I am currently 3 weeks into Rituximab for CFS and MCS (multiple chemical sensitivity). I am seeing a 25% reduction in symptoms, greater than any therapy I have tried. I will periodically update with how I am doing.
According to Fluge and Mella case studies CFS patients that respond see benefits as early as 2 weeks, most notice something after 5-6 weeks. Reduction in symptoms continues up to the 14th week, afterwhich there is remission or a gradual return of symptoms. (R)
What Have I Noticed So Far?
Since my illness began I have had chronic fatigue, PEM, and a growing list of environmental and food sensitivities. If I ate the wrong food or breathed air with cigarette smoke I could suffer a migraine, palpitations, lassitude and asthma-like symptoms for hours after. Immunosuppressant treatments helped. My go-to remedies were breathing oxygen, IV ozone and high dose vitamin C. I have been managing fatigue with supplements and nutritional IVs.
Since the second week post-infusion I have noticed my symptoms are increasingly less severe and shorter in duration. At first it was subtle but now in the third week it is significant. Many foods I couldn't tolerate before I no longer have problems with. This includes supplements, many of which I saw significant benefits from but had to discontinue.
About Me
Before trying Rituximab I had markers of autoimmune illness. My ANA had been elevated since onset, so had Sjogren's Syndrome Antibody B, and C3 was chronically low. At one point my ANA titer was 1:1280 Homogeneous, the highest the lab can measure, typically only seen in severe autoimmune illnesses. I did not have clinical manifestations of Sjogren's or any other characterized autoimmune illness and did not respond to Plaquinol. (R1, R2)
I had other less clinical markers, including elevated IL-6 and IL-17 in PBMCs, elevated NO, elevated Nitrotyrosine, low NADPH, low ATP, low GSH, elevate lipid peroxides, dysregulated methylation cycle, dysregulated redox enzymes in RBC. (R1, R2, R3, R4, R5)
There was more. I spent hundreds of thousands of dollars on testing, treatments, supplements and countless hours reading scientific literature. You can see some of this in the link provided down below. As mentioned I respond strongly to immunosuppressants, including corticosteroids, HBOT, Ozone IV, nutritional IVs, anti-inflammatory herbs, sunshine, exercise, FTIR sauna. But none produced a lasting or significant improvement in environmental sensitivity. They were palliatives at best.
As I am sure many of you have, I was told there was nothing wrong with me, insinuated I was a hypochondriac, that I was stressed or some other nonsense palaver. Unfortunately, that is the FDA authorized response. As my knowledge of medicine and biochemistry grew this gave way to "I don't know enough to help you", "we don't know everything". I had to be more knowledgeable and kidglove (downplaying my non-specific symptoms) to be taken seriously. I was referred to both UCLA and Stanford and heard more of the same there. I have seen Dr. Rea in Dallas, OMI in Mountain View and plenty of other "experts".
On the flip side I have known people who claimed to be very unwell and then completely "recover" after DNRS...
My illness began after using Accutane for 6 weeks when I was 18 years old. Accutane is associated with autoimmune illnesses including Crohn's and IBD, as well as changes in DNA transcription and methylation patterns in T-cells. The latter can be long lasting. (R) Epigenetics is a burgeoning field with many autoimmune diseases expressing similar patterns in epigenetic control mechanisms e.g. DNA methylation, histone acetylation, miRNA. (R) For example, drug induced lupus and systemic lupus erythematosus express an identical DNA methylation pattern with no significant genetic difference to controls. But the former disappears as soon as the offending drug is discontinued. This is an important thread to unravel.
You can read about my symptoms, testing, illness onset and supplement regiment here.
How Did I Get Rituximab?
Without a well characterized illness you will have a hard time getting treatment in the West. So, I flew to Taiwan. A friend walked me through the medical system. It is ranked best in the world, it would be top of the WHO rankings if it was recognized as a sovereign nation (One China Policy).
The trip was hard on my health. Even with all my amenities I can't control the environment and get exposed to something (perfumes, foods, etc.). Fortunately my friend arranged everything in advance, the hotel didn't smell like mold or cleaning chemicals, the food was plain and I didn't react.
It took about a day to get an appointment with one of the top rheumatologists at the top hospital in the country. I brought my friend to translate but the doctor (and apparently every doctor) spoke English. We spoke for 30 minutes in a 10 minute appointment. Afterwards he asked to see me when his shift ended at 5:30pm. We spoke for an additional 90 minutes. Never was I disbelieved or disrespected. When I mentioned scientific literature they asked to see the paper, to evaluate the impact factor of the journal, etc. When I showed blood work they weren't skeptical implying only their lab was valid. It was refreshing. I made a case to try Rituximab. It was in Phase III trials, 66% of patients responded, I had responded to immunosuppressant treatments and my blood work suggested autoimmunity. I was going to pay out of pocket. The doctor agreed to try it if I was comfortable with the risks.
