Brown JWL, Coles A, Horakova D, Havrdova E, Izquierdo G, Prat A, Girard M, Duquette P, Trojano M, Lugaresi A, Bergamaschi R, Grammond P, Alroughani R, Hupperts R, McCombe P, Van Pesch V, Sola P, Ferraro D, Grand’Maison F, Terzi M, Lechner-Scott J, Flechter S, Slee M, Shaygannejad V, Pucci E, Granella F, Jokubaitis V, Willis M, Rice C, Scolding N, Wilkins A, Pearson OR, Ziemssen T, Hutchinson M, Harding K, Jones J, McGuigan C, Butzkueven H, Kalincik T, Robertson N; MSBase Study Group.
JAMA. 2019 Jan 15;321(2):175-187. doi: 10.1001/jama.2018.20588.
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.
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.
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.
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.
Hi Peeps I’m almost back on the blog but still have no idea how to use the new system so bare with the MDs. Whilst we where posting on HSCT, this paper slipped through. However, having sat through some talks by Neuros supporting the “do nothing and waiting and see”. I was thinking I am rather happy that I work with some Neurological Mammals and that they took a real interest in teaching the next generation of neuros and nurses that Time is Brain and not to be squandered by inactivity.
So my hope for the Treatment of MS this year would be to see introduction of the Neurological Chicxulub. Chicxuclub is not a new drug…although it sounds like it, but reading the above if may be be the tonic that many of you need. Chicxulub is the site that many believe is the site in Mexico where a giant comet/asteroid struck the Earth and created the climate change that killed off the Dinosaurs.
This study shows that all MS agents appeared to have a measurable, favorable effect on disease progression. Moreover, the group of therapies that was most effective at decreasing relapse rates also had the greatest benefit on disease progression. Furthermore, earlier initiation of these therapies uniformly appeared to have a more significant effect on disease course. The message is clear “Time is Brain”.
This study demonstrates that if you are prescribed one of the CRAB drugs you are more likely to develop SPMS than if you select a treatment with even modest efficacy. OK some people may respond well but the fact is many will not. They simply serve to eat up your neurological reserve. what you lose by being on such agents, you lose.
It is a dinosaur view to do nothing. For them we need preverbial asteroid to come along.
Now some say what about this Natalizumab does not stop atrophy
Gray matter atrophy in multiple sclerosis despite clinical and lesion stability during natalizumab treatment
A key observation of this study was that there was a progressive decline in brain volume despite treatment with natalizumab. This decline was seen in gray matter but not white matter structures. But it was not controlled and so how do you know how much atrophy would occur if no drug had been used. The people in the study had had MS for 9 years, which is hardly early treatment and therefore some of the damage may have been preprogrammed before natalizumab treatment that stopped new Tand T2 lesions. However we know that people with SPMS treated with natalizumab continue to progress.
COI. Multiple.. but not considered to be relevant