Nerve Conduction Studies, Endocrinology and Audiology results. SJS fatigue

[MAT51]

http://pure-oai.bham.ac.uk/ws/files/21868726/Brown_2014_TRACTISS_.pdf

Hi Jasper. I was looking for the outcome of these very new double blind trials into Rituximab as effective treatment for SJS fatigue and sicca, that someone posted here or on Healthunlocked but I'm unable to find it now. I believe the outcome showed that there was no significant improvement but I'm delighted if you have found this not to be the case and are feeling more energised as a result. I suppose I'm wary because I am not convinced I need such a hige sledgehammer for my large nut of a disease yet? I will see what the rheum team decides tomorrow though and keep an open mind. My neuropathy is rarely painful these days -it's more the feeling of palsy or weakness that afflicts be along with feeling permenantly off kilter and other minor (but massive fur me) symptoms such as awful taste (not really solved by anti acids or stomach protectors so far) and worsening numbness and tingle in my face with tinnitus, severely dry eyes and swallowing trouble and consipation. I'm not sure that anything will work for these or for the autonomic issues  but I live in hope!   

[Jasper]

Hi Mat .....

Yes, I would be interested to read the study details of that Birmingham study.

I always like to read the entire study, looking for the endpoints as well as the outcomes/results at various times points during the study. I have noticed that some studies end up being inconclusive or they do not reach their endpoints so are sometimes deemed "failures." On closer examination of the actual study details I can see that the endpoints were flawed or the time frames were flawed. 

That is why that 120 week study is interesting. It is a long study and it measures several outcomes at several time points during the study, thus giving a better understanding of the various responses throughout the trail.

I have read 6 studies on Rituximab and Sjogren's. 5 of the 6 showed significant improvement in fatigue at weeks 12 and 16. The benefit declined some by 24 weeks. That is why the time frame is important. If the study is looking for improvement at week 24 as an endpoint, that improvement is not going to be as significant as it was at weeks 12 and 16. So, that study may erroneously conclude that fatigue was not significantly improved (at week 24) even though it was improved earlier in the study. All drugs were off at some point. They don't decide that a Diabetes drug is a failure if it shows lowered blood sugar at 12 hours but not at 24 hours. They conclude that the drug has a halflife and that it needs to be repeated at intervals. I feel the same is true of Rituximab. The tiome frames need to be realistic.

I also think lumping too many endpoints into a study is counterproductive. Too many endpoints will guarantee failure, in my opinion. There may be drugs that significantly improve fatigue but that may not significantly improve dryness.

I did not see improvement in the dryness of my eyes, However, my opthamologist says my eyes look the best he has seen them since 2009. I do use Restasis and have been on it since 2011, but he says they are much improved this year (I saw him in Sept.). I have been on Rituximab since February 2016. So, while I do not notice an improvement in eye dryness since being on Restasis, he notices an improvement in the cornea a and eye surfaces as well as the inner eye lids.

I do definitely notice an improvement in saliva production. I no longer need to carry water or drink at night. I can go hours without a drink. My mouth does not feel dry. I can eat food without drinking fluid.

However, by far, the greatest improvement is in fatigue. I was dragging around unable to do much of anything, even cook or clean. Now, while I am not the energizer bunny I used to be, I can function and do things without feeling like I will topple over or need to go and sit down. Before Rituximab it was an effort to even stay awake at times and to get anything done. I also could not think straight and had memory problems, processing problems, and other cognitive problems.

I just registered for a trip to Ireland for next fall. I never would have even considered that trip last year, before Rituximab. I would not have been able to get it together enough to register and I would not have had the energy to do the trip. For me, the most debilitating of the symptoms was the fatigue. Now I feel much more normal and I have a life again.

Also, as noted, I have not had a flare since starting Rituximab.

I am pleasantly surprised at the improvement in the neuropathy. It is not gone, but it is much improved.

I don't know what would be the best drug for you. It may be a trial and error thing to find out what works for you.  Cellcept did not help me (except for pain) and I had bad side effects. Imuran did not help me and I had bad side effects. However, those drugs do help some people.

I can tell you that my Neurologist was considering IVIG for my neuropathy but they were concerned about getting insurance approval for it so I never had IVIG. I do know it has been beneficial for many with Sjogren's.

I have read that some studies indicate that the earlier in the disease process that one starts these treatments (bigger gun treatments like IVIG and Rituximab), the better the response. This makes sense to me. If they wait until nerves, glands, cells, etc. are completely destroyed, then there cannot be much improvement. If they treat while there are still functioning cells and glands and nerves, then they will see better improvement. And that may be one of the problem with some of these studies and endpoints.

Anyway, I am really happy that you have a doctor who is willing to treat with these medications. I wish more doctors were that progressive and helpful.

