What’s in a name.?..Is PPMS on its way out, or have treatment options made a change for the better?

Westerlind H, Stawiarz L, Fink K, Hillert J, Manouchehrinia A. A significant decrease in diagnosis of primary progressive multiple sclerosis: A cohort study. Mult Scler. 2016. pii: 1352458516643394. [Epub ahead of print]

BACKGROUND: Several reports indicate changes to prevalence, incidence, female-to-male ratio in multiple sclerosis. Diagnostic criteria, course definitions and clinical management of the disease have also undergone change during the recent decades.
OBJECTIVE:To investigate temporal trends in the diagnosis of primary progressive multiple sclerosis (PPMS) in Sweden.
METHODS: Through the Swedish MS registry we investigated the proportion of PPMS diagnosis in birth, diagnosis and age period cohorts.
RESULTS:A total of 16,915 patients were categorised into six birth-cohorts from 1946 to 1975 and seven date-of-diagnosis-cohorts from 1980 to 2014. We observed a decrease in the uncorrected analysis of diagnosis of PPMS from 19.2% to 2.2% and an average decrease of 23% (p < 0.001) per 5-year birth-cohort in the adjusted analysis. An average 21% (p < 0.001) decrease per diagnosis-cohort was seen. In the age-specific diagnosis period cohorts the same decreasing trend of PPMS diagnosis was observed in almost all groups.
CONCLUSION: The diagnosis of PPMS has significantly decreased in Sweden specifically after introduction of disease-modifying treatments. Such decrease can have severe impacts on the future research on PPMS. Our data also suggest that the current trend to emphasise presence or absence of inflammatory activity is already reflected in clinical practice.

A diagnosis of PPMS has been a sign to Neuros to do nothing. Hopefully, this is about to change as ocreluzimab could become the first DMT licenced for this treatment option. However this may have been happening for some time in Sweden. Access to a DMT may mean the need for a diagnosis of relapsing MS and it is of interest that since the mid 1990s the diagnosis has been dropping when beta interferon first reached the market in 1995. It is likely that people with “active” PPMS will respond to DMT to some extent

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  • PPMS is sorted already in Sweden? That I did not know.

    How in heaven's name do people starting with PPMS in their 20s live their lives on Ocrelizumab, i.e. without their B-cells?

    I'd certainly have no more problems with PPMS if I'm brought down by a malignancy in my 50s thanks to this drug. This drug is no panacea.

    • How do be ….Just like people on alemtuzumab without T or B cells.

      No panacea…indeed like the rest of them.

    • No, Alemtuzumab is an induction treatment, unlike Ocrelizamub. T & B cells recover post Lemtrada (at varying rates). Ocrelizamub chronically suppresses B-cells when administered every 6 months. It's unrealistic comparing a maintenance treatment to an induction treatment where the targets are different & so to is the length of time cells are suppressed.

  • That is such an irresponsible headline, Mouse.

    PPMS is incurable. It cannot be eradicated, period. the UK has used mitoxantrone to treat PPMS for decades, yet the progression is still patho-clinically sustained, though, perhaps it is tenuously slowed.

    Don't be so sensationalist.

    • Yet the figures speak for themselves as stated in the paper;
      " We investigated the data by assessing birth-cohorts, diagnosis-cohorts and APCs, and all showed a significant decline of patients assigned a PPMS course. This decline remained significant even after excluding the youngest cohorts of patients of which many may not yet be diagnosed. Although the factors responsible for such a decrease can only be speculated upon, our data suggest that this decline is most probably due to a shift in the clinical practice caused by the introduction on DMTs."
      They also mention other possible factors such as a greatly reduced incidence of smoking in Sweden. They must be doing something right.

    • Could it be the diagnosis off ppms has decreased but not ppms ? Cryptic I know.
      Perhaps someone will argue that for long periods drugs were not on offer to pw ppms so to correct this a change of diagnosis has evolved ? Whether intentionally or not

      Regards as always.

    • Hi Andy, yes that is a possible confounder here which the authors have tried to address, it may explain some of the effect but not all of it it appears.
      "Another possible explanation for the decreasing rate of PPMS would be that the clinical criteria, or the interpretation of these criteria, has changed, making PPMS criteria harder to fulfil. In such a case, however, older PPMS cohorts should be contaminated by patients who should have rightly been assigned RRMS/SPMS. In that case, given the constant and equal sex ratio in our PPMS cohorts and in previous reports,22,23 we would have expected a higher sex ratio in older cohorts, which was not the case. In fact, testing the sex ratio for PPMS was found to be significantly different from the ROMS (relapsing onset MS) ratio (data not shown). It therefore seems more likely that rather than misclassified ROMS patients in the earlier cohorts, some PPMS patients in the younger cohorts are misclassified as RRMS."
      "While a diagnosis of PPMS requires positive laboratory or imaging results in the McDonald criteria, PPMS diagnosis could previously be established on the ground of clinical evidence and also when patient did not satisfy the requirements for any other diagnosis category. As the Poser criteria requires less supportive evidence for diagnosis of PPMS, many of the patients in the older cohorts with unclear diagnosis could have been categorised as PPMS. Given the degree of changes in the diagnosis criteria of PPMS over time (particularly between Poser and original McDonald), we cannot fully exclude the possibility of use of different diagnosis criteria contributing to the trends."
      Hope that helps.

