High-efficacy MS therapies used earlier instead of later = far less disability

[ActiveMSers]

Volume 19, Issue 4, April 2020, Pages 307-316

Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study

AnnaHeMBBS^aBerndMerkelPhD^aJames William LBrownPhD^abcLanaZhovits RyersonMD^dIlyaKisterMD^dCharles BMalpasPhD^aSifatSharminPhD^aDanaHorakovaMD^efEvaKubala HavrdovaPhD^efTimSpelmanPhD^gGuillermoIzquierdoMDⁱSaraEichauMDⁱMariaTrojanoMD^jAlessandraLugaresiMD^klRaymondHuppertsMD^mPatriziaSolaMDⁿDianaFerraroMDⁿJanLyckePhD^o…TomasKalincikPhD^aac

https://doi.org/10.1016/S1474-4422(20)30067-3

Summary

Background
High-efficacy therapies in multiple sclerosis are traditionally used after unsuccessful treatment with first-line disease modifying therapies. We hypothesised that early commencement of high-efficacy therapy would be associated with reduced long-term disability. We therefore aimed to compare long-term disability outcomes between patients who started high-efficacy therapies within 2 years of disease onset with those who started 4–6 years after disease onset.

Methods
In this retrospective international observational study, we obtained data from the MSBase registry and the Swedish MS registry, which prospectively collect patient data that are specific to multiple sclerosis as part of routine clinical care. We identified adult patients (aged ≥18 years) with relapsing-remitting multiple sclerosis, with at least 6 years of follow-up since disease onset, and who started the high-efficacy therapy (rituximab, ocrelizumab, mitoxantrone, alemtuzumab, or natalizumab) either 0–2 years (early) or 4–6 years (late) after clinical disease onset. We matched patients in the early and late groups using propensity scores calculated on the basis of their baseline clinical and demographic data. The primary outcome was disability, measured with the Expanded Disability Status Score (EDSS; an ordinal scale of 0–10, with higher scores indicating increased disability), at 6–10 years after disease onset, assessed with a linear mixed-effects model.

Findings
We identified 6149 patients in the MSBase registry who had been given high-efficacy therapy, with data collected between Jan 1, 1975, and April 13, 2017, and 2626 patients in the Swedish MS Registry, with data collected between Dec 10, 1997, and Sept 16, 2019. Of whom, 308 in the MSBase registry and 236 in the Swedish MS registry were eligible for inclusion. 277 (51%) of 544 patients commenced therapy early and 267 (49%) commenced therapy late. For the primary analysis, we matched 213 patients in the early treatment group with 253 in the late treatment group. At baseline, the mean EDSS score was 2·2 (SD 1·2) in the early group and 2·1 (SD 1·2) in the late group. Median follow-up time for matched patients was 7·8 years (IQR 6·7–8·9). In the sixth year after disease onset, the mean EDSS score was 2·2 (SD 1·6) in the early group compared with 2·9 (SD 1·8) in the late group (p<0·0001). This difference persisted throughout each year of follow-up until the tenth year after disease onset (mean EDSS score 2·3 [SD 1·8] vs 3·5 [SD 2·1]; p<0·0001), with a difference between groups of −0·98 (95% CI −1·51 to −0·45; p<0·0001, adjusted for proportion of time on any disease-modifying therapy) across the 6–10 year follow-up period.

Interpretation
High-efficacy therapy commenced within 2 years of disease onset is associated with less disability after 6–10 years than when commenced later in the disease course. This finding can inform decisions regarding optimal sequence and timing of multiple sclerosis therapy.

Funding
National Health and Medical Research Council Australia and MS Society UK.

[ActiveMSers]

This is really eye-opening. Timing definitely matters with the big guns. The old "escalation" model, where you gradually increase the power of meds as they fail, appears outdated and perhaps even risky.

[Ashleyvanj]

Oops! I decided to wait and see for four years. Starting Ocrevus this month. Hopefully didn't do too much damage.