TY - JOUR
T1 - Early use of high-efficacy disease‑modifying therapies makes the difference in people with multiple sclerosis
T2 - an expert opinion
AU - Filippi, Massimo
AU - Amato, Maria Pia
AU - Centonze, Diego
AU - Gallo, Paolo
AU - Gasperini, Claudio
AU - Inglese, Matilde
AU - Patti, Francesco
AU - Pozzilli, Carlo
AU - Preziosa, Paolo
AU - Trojano, Maria
N1 - Funding Information:
MF is Editor-in-Chief of the Journal of Neurology and Associate Editor of Radiology, Human Brain Mapping and Neurological Sciences, received compensation for consulting services and/or speaking activities from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck-Serono, Novartis, Roche, Sanofi, Takeda, and Teva Pharmaceutical Industries, and receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi, Almiral, Eli Lilly, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). MPA has served on Scientific Advisory Boards for Biogen, Novartis, Roche, Merck, Sanofi Genzyme and Teva; has received speaker honoraria from Biogen, Merck, Sanofi Genzyme, Roche, Novartis and Teva; has received research grants for her Institution from Biogen, Merck, Sanofi Genzyme, Novartis and Roche. She is co-Editor of the Multiple Sclerosis Journal and Associate Editor of Frontiers in Neurology. DC is an Advisory Board member or has given advice to Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva; has received honoraria for speaking or consultation fees from Almirall, Bayer Schering, Biogen, GW Pharmaceuticals, Merck Serono, Novartis, Roche, Sanofi-Genzyme, and Teva; is the principal investigator in clinical trials for Bayer Schering, Biogen, Merck Serono, Mitsubishi, Novartis, Roche, Sanofi-Genzyme, and Teva. His preclinical and clinical research was supported by grants from Bayer Schering, Biogen Idec, Celgene, Merck Serono, Novartis, Roche, Sanofi-Genzyme and Teva. PG has been a consultant and member of Advisory Board for Biogen Italy, Sanofy, Merck, Almirall, Roche and Novartis, has received funding for travel and speaker honoraria from Merck-Serono, Biogen Idec, Sanofi, Novartis-Pharma, Roche, has received research support from Bayer, Biogen Italy, Merk, Sanofi, Roche, Novartis. CG has served on Scientific Advisory Boards for Biogen, Novartis, Roche, Merck, Sanofi Genzyme; has received speaker honoraria from Biogen, Merck, Bayer, Sanofi Genzyme, Roche, Novartis, Almirall, Mylan. MI has received research grants from NIH, NMSS, FISM, EU. She is co-Editor of multiple sclerosis journal. She has received fees for participation in advisory boards from Biogen, Merck, Janssen, Novartis, Roche, Sanofi. FP is involved in Advisor activity for: Alexion, Almirall, Bayer, Biogen, Bristol Meyers Squibb, Merck, Novartis, Sanofi and TEVA; in Speaking activity for: Almirall, Bayer, Biogen, Bristol Meyers Squibb, Merck, Sanofi and TEVA and in Research grants for: Biogen, Merck, Roche, ISS, FISM and MIUR FIR. CP is involved in scientific advisory boards for Biogen, Hoffmann-La Roche, Merck, Novartis, Janssen and Almirall; consulting and/or speaking fees from Almirall, Biogen, Bristol Myers, Janssen Hoffmann-La Roche, Merck, Novartis, and Biogen. Research support from Merck, Hoffman- La Roche, Novartis, Biogen. PP received speaker honoraria from Roche, Biogen, Novartis, Merck Serono, Bristol Myers Squibb and Sanofi Genzyme. He has received research support from Italian Ministry of Health and Fondazione Italiana Sclerosi Multipla. MT has served on scientific AB for Biogen, Novartis, Roche, Merck, BMS and Genzyme; has received speaker honoraria from Biogen, Roche, Sanofi, Merck, Genzyme and Novartis; and has received research grants for her Institution from Biogen, Merck, Novartis and Roche.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
PY - 2022/10
Y1 - 2022/10
N2 - Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients’ preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients’ preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable.
AB - Multiple sclerosis (MS) is a chronic and progressive neurological disease that is characterized by neuroinflammation, demyelination and neurodegeneration occurring from the earliest phases of the disease and that may be underestimated. MS patients accumulate disability through relapse-associated worsening or progression independent of relapse activity. Early intervention with high-efficacy disease-modifying therapies (HE-DMTs) may represent the best window of opportunity to delay irreversible central nervous system damage and MS-related disability progression by hindering underlying heterogeneous pathophysiological processes contributing to disability progression. In line with this, growing evidence suggests that early use of HE-DMTs is associated with a significant greater reduction not only of inflammatory activity (clinical relapses and new lesion formation at magnetic resonance imaging) but also of disease progression, in terms of accumulation of irreversible clinical disability and neurodegeneration compared to delayed HE-DMT use or escalation strategy. These beneficial effects seem to be associated with acceptable long-term safety risks, thus configuring this treatment approach as that with the most positive benefit/risk profile. Accordingly, it should be mandatory to treat people with MS early with HE-DMTs in case of prognostic factors suggestive of aggressive disease, and it may be advisable to offer an HE-DMT to MS patients early after diagnosis, taking into account drug safety profile, disease severity, clinical and/or radiological activity, and patient-related factors, including possible comorbidities, family planning, and patients’ preference in agreement with the EAN/ECTRIMS and AAN guidelines. Barriers for an early use of HE-DMTs include concerns for long-term safety, challenges in the management of treatment initiation and monitoring, negative MS patients’ preferences, restricted access to HE-DMTs according to guidelines and regulatory rules, and sustainability. However, these barriers do not apply to each HE-DMT and none of these appear insuperable.
KW - Disease progression
KW - Disease-modifying drugs
KW - Multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85130759900&partnerID=8YFLogxK
U2 - 10.1007/s00415-022-11193-w
DO - 10.1007/s00415-022-11193-w
M3 - Article
C2 - 35608658
AN - SCOPUS:85130759900
SN - 0340-5354
VL - 269
SP - 5382
EP - 5394
JO - Journal of Neurology
JF - Journal of Neurology
IS - 10
ER -