    • Could it be the diagnosis off ppms has decreased but not ppms ?

      Yes this is my point if you get diagnosis of PPMS you are not getting anytreatment diagnose as RRMS and people with relapsing PPMS benefit.

    • @Andy Clarke
      Yes, that is the key question, is it ppms or diagnosis of ppms that is decreasing? With our data we can only address the diagnosis, and yes, the diagnosis of ppms is decreasing in Sweden. As to why, and the number of "true" ppms patients (how would you even investigate a decrease of actual ppms?), we can only speculate and do to some extent in our paper. The dramatic drop of ppms diagnosis around the time of the introduction of DMTs is very interesting.
      I am curious to see what the pattern of ppms diagnosis looks like in other countries and hope that someone has the data to investigate it.

      /Helga Westerlind

    • The scandarnavians have the best registries, I suspect it is about treating people with a diagnosis of PPMS you get nothing with a RRMS you try a DMT at least 15% of PPMSers will benefit because they have evidence of gadolinium/relapsing activity

  • "is PPMS on its way out or has treatment options made a change for the better"

    Premature and very silly headline.

    I do not for one minute agree with this positive slant on developments for PPMS thus far, and I do not think all neurologists would either.

    • Oh come on – there are so many potential yawning gaps in this, e.g. the basis of diagnosis with "PPMS".

      And these drugs have _serious_ potential side effects.

      Don't go trumpeting the end of PPMS as though it can perhaps now be forgotten. There is a _long_ way to go with progressive MS, and I, for one, do not believe these money-spinning, immune system-knobbling drugs are the answer.

      Now I'm off to this place for future interpretation of MS research: http://www.bbc.co.uk/news/magazine-36076411

      Site bookmark deleted.

    • Ascension Island

      ….sit down and read what's written. There is no suggestion that immune modulators are the answer for progressive MS, likewise you need to realise some people with progressive disease can benefit. You appear to be having a hissy fit for no reason.

    • You're dealing with people who have MS. Maybe Dr. G was right, it should be labeled as a dementing disease.

    • You can patronise with hissy fit accusations and publish cretinous, nasty little comments about dementia all you like, but the fact is that not everyone with PPMS *today* will be helped by Ocrelizumab. Their PPMS is not on the way out. And there is no explanation for the drop in diagnosis of PPMS in Sweden given here. This is a post of supposition, nothing more, giving premature credit to DMTs.

    • You are putting words in my mouth…whilst blowing a gasket. Stop being a troll.

      "The fact is that not everyone with PPMS *today will be helped by ocrelizumab…totally agree we need a differnt form of treatment for progressive MS , however this has nothing what so ever about whether DMT stop PPMS is is about whether people get access to DMT, a label of PPMS stops that…that is the point I am making. I can't put it simpler than that.

    • Seems to me that a few of the grumpies seem to be missing the point a bit here. My medical record formally records my diagnosis as RRMS, but I have never had an identifiable relapse. Early attempts to discuss this with my neuro just ended up with the subject being changed. It doesn't worry me particularly – I'm pretty certain he classifies me as RRMS because it still leaves the door open for meds which are not officially approved for use in SP or PP (although I'm not on anything at present). Probably much harder to get "reclassified" from SP or PP back to RR without a massive relapse, so to be officially RR but "not having relapses at present" is not entirely a bad thing, although the downside is as stated above: "Such decrease can have severe impacts on the future research on PPMS".

      So, I suspect the reduction in diagnosis of PPMS is in many ways just a tactical manoeuvre to leave the doors open.

    • Anon 7:33,

      You totally missed the point of the post and hence you and many of your blog readers have a lack of compression or as I put it more politely it is due to your illness. But I guess maybe the former is the case here.

      He is not saying PPMS is over or any DMD'S put an end to it, it is just the DX of PPMS is dying because it is a diagnosis that nothing could be done. If I were really PPMS I would not want this diagnosis either as it has been shown DMD'S can have an effect in PPMS that is not captured in a 2 year trial.

      But the atmosphere here is extremely dense.

    • You should not label people who just passionately disagree with you trolls.

      But I have been feeling frustrated with the angle taken on this blog quite a lot, so I will not be commenting on any more posts. Problem solved. I wish you well in the future.

    • In reply to Anonymous 9:35
      My situation is very similar. Hard to identify relapses – something did "happen" occasionally but it felt not big enough to really say that I was RR.
      I propose (tongue in cheek) a new category mid way between PP and SP. Let's call it "sesqui progressive"

  • I see nothing wrong with the wording if the title except perhaps it should have a question mark at the end, perhaps? I think it it reflects nicely, even with some irony, the paper it is leading into.

  • I don't understand what PPMS actually is. Since it is usually people in their 30s 40s diagnosed with it, how can you tell if it is SPMS (and all previous relapses were unexplained/undiagnosed) or PPMS?

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