My Rituximab experience for ME

[leokitten]

While I hope you are right that many PWME will benefit from Rituximab, I also hope it will not be the end-all treatment for ME/CFS. At present there is something like a 33% non-responder rate. Add to that the fact that a fair number of us will not be able to take Ritux because we have contraindicating conditions, it is likely that more than 50% of us will not benefit from Ritux for one reason or another.

A 33% non-responder rate, if it turns out to be true in a larger cohort, is basically a home run by pharma standards. Most drugs on the market have an approx. 30-40% responder rate.

Brincidofovir is interesting because it will replace Valcyte and will already be on the market by the time the rituximab trials are completed. I believe unless there is some kind of drug interaction we will be able to take both rituximab and brincidofovir together.

Unlike Valcyte, I believe brincidofovir is not immunosuppressive. Even if Kogelnik wants to combine Valcyte with Rituximab it will be complicated because Valcyte causes immunosuppression incl neutropenia, so will be touch and go with many patients having to closely monitor CBC w diff.

 

[heapsreal]

Nk cells fight viruses and help stop viruses from reactivating. So if one has low nk function then they are at risk of viruses reactivating. Its been said a few times by some here that low nk function probably doesnt mean much, theres no proof of this. If we look at a more recognized immune defiency, low nk cell defiency (not function) its common knowledge that herpes viruses often reactivate in these people and prophylactic antivirals are commonly prescribed . low nk function vs numbers have the same end result .

igg result isnt conclusive of an active infection but if a low nk function then one would have to have a higher risk of viruses reactivating especially if run down or another ongoing infection . A good clinician should be able to have an idea of ebv/cmv reactivating going off symptoms as well as other immune tests like lymphocyte counts and neutrophil counts. Also igg titres above a certain range is considered by many immunologist to show an active infection
.
although certainly no cure, a treatment trial with avs showing symptom improvement as well as reducing elevated lymphocyte counts is showing more evidence of these viruses being active. When this cycle has been repeated a few times it gives more evidence to active viruses.

there is a definite subset of mecfsers who fit the above. Until specific research on rituximab in this subset of mecfsers is done , I wouldn't touch it. Those that don't fit this subset than i think any adverse risks are low if the current research in Norway positive.

one problem is that they cant 100% guarantee diagnosing a chronic active infection ? ??

 

[Bob]

@heapsreal, I'm not saying you're wrong to be cautious but if any NK cell dysfunction is caused (either directly or indirectly) by autoimmunity then rituximab could help to correct that dysfunction. Likewise, if any reactivated infections are the result of immune dysfunction caused by autoimmunity, then they might also be resolved by rituximab.

 

[heapsreal]

@heapsreal, I'm not saying your wrong to be cautious but if any NK cell dysfunction is caused (either directly or indirectly) by autoimmunity then rituximab could help to correct that dysfunction. Likewise, if any reactivated infections are the indirect result of autoimmunity, then they might also be resolved by rituximab.

Yes, i do recall someone a few years back saying that maybe b cell depletion increases nk function but its unknown at this stage.

I assume the rituximab research is measuring things llike nk function etc? Has anyone seen or heard of before and after nk function testing with Rituximab ?

Im not anti rituximab but very cautious due to its contraindictions that fit many mecfsers. Why im also interested in any findings on combined antiviral/rituximab treatments .

I get the feeling that many think autoimmunity and chronic infections don't happen together or dont consider it. I just think its possible we just may have both??

 

[Marky90]

Also, for those who do respond to rituximab, most don't experience a full remission, as far as I understand the data, and the improvements are not necessarily permanent. So it will not be a panacea for most of us, unfortunately. Also, clinical trials can often have better results than clinical practice, for various reasons, including because of the careful characterisation of participants in the trial. The general ME/CFS population will be more heterogeneous.

It is my impression that the remissions are substantially longer in the phase 2 trials, because of the new dosage regiment.

 

[leokitten]

Also, for those who do respond to rituximab, most don't experience a full remission, as far as I understand the data, and the improvements are not necessarily permanent. So it will not be a panacea for most of us, unfortunately. Also, clinical trials can often have better results than clinical practice, for various reasons, including because of the careful characterisation of participants in the trial. The general ME/CFS population will be more heterogeneous.

None of us is looking for a panacea or cure in the near future, yes that would be absolutely wonderful but I would be happy with an effective treatment to minimize symptoms and further damage so we can have our lives back.

