Ciggies are bad for you drugs are not.

C

Now before you start I am not talking about the class A’s (illegals)…which I now realise is an age thing because when making a joke about class A’s at the pint of Science meeting 2022, no-one seemed to get it. However if you take drugs at an early time point you may live longer. This was shown when they looked at survival times following no drugs, verses the early offerings, verses the more effective agents. Even if you take the drugs that I dont talk about there was a 25% survival benefit rising to 33% with more recent offerings.

Now before you can say they missed a trick…Just to say they group the treatments in two ways

By generation: first (beta-interferon and glatiramer acetate) and second (natalizumab, fingolimod, dimethyl fumarate, teriflunomide, alemtuzumab, and ocrelizumab).

By expected efficacy: lower (beta-interferon, glatiramer acetate, and teriflunomide), moderate (fingolimod and dimethyl fumarate), and higher (natalizumab, alemtuzumab, and ocrelizumab).

Exposure to a DMT was defined as ≥6 months (180 days) of cumulative use for beta-interferon and glatiramer acetate and 3 months (90 days) of cumulative use for natalizumab, fingolimod, dimethyl fumarate, and teriflunomide. 

However for the first generation there were over ~8,200 verses only ~3,100 second generation and for low efficacy it was ~8,500, modest 2,100 (read this as largely dimethyl fumarate) and high ~800 (read this as natalizumab as there were less than 6 people on ocrelizumab)

So at this point say the pyramid needs to be flipped as in this cohort most people get low efficacy drugs and you say yikes according to the data the people on high efficacy drugs did worse than low efficacy (Symbol more to the right of the line which is no treatment) which was the same as medium efficacy for for low there was a 23% drop but there was a 14% increase over nothing for the high efficacy agents. However when you look at the range of the high efficacy drugs it ranged from an 80% drop to hundreds of times increased and this may reflect thay people on high efficacy drugs probably had worse disease.

However I would argue that we need this study done in a decade or more when hopefully low efficacy agents as first-line area thing of the past. I bet if people started on HSCT the results would be very different. However it sys get treatment as soon as possible.

Ng HS, Zhu F, Kingwell E, Yao S, Ekuma O, Evans C, Fisk JD, Marrie RA, Zhao Y, Tremlett H. Disease-Modifying Drugs for Multiple Sclerosis and Association With Survival. Neurol Neuroimmunol Neuroinflamm. 2022 Jun 14;9(5):e200005. 

Background and objectives: We examined the association between the disease-modifying drugs (DMDs) for multiple sclerosis (MS) and survival in a multiregion population-based study.

Methods: We accessed multiple administrative health databases from 4 Canadian provinces. Persons with MS were identified and followed from the most recent of the first MS or demyelinating event or January 1, 1996 (index date), until death, emigration, or December 31, 2017. Association between the first-generation and second-generation DMDs and all-cause mortality was examined using stratified Cox proportional hazard models, reported as adjusted hazard ratios (aHRs). Timing of DMD initiation was explored, with findings reported at 2, 5, or 10 years postindex date, representing very early, early, or late initiation.

Results: We identified 35,894 persons with MS; 72% were female. The mean age at index date was 44.5 years (SD = 13.6). The total person-years of follow-up while DMD-exposed was 89,180, and total person-years while unexposed was 342,217. Compared with no exposure, exposure to any DMD or to any first-generation DMD was associated with a 26% lower hazard of mortality (both aHRs 0.74; 95% CI 0.56-0.98), while any second-generation DMD exposure was associated with a 33% lower hazard (aHR 0.67; 95% CI 0.46-0.98). Earlier DMD initiation (beta-interferon or glatiramer acetate vs no exposure) was associated with a significant mortality effect (p < 0.05), while later initiation was not (95% CIs included 1). However, the survival advantage with earlier initiation diminished over time, no longer reaching statistical significance at 15 years postindex date.

Discussion: Our study demonstrates an association between the DMDs for MS and improved survival in the real-world setting.

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