[MAT51]

Hi again Jasper. I am off to bed now as waking at dawn GI travel home tomorrow - but here are the preliminary results of the ARUK recent double blind trial of Rituximab for SJS. A different perspective to others and I'm still very open minded for myself as it wasn't testing for SFN or the main problems that afflict me most with my version of SJS. Mat

http://acrabstracts.org/abstract/preliminary-results-of-a-double-blind-randomised-trial-of-rituximab-anti-b-cell-therapy-in-patients-with-primary-sjogrens-syndrome/

Conclusion: TRACTISS is the largest randomised trial of biologic therapy in PSS. No improvement in symptoms was seen in the Rituximab arm (unlike the TEARS study) but modest benefit for Rituximab in salivary flow was observed.

Funding: Funded by Arthritis Research UK.

[anita]

MAT,

You might want to forward him Dr. Birnbaum's papers so he can see what "established treatment protocols' are out there already.  Seriously...those of us with this are being treated with the same protocols, so someone long ago established these treatments.  And it's not just doctors like Birnabum...doctors all over are treating patients with Sjogren's neuropathy.  They had to learn it from somewhere.  I just think your doctors don't see it often and therefore are unaware there are already established treatments.  But it sounds like you are educating him some in the process (and very good that he was receptive to your suggestion)!!  I hope he allows you to start a trial of Cellcept before Rituxan.

You might find this article interesting.  I noted that they even made reference to high % of patients in the UK.  I think your doctors just don't see this often, so they make these comments to protect their egos...LOL

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618621/

Just so sad that your neuro is completely in the dark about IVIG.  This 'established' treatment for Sjogren's neuropathy (and SFN from any AI disease) has been around for years.  This is your best bet, yet it doesn't sound like you will benefit from being able to try it.  Have you asked about it specifically...had a conversation about it??

There are threads/posts on this forum about Rituxan...you should search this topic and read what others here have to say.   

Keeping my fingers crossed that you get the Cellcept!!

[MAT51]

Thanks Anita. It's ironic that I moved to be nearer a bigger teaching hospital with more emphasis on research etc isn't it?! Mind you they did work out that I had Sjogrens and this young senior registrar is reporting back to the consultant rheumatologists who are all young and mostly of non British descent from what I can see -so I am not getting a very parochial input only and I think it's just that this particular chap is applying for the job as consultant rheum now and is erring on the protocol side of things I suspect. In my opinion the neuro is as you say and does not know as much about SS as she likes to think and I'm less optimistic for her keeping an open mind than I am about the rheum. I now have a copy of her clinical letter and she says she hopes I don't start anymore immunesuppressants because I've shown such a poor tolerance to date and there is no evidence that this will help a small fibre neuropathy such as mine.

She says we had a long discussion about this but actually it was a lecture from her with me interjecting a lot about getting another skin biopsy! I know this because I recorded it. If I don't get offered either drug this time then I will be fierce and say that I'd like a referral to a specialist centre for a second opinion. But the impression I got is that the rheumatology people do want to treat me ASAP. He asked me how the SFN has responded to immunesupression previously and how it had responded to steroids. I told him it had responded very well on both fronts and it was only that my body had been unable to tolerate any of these so far.

I also told him that I have gathered that Cellcept is better tolerated by many than other immunesuppressants which is why I suggested it as the next option. I know I'll be well monitored on it and if I can't tolerate it then I can just stop. Unlike drugs such as Cymbalta and Pregabalin which I know from personal experience, can be terribly hard to get off. After my Imuran reaction last year it's a bit scary for me and the neuro has clearly studied my case files from last year's hospital admissions. But what she doesn't realise is that it was my attempts at withdrawing from Cymbalta that precipitated all my health troubles last year I firmly believe. No one monitors us on these powerful antidepressant or anti convulscent medications or warns us about how difficult it may be to stop.

Yes Imuran caused me chaos but only briefly and only because they put me back on it twice, assuming it was my gallbladder or a UTI sepsis rather than pancreatitis as it turned out to be!

The NHS is really falling apart now so it is a postcode lottery as to what meds are offered for sjogrens neuropathy in the UK. So being in a bigger place than this wouldn't necessarily guarantee better treatment for Sjogrens. I can see this from other forum users here and from other social networks. I'm fairly sure there's no way that my SFN will be thought to warrant IViG. It is very diffuse but also relatively painless these days so maybe the neuro is right to an extent although I feel she doesn't grasp the workings of rheumatic diseases and clearly has no concept of living with autoimmunity 24/7.

For myself it's the autonomic issues and disequilibrium, tinnitus and awful taste that are most alarming and impact most on my daily quality of life at present. I'll let you know what comes of today's clinical meeting and what they decide to offer me, if anything. Mat x

[MAT51]

Ps - the UK Rituximab trial I've posted a link for in my reply to Jasper above, is a much bigger study than the one you linked me to here - but the outcome seems similar from what I can gather.