With so many other diseases, in particular autoimmune illnesses, people have to take medication or do treatments indefinitely. There is no cure even though with many of these diseases we have a much better understanding of the pathology. But people get their lives back and can look forward to the future because they aren't constantly managing symptoms and having such severe symptoms that it prevents them from living a pseudo-normal life.

 

[lansbergen]

I get the feeling that many think autoimmunity and chronic infections don't happen together or dont consider it. I just think its possible we just may have both??

Why could autoimmunity not be the result of chronic infections?

 

[Bob]

I get the feeling that many think autoimmunity and chronic infections don't happen together or dont consider it. I just think its possible we just may have both??

Yes, some of us may have both autoimmunity and chronic/reactivated infection, but my point was that chronic/reactivated infection may be caused by autoimmunity in some of us, in which case the infection may be resolved by rituximab. (But, equally, it may not be resolved.)

I'm cautious about rituximab as well, for various reasons. I'm eager to see the latest phase ii study which should be published any day soon. But I'll wait till the phase iii study is published before I make any personal decisions.

 

[Jonathan Edwards]

@Jonathan Edwards is it true that if you have positive IgG antibodies to CMV, HSV, PVB19, or VZV that you cannot take Rituximab?

That just doesn't seem right because these viruses are very common and that would basically rule out everyone, most people are IgG positive to at least one of those.

I think @SOC the text is possibly meaning that if you are currently undergoing an acute infection caused by the above viruses that you cannot take rituximab at that time?

Did anyone say that - I am not aware of any reason to think an IgG response to these is a contraindication.

 

[leokitten]

Did anyone say that - I am not aware of any reason to think an IgG response to these is a contraindication.

@SOC listed from WebMD Rituximab contraindications http://www.webmd.com/drugs/2/drug-5208/rituximab intravenous/details/list-contraindications saying that if you have any of these infections that you shouldn't take the drug. Though the language of the text is a bit vague to me as does it mean you shouldn't take rituximab if you have an active infection or if you have ever been infected in the past? If you were ever infected in your life with CMV, HSV, PVB19, or VZV would that mean you cannot take Rituximab?

 

[Jonathan Edwards]

@SOC listed from WebMD Rituximab contraindications http://www.webmd.com/drugs/2/drug-5208/rituximab intravenous/details/list-contraindications saying that if you have any of these infections that you shouldn't take the drug. Though the language of the text is a bit vague to me as does it mean you shouldn't take rituximab if you have an active infection or if you have ever been infected in the past? If you were ever infected in your life with CMV, HSV, PVB19, or VZV would that mean you cannot take Rituximab?

I have no idea what WebMD is - I would be doubtful of the provenance. And all I can see is reference to active infections. An IgG response is not an indication of active or even recent infection - it is an indication of some level of immunity gained from past infection.

 

[leokitten]

While I hope you are right that many PWME will benefit from Rituximab, I also hope it will not be the end-all treatment for ME/CFS. At present there is something like a 33% non-responder rate. Add to that the fact that a fair number of us will not be able to take Ritux because we have contraindicating conditions, it is likely that more than 50% of us will not benefit from Ritux for one reason or another.

Rituximab contraindications (I've bolded some that are known to co-exist in a substantial number of PWME)

Resolved Hepatitis B, Relapse of Hepatitis B Infection Symptoms, Hypogammaglobulinemia, Hepatitis C, Progressive Disease in the White Matter of the Brain, Disease due to West Nile Virus, Parvovirus Infection, Angina, Abnormal Heart Rhythm, Herpes Simplex Infection, Disease caused by Cytomegalovirus Infection, Stomach or Intestine Blockage, Acute Kidney Disease, Kidney Disease, A Mother who is Producing Milk and Breastfeeding, Infection caused by a Fungus, Pneumonia caused by Pneumocystis Jirovecii Organism, Severe Infection, Increased Uric Acid due to Cancer Chemotherapy, Infection caused by the Varicella Zoster Virus, High Amount of Phosphate in the Blood, Low Amount of Calcium in the Blood, High Amount of Potassium in the Blood, A Rupture in the Wall of the Stomach or Intestine, Anemia, Decreased Blood Platelets, Decreased Neutrophils a Type of White Blood Cell

@SOC please read the responses by @Jonathan Edwards in this thread, I don't think rituximab is necessarily contraindicated just because one has high IgG antibodies to the viruses you highlighted.

We must also wonder that maybe, just maybe, the reason many PWME have high IgG antibodies to intracellular pathogens is because of the underlying immune dysfunction or autoimmunity that might actually correct itself with B-cell depletion.

