigilance
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Abstract
In the light of the latest scientific achievements, the concept of the pathogenesis of multiple sclerosis (MS) is subject to verification and recognition of the continuity of inflammatory processes taking place in a permanent manner, referred to as “smoldering” in the nervous system of patients with MS. This changing knowledge of the pathogenesis of the disease and the mechanisms involved in the progression of disability results in the search for new treatments, which has led in recent years to the development of therapies that have been widely implemented in medical practice or are at the late stage of advanced clinical trials. An example of such drugs are Bruton tyrosine kinase inhibitors that are currently in the third phase of clinical trials aimed at their registration. At the same time, the requirement to monitor not only the efficacy but also the safety of medicinal products, those already on the market, serves to optimise the available pharmacotherapy. Today’s understanding of the mechanisms involved in the course and prognosis of MS directly affects the treatment options for the disease, changes our daily management and perspective on future diagnostic and therapeutic activities.
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References
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2. Zettl UK, Tumani H. Multiple sclerosis and cerebrospinal fluid. Blackwell Publishing Ltd. 2005: 1-10.
3. Schumacher GA, Beebe BL, Kabler RF. Problems of experimental trials of therapy in multiple sclerosis. Ann NY Acad Sci. 1965; 122: 552-68.
4. Poser CM, Paty DW, Scheinberg L et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983; 13: 227-31.
5. McDonald WI, Comspton A, Edan G et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001; 50(1): 121-7.
6. Thompson AJ, Banwell BL, Barkhof F et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018; 17(2): 162-73.
7. Ransohoff RM, Hafler DA, Lucchinetti CF. Multiple sclerosis – a quiet revolution. Nature Rev Neurol. 2015; 11(3): 134-42.
8. Geladaris A, Torke S, Weber MS. Bruton’s tyrosine kinase inhibitors in multiple sclerosis: pioneering the path towards treatment of progression. CNS Drugs. 2022; 36: 1019-30.
9. Giovannoni G, Popescu V, Wuerfel J et al. Smouldering multiple sclerosis: the ‘real MS’. Ther Adv Neurol Disord. 2022; 15: 1-18.
10. Kappos L, Wolinsky JS, Giovannoni G et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020; 77: 1132-40.
11. De Stefano N, Giorgio A, Battaglini M et al. Assessing brain atrophy rates in a large population of untreated multiple sclerosis subtypes. Neurology. 2010; 74: 1868-76.
12. Kuhlmann T, Lingfeld G, Bitsch A et al. Acute axonal damage in multiple sclerosis is most extensive in early disease stages and decreases over time. Brain. 2002; 125: 2202-12.
13. Sucksdorff M, Matilainen M, Tuisku J et al. Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis. Brain. 2020; 143: 3318-30.
14. Singh S, Dallenga T, Winkler A et al. Relationship of acute axonal damage, Wallerian degeneration, and clinical disability in multiple sclerosis. J Neuroinflammation. 2017; 14: 57.
15. Choi IY, Lee P, Adany P et al. In vivo evidence of oxidative stress in brains of patients with progressive multiple sclerosis. Mult Scler. 2018; 24: 1029-38.
16. Hametner S, Wimmer I, Haider L et al. Iron and neurodegeneration in the multiple sclerosis brain. Ann Neurol. 2013; 74: 848-61.
17. Trapp BD, Stys PK. Virtual hypoxia and chronic necrosis of demyelinated axons in multiple sclerosis. Lancet Neurol. 2009; 8: 280-91.
18. Buljevac D, Flach HZ, Hop WCJ et al. Prospective study on the relationship between infections and multiple sclerosis exacerbations. Brain. 2002; 125: 952-60.
19. Neumann B, Segel M, Chalut KJ et al. Remyelination and aging: reversing the ravages of time. Mult Scler. 2019; 25: 1835-41.
20. Giovannoni G, Turner B, Gnanapavan S et al. Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord. 2015; 4: 329-33.
21. O’Connor P, Wolinsky JS, Confavrex Ch et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011; 365: 1293-303.
22. Miller AE, O’Connor P, Wolinsky JS et al. Pre-specified subgroup analyses of a placebo-controlled phase III trial (TEMSO) of oral teriflunomide in relapsing multiple sclerosis. Multiple Scler J. 2012; 18(11): 1625-32.
23. Orlandi R, Gajofatto A. Tolebrutynib – Bruton tyrosine kinase (BTK) inhibitor treatment of multiple sclerosis. Drugs Future. 2022; 47(5): 325-36.
24. Owens TD, Smith PF, Redfern A et al. Phase 1 clinical trial evaluating safety, exposure and pharmacodynamics of BTK inhibitor tolebrutinib. Clin Transl Sci. 2021; 00: 1-9.
25. Reich DS, Douglas LA, Vermersch P et al. Safety and efficacy of tolebrutinib, an oral brain-penetrant BTK inhibitor, in relapsing multiple sclerosis; a phase 2b, randomized, double-blind, placebo-controlled trial. Lancet Neurol. 2021; 20: 729-38.
26. Martin E, Aigrot MS, Grenningloh R et al. Bruton’s tyrosine kinase inhibition promotes myelin repair. Brain Plasticity. 2020; 5: 123-33.
27. Lucas S, Ailani J, Smith TR et al. Pharmacovigilance: reporting requirements throughout a product’s lifecycle. Ther Adv Drug Saf. 2022. http://doi.org/10.1177/20420986221125006.
28. Berkovich R, Eskenazi J, Yakupova A et al. Progressive multifocal leukoencephalopathy risk perception in patients considering natalizumab for multiple sclerosis. Int J MS Care. 2022; 24(1): 13-7.
29. Aktualna charakterystyka produktu leczniczego Aubagio, Aubagio_ChPL_07_2021.pdf (sanofi.pl) (access: 12.10.2022).