MSBase research published in JAMA: Congratulations Will Brown, Tomas Kalincik & the MSBase Investigators
Association of Initial Disease-Modifying Therapy with later conversion to Secondary Progressive Multiple Sclerosis
Brown, J.W.L. 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.R. Ziemssen, T. Hutchinson, M. Harding, K. Jones, J. McGuigan, C. Butzkueven, H. Kalincik, T. Robertson, N; MSBase Study Group. JAMA (Jan 2019) 15;321(2): 175-187 http://dx.doi.org/10.1001/jama.2018.20588.
KEY POINTS
Question
Among patients with relapsing-remitting multiple sclerosis (MS), what is the association between disease-modifying therapies (DMTs) and the risk of conversion to secondary progressive multiple sclerosis (MS)?
Findings
In this cohort study involving 1555 patients with relapsing-remitting MS, initial treatment with fingolimod, natalizumab, or alemtuzumab was associated with a lower risk of conversion to secondary progressive MS compared with interferon beta or glatiramer acetate (hazard ratio, 0.66).
These findings, considered along with the risks associated with these therapies, may help inform decisions regarding disease-modifying treatment selection for patients with relapsing-remitting MS.
ABSTRACT
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 progressive MS. 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-remitting MS 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 progressive MS.
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 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).
Conclusions and Relevance
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.
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