Can LEQVIO side effects mimic an RA flare?

junieb1,
Leqvio, can cause inflammation of the joints and is sometimes mistaken for an RA flare.
The inflammation causes further damage to the joints.
There are no "known" drug conflicts with Leqvio, but it is new enough for there to be "unknown" interactions.
I'd want to stop the medication to see if it is making your life so difficult.
Cheers to your husband, meanwhile.
There are cardiologist wanting me to take Leqvio since I couldn't tolerate Repatha, so I've been reading about it. We may have to wait for Crispr https://newsroom.clevelandclinic.org/2025/11/08/cleveland-clinic-first-in-human-trial-of-crispr-gene-editing-therapy-shown-to-safely-lower-cholesterol-and-triglycerides

That sounds very promising! May I ask where you got the info that LEQVIO can be mistaken for an RA flare? I have tried to find information online and I have not been able to find much. Maybe just the fact that it can cause joint pain is enough to confuse it with RA. Thank you!

I had my first Leqvio injection on June 1st. Two days later I had flu-like symptoms and a fever which abruptly stopped. 4 days later I had high fever and a severe UTI, treated with antibiotics. 60 days after injection I woke up in pain, all my joints and muscles, headache, I could barely walk stairs, intermittent hot flashes (I‘m way beyond menopause). I have Sjögrens and my doctor said it was not a flare as my blood work was good, he concluded it was side effects of Leqvio. The severe pains lasted about three weeks, mostly subsided to intermittent stabbing pains. Then came the stinging, burning sensations throughout my body, even my scalp, mouth and tongue. This lasted intensely about two weeks and now continues mostly at night but dissipates with morning treadmill and light exercise. My feet and hands are the most intense and I‘ve had a headache for weeks. The sensations wake me around 3am and I also have loud heartbeat in my ears, great anxiety. The anxiety comes and goes. My hips have some inflammation still and will make walking tough, but other days no problems. The prescribing doctor said never again for me and I agree. My immunologist recommends a neurologist to analyze a kind of neuropathy, as a side effect of Leqvio. I was in very good physical condition before the injection. Every type of cholesterol medication either doesn’t work or eventually fails. I did well on Repatha for 2 years and then we went to Leqvio because my LDL rose from 51 to 101. Leqvio brought LDL only down to 85. My doctor said he‘ll see me in January about my cholesterol but has no help for my current symptoms. How long will these symptoms last? Would gabapentin help? The only real relief I get is a very hot sauna (2 x 15 minutes), followed by a 15 to 30 minute swim in a cold pool, then the sensations are calm for awhile but return over time.

@junieb1 I have the exact same questions as you do. So far, my immunologist is certain my symptoms are side effects of Leqvio and not Sjögrens flare up because of the extensive blood work. My endocrinologist also said blood work is normal. Neither gave a direct answer as to whether this could be something new. I am debating whether to go to a neurologist to test for small fiber neuropathy. It is frustrating to feel better for a few hours and then have all symptoms return with a vengeance. I am pushing myself to walk each day, do some easy yoga and lift light hand weights which can boost my energy or leave me totally wiped out. It requires a tremendous amount of willpower, but long term feeling is I’m not worse at least. I have looked into PCSK9 and how much it can impact nerves when the level drops. I think it is a waiting game until the messaging stops. I‘ve had some limited temporary relief with 4-7-8 breathing (you can find the method online). Hot sauna followed by cold pool. Dead heading our rose bushes. Not drinking coffee (or any caffeine), no alcohol but drinking electrolyte water 1 liter each day. I hope you find a way to some relief.

I am to begin Leqvio as soon as it’s approved and I’m very hesitant after reading your posts. Everything else I’ve tried has failed due to symptoms except Praluent 150mg because my labs didn’t improve enough to keep using it. Were all of your symptoms seen in the clinical trials??? I hope you all gel better as soon as possible!

@patma Your symptoms sounds very similar to mine and lead me to ask even more questions. LEQVIO leaves your system in a few hours but because the drug has to last 6 months, the biological effects will last at least that long. I decided that in order to know for sure if my symptoms were from LEQVIO I would stay off my RA meds until the LEQVIO was past the 6 month mark. At 8 months I was still having the symptoms. So, that (maybe erroneously) led me to think it was not the LEQVIO after all. But now, hearing your story, I wonder if the drug can have lasting effects that the doctors don't know about. I like that your doc recommended a neurologist. I think I will mention that to my doc. I had the same experience as you with the oral cholesterol medications. One of my docs recommended I try Praluent but I am drug-shy at the moment.

As for my symptoms, after the 8 months and I was still having severe joint pain, my rheumatologist suggested Prednisone. So I take 10mg a day and feel pretty good - except for the annoying side-affects of Prednisone! My joint pain has subsided and I can use my hands again. I have to build back the strength in my wrists though.

I do take 300mg of gabapentin at night. (my most excellent internist told me to take it at night rather during the day because of the effects it can have on your brain). Still off my other RA meds at the moment because of lung issues. Is it really true that what doesn't kill you will makes you stronger? lol I'm doubtful sometimes.

@clj9821 I don't think you want to base your decisions on my experience but it is good to be armed with all the information you can find.

My cardiologist told me that NONE of his patients experienced the symptoms that I experienced and I believe him. Also, because I have an underlying autoimmune disease, I can't ignore the possibility that it has played a role in my symptoms., even though my labs said everything was good.

From what little I read about the clinical trials, there were people who experienced joint pain but for most people it went away after a few days.