After additional blood work and two days later I received my first 1000mg infusion, two weeks later I received the second, as per the Phase II study's protocol. (R) Each infusion, including necessary screening, blood work and hospitalization, was ~$4000USD. The Rituximab itself was $1200 per 500mg. During the first IV I had a mild infusion reaction of urticaria which happens ~30% of the time and dissipated with corticosteroids. (R)
The first two weeks I noticed nothing or only subtle improvements. I also noticed transient side effects, like aches and itches. This is not mentioned in the medical literature but anecdotal reports corroborate it. After the third week it was difficult to deny I was seeing significant improvements.
How Does Rituximab Work?
The following paper discusses Rituximab's MOA in Rheumatoid Arthritis, you can extrapolate to autoimmune illnesses in general. I have included excerpts below.
Side effects are "rare but there", please read the following paper:
http://www.tandfonline.com.sci-hub.cc/doi/full/10.1080/10428190902934944
According to Fluge and Mella case studies CFS patients that respond see benefits as early as 2 weeks, most notice something after 5-6 weeks. Reduction in symptoms continues up to the 14th week, afterwhich there is remission or a gradual return of symptoms. (R)
What Have I Noticed So Far?
Since my illness began I have had chronic fatigue, PEM, and a growing list of environmental and food sensitivities. If I ate the wrong food or breathed air with cigarette smoke I could suffer a migraine, palpitations, lassitude and asthma-like symptoms for hours after. Immunosuppressant treatments helped. My go-to remedies were breathing oxygen, IV ozone and high dose vitamin C. I have been managing fatigue with supplements and nutritional IVs.
Since the second week post-infusion I have noticed my symptoms are increasingly less severe and shorter in duration. At first it was subtle but now in the third week it is significant. Many foods I couldn't tolerate before I no longer have problems with. This includes supplements, many of which I saw significant benefits from but had to discontinue.
About Me
Before trying Rituximab I had markers of autoimmune illness. My ANA had been elevated since onset, so had Sjogren's Syndrome Antibody B, and C3 was chronically low. At one point my ANA titer was 1:1280 Homogeneous, the highest the lab can measure, typically only seen in severe autoimmune illnesses. I did not have clinical manifestations of Sjogren's or any other characterized autoimmune illness and did not respond to Plaquinol. (R1, R2)
I had other less clinical markers, including elevated IL-6 and IL-17 in PBMCs, elevated NO, elevated Nitrotyrosine, low NADPH, low ATP, low GSH, elevate lipid peroxides, dysregulated methylation cycle, dysregulated redox enzymes in RBC. (R1, R2, R3, R4, R5)
There was more. I spent hundreds of thousands of dollars on testing, treatments, supplements and countless hours reading scientific literature. You can see some of this in the link provided down below. As mentioned I respond strongly to immunosuppressants, including corticosteroids, HBOT, Ozone IV, nutritional IVs, anti-inflammatory herbs, sunshine, exercise, FTIR sauna. But none produced a lasting or significant improvement in environmental sensitivity. They were palliatives at best.
As I am sure many of you have, I was told there was nothing wrong with me, insinuated I was a hypochondriac, that I was stressed or some other nonsense palaver. Unfortunately, that is the FDA authorized response. As my knowledge of medicine and biochemistry grew this gave way to "I don't know enough to help you", "we don't know everything". I had to be more knowledgeable and kidglove (downplaying my non-specific symptoms) to be taken seriously. I was referred to both UCLA and Stanford and heard more of the same there. I have seen Dr. Rea in Dallas, OMI in Mountain View and plenty of other "experts".
On the flip side I have known people who claimed to be very unwell and then completely "recover" after DNRS...
My illness began after using Accutane for 6 weeks when I was 18 years old. Accutane is associated with autoimmune illnesses including Crohn's and IBD, as well as changes in DNA transcription and methylation patterns in T-cells. The latter can be long lasting. (R) Epigenetics is a burgeoning field with many autoimmune diseases expressing similar patterns in epigenetic control mechanisms e.g. DNA methylation, histone acetylation, miRNA. (R) For example, drug induced lupus and systemic lupus erythematosus express an identical DNA methylation pattern with no significant genetic difference to controls. But the former disappears as soon as the offending drug is discontinued. This is an important thread to unravel.
You can read about my symptoms, testing, illness onset and supplement regiment here.
How Did I Get Rituximab?
Without a well characterized illness you will have a hard time getting treatment in the West. So, I flew to Taiwan. A friend walked me through the medical system. It is ranked best in the world, it would be top of the WHO rankings if it was recognized as a sovereign nation (One China Policy).
The trip was hard on my health. Even with all my amenities I can't control the environment and get exposed to something (perfumes, foods, etc.). Fortunately my friend arranged everything in advance, the hotel didn't smell like mold or cleaning chemicals, the food was plain and I didn't react.
