Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

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 progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and ne...

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Vydané v:	JAMA : the journal of the American Medical Association Ročník 321; číslo 2; s. 175
Hlavní autori:	Brown, J William L, Coles, Alasdair, Horakova, Dana, Havrdova, Eva, Izquierdo, Guillermo, Prat, Alexandre, Girard, Marc, Duquette, Pierre, Trojano, Maria, Lugaresi, Alessandra, Bergamaschi, Roberto, Grammond, Pierre, Alroughani, Raed, Hupperts, Raymond, McCombe, Pamela, Van Pesch, Vincent, Sola, Patrizia, Ferraro, Diana, Grand'Maison, Francois, Terzi, Murat, Lechner-Scott, Jeannette, Flechter, Schlomo, Slee, Mark, Shaygannejad, Vahid, Pucci, Eugenio, Granella, Franco, Jokubaitis, Vilija, Willis, Mark, Rice, Claire, Scolding, Neil, Wilkins, Alastair, Pearson, Owen R, Ziemssen, Tjalf, Hutchinson, Michael, Harding, Katharine, Jones, Joanne, McGuigan, Christopher, Butzkueven, Helmut, Kalincik, Tomas, Robertson, Neil
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 15.01.2019
Predmet:	Adult Alemtuzumab - therapeutic use Cohort Studies Disease Progression Female Fingolimod Hydrochloride - therapeutic use Glatiramer Acetate - therapeutic use Humans Immunologic Factors - therapeutic use Immunosuppressive Agents - therapeutic use Interferon-beta - therapeutic use Male Multiple Sclerosis, Relapsing-Remitting - drug therapy Natalizumab - therapeutic use Time-to-Treatment
ISSN:	1538-3598, 1538-3598
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Shrnutí:	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 progressive MS. The association between disease-modifying treatments (DMTs), and this conversion has rarely been studied and never using a validated definition. 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. Cohort study with prospective data from 68 neurology centers in 21 countries examining patients with relapsing-remitting MS commencing DMTs (or clinical monitoring) between 1988-2012 with minimum 4 years' follow-up. 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). Conversion to objectively defined secondary progressive MS. 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 progressive MS 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). Among patients with relapsing-remitting MS, initial treatment with fingolimod, alemtuzumab, or natalizumab was associated with a lower risk of conversion to secondary progressive MS vs initial treatment with glatiramer acetate or interferon beta. These findings, considered along with these therapies' risks, may help inform decisions about DMT selection.
Bibliografia:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3
ISSN:	1538-3598 1538-3598
DOI:	10.1001/jama.2018.20588