Rituximab and biologics

General
1

As I expected the news about rituximab is not good from the SS point of view.

I'm not surprised because it was never developed for SS none of the current biologics are! They are all anti cancer drugs that work by reducing the number and effectiveness of B cells.

http://www.ncbi.nlm.nih.gov/pubmed/24727841

Most current research says that it is T cells particularly th17 and Treg that are involved in the development of A.I. so it should be expected that such treatments will fail.

This is why I am trying to contact Prof Tom Gordon (and I see a new team in the USA who I shall try to contact next week) as they are working on "biologics" specific to this part of the immune system.

One study suggests it may help in peripheral neurological disease and vasculitis but it is very weak

I attach the study

77-AnnRheumDis2013Gottenberg102631.pdf (122 KB)
2

Thanks for posting this information, I'm very interested but just do NOT have the mental faculties to tackle this right now! I'm glad I am able to come back to it on a clear day!

3

I have read a couple case reports where someone initially diagnosed with lymphoma and sjogrens had complete remission of their sjogrens from rituxan(sicca included). A couple people on the sjogrens world forum said they experienced the same.

4

My doctor is starting me on Rituxan on Monday. prednisone isn’t strong enough to get me over the inflammation flare-up in the lining of my lungs. I’m in intense pain most of the time so I hope this helps. She gave me an IV Steriod infusion on Friday and I felt better for about 24 hours.

My rheumatologist has explained Sjogren’s to me in a way I can understand what is happening to my body when irritants get in my sinuses and lungs and the role B-cells play in the immune system. B- cells are responsible for creating inflammation to protect the normal body while it’s healing. Sjogren’s patients have corrupted B-cells so they produce more inflammation than needed. Rituxan is supposed to suppress the immune system so it won’t produce inflammatory markers.

She also explained that inflammation in joints, tendons, cartilage, muscles, etc can actually close off veins, cause numbness and tingling in hands and feet by pressing on the nerve that runs close to the joint (I thought I had carpal tunnel & she put me on prednisone and the pain went away). Hope this helps!

5

Hi Mary, My asthma/allergy doc explained it much the same way. I had not heard it like that about the joints. Interesting.

I am sorry to hear you deal with the respiratory bit too. I get bad infections every 4-6 months somewhere in the resp. area. I as doubled up on steroid shots last time but never had IV infusion, thankfully.

Assybish, as always, thanks for the research!

6

Hm - don't know where to start.

Hate being negative but do believe in honesty and scientific fact.

The B cells aren't all "corrupted" they are responding to incorrect triggers (self antigens) there is no evidence that I have seen that they respond inappropriately to external antigens plus some cells are failing to commit suicide as they should do after doing their job. They produce anti bodies and seem to produce inflammation to self which causes the cells of the exocrine glands to be attacked. No one actually understands the true and total mechanusm of the immune response found in SS.

Rituximab is not an anti inflammatory and it doesn't just target the so called corrupt B cells it hits all B cells.

I hope the treatment helps you Mary and will be delighted to hear of any improvements.

One Japanese single patient study claimed that a 66 year old man was admitted to hospital with SS and severe clinical symptoms he was "near deathh" they gave him a massive dose of steroids and he was saved and allegedly his SS disappeared. I state this as it was a scientific paper but I think it as relevant and likely as people being cured of SS by rituximab. The only way this could happen would be to completely wipe out the immune system and reintroduce fresh stem cells for bone marrow etcc - it has been tried and failed and the patients are open to every disease going and their whole vaccination program and past immunity is removed !

There have been multiple trials of rituximab in SS and none have produced any significant improvement is SS glanular symptoms - I have read the few anecdotal cases that claim people have gone into remission with it but they weren't trials.

If it worked I would take cyanide to cure SS but there is nothing I can find that has any effect and I am on no treatment at all as the mdics here say they have nothing to offe even if they believed I had SS which they don't as I was sero negative on last test.

7

Actually rituxan isn't chemo it's a so called "biologic" it's a monoclonal anti body to Cd 20 receptors on B cells.

It has had several trials world wide and most have shown no benefit for "primary" sjogrens" amd limited benefit for SLE and RA. The trial is being run a 3 centres not just the QE ( I am a Brummie!)

Don't know why the UK is wasting 100K on the trial the money would be far better spent doing novel research into causes and therapies by good immunologists.

