Does anyone have any knowledge about whether Rituximab can be used if you are ANCA negative?
I have CSS for nearly 2 years, but luckily a mild severity. My consultant has suggested I should perhaps change from Azathioprine since it does not appear to be controlling the CSS based on CRP levels (never < 50 against spec of < 10) and ongoing symptoms with pred at 14 mg. In his words in the letter to my GP I received this week ...."Rituximab would be attractive but would be difficult if he is still ANCA negative".
I have only been ANCA tested when dx in April 2013 which was -ve, and will be retested next week, but it sounds as if still negative, then Rituximab will not be possible?
I welcome your comments ... many thanks.... Jonty
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JontyW
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RITUXIMAB is a perfectly normal medical option when your Anca is negative.. I have no idea who your GP is or who your consultant is. However, Your GP is most unlikely to be in a "knowledge and experience" situation to make any decision relating to this . It is a decision for your consultant who is in a much better position to make the call.
To take Rituximab, you will need the endorsement of NICE because it is quite an expensive option. Rituximab is not suitable for ALL but the main way of finding out is to try it.
I have been on Azathioprine for 8 years with occasional brief interludes taking Mycophenolate and Methatrexate both of which seriously disagreed with my body.
I am struggling a little with Azathioprine because of side effects . Rituximab may be the next step for me ( I have permission from NICE ).
My strong advice to you is to discuss this with your consultant . Dont shy away from asking him/her difficult questions!
Thank you for your useful feedback Paul. I have a good working relationship with my rheumatologist and regularly communicate via email between appointments, and he always answers openly to all my questions, so I will email him on Monday requesting further clarification.
Having had similar feedback, related to the cost, from other support groups where I posted this same question, it seems that he is probably referring to the cost issue and hence the need for NICE approval.
But there is still the question as to why he said .. "but would be difficult if he is still ANCA negative", since this implies that an ANCA +ve patient has a greater need for this drug, possibly due to the organs affected. My understanding is that about 40% of CSS patients are ANCA +ve and those tend to have more vital organs affected, such as kidney and heart, compared to ANCA -ve patients. Although multiple studies seem to have given varying results.
I was under the impression that Rituximab was only approved by NICE for ANCA positive vasculitis, particularly GPA and MPA.
I know that Addenbrookes have used it to treat EGPA ( CSS ) but that may be because their vasculitis clinic is a Centre of Excellence, they do seem to have access to drugs that other hospitals struggle to get ( I think they do a lot of drug trials and research as well which probably helps ).
Have you ever had any other treatment such as Mycophenolate or Methotrexate ?
I was on Mycophenolate (CellCept) from dx in Apr-13, then changed to Azathioprine (Imuran) in Sep-13 after getting a chest infection, to see if that was better at controlling my immune system. I had 2 more inpatient chest infections in Oct-13 and Dec-13, so Azithromycin (background antibiotic, 3 times/week) was started in addition . I've had no further inpatient chest infection stays for 15 months, but did have 2 slight infections which extra antibiotics fixed.
So the plan is to decide how to reduce the CSS activity, as measured on limited symptoms (breathlessness, purpura & muscle/joint ache) and out of spec CRP, without compromising anything else. I'm lucky that I never have any allergies or side effects to any drugs.
So that is why the possibility of trying Rituximab to replace the current Azathioprine is being suggested.
Hello, Jonty. I have MPA that is ANCA negative - initially causing acute kidney failure. I was treated by Azathioprine ,which reacted against my liver so then Mycophenalate but relapsed while on that. Rituxamab was never mentioned by my kidney consultant so I asked my GP to refer me to Addenbrokes in Cambridge who treated me with Rituximab
That was 18 months ago and I have since been in remission.