 

[Avena]

Congratulations, @funkyqueen! This gives so much hope for an fellow severe sufferer! May I ask how many years you had severe ME prior to the treatment start? I have the impression that longetivity seems to make a difference in the response rate as well as severity?

I assume you got the infusions in the US? May I ask how you managed the journey from Europe?

 

[heapsreal]

Why could autoimmunity not be the result of chronic infections?

Thays what i think.

 

[heapsreal]

Yes, some of us may have both autoimmunity and chronic/reactivated infection, but my point was that chronic/reactivated infection may be caused by autoimmunity in some of us, in which case the infection may be resolved by rituximab. (But, equally, it may not be resolved.)

I'm cautious about rituximab as well, for various reasons. I'm eager to see the latest phase ii study which should be published any day soon. But I'll wait till the phase iii study is published before I make any personal decisions.

I think we are on the same wave length . I guess we just have to see the research findings when they release them. Nice to know how its set up and if its broken patients into some types of sub groups.

We are all eager to know if they can tell us who are the best candidates for rituximab and what tests can be done to tell us if we fit this group ?

 

[SOC]

@SOC please read the responses by @Jonathan Edwards in this thread, I don't think rituximab is necessarily contraindicated just because one has high IgG antibodies to the viruses you highlighted.

I never said so. The contraindications I highlighted clearly indicate they mean disease caused by herpesviral infections, that is, acute or reactivated infections. I am very well aware and have pointed out many times on PR that most of the population has latent herpesviral infections. That is not what is in question here.

The issue is that many PWME have reactivated herpesviral (and parvoviral, and other) infections. Not just high titres, but symptoms of the infections as well. That's how reactivations are diagnosed, especially when the patient is known to be immune-impaired. Of course there are ignorant people who claim that herpesviral reactivations don't exist, managing to ignore that reactivations are well-known in a number of immune-compromised situations -- transplant, CVID, SCID, HIV. But then, there are people who chose not to believe, in the face of clear evidence, that a significant subset of PWME are immune impaired. There's no convincing people who ignore facts and prefer belief systems over scientific evidence.

We must also wonder that maybe, just maybe, the reason many PWME have high IgG antibodies to intracellular pathogens is because of the underlying immune dysfunction or autoimmunity that might actually correct itself with B-cell depletion.

Yes, one could wonder that. One could also wonder what it means when people with low gamma globulins have high IgG titres to intracellular pathogens. What would their titres be like if they had normal gamma globulin production?

It would be great if B-cell depletion corrected the underlying immune dysfunction, but that won't matter if the rules forbid patients with active infections from getting the therapy whether or not it will help.

 

[funkyqueen]

@Jonathan Edwards
Hi Professor, I understand that most chemotherapy, found it hard to cross the blood brain barrier ... It seems that only a small percentage of heavy and complex molecules of chemo would be able to pass this barrier .. So I ask myself the question: what about for Rituximab especially ? Would you please tell us , in your opinion, how many percent of Rituximab is able to pass the blood-brain barrier to work where it is headquarters of our chronic inflammation? Thanks !

 

[SOC]

I have no idea what WebMD is - I would be doubtful of the provenance. And all I can see is reference to active infections. An IgG response is not an indication of active or even recent infection - it is an indication of some level of immunity gained from past infection.

Limited, oversimplified, and outdated analysis of high IgG titres. The actual analysis says that healthy people can have high IgG titres, particularly within a decade or two of the original infection. In that case, high titres only mean that the individual has developed immunity from a past infection and antibody production has not yet dropped back to normal levels.

Proper analysis says that clinical symptoms should also be considered in the context of high IgG titres. Look it up. If the patient shows symptoms of the infection in question, there is a greater likelihood that the high titre is indicative of a reactivated infection.

Additionally, antibody titres drop over time. That is why older people are advised to get a shingles (chicken pox, VZV, HHV-3) booster. If a patient is decades past the original infection, IgG titres should not be high. Extremely high titres in patients past their 30's are suspicious, particularly in the light of symptoms of the illness, because it is highly unusual to have high CMV or HHV6 titres at that age.

Lastly, high titres are not considered irrelevant if the patient is immune impaired. They are considered a matter of concern in post-transplant patients, HIV patients, and other immune-impaired populations. Since a significant portion of ME/CFS patients are immune impaired, high titres are not irrelevant in ME/CFS and can be indicative of reactivated infections. There's a reason most top ME/CFS specialists use antivirals with a reasonable degree of success.

