Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis
Por:
Brown, J, Coles, A, Horakova, D, Havrdova, E, Izquierdo, G, Prat, A, Girard, M, Duquette, P, Trojano, M, Lugaresi, A, Bergamaschi, R, Grammond, P, Alroughani, R, Hupperts, R, McCombe, P, Van Pesch, V, Sola, P, Ferraro, D, Grand'Maison, F, Terzi, M, Lechner-Scott, J, Flechter, S, Slee, M, Shaygannejad, V, Pucci, E, Granella, F, Jokubaitis, V, Willis, M, Rice, C, Scolding, N, Wilkins, A, Pearson, O, Ziemssen, T, Hutchinson, M, Harding, K, Jones, J, McGuigan, C, Butzkueven, H, Kalincik, T, Robertson, N, Onofrj, M, De Luca, G, Di Tommaso, V, Travaglini, D, Pietrolongo, E, di Ioia, M, Farina, D, Mancinelli, L, Hodgkinson, S, Oreja-Guevara, C, Boz, C, Prevost, J, Olascoaga, J, Van Wijmeersch, B, Barnett, M, Verheul, F, Rojas, J, Spitaleri, D, Rio, M, Taylor, B, Sanchez-Menoyo, J, Ramo-Tello, C, Solaro, C, Csepany, T, Iuliano, G, Skibina, O, Petersen, T, Bolanos, R, Sidhom, Y, Riadh, Vucic, S, Macdonell, R, Sempere, A, Simo, M, Kister, I, Shuey, N, Radek, Dominguez, J, Amato, M, Saladino, M, Kermode, A, Butler, E, Moore, F, Hughes, S, McDonnell, G, Piroska, I, Yamout, B, Soysal, A, Ozakbas, S, Zwanikken, C and MSBase Study Grp
Publicada:
15 ene 2019
Resumen:
IMPORTANCE Within 2 decades of onset, 80% of untreated patients with relapsing-remitting multiple sclerosis (MS) convert to a phase of irreversible disability accrual termed secondary progressiveMS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition.
OBJECTIVE To determine the association between the use, the type of, and the timing of DMTs with the risk of conversion to secondary progressive MS diagnosed with a validated definition.
DESIGN, SETTING, AND PARTICIPANTS Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remittingMS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up.
EXPOSURES The use, type, and timing of the following DMTs: interferon beta, glatiramer acetate, fingolimod, natalizumab, or alemtuzumab. After propensity-score matching, 1555 patients were included (last follow-up, February 14, 2017).
MAIN OUTCOME AND MEASURE Conversion to objectively defined secondary progressiveMS.
RESULTS Of the 1555 patients, 1123 were female (mean baseline age, 35 years [SD, 10]). Patients initially treated with glatiramer acetate or interferon beta had a lower hazard of conversion to secondary progressiveMS than matched untreated patients (HR, 0.71; 95% CI, 0.61-0.81; P <.001; 5-year absolute risk, 12%[49 of 407] vs 27%[58 of 213]; median follow-up, 7.6 years [IQR, 5.8-9.6]), as did fingolimod (HR, 0.37; 95% CI, 0.22-0.62; P <.001; 5-year absolute risk, 7%[6 of 85] vs 32%[56 of 174]; median follow-up, 4.5 years [IQR, 4.3-5.1]); natalizumab (HR, 0.61; 95% CI, 0.43-0.86; P =.005; 5-year absolute risk, 19% [16 of 82] vs 38%[62 of 164]; median follow-up, 4.9 years [IQR, 4.4-5.8]); and alemtuzumab (HR, 0.52; 95% CI, 0.32-0.85; P =.009; 5-year absolute risk, 10% [4 of 44] vs 25%[23 of 92]; median follow-up, 7.4 years [IQR, 6.0-8.6]). Initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion than initial treatment with glatiramer acetate or interferon beta (HR, 0.66; 95% CI, 0.44-0.99; P =.046); 5-year absolute risk, 7%[16 of 235] vs 12%[46 of 380]; median follow-up, 5.8 years [IQR, 4.7-8.0]). The probability of conversion was lower when glatiramer acetate or interferon beta was started within 5 years of disease onset vs later (HR, 0.77; 95% CI, 0.61-0.98; P =.03; 5-year absolute risk, 3%[4 of 120] vs 6%[2 of 38]; median follow-up, 13.4 years [IQR, 11-18.1]). When glatiramer acetate or interferon beta were escalated to fingolimod, alemtuzumab, or natalizumab within 5 years vs later, the HR was 0.76 (95% CI, 0.66-0.88; P <.001; 5-year absolute risk, 8%[25 of 307] vs 14%[46 of 331], median follow-up, 5.3 years [IQR], 4.6-6.1).
CONCLUSIONS AND RELEVANCE Among patients with relapsing-remittingMS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressiveMS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.
