ClinicSpeak: switching from first-line therapies to natalizumab drops relapse rates

Switching upwards, not sideways, gives you the best chance of controlling your MS #ClinicSpeak #MSResearch #MSBlog

“The following study demonstrates that sequencing DMTs (disease-modifying therapies) by moving sideways gives you a lower chance of having your disease controlled than moving upwards. In other words if you are being treated with either interferon-beta or glatiramer acetate you do much better on average if you are switched to natalizumab, i.e. upwards, that if you are switched sideways from IFNbeta to GA, or GA to IFNbeta. This is why in our treat-2-target algorithm of NEDA we only recommend one chance on a lower efficacy therapy, before moving upwards to a more efficacious. Please note our BARTS-MS treat-2-target algorithm is only a guide and there are many individualised factors that may affect your choice of therapy.”

“Again I must congratulate the MS-BASE group for their work. The type of analyses they are doing with real-life data is helping shape the way we use DMTs in MS. A very hot topic in MS at the moment is the sequencing of DMTs; without head-2-head studies and trials we simply have to rely on analyses of real-life data sets such as MS-BASE.”

“The cynics out there will say of course relapse rates will drop when you switch from IFNbeta or GA to natalizumab. We know this already. I agree we know this already, but it is reassuring to know that real-life data sets show this. Importantly, there will be MSers on IFNbeta and GA who do well and have NEDA  that won’t need to switch; so called responders. If only we could identify these MSers prior to them starting a DMT it would improve the outcomes for everyone.”

Spelman et al. Comparative efficacy of switching to natalizumab in active multiple sclerosis. Ann Clin Transl Neurol. 2015;2(4):373-87.

OBJECTIVE: To compare treatment efficacy and persistence in MSers who switched to natalizumab versus those who switched between glatiramer acetate (GA) and interferon-beta (IFNβ) after an on-treatment relapse on IFNβ or GA using propensity score matched real-world datasets.

METHODS: MSers included were registered in MSBase or the TYSABRI Observational Program (TOP), had relapsed on IFNβ or GA within 12 months prior to switching to another therapy, and had initiated natalizumab or IFNβ/GA treatment ≤6 months after discontinuing prior therapy. Covariates were balanced across post switch treatment groups by propensity score matching at treatment initiation. Relapse, persistence, and disability measures were compared between matched treatment arms in the total population (n = 869/group) and in subgroups defined by prior treatment history (IFNβ only [n = 578/group], GA only [n = 165/group], or both IFNβ and GA [n = 176/group]).

RESULTS: Compared to switching between IFNβ and GA, switching to natalizumab reduced annualized relapse rate in year one by 65-75%, the risk of first relapse by 53-82% (mean follow-up 1.7-2.2 years) and treatment discontinuation events by 48-65% (all P ≤ 0.001). In the total population, switching to natalizumab reduced the risk of confirmed disability progression by 26% (P = 0.036) and decreased the total disability burden by 1.54 EDSS-years (P < 0.0001) over the first 24 months post switch.

INTERPRETATION: Using large, real-world, propensity-matched datasets we demonstrate that after a relapse on IFNβ or GA, switching to natalizumab (rather than between IFNβ and GA) led to superior outcomes for patients in all measures assessed. Results were consistent regardless of the prior treatment identity.

CoI: multiple

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.


    • Re: "superior outcomes, that is a very fulsome endorsement"

      Yes, please note that I didn't use this adjective, it was the MS-BASE authors'.

  • Prof G,

    What percentage of patients are opting for induction treatment. Is lemtrada showing good results for these patients?

    • I would say not high…….as I heard Lemtrada was not selling as well as hoped…Maybe DrK/ProfG knows…

      but I would suspect that it is going to get a lot harder for those thinking about it, with extra post-election rationing of MS drugs coming for the English at least.

  • Relapses and progression have different pathologies. Stopping relapses will not stop progression.

    • If you look at the alemtuzumab trials over 10 years only 5% had moved to secondary progressive rather than 50% that you would expect from the natural history of this disease. I'm no scientist but that looks like slowing progression to me. I guess time will tell us the definitive answer

    • In the meeces stopping relapses before too much damage stops clinical progression from materialising

  • Prof G,

    What proportion of new patients opt for induction therapy? Are those that do seeing good resuls?

  • Low percentages, there are about 6000 new diagnosis each year in UK, virtually all would be eligible for Lemtrada by being "active MS" if they and more importantly their neuros wanted it.

  • If the average neuro in the UK is treating it as mine in the US does, that's no surprise! There's a lot of misinformation about how it works and a lot of mistrust over the trial data here.

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