When you say, "Everything else I’ve tried has failed due to symptoms...." does that mean the oral medications or the biologics? My cholesterol is just borderline. I tried 3 oral medications at the suggestion of my cardiologist and they all gave me joint pain - mostly in my thighs which made it difficult to stand from a sitting position. He said it was a very common side-effect and that for some people the pain was temporary but for others it was long-lasting.

That's a shame about the Praluent! The person who commented above had some success with Repatha. These meds are all very complicated and our bodies are very complicated, and none of us are the same! Oy!

Good luck. Would love to hear more about your journey.

@junieb1 The Leqvio is an siRNA drug. I have read some scientific studies on it and the drug trials, but am not a doctor or in the medical field at all, so this is my very basic understanding of what happens next - certain cells in your liver receive a message/change to your RNA to stop producing PCSK9 (a protein) and although there is no „drug“ (which is just the transporter) left after two days (what my doctor said too), the messaging continues for around 6 (I‘ve also read 8) months. PCSK9 is a protein that stops your liver from making receptors that would normally catch LDL cholesterol and pull it from your bloodstream. Without the PCSK9 protein, you have more receptors pulling cholesterol out of your blood. I have tried to understand how that causes all the pain and nerve issues. What I have read is that when you reduce PCSK9 levels dramatically, you lose the protections it would normally provide. I will leave it at that because it is really complicated science and I don’t know half the words! But this lack of PCSK9 can cause our symptoms because it‘s not there to do the good things our body produces it for and needs it for in the first place. Repatha, on the other hand, blocks the PCSK9 protein from interfering with the cholesterol receptors. The PCSK9 is still produced in liver cells, but this function of destroying the cholesterol receptors is blocked. For some reason, this method did not cause any side effects for me. It just stopped being effective after 2 years, so maybe my cells found a work around. It could be I had such a severe pain reaction because I was only 4 weeks from my last Repatha injection when I got Leqvio, and at 60 days is about when the messaging really kicks in. Repatha can apparently keep working for weeks longer so I got a double attack on the PCSK9 protein, meaning I probably lost all or most of the protections, perhaps resulting in first the pain, then as the Repatha wears down, less pain but now the nerve stinging, inner tremors, anxiety all of which can happen when this protective process of nerve fibers is interrupted. Not sure if that is helpful to you, but I too have an autoimmune illness and was certain Leqvio caused a flare up, but blood work proved no. My immunologist has no other recommendations for me, would not give me gabapentine, which is what I read would help my symptoms, so I have to see a neurologist for more specialized testing, and see if I can get some symptom relief. My endocrinologist just said he‘ll see me when the 6 months after the time on the Leqvio injection is up, also not willing to address my symptoms. You are lucky to have an internist who hears you! Despite my symptoms, I still drag myself into our exercise room and do 15 minutes on the treadmill, use 1 pound hand weights, and 15 minutes of yoga stretching. Gradually I feel more mobile, less stiff, pains come and go, headaches come and go, the stinging etc hits hard at night (also read about the autonomic nervous system), but driving myself to move which can bring on real fatigue seems to over days and weeks bring on improvements too. For you it‘s difficult to know how much your other medications or RA could be complicating your recovery from Leqvio, I don‘t know if people involved in the trials included some with autoimmune diseases. Unfortunately we are kind of on our own as our bodies work through the process Leqvio started. Believe me, I feel your frustration!

@patma
Thanks for this info on Leqvio. I wanted to add some testing info that may be helpful. Statins caused severe pain for me and I had esophageal spasms. Through testing at Mayo, I learned I have gene SLCO1B1, which results in statin intolerance and muscle pain. I have tried every cholesterol medicine from Lipitor to Crestor, to Repatha to Leqvio. Unfortunately, all of them caused severe side effects.
The Leqvio first injection was over 15 months ago and I am still clearing the side effects. I have been prescribed Bempedoic acid but there is a risk of sudden tendon rupture. So with my Drs we are trying to reduce my cholesterol through more natural routes to see if I can naturally reduce it. The one medicine I can tolerate is Zetia and it is helping reduce my cholesterol modestly.
If you haven’t had your gene testing, you may want to see if this is available to you? My doctor now uses it for every patient that’s newly prescribed Statins to avoid these known medication impacts. Leqvio certainly reduced my cholesterol immediately, but I may never recover from some of the side effects. Wishing you the very best.

@patma And I feel yours. You have helped me understand a little more about the biologics. They are some heavy duty drugs for sure, to be able to get down to that molecular level! I might try the Praluent next. I am looking for a new cardiologist and will hear what they have to say. At least my pain is gone for now and I'm off of pretty much everything except prednisone, which I don't want to become permanent, so I have a ways to go. Almost feels like back to square one with both the RA (which I have had since '82!) and the cholesterol treatment. I don't understand why your primary won't give you gabapentin. It's designed for nerve pain. My internist first gave it to me when I had a severe reaction to the shingles vax. Nerve pain from my hip to my calf, couldn't walk to the bathroom without screaming, etc., etc.. None of my other docs considered gabapentin and even when I told my pain management doc that it had helped me get out of bed he said, "Oh, I would have never prescribed that!". Does your doc say WHY they don't want you to have gabapentin? On a low dose I don't really notice that I am taking it but on the higher doses it made me forget words and my brain felt scrambled. The side-effects were worth being able to walk without such awful pain though, and I guess that's what meds are all about. Do the benefits outweigh the risks? That said, I am serious when I say that I can't think of a single drug that doesn't have side-effects for someone! I don't know why they can't fix that. Good luck to you. I'm looking forward to hearing about your next move.