Iaffaldano P, Lucisano G, Butzkueven H, Hillert J, Hyde R, Koch-Henriksen N, Magyari M, Pellegrini F, Spelman T, Sørensen PS, Vukusic S, Trojano M. Early treatment delays long-term disability accrual in RRMS: Results from the BMSD network. Mult Scler. 2021 Apr 26:13524585211010128. doi: 10.1177/13524585211010128.
Background: The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.
Objective: The aim of this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.
Methods: Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference.
Quintiles (Q) of time from disease onset to the first DMT start, years, median, (min–max). Q1 0.6 (0.0–1.2), Q2 1.8 (1.3–2.7), Q3 3.8 (2.8–5.3), Q4 7.3 (5.4–10.1), Q5 14.6 (10.2–41.0)
Results: A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients’ group.
Conclusion: Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
This study suggests that early treatment (The first DMT was a first-line agent (n = 10,925 interferon beta (IFN beta) or glatiramer acetate (GA); n = 814 azathioprine) in 98.9% of patients, whereas it was a second-line agent (natalizumab, fingolimod or mitoxantrone) in 1.1% of patients) is important to limit the potential for the accumulation of disability in the future. This view is supported by other studies. You have asked how quickly should ideally treatment be started and this real world data suggests ASAP as it is clear that there can be disability progression even if treatment is started early on. Whilst I appreciate that many readers of the blog will not have had this experience, it is important that we do better now than we did in the past. The http://www.msbrainhealth.org has set standards to aspire too, it would be good to see who are achieving these. The only way to know this is to monitor this and I know that our Health Care Team are doing this
Hobart J, Bowen A, Pepper G, Crofts H, Eberhard L, Berger T, Boyko A, Boz C, Butzkueven H, Celius EG, Drulovic J, Flores J, Horáková D, Lebrun-Frénay C, Marrie RA, Overell J, Piehl F, Rasmussen PV, Sá MJ, Sîrbu CA, Skromne E, Torkildsen Ø, van Pesch V, Vollmer T, Zakaria M, Ziemssen T, Giovannoni G. International consensus on quality standards for brain health-focused care in multiple sclerosis. Mult Scler. 2019;25(13):1809-1818.
The next question what is the time window and how to optimise benefit, I have seen data that sugggests based on different treatments there is a window larger than that recorded above. However, it is logical that when ever effective treatment is started, there will be benefit. Next up does it matter about the treatment and its percieved level of efficacy. I also believe there is data on that too, but you know I’m a broken record on that one.
ProfK is about to start a study of natalizumab use at presentation in a study called ATTACK MS. At the moment I believe this study will be done at three centres in the London area. The idea is to get people onto high-efficacy therapy ASAP to stop further attacks occuring in untreated MS, whilst the person/neuro decides how best to move forward.
Disclaimer: Please note that the opinions expressed here are those of the author and do not reflect the positions of the Barts and The London School of Medicine and Dentistry nor Barts Health NHS Trust or Queen Mary Univeristy of London.