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      Current therapeutic landscape in multiple sclerosis : an evolving treatment paradigm

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          Abstract

          <p class="first" id="d4240641e83">To critically assess the current landscape of disease-modifying agents for multiple sclerosis (MS). Treatment algorithms will be discussed and studies for new agents in late development or recently approved are analyzed in terms of their impact on current treatment strategies. </p>

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          Most cited references52

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          ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis

          Multiple sclerosis (MS) is a complex disease with new drugs becoming available in the past years. There is a need for a reference tool compiling current data to aid professionals in treatment decisions.
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            Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis

            Neurology, 90(17), 777-788
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              Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis

              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). Meaning 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. 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. In this cohort study, initial treatment of patients with relapsing-remitting multiple sclerosis (MS) with disease-modifying therapies (fingolimod, natalizumab, or alemtuzumab) was associated with a lower risk of conversion to secondary progressive MS compared with interferon beta or glatiramer acetate therapy.
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                Author and article information

                Journal
                Current Opinion in Neurology
                Current Opinion in Neurology
                Ovid Technologies (Wolters Kluwer Health)
                1350-7540
                2019
                June 2019
                : 32
                : 3
                : 365-377
                Article
                10.1097/WCO.0000000000000700
                30985372
                69669021-8376-4cd4-b8a6-69d5cff55949
                © 2019
                History

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