rituximab questions

[Gingergrrl]

I've seen from two different places warnings about the RituxME-trial that one can't trust its results when it gets published because Rituximab has so many side-effects those who get infusions with the medicine will know they are not getting placebo.

This is just my own opinion from speaking w/my doctor and the nurses at my infusion center but for me, I think the biggest risk would be if I am allergic to RTX. If the placebo was normal saline or D5-Dextrose, I am not allergic to these so it would be obvious immediately that I had received something different. I would start the RTX at the slowest infusion rate humanly possible and was told if I am allergic, we'd stop the infusion immediately and give IV saline and IV Benadryl.

But from the perspective of the amount of fluid being given plus the infusion speed, I could react to anything and this would not give away if RTX vs. placebo. But in a person who can do normal infusion speeds, this is probably not an issue. (I am not in any study and am speaking hypothetically)!

 

[Jonathan Edwards]

@Jonathan Edwards

Is there any risk or wisdom in administering anti-viral drugs alongside Rituximab? The rational being to ward off opportunistic infections that might occur with diminished B-cells.

And if one has high IgG titers for a given virus (such as coxsackie B4) is there a risk of the latent virus reactivating while receiving Rituximab?

Thank you!

I see no point in taking antivirals while on rituximab. The most likely effect I suspect would be a neutropenic reaction to the anti-viral and much worse immunosuppression. Shingles (herpes zoster) does occur rather more often after rituximab but it is usually transient and can be treated at the time. Other viruses in general do not seem to be a problem. Coxsackie is only a problem as far as I know for people who have high dose chemotherapy for bone marroww transplantation and the like (who may also get rituximab).

Antibody titres to viruses and bacteria do not go down with rituximab significantly. The antibodies are almost certainly produced by long lived plasma cells which are not affected.

 

[SK2018]

But aren't long live plasma cells the problem in many autoimmune diseases ,thus if RTX doesn't hit them where does it's efficacy come from ?i have learned about some cases of anti NMDA that responded to nothing except a new drug that destroys plasma cells,so is it the memory B cells or plasma cells that drive the process usually ?

I see no point in taking antivirals while on rituximab. The most likely effect I suspect would be a neutropenic reaction to the anti-viral and much worse immunosuppression. Shingles (herpes zoster) does occur rather more often after rituximab but it is usually transient and can be treated at the time. Other viruses in general do not seem to be a problem. Coxsackie is only a problem as far as I know for people who have high dose chemotherapy for bone marroww transplantation and the like (who may also get rituximab).

Antibody titres to viruses and bacteria do not go down with rituximab significantly. The antibodies are almost certainly produced by long lived plasma cells which are not affected.

ut

 

[Jonathan Edwards]

But aren't long live plasma cells the problem in many autoimmune diseases ,thus if RTX doesn't hit them where does it's efficacy come from ?i have learned about some cases of anti NMDA that responded to norbiht except a new drug that destroys plasma cells,so is it the memory B cells or plasma cells that drive the process usually ?

ut

No, it seems that most autoantibodies are produced by relatively short lived plasma cells. If the y weren't they would not go down

 

[Jesse2233]

I see no point in taking antivirals while on rituximab. The most likely effect I suspect would be a neutropenic reaction to the anti-viral and much worse immunosuppression. Shingles (herpes zoster) does occur rather more often after rituximab but it is usually transient and can be treated at the time. Other viruses in general do not seem to be a problem. Coxsackie is only a problem as far as I know for people who have high dose chemotherapy for bone marroww transplantation and the like (who may also get rituximab).

Antibody titres to viruses and bacteria do not go down with rituximab significantly. The antibodies are almost certainly produced by long lived plasma cells which are not affected.

Interesting. If anti-virals potentially make immunosuppression worse, might this explain why Fluge and Mella are having better reported results than the anecdotal Rituximab stories we're hearing from OMI? My understanding is that OMI may at times combine anti-virals such as Valcyte with Rituximab.

 

[Jonathan Edwards]

Interesting. If anti-virals potentially make immunosuppression worse, might this explain why Fluge and Mella are having better reported results than the anecdotal Rituximab stories we're hearing from OMI? My understanding is that OMI may at times combine anti-virals such as Valcyte with Rituximab.

No, immunosuppression with antivirals would be an uncommon side effect that would come to light - such as a severe neutropenia.

 

[SK2018]

No, it seems that most autoantibodies are produced by relatively short lived plasma cells. If the y weren't they would not go down

And this article seems to be about exactly what you just said.
http://www.pnas.org/content/107/10/4658.full.pdf

 

[Jonathan Edwards]

And this article seems to be about exactly what you just said.
http://www.pnas.org/content/107/10/4658.full.pdf

Except that that study is upside down. We showed that rituximab depleted autoantibodies and not protective antibodies in HUMAN AUTOIMMUNE DISEASE in 2000. Dear Dr Mathis has subsequently shown that an irrelevant animal model of arthritis shows the same thing. As I rather unfairly pointed out to her at a Keystone Conference around 2002, it is always nice to see that findings in human models are confirmed by the real mouse disease!!!

Mouse disease models tell us nothing. The good mouse science is on the basic normal immune mechanisms - that stuff set the whole subject up. But 'models' of disease are almost entirely unhelpful.

 

[Gingergrrl]

i have learned about some cases of anti NMDA that responded to norbiht

@Shawn What is norbiht (or is that a typo? ).

We showed that rituximab depleted autoantibodies and not protective antibodies in HUMAN AUTOIMMUNE DISEASE in 2000.

I cannot tell you how much hope that one sentence just brought me. I know it is nothing new, but I think I must have read it in a new way. Thank you and I am absolutely determined to get to try RTX by the end of 2017. I will find a way to make it happen.

 

[SK2018]

Except that that study is upside down. We showed that rituximab depleted autoantibodies and not protective antibodies in HUMAN AUTOIMMUNE DISEASE in 2000. Dear Dr Mathis has subsequently shown that an irrelevant animal model of arthritis shows the same thing. As I rather unfairly pointed out to her at a Keystone Conference around 2002, it is always nice to see that findings in human models are confirmed by the real mouse disease!!!

Mouse disease models tell us nothing. The good mouse science is on the basic normal immune mechanisms - that stuff set the whole subject up. But 'models' of disease are almost entirely unhelpful.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2211779/

 

[slysaint]

I noticed that for the phase 3 trial the ME patients 'cut off' was 15 years. Anyone know why?