The persons running it are the 2 worst rheumatologists I've ever met.

You can only be a volunteer if you meet the American European criteria which means Ro/La positive and lip biopsy etc....

Not aware of any major negative side effects of Rituxan but I've not studied it as it was clear to me that it held no promise for Sjogrens as it is targetting the wrong cells.

8

wow and I am starting this soon :-(

9

Country girl that's why I posted as many are trying it.

It may well be of benefit to you .

I am very controversial as I don't accept the primary secondary Sjogrens definitions and I'm not sure about many of the "boxes" or pigeon holes the rheumatologists try to fit us all in to. I beleive AI is a spectrum of disorders and symptoms that can vary between every one ( not every one with SS diagosed by the same bloods will have the same symptoms, similarly SLE etc we all vary just a bit so boxes aren't useful except to box tickers. So therapies can and do show different effecs on different people with the "same" disease when it comes to AI in my opnion - not yet accepted medical fact - may never be but it's at least as good a hypothesis as the box tickers who can't explain why 50% of Sjogrens sufferers don't fit into their boxes!.Have a look at these 2 snippets.

http://www.medscape.com/viewarticle/825491

http://www.medscape.com/viewarticle/833068

First time I've seen medics get it right - we are patients not blood tests!

The evidence isn't as far as I'm aware that it causes problems to organs hence my comments but it hasn't shown much benefit on the dryness and mucous membrane issues of Sjogrens but has helped significantly some with so called secondary or extra glandular issues.

Rituximab as I said is a mono clonal anti body first created to act as an anti cancer agent.

So don't worry unecessarily it isn't likely to be harmful and is less harmful than methotrexate and prednisolone for example.

My anger is in the UK with 2 particular rheumatologists and why we are spending this sum on a therapy that has already been trialled in several countries with mixed results ( not negative just non effective in some trials on some symptoms) but we are doing NO original research in the UK at all into Sjogrens. These 2 rheumatologists main "research" for many years has been trying to fit people into the American European criteria so as to provide guinea pigs for trials all of whom fit the criteria. Wow like so useful????

I wasn't going to post but I saw the comment about it being "chemo" and causing damage to organs - not that I've seen. It has been trialled and licensed in several countries and to do ths it has to pass safety tests even more than efficacy tests. My reservation is that it doesn't seem in many cases to help primary Sjogrens symptoms and we in the UK shouldn't be retrialling it and wasting money - it should be possible to use it here without extra trials amd use the money for other research with novel appraoches.

I am a scientist and 1 thing good scientists know is that truth is very flexible in nature as it is so complex especially in biology and there may be no 1 answer - not easy for all of us to grasp especially politicians and voters who like simple 1 phrase answers which just isn't possible in science in most cases.

10

Chemo is a bit of a slippery term. If it is used just to mean a medication that is prescribed for cancer patients, then Rituximab might be considered chemo, but if it is used in the stricter sense to refer specifically to drug treatments for cancer that destroy cancer cells by stopping their ability to grow and divide, then it wouldn't be. AB is right that Rituximab is a monoclonal antibody and a biologic. Here is some additional information about it: http://www.cancerresearchuk.org/about-cancer/cancers-in-general/treatment/cancer-drugs/rituximab

11

My nerologist is working with me to start the Rituximab. He said treating sjogrens is difficult. He thought the rituximab was a good choice for me. I have the secondary sjogrens disease. The main problem for me is the CNS and prep nerve problems. He said there is still a lot of studies on treating sjogrens and this may not work, but worth a try.

I was bummed about the news. I looked it up on line and its true not many good results. I do know its used for both arthritis as well as for those with cancer.

Today is not a good day for me. I had a seizure due to the sjogrens effecting my brain. I am exhausted.

Love ya all

12

Seizures are no fun, Country girl. I hope it was an isolated event for you, and that you feel better soon.

13

Hi Country girl
I hope you are ok
I did try to contact you yesterday but you had gone. hope you can see I was trying to give the best scientific advice I can and I agreethat rituxan may be helpful in some so called secondary ss symptoms.
I have a really good friend who is a neuro psychologist who specialises in auto immune diseases especially MS but also sjogrens - I can talk to him if you like but I know that you ideally need a brain and spine MRI with contrast to look at the nerves to see if there is any damage and that then should advise the next step and possible treatment. Sjogrens can affect the brain and CNS in some but it is not inevitable and is not the only AI that can cause neuro/brain symptoms.
What do you mean by "prep nerve problems" please?
I am not a medic but will do my best to help and can put things together in a way that may help your medics help you best if you wish. Can yu confirm that you have had a brain and spinal MRI with contrast to get to the diagnosis and what you blood tests are that inform the comment that you have secondary Sjogrens please?