It took about a day to get an appointment with one of the top rheumatologists at the top hospital in the country. I brought my friend to translate but the doctor (and apparently every doctor) spoke English. We spoke for 30 minutes in a 10 minute appointment. Afterwards he asked to see me when his shift ended at 5:30pm. We spoke for an additional 90 minutes. Never was I disbelieved or disrespected. When I mentioned scientific literature they asked to see the paper, to evaluate the impact factor of the journal, etc. When I showed blood work they weren't skeptical implying only their lab was valid. It was refreshing. I made a case to try Rituximab. It was in Phase III trials, 66% of patients responded, I had responded to immunosuppressant treatments and my blood work suggested autoimmunity. I was going to pay out of pocket. The doctor agreed to try it if I was comfortable with the risks.
After additional blood work and two days later I received my first 1000mg infusion, two weeks later I received the second, as per the Phase II study's protocol. (R) Each infusion, including necessary screening, blood work and hospitalization, was ~$4000USD. The Rituximab itself was $1200 per 500mg. During the first IV I had a mild infusion reaction of urticaria which happens ~30% of the time and dissipated with corticosteroids. (R)
The first two weeks I noticed nothing or only subtle improvements. I also noticed transient side effects, like aches and itches. This is not mentioned in the medical literature but anecdotal reports corroborate it. After the third week it was difficult to deny I was seeing significant improvements.
How Does Rituximab Work?
The following paper discusses Rituximab's MOA in Rheumatoid Arthritis, you can extrapolate to autoimmune illnesses in general. I have included excerpts below.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392126/
While time will tell whether this major alteration of the immune system has other consequences, it is remarkable that drastic reduction of B-cell numbers over the long term is tolerated so well, and that it maintains efficacy in RA therapy.
The mechanism of action of rituximab in RA remains controversial but is unlikely to be simply from decreased humoral immunity. Rituximab treatment results in a rapid fall in all mature B-cell subsets, with the exception of plasma cells [9]. Antibody levels (*and autoantibody) are unchanged or fall modestly [10], probably reflecting an incomplete depletion of B cells in the spleen, lymph nodes and marrow [11].
The most alarming rituximab-associated opportunistic infection is reactivation and neurologic infection by JC virus, causing progressive multifocal leukoencephalopathy (PML). There have been only limited case reports in RA patients treated with rituximab. A few of these reports are confounded by treatment with other immunosuppressive agents and, in one case, chemotherapy and radiation therapy after rituximab and a few months prior to onset of PML [36,37]. The incidence of PML in RA has been estimated at 0.4 per 100,000 versus 0.2 per 100,000 in the general population, so there is a suggestion of increased risk with rituximab-treated RA patients. There have been more cases and probably more risk of PML in systemic lupus erythematosus patients and hematologic malignancy patients treated with rituximab.
In summary, with the notable exception of hepatitis B, and not including the remote risk of PML, there is little evidence that patients whose B cells are chronically depleted are at any higher risk of infection.
-
Is Rituximab Safe?While time will tell whether this major alteration of the immune system has other consequences, it is remarkable that drastic reduction of B-cell numbers over the long term is tolerated so well, and that it maintains efficacy in RA therapy.
The mechanism of action of rituximab in RA remains controversial but is unlikely to be simply from decreased humoral immunity. Rituximab treatment results in a rapid fall in all mature B-cell subsets, with the exception of plasma cells [9]. Antibody levels (*and autoantibody) are unchanged or fall modestly [10], probably reflecting an incomplete depletion of B cells in the spleen, lymph nodes and marrow [11].
*According to Jonathan Edwards autoantibody levels fall in proportion to the reduction of inflammatory markers e.g. CRP, which are affected by B-cell depletion.
It seems probable that the mechanism of B-cell depletion in autoimmune diseases such as RA in part reflects the role of B cells as a source of cytokines, or as antigen-presenting cells [11,15]. Additional mechanisms are possible, such as a role for B cells in influencing dendritic cells or T cells [16], or effects on a small CD20+ T-cell population that may be more prevalent in RA patients [17].
The most alarming rituximab-associated opportunistic infection is reactivation and neurologic infection by JC virus, causing progressive multifocal leukoencephalopathy (PML). There have been only limited case reports in RA patients treated with rituximab. A few of these reports are confounded by treatment with other immunosuppressive agents and, in one case, chemotherapy and radiation therapy after rituximab and a few months prior to onset of PML [36,37]. The incidence of PML in RA has been estimated at 0.4 per 100,000 versus 0.2 per 100,000 in the general population, so there is a suggestion of increased risk with rituximab-treated RA patients. There have been more cases and probably more risk of PML in systemic lupus erythematosus patients and hematologic malignancy patients treated with rituximab.
In summary, with the notable exception of hepatitis B, and not including the remote risk of PML, there is little evidence that patients whose B cells are chronically depleted are at any higher risk of infection.
-
Side effects are "rare but there", please read the following paper:
http://www.tandfonline.com.sci-hub.cc/doi/full/10.1080/10428190902934944
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