Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies
Background and aims: No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moder...
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Published in | Therapeutic advances in neurological disorders Vol. 14; p. 17562864211019574 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London, England
SAGE Publications
2021
SAGE PUBLICATIONS, INC SAGE Publishing |
Subjects | |
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Abstract | Background and aims:
No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC).
Methods:
RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups.
Results:
The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5–11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01–0.19, p = 0.03) at 1 year to 0.30 (0.07–0.53, p = 0.009) at 5 years and to 0.67 (0.31–1.03, p = 0.0003) at 10 years.
Conclusion:
Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time. |
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AbstractList | No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC).BACKGROUND AND AIMSNo consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC).RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups.METHODSRRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups.The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19, p = 0.03) at 1 year to 0.30 (0.07-0.53, p = 0.009) at 5 years and to 0.67 (0.31-1.03, p = 0.0003) at 10 years.RESULTSThe study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19, p = 0.03) at 1 year to 0.30 (0.07-0.53, p = 0.009) at 5 years and to 0.67 (0.31-1.03, p = 0.0003) at 10 years.Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time.CONCLUSIONOur results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time. Background and aims: No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5–11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01–0.19, p = 0.03) at 1 year to 0.30 (0.07–0.53, p = 0.009) at 5 years and to 0.67 (0.31–1.03, p = 0.0003) at 10 years. Conclusion: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time. Background and aims: No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). Methods: RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. Results: The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5–11.7) years. Mean annual delta-EDSS values were all significantly ( p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01–0.19, p = 0.03) at 1 year to 0.30 (0.07–0.53, p = 0.009) at 5 years and to 0.67 (0.31–1.03, p = 0.0003) at 10 years. Conclusion: Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time. No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC). RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups. The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5-11.7) years. Mean annual delta-EDSS values were all significantly ( < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01-0.19, = 0.03) at 1 year to 0.30 (0.07-0.53, = 0.009) at 5 years and to 0.67 (0.31-1.03, = 0.0003) at 10 years. Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time. |
Author | Zaffaroni, Mauro Pozzilli, Carlo Totaro, Rocco Lucisano, Giuseppe Rovaris, Marco Caputo, Francesca Comi, Giancarlo Granella, Franco Bergamaschi, Roberto Iaffaldano, Pietro Filippi, Massimo Paolicelli, Damiano Salvetti, Marco Patti, Francesco Torri Clerici, Valentina Liliana Adriana Maniscalco, Giorgia Teresa Cocco, Eleonora Scarpini, Elio Brescia Morra, Vincenzo Maimone, Davide Capobianco, Marco Salemi, Giuseppe Gasperini, Claudio De Luca, Giovanna Conte, Antonella Inglese, Matilde Trojano, Maria Amato, Maria Pia Lus, Giacomo Bellantonio, Paolo Sola, Patrizia |
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Camillo Forlanini, Rome, Italy – sequence: 20 givenname: Paolo surname: Bellantonio fullname: Bellantonio, Paolo organization: UOC di Neurologia, IRCCS Neuromed, Pozzilli (IS), Italy – sequence: 21 givenname: Rocco surname: Totaro fullname: Totaro, Rocco organization: Centro Malattie Demielinizzanti - Clinica Neurologica, Ospedale San Salvatore, L’Aquila, Abruzzo, Italy – sequence: 22 givenname: Marco surname: Rovaris fullname: Rovaris, Marco organization: Multiple Sclerosis Center, IRCCS Fondazione don Carlo Gnocchi ONLUS, Milan, Italy – sequence: 23 givenname: Marco surname: Salvetti fullname: Salvetti, Marco organization: CENTERS Centro Neurologico Terapie Sperimentali – Sapienza University, S. Andrea Hospital, Roma, Lazio, Italy – sequence: 24 givenname: Valentina Liliana Adriana surname: Torri Clerici fullname: Torri Clerici, Valentina Liliana Adriana organization: Fondazione IRCCS Istituto Neurologico “C. Besta” U.O. 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Cesare, 11, Bari, 70124, Italy |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34104220$$D View this record in MEDLINE/PubMed |
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CorporateAuthor | on behalf of the Italian MS Register Italian MS Register |
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Keywords | disability trajectories big data disease registry multiple sclerosis |
Language | English |
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PublicationTitle | Therapeutic advances in neurological disorders |
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References | Prosperini, Mancinelli, Solaro 2020; 17 Cohen, Barkhof, Comi 2010; 362 Kalincik, Horakova, Spelman 2015; 77 Baroncini, Ghezzi, Annovazzi 2016; 22 Buron, Chalmer, Sellebjerg 2020; 95 Coles, Fox, Vladic 2011; 10 Cohen 1992; 112 Hutchinson, Kappos, Calabresi 2009; 256 Hauser, Bar-Or, Comi 2017; 376 Rudick, Stuart, Calabresi 2006; 354 Trojano, Tintore, Montalban 2017; 13 Coles, Twyman, Arnold 2012; 380 Edan, Comi, Le Page 2011; 82 Harding, Williams, Willis 2019; 76 Kalincik, Brown, Robertson 2017; 16 Merkel, Butzkueven, Traboulsee 2017; 16 Fernández, Delvecchio, Edan 2017; 24 Giovannoni, Cook, Rammohan 2011; 10 Trojano, Bergamaschi, Amato 2019; 40 Austin, Grootendorst, Anderson 2007; 26 Montalban, Gold, Thompson 2018; 24 Lublin, Reingold, Cohen 2014; 83 Rotstein, Montalban 2019; 15 Brown, Coles, Horakova 2019; 321 Kalincik, Jokubaitis, Spelman 2018; 24 He, Merkel, Brown 2020; 19 Rae-Grant, Day, Marrie 2018; 90 bibr15-17562864211019574 bibr12-17562864211019574 bibr2-17562864211019574 bibr7-17562864211019574 bibr5-17562864211019574 bibr22-17562864211019574 bibr25-17562864211019574 bibr28-17562864211019574 bibr8-17562864211019574 bibr18-17562864211019574 bibr9-17562864211019574 bibr3-17562864211019574 bibr6-17562864211019574 bibr16-17562864211019574 bibr14-17562864211019574 bibr19-17562864211019574 bibr24-17562864211019574 bibr21-17562864211019574 bibr11-17562864211019574 bibr1-17562864211019574 bibr10-17562864211019574 bibr4-17562864211019574 bibr17-17562864211019574 bibr13-17562864211019574 bibr20-17562864211019574 bibr26-17562864211019574 bibr27-17562864211019574 bibr23-17562864211019574 |
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No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The... No consensus exists on how aggressively to treat relapsing-remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study... Background and aims: No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The... |
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SubjectTerms | Azathioprine Cladribine Copolymer 1 Interferon Mitoxantrone Monoclonal antibodies Multiple sclerosis Original Research Patients |
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Title | Long-term disability trajectories in relapsing multiple sclerosis patients treated with early intensive or escalation treatment strategies |
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