Rapamycin with autoimmune disease: a small success story

#1

I just want to share a brief story. Somebody I know well (44F) has mild Sjögren’s syndrome (where the body attacks the glands in the mouth). They also have a kinda inconclusive diagnosis of rheumatoid arthritis, where they meet some of the key diagnostic criteria, but not all. Basically, she has no overt joint issues, but positive blood markers (including positive anti-cardiolipin antibodies and RA factor). She has had a few previous autoimmune flare-ups, including an attack on both ureters, and an apparent attack on some peripheral nerves in her legs. Other than that, she is extremely fit, healthy, athletic etc.

Her doctor generally tracks progress by measuring serum RA factor. I have seen her blood tests since 2014 and RA factor has always fluctuated between 150-300 IU/ml, getting notably worse during and after pregnancies. Highest level was 3 months after giving birth where it was 533IU/ml, and the average from 2014 to 2025 is 247IU/ml. (For reference, I once tested mine out of curiosity and it was 0. Apparently normal people are usually <5IU/ml).

The main tool has been prednisolone which got her through pregnancies, and her doctor uses to bring RA factor down when it climbs too high. Obviously that’s an unpleasant drug which gives you water retention, moon-face, messes with bone density and disrupts sleep. She’s taken 200mg hydroxychloroquine for decades, and she’s also occasionally used a very expensive antibody infusion (Belimumab) to deal with acute attacks. One of the biggest issues is that the condition makes her tired quite easily, and that’s the strongest correlation with RA mark. i.e. usually if she’s really tired, RA mark will be high.

Anyway, long story short, her most recent RA mark results are below:
173, 193, 163, 167, 194, 114, 149, 64, 75

I bet people can guess between which two tests she started taking Rapamycin!

64IU/ml is an all-time lowest result. Lower than ever achieved while on high doses of prednisolone. We thought maybe it’s a coincidence, but another test 3 months later came back with 75IU/ml which is still less than half of her average level over the last several years.

And the best thing is - she’s only taking 2mg per week. Edit: she weighs around 50kg.

She says that subjectively her energy level is also a bit better, but the good news is that RA levels are predictive of future progression into full-blown rheumatoid arthritis, and it reflects B-cell/auto-antibody activity. Seems like Rapamycin, even at a very low dose, is really quite effective at dialing that down.

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#2

Great results.

Have her doctor’s considered Granulomatosis with polyangiitis (GPA)?
Formerly known as Wegener’s granulomatosis, a rare autoimmune disease where the body’s immune system mistakenly attacks healthy tissues, leading to inflammation and damage.

As it attacks fine vascularity, it can affect almost anything in the body.

Often associated with high RA factor.

Similar treatment protocol to what she has had, but the infusion might go to Rituximab or Cyclophosphamide.

My wife has this maybe I should press her to try Rapamycin.

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#3

2mg a week ? How much does she weigh ?

#4

I can definitely relate to all of this, except I didn’t have any significant improvements until I got to 10mg per week. but I am a large guy.

I don’t have Sjögren’s, I have Crohn’s disease, but I have the same dynamic. Prednisone was the only thing in the world that really ‘cured’ me, not just from a flare-up, but more importantly, from a nonstop fatigue. But prednisone is an awful drug, with horrible side effects, so I’ve been searching for an alternative for over a decade.

Rapam has helped me tremendously. I don’t measure RA, but my hsCRP levels which have previously hovered between 3 to 10 are now around 1.0.

btw, for people with ME/CFS, based on a new study, hsCRP levels match almost perfectly with levels of fatigue.

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#5

I am not sure, to be honest. I think the current plan is just to manage symptoms and keep an eye on the numbers for anything getting worse. That’s really useful information though, thanks.

Around 50kg. I will also add that she is generally very “sensitive” to most medications. e.g. she gets very effective pain relief from only 500mg paracetamol, or 200mg ibuprofen. So that may be a factor.

That’s great new and I’m really happy to hear it. A reduction from 3-10 down to 1 is definitely significant. When taking 10mg per week, did you ever test your blood Rapamycin levels?

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#6

I’m actually doing 15mg as of now. I will test it next month for sure.

#7

Bumping the thread here with a small update.

While still on Rapamycin, there was a 3rd RA mark result; this time 93.6. She then stopped Rapamycin for an unrelated reason and the new RA mark after 2 months off Rapa is 175 - i.e. back to normal.

So I believe this is very strong evidence that Rapamycin does significantly lower RA levels. And that’s with only 2mg per week.

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#8

What they tried GLP1 for RA? I know tirzepatide is a powerful antiinflammatory.

#9

Maybe - though to my understanding the RA mark is an antibody which is part of a specific immune response, rather than generalised “inflammation”. As for the exact details of how and why it’s produced, I really don’t know.

But for her, at 50kg body weight with no excess fat to lose, I don’t think it would be a good idea to use a GLP1RA.

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#10

It’s a shame that people without excess body weight cannot use GLP1RA’s for their anti-inflammatory effects.