Hi, Jonty. No, Addenbrokes said being ANCA - or ANCA + made no difference to being treated with rituximab although other criteria, such as reactions to previous drugs and relapses were taken into consideration. I was diagnosed in 2008, eventually had two rituximab infusions in 2013 and ,so far, have not needed another one. I still attend Addenbrokes - who have told me the Vasculitis in remission, as well as attending my local kidney unit who originally diagnosed the MPA by kidney biopsy, for ongoing care of the kidney disease and they also monitor for Vasculitis. The drugs that I'm on at present are mostly for kidney disease + hydrocortisone replacement therapy as I was on prednisolone for so long that my body stopped making its own steroids. So, I feel the rituximab really helped me. However, I'm sure many with this illness will tell you, we are all very different, the illness can be different in each individual and what works for one person may not work for another. Hope some of what I have said is of some help. With best wishes. Trebar
To me, telling the V. patients that you cannot get Rituximab because you are Anca- is just simply unacceptable. It's only a cost cutting measure. Perhaps, Addenbrooks may be far better funded due to its status. I honestly don't know.
Not all types of Vasculitis can be defined by ANCA positive or negative. I have Takayasu's which is difficult to define by blood tests, so does not fit the criteria that NICE work on. I'm on steroids, but reacted badly to both methotrexate and cyclophosphamide, so had to go onto rituximab. Some of the decision seems to depend on how your consultant understands the criteria - so if you have a good relationship with him, I think you should discuss all the different bits of information that you've gained by your question. Hope it works!
Personally I've not had a problem with NICE. I didn't fit their initial criteria, but when I proved that the alternatives made me more ill, they seem to have made an exception. The rituximab has been pretty good on the whole, so I hope they will widen the regulations to include ore people.
Sorry, Bronte, what I really meant was NICE's Guidelines for diagnostic criteria (not ref. V) -it was totally "off topic" I know. Luckily, some MDs are aware of this and would be willing to work around NICE shortcomings. This comment essentially has hit the nail to me: "so does not fit the criteria that NICE work on" - their criteria is not too well formulated and not correct missing things out. There are so many "exceptions" which fall outside their simple "criteria" when patients suffer from the illness. However, according to the NICE Guidelines, simply you don't have the illness as you won't fit the criteria. Big problem. NICE's guideline criteria do have a tendency to exclude people who have the illness. Their criteria needs constant updating when new info becomes available (which is very common in medical science) rather than keeping the outdated criteria as absolute to confuse people. In particular, in autoimmune diseases which are so complex hard to diagnose, they need to keep an eye on inadequate criteria which may need updating. Thank you for sharing.
Thank you for that, Ferntree. I suspect a lot of the problem comes down to individual consultants. The first one I saw insisted that MTX was the only available treatment, and the only way to take it was by mouth. I had to swap hospitals because it was making me so I'll!
That's terribly so kind, Bronte xx Really...?? I must say, I was the only one who had so much trouble with some Rheumy M.Ds with their fixed opinions (often mixed with unscientific excuses..) It's so so tricky... I know I wouldn't tolerate oral MTX myself. What a struggle!! Thank you for your helpful comment. Glad that you were able to receive the care you fought to get xx
I think that part of the problem is that Rituximab hasn't been evaluated for ANCA negative vasculitis and the evidence for it's use may not exist in the same way that it does for ANCA +ve. Obviously Addenbrookes, as a centre of Excellence, use it for other types but that will only be after careful consideration and because they have a wealth of experience.
These decisions are clinical ones, cost is only one consideration.
i've spent much of the afternoon doing research on this subject and the NICE guidelines list many links related to the results of clinical trails of RTX versus AZA, and one paper list the key unanswered questions of these as ...
"Unanswered questions regarding the use of Rituximab in AAV
In addition to questions surrounding the use of RTX for remission induction in EGPA and for remission maintenance in GPA and MPA, several other questions remain regarding the use of RTX in AAV.
1) First, given that all of the patients studied in RAVE and RITUXVAS were ANCA positive, it remains unclear whether RTX is also effective in ANCA-negative patients.
2) Second, it is not yet established whether RTX has a clear role in the treatment of limited GPA and MPA, as both RAVE and RITUXVAS included only patients with severe disease.
I am ANCA -ve and also have 'mild' CSS ... so not too sure about the evidence. Anyway I'm sending these conclusions to my consultant (who I'm sure is aware of this) to get his response. Isn't the interwebwebweb absolutely brilliant? I spent my working life in the silicon chip industry (semiconductors) and believe that I may have made a small contribution to this communication miracle
Hi Jonty. I'm across the big pond in the States and was diagnosed 18 months ago with MPA with kidney involvement.
