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Publication - Dr Claire Rice

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

    Citation

    Brown, JW, Coles, A, Horakova, D, Havrdova, E, Izquierdo, G, Prat, A, Girard, M, Duquette, P, Alroughani, R, Hupperts, R, McCombe, P, van Pesch, V, Sola, P, Ferraro, D, Grand'Maison, F, Terzi, M, 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, 2019, ‘Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis’. JAMA Neurology, vol 321., pp. 175-187

    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.

    Full details in the University publications repository