“This study suggests that the use of GLP-1RAs can improve RA disease activity and cardiovascular risk profile. Although further research is needed, this novel finding has significant clinical implications because it suggests that anti-obesity medications may improve both cardiovascular and RA outcomes.”

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#11

It’s definitely interesting - but I have to wonder whether it’s the GLP1RA causing the weight loss which subsequently lowers inflammation, or whether the drug has a direct effect. Basically, if somebody is already at an optimal body composition (with resulting low inflammation), would they still benefit?

#12

It’s both. It has a direct effect for sure.

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#13

Yeah apparently it’s independent of weight loss.

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#14

“Tirzepatide, a dual GIP and GLP-1 receptor agonist, has shown significant metabolic benefits and weight reduction, but its anti-inflammatory effects have been less studied. This study was conducted in accordance with PRISMA guidelines, including observational (cohort) studies and randomized clinical trials that evaluated tirzepatide use and reported percentage changes in high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). A random-effects model was used. Seven randomized clinical trials and one observational study were included (six studies were eligible for meta-analysis). Compared to placebo, tirzepatide reduced hsCRP (mean difference [MD]: -32.9; 95% confidence interval [CI]: -33.6 to - 32.2; I²=15.3%) and IL-6 (MD: -17.8; 95% CI: -24.3 to - 11.3; I² = 1.6%). Levels of hsCRP were significantly reduced with tirzepatide at 15 mg (MD: -32.9; 95% CI: -33.6 to - 32.2; I²=4.4%), 10 mg (MD: -33.9; 95% CI: -50.3 to - 17.6; I²=41.8%), and 5 mg (MD: -20.3; 95% CI: -35.2 to - 5.3; I²=0%). Similarly, IL-6 levels were significantly reduced with tirzepatide at 5 mg (MD: -18.8; 95% CI: -32.9 to - 4.6; I²=17.2%), 10 mg (MD: -17.9; 95% CI: -28.2 to - 7.7; I²=2.1%), and 15 mg (MD: -16.8; 95% CI: -31.1 to - 2.6; I²=47.4%). This study demonstrated that tirzepatide use is associated with a significant reduction in inflammatory markers, regardless of the population studied or treatment regimen.”

Anti-inflammatory effects of tirzepatide: a systematic review and meta-analysis Anti-inflammatory effects of tirzepatide: a systematic review and meta-analysis - PubMed

“We evaluated Tirzepatide in the Winnie mouse, a model of spontaneous UC-like colitis and CAC. Weekly administration of Tirzepatide (30 nmol/kg, 8 weeks) markedly reduced colitis severity and tumor burden compared to vehicle controls. Treated mice exhibited improved weight stability independent of obesity, reflecting attenuation of inflammation and tumorigenesis rather than metabolic effects. Histologic analyses confirmed reduced inflammatory scores, preservation of crypt architecture, and fewer dysplastic lesions. At the molecular level, Tirzepatide suppressed transcription of colon cancer-associated genes (Axin2, Myc, Cdkn1a, Lgr5) and reduced pro-survival and proliferative signaling proteins (p-AKT, p-PFK2, Cyclin D1). Inflammatory cytokine transcripts (Il6, Il1β, Tnf) and stool lipocalin-2 levels were significantly decreased, corroborating broad anti-inflammatory activity. These findings align with reports of Tirzepatide suppressing tumor growth in patient-derived CRC xenografts, reinforcing a potential direct effect on epithelial oncogenic pathways rather than an indirect consequence of weight loss. Our results support Tirzepatide as a promising therapeutic candidate that bridges metabolic and immune pathways to mitigate colitis and CAC. Its dual receptor activity may synergize with existing therapies such as mesalamine or biologics, offering an advanced combination therapeutic approach to IBD management and cancer prevention. Future studies are warranted to define dosing strategies that dissociate metabolic from anti-inflammatory effects and to evaluate long-term outcomes in translational and clinical settings.”

REPOSITIONING DUAL GLP-1/GIP RECEPTOR AGONISTS FOR THE TREATMENT OF COLITIS AND COLITIS-ASSOCIATED TUMORIGENESIS https://academic.oup.com/ibdjournal/article/32/Supplement_1/izag006.012/8436081

“Therapies based on glucagon-like peptide-1 (GLP-1) reduce rates of cardiovascular and chronic kidney disease in people with type 2 diabetes and/or obesity, with ongoing clinical trials investigating their effects in people with metabolic liver disease, arthritis, and both substance use and neurodegenerative disorders. Acute and chronic activation of GLP-1 receptor signaling also reduces systemic and tissue inflammation in mice and humans, through weight loss–dependent and –independent mechanisms, actions that may contribute to the expanding spectrum of clinical benefits ascribed to GLP-1 medicines. In this Review, we highlight current understanding of the direct and indirect antiinflammatory effects and mechanisms of GLP-1 medicines in both preclinical and clinical studies, covering emerging concepts, clinical relevance, and areas of uncertainty that require further investigation.”

Antiinflammatory actions of glucagon-like peptide-1–based therapies beyond metabolic benefits https://www.jci.org/articles/view/194751

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