14


Countrygirl, I just read assybish's advice, and I think he is right. Getting several opinions and a more thorough workup, with the MRIs he recommends, could be a lot more illuminating and might get you better results. Keep us posted.

15

Slow down a bit Country Girl. Assybishs advice is dead on. Beyond that there is a ton of misinformation, especially Rituximab. It APPEARS you have neurological involvement brought on by inflammation. Don't care whether its primary or secondary, thats purely an academic argument. Almost all of those arguments are by PhD in a lab. Better known as piled higher and deeper. The most common CNS complications of Sjögren’s syndrome include myelitis and optic neuritis, which are syndromes that can occur in MS. Because of this symptomatic overlap, patients with Sjögren’s syndrome may erroneously receive a diagnosis of MS.

Because the treatments for MS are not only ineffective for Sjögren’s syndrome, but may actually precipitate flares of Sjögren’s disease, accurate distinction between MS and Sjögren’s syndrome is crucial. When the myelitis is particularly severe, associated with optic neuritis, or involves extensive regions of the spine, then the diagnosis of Neuromyelitis Optica should be considered.

Spinal taps and brain MRIs may help in the distinction between primary-progressive MS and Sjögren’s syndrome. All patients with myelitis in the context of Sjögren’s syndrome deserve a trial of immunosuppressant therapy. (rituximab) Because Rituximab is an IL7 )among other interleukins one would expect a pretty good result. It after all was designed for that.

thats the good news, the bad news is that even the BEST of biologics are only 60% effective. The reason you are seeing bad results in the internet is because its the internet first of all. BUT only 10% or so of SS patients have the kind of inflammation that cause the CNS and peripheral neuralgias. not a lot of those are getting Rituximab and of those that do about half will get results.

You have a lot of reasons to be hopeful. Hang in there.

Country girl said:

My nerologist is working with me to start the Rituximab. He said treating sjogrens is difficult. He thought the rituximab was a good choice for me. I have the secondary sjogrens disease. The main problem for me is the CNS and prep nerve problems. He said there is still a lot of studies on treating sjogrens and this may not work, but worth a try.

I was bummed about the news. I looked it up on line and its true not many good results. I do know its used for both arthritis as well as for those with cancer.

Today is not a good day for me. I had a seizure due to the sjogrens effecting my brain. I am exhausted.

Love ya all

16

Thank you all for the support! Tez thank you for the prayers. I feel much better today. It usually takes time for me to get better after that kind of a episode, but I am sure God heard your prayers.
Assybish thank you for taking the time to write and offering the help. That is very nice. I hope I can answer all your questions.
I have psoriatic arthritis, ect. My neuro says I have what is know as multiple autoimme system disease. My blood tested positive for multiple immune syst. Issues. I have no idea what the test are, just that it was different blood tests done.
I have had lessions on my brain for years and myoclonus. Last year my seizure issues got worst. I had another MRI done and it showed chronic lessions, white matter disease , ect ect. The DX from the MRI was possible MS.
A few months a go I had another MRI done with increased lesions and the MRI was to compare Sjogrens Vs. MS. Neuro has DX me negative for MS after my spinal tap two months ago showed no markers for MS.
I have nureopathy in my legs.
My lesions are what’s causing my seizures. The neuro believes the sjogrens is the underlining cause for the lesions.
He also believes I have autonomic sjogrens as well. My blood pressure is up and down and I pass sometimes when standing. I sit down as soon as I feel it.
Over the years I have been on DMARDS, biologics and remicade for my psoriatic arthritis. Nothing helped besides enbrel and that caused my nerve problems to get worst.
Oh my blood tested positive for sjogrens. I am sorry but I am not sure on the blood test name. I am so new to sjogrens and the whole DX has only been a few months now. It’s overwhelming! As I read more and more everything truly ties into how I feel. I have the dry mouth, dry eyes, dry skin, dry hair…
I have learned to live around it all. However the CNS issues are scary and dangerous. I don’t like feeling “dumb” but it makes me concentrated harder on everything and that’s exhausting. I put 200 percent in my work and the brain issues make me feel hmmmmm. Anyway I just get around it and look for the positive and hope the rutuximab works and if not the grace of God has gotten me further than any medicine, and that is the truth!!!