Filiaciones:
Brown, J:
Univ Cambridge, Dept Clin Neurosci, Cambridge, England
UCL, NMR Res Unit, Queen Sq Multiple Sclerosis Ctr, Inst Neurol, London, England
Univ Melbourne, Melbourne Brain Ctr, Clin Outcomes Res Unit, Melbourne, Vic, Australia
Coles, A:
Univ Cambridge, Dept Clin Neurosci, Cambridge, England
Horakova, D:
Gen Univ Hosp, Dept Neurol, Prague, Czech Republic
Gen Univ Hosp, Ctr Clin Neurosci, Prague, Czech Republic
Charles Univ Prague, Katerinska, Czech Republic
Havrdova, E:
Gen Univ Hosp, Dept Neurol, Prague, Czech Republic
Gen Univ Hosp, Ctr Clin Neurosci, Prague, Czech Republic
Charles Univ Prague, Katerinska, Czech Republic
Izquierdo, G:
Hosp Univ Virgen Macarena, Seville, Spain
Prat, A:
Hop Notre Dame De Bon Secours, Montreal, PQ, Canada
CHUM, Montreal, PQ, Canada
Univ Montreal, Montreal, PQ, Canada
Girard, M:
Hop Notre Dame De Bon Secours, Montreal, PQ, Canada
CHUM, Montreal, PQ, Canada
Univ Montreal, Montreal, PQ, Canada
Duquette, P:
Hop Notre Dame De Bon Secours, Montreal, PQ, Canada
CHUM, Montreal, PQ, Canada
Univ Montreal, Montreal, PQ, Canada
Trojano, M:
Univ Bari, Dept Basic Med Sci Neurosci & Sense Organs, Bari, Italy
Lugaresi, A:
Univ G dAnnunzio, Dept Neurosci Imaging & Clin Sci, Chieti, Italy
Bergamaschi, R:
C Mondino Natl Neurol Inst, Pavia, Italy
Grammond, P:
CISSS Chaudire Appalache, Ctr Hosp, Levis, PQ, Canada
Alroughani, R:
Amiri Hosp, Kuwait, Kuwait
Hupperts, R:
Zuyderland Med Ctr, Sittard Geleen, Netherlands
McCombe, P:
Univ Queensland, Brisbane, Qld, Australia
Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia
Van Pesch, V:
Catholic Univ Louvain, Clin Univ St Luc, Brussels, Belgium
Sola, P:
Azienda Osped Univ, Dept Neurosci, Modena, Italy
Ferraro, D:
Azienda Osped Univ, Dept Neurosci, Modena, Italy
Grand'Maison, F:
Neuro Rive Sud, Greenfield Pk, PQ, Canada
Terzi, M:
Ondokuz Mayis Univ, Med Fac, Kurupelit, Turkey
Lechner-Scott, J:
Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia
John Hunter Hosp, Hunter New England Hlth, Dept Neurol, Newcastle, NSW, Australia
Flechter, S:
Asaf Harofen Med Ctr, Zerifin, Israel
Slee, M:
Flinders Univ S Australia, Adelaide, SA, Australia
Shaygannejad, V:
Isfahan Univ Med Sci, Esfahan, Iran
Pucci, E:
Azienda Sanit Unica Reg Marche, UOC Neurol, Macerata, Italy
Granella, F:
Univ Parma, Parma, Italy
Jokubaitis, V:
Univ Melbourne, Dept Med, Melbourne, Vic, Australia
Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic, Australia
Willis, M:
Cardiff Univ, Univ Hosp Wales, Dept Neurol, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales
Rice, C:
Univ Bristol, Dept Neurol, Southmead Hosp, Bristol, Avon, England
Univ Bristol, Clin Neurosci, Bristol, Avon, England
Scolding, N:
Univ Bristol, Dept Neurol, Southmead Hosp, Bristol, Avon, England
Univ Bristol, Clin Neurosci, Bristol, Avon, England
Wilkins, A:
Univ Bristol, Dept Neurol, Southmead Hosp, Bristol, Avon, England
Univ Bristol, Clin Neurosci, Bristol, Avon, England
Pearson, O:
Abertawe Bro Morgannwg Univ Local Hlth Board, Swansea, W Glam, Wales
Ziemssen, T:
MS Ctr Dresden, Ctr Clin Neurosdence, Dept Neurol, Dresden, Germany
Hutchinson, M:
Univ Coll Dublin, Sch Med & Med Sci, St Vincents Univ Hosp, Dublin, Ireland
Harding, K:
Cardiff Univ, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales
Jones, J:
