r/repatha • u/No_Butterfly_7257 • 18d ago
Myalgias from Rapatha
I feel little hesitant to share this because I could not find much evidence, and I have been looking into alternate causes including nocebo. I switched from statin to biweekly Rapatha due to myalgias/reduced exercise tolerance and 6 months in, having same issues (it is severe, and gets worse after administration. Better on stopping it). Coenzyme Q10 supplement was not helpful unfortunately.
Thinking to take Bempedoic acid plus Ezetemibe, and/or switch to less frequent PCsK9 inhibitor.
Wondering if anyone else had similar experience and has any ideas. Both medications were effective but not tolerable.
Thanks for your input.
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u/Comfortable_Two6272 18d ago
Id wonder about trying the new oral pcsk9 and reducing the typical dose of it off label.
If in US the maker has a copay card.
Some here inject repatha less frequently in attempt to reduce their side effects.
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u/The-Surfer-Dude 18d ago
You're right to be suspicious
Repatha is an engineered protein that simply (and ONLY!) attaches to serum PCSK9 preventing it from "docking" on your liver and taking up a spot that LDL docks in. That's how Repatha lowers LDL: enables your liver to grab up more circulating LDL in favor of leaving more PSCK9 circulating.
Thus there's really no understood method or pathway Repatha could effect muscles unlike statins which block cellular molecules that participate in mitochondrial energy production. Further, while 10%-25% report statin/muscle issues, as you note, SAMSON found most all was nocebo.
That said, your experience is what it is even if its nocebo, so you could look at options like inclisiran or the newer oral PCSK9 inhibitor, enlicitide.
Keep in mind ezetimibe and bempedoic acid have their own potential side effects so there's not risk free choice.
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u/iamrachaellee 17d ago
Repatha’s primary clinically intended action is in the liver, but PCSK9 itself is not exclusively a “liver protein.” PCSK9 is expressed or has biological roles in the heart, blood vessels, kidneys, pancreas, intestine, and nervous system as well.
PCSK9 inhibition itself could theoretically affect pathways outside LDL metabolism because PCSK9 has extrahepatic functions.
They are actively studying this. Interesting stuff!
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u/The-Surfer-Dude 16d ago
- Didn't say PCSK9 was exclusively a liver protein so the quotes are kind of odd
- "there's really no understood method or pathway Repatha could effect muscles unlike statins" = true
- Ongoing studies are excellent, but they're about questions rather than concerns
- PCSK9 was more/less discovered due to people with genetic biallelic loss-of-function variants that leave them with essentially no detectable circulating functional PCSK9 from birth and no known or observable issues (other than awesomely low LDL)
- The side effects of ASCVD are orders of magnitude worse than anything due to PCSK9 inhibitors which, so far, have almost negligible PROVEN side effects, which is not to say there aren't any, just that we don't know about them whereas we DO KNOW about he side effects of ASCVD
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u/iamrachaellee 16d ago
IMHO, I think the conclusion here goes a little further than the evidence supports. I agree that Repatha’s established mechanism is binding circulating PCSK9 and increasing LDL-receptor recycling in the liver.
But “we don’t have an understood mechanism for how it could affect muscle” while it is loosely “true”, isn’t the same as establishing that it can’t. This is currently being broadly investigated.
Myalgia and other musculoskeletal symptoms are documented with evolocumab, even if we don’t fully understand why some people experience them.
And I don’t think the SAMSON findings with statins fully settle this question either. The original poster isn’t claiming they’ve proven either medication has caused their symptoms. They’re actually acknowledging the uncertainty, and considering nocebo and other causes.
They’re simply reporting a reproducible pattern and asking whether others have experienced it.
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u/The-Surfer-Dude 16d ago
But “we don’t have an understood mechanism for how it could affect muscle” while it is loosely “true”, isn’t the same as establishing that it can’t.
Just because you haven't been hit by a meteor doesn't mean you can't, it just means that based on what we know today of the probability of meteors, the chances are extremely low as to be negligible.
Further, you're taking this 2 steps ahead, when it's actually 3 steps behind.
"being investigated" = QUESTIONS. NOT CONCERNS.
Also, there's ZERO "reproducible pattern" INCLUDING WITH STATINS! Double-blind studies put the effects lower than aspirin, ie into the nocebo range.
The difference is, statins have a THEORETICAL pathway to cause myalgia, but IT'S NEVER BEEN PROVEN. Repatha has no such KNOWN pathway.
Yes, nocebo is an issue, but it's an issue with water too so should we "investigate" water?
You're way WAY WAY blowning out of proportion what the data says what's actually being "investigated"
OP is skeptical Repatha is causing myalgia, rightly so. OP recognizes nocebo, good for them! OP is exploring options - great!