I have undergone two sets of Rituxan infusions, at 4 rounds each (6 months apart). My most recent round of infusions began in January while my ANCA was still negative. My creatinine levels, however, were steadily on the rise and the aching pain in my joints had become debilitating.
The Rituxan infustions changed all that.
I will not see my nephrologist until June. In the meantime, she will be researching what lab work is required to test for B cells. (A cell that is destroyed by Rituxan and seemingly linked to Vasculitis/MPA.
I have been having Rituximab for the past 6 years and have been ANCA - since diagnosis over 16 years ago. I attend Addenbrookes too. I have Wegeners and I have the infusions every 6 months to keep me in remission.
I've spent much of the afternoon doing research on this subject and the NICE guidelines list many links related to the results of clinical trials of RTX versus AZA, and one paper lists the key unanswered questions of these as ...
"Unanswered questions regarding the use of Rituximab in AAV
In addition to questions surrounding the use of RTX for remission induction in EGPA (CSS) and for remission maintenance in GPA and MPA, several other questions remain regarding the use of RTX in AAV.
1) First, given that all of the patients studied in RAVE and RITUXVAS were ANCA positive, it remains unclear whether RTX is also effective in ANCA-negative patients.
2) Second, it is not yet established whether RTX has a clear role in the treatment of limited GPA and MPA, as both RAVE and RITUXVAS included only patients with severe disease.
I am ANCA -ve (but being retested next week) and also have 'mild' CSS ... so not too sure about the evidence. Anyway I'm sending these conclusions to my consultant (who I'm sure is aware of this) to get his response. Isn't the interwebwebweb absolutely brilliant? I spent my working life in the silicon (computer) chip industry (semiconductors) and believe that I may have made a small contribution to this communication miracle
Thanks for all your useful comments, and I think the key points are ....
1) There is little trial data based on -ve ANCA cases
2) All the trials were done on 'serious' cases (affecting main organs), and mine is a mild severity, but still doesn't seem to be responding after nearly 2 years.
This trial result sent by Susan appears to be the latest results and included -ve cases ...
I've got my blood test results back which show liver marker ALT is still in spec even though I'm on 150mg AZA (Imuran), but CRP is still high at 52 and so has been out of spec for the last 5 months. So now waiting for the ANCA test result which I think takes longer to be done.
Then we will have all the data to see if RTX is a possible replacement for AZA.
Last question: If NICE will not fund the RTX treatment, is it possible for me to pay for this privately, and if so, how is this arranged?
Hi , I've read a paper by a renowned doctor who states that Rituximab can cause flare ups and that there's incriminating evidence that it can actual advance CSS in negative ANCA patients . I've spoken to the consultants responsible for my care and this new insight . They seemed to be of the same opinion that Rituximab is not for negative ANCA patients . There does not seem to be any consistent written approach concerning this issue so I think the only thing we can do is to trust the consultants . I hope this helps somewhat . Regards Mike .
Well, I'm ANCA negative as it happens, but as I have CSS / EGPA which involved nerves, heart, lungs, bowel sinuses and skin, the consultant Tim Howell at Plymouth Derriford hospital got the go-ahead for RTX for me after Cornwall / Devon peninsula agreed to fund RTX for vasculitides which didn't respond to the 'cheap stuff' (my words).
I was treated with CYC to start with + big steroids, then azathioprine maintenance (no good),
Mycophenolate (no good),
then methotrexate (pills from hell - permanent loss of breathing capacity - so now got COPD with less than 50% of normal breath in 1 second. 'Thanks a lot, methotrexate'...
so I stopped MTX and went back to T.H. at Derriford who spoke to Dr / prof Jane at Addenbrookes, who advised RTX would be suitable. I have now had a couple of years at 2 x infusion courses and this Nov I go on to the 1 - per - year regime. I am gradually climbing back to something resembling fitness but it has taken since 2007 when I was diagnosed. It is B---dy Hard but I'm not giving up. Weirdly, my eosinophils are still there (I thought RTX was supposed to stop their production) and always at levels on high side of normal. The COPD has meant a lot of chest bugs - about 1 a month - but I've pretty much fixed this by taking 4,000 or 5,000 i.u. of vit D3 a day - it only helps the COPD itself slightly as the damaged alveoli thingies are supposed to be unrepairable - but most importantly it helps keep the bugs out by making it hard for them to stick (you can read the science if you like - I've simplified here).
