Pred dosage and Large vessel vasculitis

[Rabbit090]

(just as a precursor, despite having neither GCA nor PMR, I do have a form of Vasculitis similar to non-cranial GCA - takayasu’s vasculitis, which affects my aorta but no organ involvement so far. I post here rather than in the Vasculitis forums because there’s a lot more information that seems more relevant, it’s busier and I like you all! So knowledgeable!).

So, I have now had my second infusion of cyclophosphamide to try and get the disease under control as well as in my 6th week of prednisolone. Currently at 32.5mg from 60mg then 40 in the first and second weeks which I take first thing in the morning.

Because I don’t have intense symptoms - which is why it apparently got quite bad before I was diagnosed - it’s hard to know what is the right course of action. I do find that this week I’m experiencing a bit of hot flashing around mid day (which I know now is a symptom) and my intermittent arm claudication from the inflamed artery is worse in the early morning but gets much better by the late afternoon.

I guess what I’m not sure of is if the Pred is basically worn off by the morning and if that’s a problem in my recovery. I have no idea when the cyclophosphamide is supposed to improve things.

Interested in any theories! I do plan to speak to my consultant next week of course.

[SnazzyD]

This is my guess - It might be that your Pred effect gets to a low level, then you take it, it then takes a couple of hours to get into your system (longer if it is coated Pred)by which time your inflammation has built up so you get symptoms until the inflammation has got it under control by the afternoon. Sounds like Cyclophosphamide may not be working 100% yet so perhaps the Pred is still doing some heavy lifting. As you said, you are going to speak to your medics.

[Rabbit090 in reply to SnazzyD]

Thanks. Kind of my thinking too. Makes me wonder why we taper before knowing if the Cyclophosphamide is doing anything. Are there any parallels in methotrexate therapies that you know of?

[SnazzyD in reply to Rabbit090]

How do you mean parallels? I don’t know whether this is any use, but this describes the different medications for Takayasu’s and their actions. In the case of Methotrexate it says its mode of action is unknown. In PMR/GCA it can take weeks or months to take full effect and isn’t effective for everyone. It is used as a steroid sparer to allow a lower dose of Pred to be used.

emedicine.medscape.com/arti...

[Rabbit090 in reply to SnazzyD]

I’ve read that methotrexate is an alternative to cyclophosphamide in Takayasu as is azathioprine, mycophenolate mofetil, and leflunomide so wondered if GCA treatment was ever similar. In my case, cyclophosphamide is not a steroid sparer but a first line because the damage is severe (or so says my doctor’s notes). Im assuming it’s to “reset” the immune system - like it does in cancer treatments. I’m meant to move to Tocilizumab as a steroid sparer once the course of cyclophosphamide is completed.

Struggling with that medscape link on my phone - will need to try setting up an account on a computer tomorrow.

[Noni71]

I too have LVV and cranial GCA and had no symptoms from the LVV. It was diagnosed from a PET CT scan. I took Tocilizumab for a year and felt great. Methotrexate didn’t suit me and now on Leflunomide. All seems to be going well and inflammation markers are at a normal level.

[Rabbit090 in reply to Noni71]

Thank you! I’m going to ask about Leflunomide as I read it’s worked better that cyclophosphamide with fewer side effects.

[Oddmanout in reply to Noni71]

I had Tocilizumab for a year but it had to be stopped due to protocol. I too felt great. I'm now on Prednisolone, Methotrexate and Leflunomide for LVV. No particular side effects and now inflammation levels are steady.

[Rabbit090 in reply to Oddmanout]

Thanks! I hate the cyclophosphamide as it’s giving me awful constipation and edema even though I have a good diet and drink at least 2 litres of water a day. I am super concerned about what it’s doing to my kidneys.

[SnazzyD in reply to Rabbit090]

I’m not surprised. I don’t know what dose you have with TKY but when I had it for cancer it was unpleasant and affected everything. Did they give you a rationale for going for that as first line instead of the usual suspects, above that your LVV was bad?

[Rabbit090 in reply to SnazzyD]

He said Leflunomide and Methotrexate are medications he would use in people with less severe disease and as such switching from Cyclophosphamide to Leflumomide would be considered a "down-grade" in my therapy rather than "up-grade".

My CRP has been normal since early March which means the inflammatory component of the disease has responded. But the narrowing in my upper limb vessels are very tight and he says in TAK it is difficult to discern from the imaging how much of this is inflammation (I.e likely to respond to steroids and cyclophosphamide) and how much is (chronic) thickening of the artery (I.e less likely to respond to steroids).

The cyclophosphamide dose is quite low though - far less than is used in cancer treatment. So, I guess I need to be patient!

[SnazzyD in reply to Rabbit090]

Ok so you’re well and truly in one day at a time territory.

Your fluid retention could be something to do with Pred, especially at your doses of late. It makes the body retain sodium so fluid retention can be an issue unless you cut down salt. I had to have virtually no salt in my diet for a while or suffer from fluid bloat and puffy around the eyes. So along with very low carb and low low salt my diet was in a culinary wasteland.

[Rabbit090 in reply to SnazzyD]

So it seems!

I did cut out salt entirely (and sugar and most carbs save the odd bit of brown rice, beans, sweet potato and oats now and again - probably only a couple of times a week). I managed to lose 20lbs since the beginning of the year, so I’m happy with that.

What I noticed was that after my cyclophosphamide IVs, I would get quite bloated, probably from the saline drip, and it was difficult to pee the following day (not painful, just not happening). But I also read that it does sometimes make the kidney hang on to water but that’s usually high doses. Anyway, by the second day that seems to go away. I imagine the two things are not doing good things together.

I’ve acquired a new fondness for lemon, vinegar and seaweed seasonings but oh, do I crave cured meats and salted caramel on a regular basis!

[SnazzyD in reply to Rabbit090]

ah yes, vinegary dressings got me through.

[Sharitone]

Has anyone mentioned tocilizumab? Takayasu's makes you eligible to have it permanently, unlike the limit of one year for GCA/LVV sufferers.

[Rabbit090 in reply to Sharitone]

Yes, that’s scheduled for after the cyclophosphamide regime is done (June probably). I’m hopeful it works!

[PMRpro Ambassador]

Why are they using cyclophosphamide for Takayasu's - which is part of the PMR/GCA spectrum and the only one with approval for unlimited use of tocilizumab.

[Rabbit090 in reply to PMRpro]

They are using it as first line to kill my immune system since the damage is so severe apparently. Tocilzumab will come once the cyclophosphamide is done. I do the third infusion next week then it moves to 3 more at 3 week intervals.

[PMRpro Ambassador in reply to Rabbit090]

I didn't think it worked like that - but hey-ho, they are the experts.

[Rabbit090 in reply to PMRpro]

I honestly have no idea either but he seems very confident in his strategy. I have seen this mentioned as a method in papers from Japan about TAK I think.

[Rabbit090 in reply to PMRpro]

Thinking about it, I wonder if it’s because the Pred would need to be on quite high doses for rather a long time as at the moment I get symptoms of inflammation back when I drop even small amounts. Because the inflammation has caused so much damage, he’s trying to stop my immune system entirely - like cyclophosphamide does for other diseases. He wants to get to a point where putting in stents doesn’t damage the vessel walls and that can’t happen until there’s no chance of inflammation.

Total hypothesis though. I could be wrong.

[PMRpro Ambassador in reply to Rabbit090]

Seems fair. I always wonder why they don't use other things like that for GCA - they do for other forms of vasculitis.