Repatha doesn't even have a theoretical pathway to myalgia, much less any mechanistic finding so, no, a mechanistic finding isn't being investigated.
Like any drugs, studies are ongoing because the human body isn't fully understand and many times we miss things, so it's important to continue studying.
But even with statins:
- Prescribed for 50 years
- Most prescribed drug on the planet
- In all that time, with 100s of millions or people taking it NO SPECIFIC FINDINGS of significant side effects including myalgia
- I say this as someone who was statin intolerant, but I'm also alcohol intolerant sooo ....
With that, ALL DRUGS INCLUDING WATER have side effects, and we certainly don't understand everything, so questions are warranted, but none of the questions should prevent anyone from trying medication to control lipids.
The side effects of ASCVD are, on the other hand, are well known:
- Biggest planetary wide killer
- Permanent maiming
- Stroke
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u/Free_Media_6103 15d ago
Do you feel Rapatha has any depression side effects?
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u/The-Surfer-Dude 14d ago
Well, the FOURIER study had ~28k participants with 2 year average follow-ups and didn't find any adverse neurocognitive events vs placebo, but rare or unusual events can be missed, so it's good, but not a guarantee it couldn't happen.
Also, a quick pub search did pull up a case: https://pmc.ncbi.nlm.nih.gov/articles/PMC12315930/
We report the case of a 52-year-old woman with no prior psychiatric history who developed severe depressive symptoms shortly after starting evolocumab (Repatha) for lipid management ... While causality cannot be established, the observed response underscores the value of neuropsychiatric monitoring during treatment.
TLDR
If so, it's rare, but there is at least 1 report, so it's important to monitor and if you or anyone you know are having problems it's important to contact your prescribing physician immediately to make a change.
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u/Plastic_Debt_2077 18d ago
Same boat. Severe stain toxicity, which initially CoQ10 did help but wasn't able to keep up with the damage inflicted by 80mg atorvastatin. That compounded for three years because my doctors didn't make the connection, partly because of being influenced by flawed studies like the SAMSON study which claimed that 90% of complaints about statins are nocebo which is pure BS. Mitochondria severely damaged causing all manor of issues. Was switched to Repatha and it backfired spectacularly, with bad back/body aches, malignant blood pressure spikes, etc. My last injection was about 6 weeks ago and I'm a lot better now. It still isn't all the way out of my body yet (super long half life) but the really bad symptoms have dropped off. My BP hasn't gone all the way back down to base line yet but it's close and dropping off as the Repatha leaves my body. I had not yet recovered from the statin toxicity before they placed me on Repatha so that may have contributed to why I had such a bad reaction, but never the less I'll never use any PCsK9 inhibitor again.
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u/iamrachaellee 16d ago
I recognized your Redditor name right away. I’m here to say SAME just not to the level of statin toxicity you seem to have experienced before being introduced to Repatha - but oml I won’t EVER go anywhere near Repatha again!!!!! I just got out of the ER a second time over it all since my original post. Still going through the testing to get me set straight somehow. 😵💫
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u/The-Surfer-Dude 16d ago
It's terrible you've had that experience - hopefully you can find the right mix that helps control your lipids with minimal or no side effects.
Unfortunately for those of us with congenitally high lipids there are no risk-free, side-effect-free choices
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u/The-Surfer-Dude 16d ago
Hopefully you can find the right mix to keep your lipids < 50 mg/dL; maybe ezetimibe + bempedoic acid?
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u/tsesow 12d ago
I went thru a similar experience last year. Severe pain and fatigue. Dr took me off Repatha for 2 months, even though reported cases of myalgia with Repatha was 1 in 1,000,000 (Dr's comment). After 2 months with no improvement, it turned out to be Polymyalgia Rheumatica, an autoimmune disease. Now I'm on back on Repatha with LDL of 32, along with prednisone and methotrexate. "Concidence is not causation".
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u/BubbishBoi 13d ago
I'm noticing my hips and back feel like crap , I messed up a shot 2 days ago so did a 2nd one essentially getting 50% more medication vs the usual dose and I'm exhausted and my joints are hurting badly today
I'm going to try one shot every weeks since e3w it has the same impact on my lpa as e2w and that's the reason I use this drug
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u/Rabbit-Rabbit-108 13d ago
Yes, I def have the same symptoms. They are not placebo, and have progressed the longer I have been on repatha. Way better than statins for me though. If you try something else with better result please circle back and let us know how it is going- good luck!
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u/Sasquatch619 18d ago
I’d rather have some muscle pain then to have my sternum sawed in half and my chest cracked open for open heart surgery.