How important is age in the development of progressive MS?

More about ageing and MS; this time about the development of progressive MS. 

The main message below is that most pwMS who are destined to develop progressive MS do so before age 75 and the onset of this phase of the disease is more dependent on age than the duration of MS.

Does this mean you are all destined to develop progressive MS? No in this study only 38% people with RRMS went onto develop progressive MS by age 75. Why some RRMSers don't develop progressive MS is probably due to biological factors and DMTs.

So the message in this post is mixed, i.e. the onset of the progressive phase of MS is age-dependent and not all pwRRMS become progressive.

This is no consolation for PPMSers. However, with the licensing of ocrelizumab for treating early-active PPMS we now have a DMT that can modify the course of PPMS, despite the treatment response to ocrelizumab being age-related. As with RRMS is better to treat PPMS as soon as possible after the onset of the disease; there is no point in waiting to lose reserve and neurological function and the advantage of youth before starting ocrelizumab.

The important question from a biological perspective is how is age modifying the course of MS and is there anything we can do to slow down or stop the ravages of ageing? I would start with a Brain Healthy Lifestyle. However, ageing is a biological programme and I have little doubt that scientists will crack the code and identify pathways that are modifiable. One hurdle still exists, however, society still considers ageing a normal phenomenon. Until we redefine ageing as a disease and healthcare payers agree to pay for anti-ageing treatments the incentive for Pharma to invest in ageing research won't materialise anytime soon.

We have had this debate before on the blog. Do you agree that ageing is a disease? 

I would be interested in your thoughts on the issues above. 

Tutuncu, et al. Onset of Progressive Phase is an Age Dependent Clinical Milestone in Multiple Sclerosis. Mult Scler. 2013 Feb; 19(2): 188–198.

Background: It is unclear if all patients with RRMS ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration dependent. Some forms of progressive MS (e.g. PPMS) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age-of-progression-onset between SPMS and PPMS but may introduce unclear biases.

Objective: To confirm that onset of progressive disease course is more relevant to patient's age than the presence or duration of a pre-progression relapsing disease course in MS.

Methods: We studied a population-based MS cohort (n=210, relapsing-remitting MS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary- (PPMS; n=322), single attack- (SAPMS; n=112) and secondary-progressive (SPMS; n=421). We studied demographics (chi2 or t-test), age-of-progression-onset (t-test) and time-to-EDSS6 (Kaplan-Meier analyses).

Results: Sex-ratio (p=0.58), age-of-progression-onset (p=0.37) and time-to-EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age-of-progression-onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS 6 before the onset of progression.

ConclusionsPatients with RRMS do not inevitably develop progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.


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