For Relapsing-remitting MS we currently have option of highly active therapies, as well as first-line therapies that are less efficacious. You may question why anyone in their right mind would develop a treatment that was no good, then conversely ask yourself, why if there are treatments available, even not so good ones, are some people not any of it? This is not me pitching for the next presidency, but this is the paradox that we currently live in. The naysayers will tell you that there is the so-called benign MS, resulting in a small few that would never have needed treatment in the first place; a hat-trick that you cannot argue against, despite the multitude of graphs that you produce demonstrating otherwise. Just the mention of it is enough to introduce doubt into the most learned of our colleagues.
Maybe, we were going about this the all wrong way. From now instead of fighting it, my tactic is going to be to say that “some treatment is better than no treatment“.
So what am I basing this all on? Just recently made available to us is data spanning 21 countries (the MS-Base project) on real life RRMS management. The findings are not staggering, but just maybe what the doctor ordered.
The most significant of the findings is that outcome that on a wide scale even the lowest efficacy drugs (interferons, glatiramer acetate) do something meaningful (see figure below). It goes without saying that the highest efficacy drugs do more, but the principle is treat MS.
For those initially treated with glatiramer acetate and interferons compared to untreated PwMS the conversion to secondary progressive MS at 5y was 12% vs 27%, and at 11y was 47% vs 57% (Figure A above). For fingolimod this was 7% vs 32% at 5y, and 7% vs 39% at 6y (Figure B above), and for nataluzimab this was 19% vs 38% at 5y, and 34% vs 48% at 6y (Figure C above). Alemtuzumab figures were 10% vs 25% at 5y, and 21% vs 41% at 8y (Figure D above).
Moreover, it would also seem that fortune favors those who don’t hang about (see figure below). The benefit of earlier treatment with either glatiramer acetate or interferons waned (Figure C below) when commenced later than 5y (duration of disease was ~12y), and disappeared at approx. 8y (duration of disease was ~15y). The same applies if you escalate from glatiramer acetate or interferons to fingolimod, alemtuzumab or natalizumab within 5y versus those escalated later (Figure D below). Raising the point that those on treatment should be monitored carefully for disease activity in the early half of the disease.
And as mentioned before, those receiving fingolimod, alemtuzumab or natalizumab at the outset had a significantly lower risk of progression than those initially receiving either glatiramer acetate or the interferons (see figure below). At 5y the difference was 7% vs 12% respectively, and at 9y it was 16% vs 27%, respectively.
Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis
J. William L. Brown, MRCP; Alasdair Coles, PhD; Dana Horakova, PhD; et al
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.