Down to 6mg a day of preds as of writing this and this reduction - from 35 or 40 a day - makes me feel less tired, for sure!
Watch what you eat, too.
Hope you get at least a try at this RTX treatment.
maybe my stuff re helping damaged lungs may help someone else in the same boat?
Many thanks for the detailed feedback and you certainly seem to have gone through it with an obviously severe case of CSS / EGPA.
An update on my situation (16-May-15): The latest ANCA test came back still negative, and just yesterday I got a letter from my consultant stating ...
" I have been back through your notes and you have only had Azathioprine & Mycophenolate for your vasculitis.
Being ANCA negative does make things a little awkward but if we need to give you Rituximab I am sure we could find a way. In the meantime I think Methotrexate would be the next option to consider, as it is fairly high up the order in the current ANCA vasculitis guidance.
I look forward to discussing things in clinic on 1st June"
He attached a hard copy of this paper called .."BSR and BHPR guideline for the management of adults with ANCA-associated vasculitis" ...
Note in this paper the definition of remission....
"Definition of disease states
------------------------------------
Remission: well-controlled disease.
(i) On drug remission: prednisolone dose <=10 mg/day
and a BVAS <=1 for >= 6 months.
(ii) Drug-free remission: >= 6 months off all treatment
for vasculitis."
So I will get latest bloods done in 2 weeks and depending upon ALT and CRP we wil decide whether to change from AZA to either MTX or RTX. I'm now down to 10mg and all is good so far, so fingers crossed.
BTW: I know Derriford Hospital well since we lived in Plympton for 18 years before moving back to Hampshire in 1998. So I visited it regularly due to 999 visits with acute asthma attacks and I'm also a Type 1 diabetic for 46 years now.
I have variable memories of that hospital and was not impressed with the food I experienced as an inpatient. I'm very lucky now that my local hospital is Frimley Park Hospital (15 mins drive away), and they are rated the Best Hospital in Southern England, and are first class in every respect, and especially the food! They are not a vasculitis specialist hospital but I was dx two years ago after just 30 mins examination / questioning by my chest consultant after being in Stage 3 for about 3 weeks. So I am impressed with their knowledge and treatment.
Good luck with the MTX if that's what they decide. As you're clearly quite a serious asthmatic, keep an eye on your peak flows and breathing comfort in case you get MTX lung as I did! If your breathing deteriorates / drops, can I suggest you go back to the doc... sharpish just in case?
Interestingly your comment ..." As you're clearly quite a serious asthmatic, keep an eye on your peak flows.." relates to a quick survey I did yesterday on another support group, which is solely for Churg Strauss Syndrome (CSS / EGPA) patients.
Firstly I no longer suffer from asthma since the use of long term inhalers has kept it under control for the past 30+ years. But for somebody with CSS, that is rather unusual, as my survey showed. So on a site with 555 members who have CSS / EGPA, I asked ... "who currently suffers from asthma", and only about three are like me with no asthma problems. CSS patients all have shown a background of late-onset asthma, and almost 'all' still suffer from quite severe asthma as well as CSS. But just a few of us are free from such severe asthma and it is not quite clear why that should be.
Hi Jonty, all I was thinking was, if your asthma is under control that's great! but if it is still there 'underlying' the asthma drugs, keep an eye out for any lung effects from the MTX. . In my case, it's asthma plus COPD from the MTX.
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I agree with you. NICE is rubbish. I know this in my direct experience with another condition. 
I must say, I was the only one who had so much trouble with some Rheumy M.Ds with their fixed opinions (often mixed with unscientific excuses..) It's so so tricky... I know I wouldn't tolerate oral MTX myself. 
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