17

Tj1

Thank you for the reply. I do have a lot to be hopeful for. It took a long time to get a proper diagnoses. Just that alone is hope. The different diseases I have over Lap and the doctors focus on one thing and not the over all picture. I finally got a doctor who views the whole picture.

I am very thankful for this site and for each person who shares, informs, cares and comforts each other.

I will get copies of my reports and tests to better respond to the questions. As I said in a earlier post I am just so new to all of this.

I will keep everyone posted.

18

TJ

thanks for the additional comment I wasn't going to go that deep but I think you're right to do so now.

Pleased I'm not the only one who thinks the definition of primary and secondary is spurious and at best academic and at worst misleading - I can expand but not here.

I find it strange that Rhematologists can't even get a test or definition or classifcation that coves all Primary Sjogrens sufferers then argue about whether chicken or eggs came first!

Also worth mentioning here that there are auto immune conditions which create auto anti bodies to Calcium receptors which can cause neuro and brain disease. Sadly immunology is complex and a very young science and many clinicians are well behind the curve when it comes to AI.

Keep going C- girl it is worth a trial and so are some of the other biologics in your case - it is in Sjogrens that they have little benefit.

tj1 said:

Slow down a bit Country Girl. Assybishs advice is dead on. Beyond that there is a ton of misinformation, especially Rituximab. It APPEARS you have neurological involvement brought on by inflammation. Don't care whether its primary or secondary, thats purely an academic argument. Almost all of those arguments are by PhD in a lab. Better known as piled higher and deeper. The most common CNS complications of Sjögren’s syndrome include myelitis and optic neuritis, which are syndromes that can occur in MS. Because of this symptomatic overlap, patients with Sjögren’s syndrome may erroneously receive a diagnosis of MS.

Because the treatments for MS are not only ineffective for Sjögren’s syndrome, but may actually precipitate flares of Sjögren’s disease, accurate distinction between MS and Sjögren’s syndrome is crucial. When the myelitis is particularly severe, associated with optic neuritis, or involves extensive regions of the spine, then the diagnosis of Neuromyelitis Optica should be considered.

Spinal taps and brain MRIs may help in the distinction between primary-progressive MS and Sjögren’s syndrome. All patients with myelitis in the context of Sjögren’s syndrome deserve a trial of immunosuppressant therapy. (rituximab) Because Rituximab is an IL7 )among other interleukins one would expect a pretty good result. It after all was designed for that.

thats the good news, the bad news is that even the BEST of biologics are only 60% effective. The reason you are seeing bad results in the internet is because its the internet first of all. BUT only 10% or so of SS patients have the kind of inflammation that cause the CNS and peripheral neuralgias. not a lot of those are getting Rituximab and of those that do about half will get results.

You have a lot of reasons to be hopeful. Hang in there.

Country girl said:

My nerologist is working with me to start the Rituximab. He said treating sjogrens is difficult. He thought the rituximab was a good choice for me. I have the secondary sjogrens disease. The main problem for me is the CNS and prep nerve problems. He said there is still a lot of studies on treating sjogrens and this may not work, but worth a try.

I was bummed about the news. I looked it up on line and its true not many good results. I do know its used for both arthritis as well as for those with cancer.

Today is not a good day for me. I had a seizure due to the sjogrens effecting my brain. I am exhausted.

Love ya all

19

Sjögren syndrome. When associated with central and peripheral nervous system lesions, classic Sjögren symptoms (sicca and rheumatic) are less common than in primary Sjögren disease. Serum antibodies to Sjögren syndrome A and B proteins (SSA and SSB) are positive in only one third of patients and are more often negative than in Sjögren disease without neurologic symptoms. A lip or parotid biopsy is needed to clinch the diagnosis (Alexander et al 1986; Sandberg-Wollheim et al 1992; Javed and Reder 2006).
In CNS Sjögren syndrome, one third have MRI, CSF, or evoked potential evidence of cerebral abnormalities; one third have longitudinal spinal cord lesions; the rest have optic neuritis and diffuse symptoms such as seizures, cognitive loss, and encephalopathy (Delalande et al 2003). In patients with CNS Sjögren lesions, there are small white matter MRI lesions in two thirds (occasionally in basal ganglia, infrequently in corpus callosum), oligoclonal bands in one third, and abnormal visual evoked potentials in about two thirds (de Seze et al 2003). PNS Sjögren disease can cause sensory ganglionitis, painful sensory neuropathy, and distal sensory-motor axonopathy.