Univ Cambridge, Dept Clin Neurosci, Cambridge, England
McGuigan, C:
Univ Coll Dublin, Sch Med & Med Sci, St Vincents Univ Hosp, Dublin, Ireland
Butzkueven, H:
Univ Melbourne, Dept Med, Melbourne, Vic, Australia
Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic, Australia
Monash Univ, Box Hill Hosp, Dept Neurol, Melbourne, Vic, Australia
Kalincik, T:
Univ Melbourne, Melbourne Brain Ctr, Clin Outcomes Res Unit, Melbourne, Vic, Australia
Univ Melbourne, Dept Med, Melbourne, Vic, Australia
Royal Melbourne Hosp, Dept Neurol, Melbourne, Vic, Australia
Robertson, N:
Cardiff Univ, Inst Psychol Med & Clin Neurosci, Cardiff, S Glam, Wales
Onofrj, M:
Univ G dAnnunzio, Chieti, Italy
De Luca, G:
Univ G dAnnunzio, Chieti, Italy
Di Tommaso, V:
Univ G dAnnunzio, Chieti, Italy
Travaglini, D:
Univ G dAnnunzio, Chieti, Italy
Pietrolongo, E:
Univ G dAnnunzio, Chieti, Italy
di Ioia, M:
Univ G dAnnunzio, Chieti, Italy
Farina, D:
Univ G dAnnunzio, Chieti, Italy
Mancinelli, L:
Univ G dAnnunzio, Chieti, Italy
Hodgkinson, S:
Liverpool Hosp, Sydney, NSW, Australia
Oreja-Guevara, C:
Hosp Clin San Carlos, Madrid, Spain
Boz, C:
Farabi Hosp, KTU Med Fac, Trabzon, Turkey
Prevost, J:
CCSS St Jerome, St Jerome, PQ, Canada
Olascoaga, J:
Hosp Univ Donostia, San Sebastien, Spain
Van Wijmeersch, B:
Overpelt & Hassell Univ, Rehabil & MS Ctr, Hosselt, Belgium
Barnett, M:
Wijmeersch Brain & Mind Ctr, Sydney, NSW, Australia
Verheul, F:
Groene Hart Ziekenhuis, Gouda, Netherlands
Rojas, J:
Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina
Spitaleri, D:
Azienda Osped Rilievo Nazl San Guiseppe, Avellino, Italy
Rio, M:
Hosp Sao Joao, Porto, Portugal
Taylor, B:
Royal Hobart Hosp, Hobart, Tas, Australia
Sanchez-Menoyo, J:
Hosp Galdakao Usansolo, Galdakao, Spain
Ramo-Tello, C:
Hosp Badalona Germans Trias & Pujol, Badalona, Spain
Solaro, C:
Ospendak PA Micone, Genoa, Italy
Csepany, T:
Univ Debrecen, Debrecen, Hungary
Iuliano, G:
Osped Riuniti Salerno, Salerno, Italy
Skibina, O:
Alfred, Melbourne, Vic, Australia
Petersen, T:
Kommunehospitalet, Aarhus C, Denmark
Bolanos, R:
Hosp Univ Virgen Valme, Seville, Spain
Sidhom, Y:
Razi Hosp, Manoubo, Tunisia
Riadh:
Razi Hosp, Manoubo, Tunisia
Vucic, S:
Gouider Westmead Hosp, Sydney, NSW, Australia
Macdonell, R:
Austin Hlth, Melbourne, Vic, Australia
:
Univ Alicante, Hosp Gen, Alicante, Spain
Simo, M:
Semellweis Univ, Budapest, Hungary
Kister, I:
NYU, Langone Med Ctr, New York, NY USA
Shuey, N:
St Vincents Hosp, Melbourne, Vic, Australia
Radek:
Nemocnice Jihlava, Jihlava, Czech Republic
Dominguez, J:
Ampapa Hosp Univ Ribero, Alizira, Spain
Amato, M:
Univ Florence, Florence, Italy
Saladino, M:
Inst Neurosci Buenos Aires, Buenos Aires, DF, Argentina
Kermode, A:
Univ Western Australia, Perth, WA, Australia
Butler, E:
Monash Med Ctr, Melbourne, Vic, Australia
Moore, F:
Jewish Gen Hosp, Montreal, PQ, Canada
Hughes, S:
Craigavon Area Hosp, Craigavon, England
McDonnell, G:
Royal Victoria Hosp, Belfast, Antrim, North Ireland
Piroska, I:
Veszprem Megyei Csolnoky Ferenc Korhaz Zrt, Veszprem, Hungary
Yamout, B:
Amer Univ Beirut, Med Ctr, Beirut, Lebanon
Soysal, A:
Bakirkoy Educ & Res Hosp Psychiat & Neurol Dis, Istanbul, Turkey
Ozakbas, S:
Dokuz Eylul Univ, Konak Izmir, Turkey
Zwanikken, C:
MS Ctr Nijmegen, Nijmegen, Netherlands
Green Published, Bronze, Green Submitted
|