Broad-based rules of thumb for healthy populations do not necessarily apply to ME/CFS patients. Intelligent professionals use basic principles instead of rules of thumb to analyze complex situations, and know what the limitations of the rules of thumb are when they apply them to simple situations.

 

[funkyqueen]

@funkyqueen I'm very happy for you, your response to Rituximab gives us a lot of hope!

There are a lot of people here on PR that are completely skeptical of the autoimmune hypothesis of ME/CFS and the work of Fluge and Mella. While I'm sure there is a smaller subset of PWME that do not respond or get worse because their disease has different underlying etiology, I believe most will have a significant recovery or remission with this medication and the results of the RituxME RCT will change the world of ME/CFS forever.

Our lives are already complete hell every day even for us with milder ME... So I think most people will take the risk of trying this medication.

@leokitten : like i said, if Rituximab help me , it not healing me completely ( far from it )... I don't know... Before trying it, i was with a lot of hope ( but it's me, i'm with a strong and very positiv mental)..i'd think it can put me in total remission...But , like i wrote, it not. ( for the moment ? ) ...For my case, and mostly for all PWME, i think we have to wait after results and see...( fingers crossed).
And on the post that had a great success, "Who would be afraid of having to take Rituximab," my opinion is that the man or woman for whom the suffering of undergoing ME has become such that he/she would prefer death rather than 'agony and yet to be no more than a beating heart and bowel functioning in a bed, buried alive in his own body, with just the brain that works enough to think of all that the disease steal to us, then yes, these people will take Rituximab and will even be infinitely grateful to have it, regardless of the risk of PML, no matter the risk of Steven -Jonhson Syndrom, regardless of the fact that it increases the probabilities of getting cancer (besides having ME in itself increases the probabiitys to declare several cancers, then) ... In short, all this to tell you that I remember I read you on this thread, and I think like you on that

@funkyqueen, if you could publish your diary in the future, or parts of it, once the cinical trials are over, I am sure many would find it inspirational. It would also help advocacy.

@alex3619 You can count on me for that ,once formal studies will be published

You have indeed given me a reason to hope that there may be a treatment before I can no longer tolerate living in hell.

And that is a really big gift. I thank you.

You made my day, sayin me that, @jimells , but, once again, my remission is far from complete, and I do not know how long it will last...

 

[leokitten]

I never said so. The contraindications I highlighted clearly indicate they mean disease caused by herpesviral infections, that is, acute or reactivated infections. I am very well aware and have pointed out many times on PR that most of the population has latent herpesviral infections.

Apologies for misunderstanding, but some of the contraindications you highlighted just said "Parvovirus Infection" or "Infection caused by Varicella Zoster Virus", so it could easily be misconstrued.

The issue is that many PWME have reactivated herpesviral (and parvoviral, and other) infections. Not just high titres, but symptoms of the infections as well. That's how reactivations are diagnosed, especially when the patient is known to be immune-impaired. Of course there are ignorant people who claim that herpesviral reactivations don't exist, managing to ignore that reactivations are well-known in a number of immune-compromised situations -- transplant, CVID, SCID, HIV. But then, there are people who chose not to believe, in the face of clear evidence, that a significant subset of PWME are immune impaired. There's no convincing people who ignore facts and prefer belief systems over scientific evidence.

Would you enlighten us on how a person with ME/CFS would know they have a CMV, HHV-6, or PVB19 reactivation based on symptoms and how you can differentiate these symptoms from the symptoms of ME/CFS?

I can understand for HSV-1 or 2 and VZV people would know, but for the other viruses unless you are having a full on acute attack that only happens in severely immunosuppressed people you would not be able to differentiate among the constellation of ME/CFS symptoms and I think you can mislead yourself to think you are having a definite reactivation.

As a person who is part of the viral subset and has very high IgG titers to EBV, CMV, HHV-6, and moderately positive IgG titers to PVB19 I know that during my illness these IgG titers have gone up and down with treatment and had absolutely no correlation to symptom improvement.

I agree a positive change in IgG titers over time is due to some level of reactivation but for many of us this is happening even though we have normal IgG subclasses, normal total IgG and low normal NK function so I ask myself maybe this is a feature of the autoimmunity/immune dysfunction?

About the hypogammaglobunemia I totally agree that this is contraindicated. But @SOC if I remember correctly your total IgG was just low normal and you do not have CVID? @Jonathan Edwards mentioned on some threads the threshold IgG level for treatment with rituximab, trying to remember something like a minimum 4 or 6 and apologies I cannot remember the units.