Adil Javed has described a new Sjögren-related entity, seen predominantly in young black women. Patients with severe destruction from optic neuritis and longitudinal cervical cord lesions resemble patients with Devic disease, but NMO-IgG levels are positive in only 40%. However, minor salivary gland biopsy is positive for Sjögren disease (inflammation grade 4+/4) in 85%, often when SSA and SSB serology is negative (Javed et al 2008). Other autoimmune diseases (myasthenia gravis, primary biliary cirrhosis) are often associated. Treatment differs from multiple sclerosis therapy, as interferons may cause worsening. Mycophenolate mofetil provides some benefit, but the best responses are with rituximab (Javed personal communication 2007).

20

Well lets start with white matter lesions. VERY common in anybody over the age of 50 and not uncommon under the age of 50. In general mean nothing unless accompanied by some rather significant ANA counts. (which would be SSA and SSB)

But lets talk numbers. The highest estimate for peripheral involvement with whats considered "Primary SjS" is 5% while up to 50% may have cutaneous involvement. Less than 10% of the time are the skin erruptions are Vasculitis.

Up until 2012 with SICCA you had to have:

According to the American-European classification system ,diagnosis of primary Sjögren syndrome requires at least four of the criteria listed below; in addition, either criterion number 5 or criterion number 6 must be included. Sjögren syndrome can be diagnosed in patients who have no sicca symptoms if three of the four objective criteria are fulfilled. The criteria are as follows:

  1. Ocular symptoms - Dry eyes for more than 3 months, foreign-body sensation, use of tear substitutes more than 3 times daily
  2. Oral symptoms - Feeling of dry mouth, recurrently swollen salivary glands, frequent use of liquids to aid swallowing
  3. Ocular signs - Schirmer test performed without anesthesia (< 5 mm in 5 min), positive vital dye staining results
  4. Oral signs - Abnormal salivary scintigraphy findings, abnormal parotid sialography findings, abnormal sialometry findings (unstimulated salivary flow < 1.5 mL in 15 min)
  5. Positive minor salivary gland biopsy findings
  6. Positive anti–SSA or anti–SSB antibody results

Secondary Sjögren syndrome is diagnosed when, in the presence of a connective-tissue disease, symptoms of oral or ocular dryness exist in addition to criterion 3, 4, or 5, above.

SINCE 2012 in the US anyway, we no longer distinguish between the two(we talk about it but that is it) except for some occular disease for which there is a blood test that a few try to apply to regular SjS:

According to the ACR criteria, the diagnosis of Sjögren syndrome requires at least two of the following three findings:

  • Positive serum anti-SSA and/or anti-SSB antibodies or positive rheumatoid factor and antinuclear antibody titer of at least 1:320
  • Ocular staining score of at least 3
  • Presence of focal lymphocytic sialadenitis with a focus score of at least 1 focus/4 mm2 in labial salivary gland biopsy samples

I don't even know where to begin. The chances of folk who have actual SjS having some of the things I see discussed on this site range from 1 in a hundred to 1 in 100,000.

I read a thread about vasculitis. In particular there was an article posted about Polyarteritis Nodosa which is a very serious large cell condition but has NO CONNECTION to SjS ever. First of all peripheral involvement only happens 5% of the . Less than 10% of the time are the skin eruptions Vasculitis (which BTW is very treatable) IF it is vasculitis, over 90% is small vessel vasculitis called Hyperglobulinemic purpura treated with a topical ointment.

SjS is a very unpleasant disease. It is life changing for many and usually associated with other autoimmune diseases. Knowledge is great but this constant attempt to find the worst is not support. There have been patients coming here reading a bit and immediately leaving because they are SCARED.

I am not dismissing the significance of SjS. I am one of those 35% of autoimmune disease sufferers that have SjS an additional gift, but for crying out loud lets keep it real.

Rituximab helps a lot of people, as does plaquenil along with a number of other meds. DO NOT try to make your experience someone elses.