Leflunomide Not Working

I have been on the Leflunomide for a year now and for 4months on an increased dose, and I am having a nasty flare which started on 21st Dec. At the same time, my blood test results showed up some renal issues and I have already had increased blood pressure, both of which are side effects from the Lef. I spoke to Rheumy today and he agreed that the Lef. isn't working and I will come off it. He mentioned trying Mycophenolate once the Lef. is out of my system and commented that my PMR is "Refractory" (meaning stubborn) and that I am quite resistant to the Pred. Both of these are bad news! The only other option he can see is to apply for funding ,which I may not get, for Toxilizumab .

I think he is worried that I am needing too much Pred. I keep flaring every time that I get below 11mgs and I have lost count of how many flares I have had in the last 2 years. I don't seem to have made any progress, despite doing very careful reductions and have had PMR for nearly 3 years now.

Any information about Mycophenolate would be gratefully received and any other words of hope or comfort while I am feeling a bit hopeless about ever making progress with either the drugs or with the PMR reducing or dying away.

11 Replies

  • How do you reduce Suzy? Why is the rheumy so desperate to get you lower? And looking at your picture - not being rude, but what do you weigh?

    I have had PMR for over 10 years now. For 5+ years I had to manage it myself, all visits to the doctor resulted in "your bloods are fine, there can't be anything wrong". Eventually, it went totally pear-shaped overnight but I still got the same from the doctor - and a prescription for voltarol suppositories! Yeah, right.

    After nearly 6 months of agony, the hip bursitis was the worst, and many hours of reading on the internet, I presented myself to the GP with "Could this be PMR?". He sent me to a rheumy who wanted it to be anything but PMR - but he DID give me 6 weeks of pred with a 15/10/5 reduction. In 6 hours I was almost entirely pain-free - but he wasn't interested. He wanted to use sulphasalazine. A different GP said fine, that's good enough for me, here's your prescription for 15mg pred. And I worked from there.

    I got to 9mg every time fine - but it was impossible to get any lower, 8.5mg just didn't work, however I tried. Then I was switched to Medrol (because I moved to Italy, no other reason) and it was hell on earth: you name the side effect, it appeared, and after 5 months I was in the middle of a major flare - while taking 20mg. It didn't kick in until mid afternoon unless I took it at night and even then it was not doing much. It was as if my body just didn't accept an antiinflammatory effect.

    My GP suggested we tried with Lodotra, just a different formulation of prednisone taken at night, the only other corticosteroid available here. I started on 15mg - I had the same response as with the original dose of pred. Over the last 2 and a bit years I have reduced to 4mg, 3mg is a step too far. I have from day 1 used the "dead slow and nearly stop" reduction plan I keep banging on about. It works for me. Any faster and it doesn't.

    I know from reading and discussions with experts that:

    1) It is now being accepted by some experts that maybe weight has a bit more to do with the required dose than was previously thought. Everyone reacts a bit differently to the same dose anyway, the 15mg that works for a 70kg lady may not be enough for someone who weighs 85kg (I weighed more than that at 5'1") and it is especially so if there is a lot of fat around. I'm not assuming either that or a weight here but your 11mg may be achieving the same as someone else's 9mg.

    2) It is impossible to know really whether the slow reduction was what made the difference for me, it may just be the PMR has gone into remission but I don't think it has - what I do know though is that a lot of other people can't cope with even tiny reductions in pred and seem to flare at the drop of a hat.

    3) For well over 3 years I was at doses above 10mg, a lot of the time nearer 15mg. The rheumy here and the GP have been totally laid back about it. It doesn't appear to have affected my bone density, I'm not even remotely pre-diabetic and my cholesterol has now fallen along with my weight.

    What I'm saying is simple: after 3 years you may simply not be ready to go below 11mg - it took me far longer to get to below 10mg without problems. It may not be you are resistant to pred, it may not be "refractory" PMR - noone here ever suggested that to me. It was just it was a very active disease that needed more pred. My body was super-sensitive to messing about with the dose. And some of the apparently PMR pain was not directly the PMR, it was bilateral hip bursitis and myofascial pain syndrome, and as soon as that was targeted more specifically with cortisone injections and manual treatments the whole picture brightened bit by bit. The bursitis improved dramatically, the MPS slowly improved so I went longer between the need for cortisone shots in my back muscles and it is now a year since the last - before I couldn't manage more than a couple of months without a treatment. And I have steadily reduced the oral pred.

    I believe that you need more than just oral pred for many PMR cases. Rather than increase the oral pred to a level that covers it all, there is a role for more specific treatment to even out those bumps. I know a few doctors who agree with me. I heard a lecture in Austria a couple of years ago, when I was still on crutches because of all the problems. That was a confirmation of the basis of my theory - I've been able to try it out. Anecdotal evidence I know - but I see it happening with others too.

  • Thank you PMRpro. Yes, I think weight is probably an issue here as that picture was taken before I put on 2.5 stones with the Pred.! Dasgupta acknowledges this as a factor but still seems very concerned at my Pred. intake. I have reduced slowly but not at the slowest pace as I have kept being promised that the Lef. Is working. Now, I do have the opportunity to stop taking any extra steroid sparer and reduce at the slowest rate, or do I try the Mycophenolate? I have not shown any signs of diabetes or osteoporosis yet but have put a lot of weight on, which was the last thing I needed. I am not sure about bursitis. I have recently been diagnosed as having OA of the right knee which has been really painful. A cortisone shot from the Prof over a month ago has helped a lot but I am still very restricted. My right hip has been an issue since before the PMR, but I wouldn't say that it is specifically a problem. My biggest problems are more the fatigue and the fact that I cannot tolerate much exercise without pain afterwards and generally feeling very sore thighs and hamstrings and hips all the time. Does that suggest myofascial pain? And, if so, what do I do about it?

  • You sound just like I was 2 1/2 years ago - except I was on 20mgs Medrol! In the autumn I'd decided that if things didn't improve a bit after xmas I would invest in a mobility scooter as I couldn't do anything! The Lodotra did make a big difference to me and as soon as I started it the weight started to come off: at the amazing rate of about a pound a month! But the fluid retention did improve a bit. I then combined the 5:2 diet with cutting carbs drastically - neither on its own did much, both together did, and I achieved the dizzy heights of 2lbs a month. I've now lost just slightly more than the weight I gained on pred.

    In retrospect, I think the myofascial pain syndrome was the biggest culprit. It stopped me walking far at all and the pain definitely was exhausting. That, and the hip bursitis. I asked the doctor I was seeing for follow-up for the atrial fibrillation what I could take for the hip pain (basically: nothing) and before my feet could touch the floor I was in A&E to see the duty orthopod to get bilateral cortisone injections in my hips. It took a few days for that to work but the difference was amazing. I had another pair of shots from my GP about 3 or 4 months later - the effect has lasted well over 2 years.

    Yes, your description of the back and upper leg pain does sound similar to what I had. My entire back was as hard as boards, with several muscle groups in spasm. The low back spasms were causing referred pain across my back and into the thighs which was different to the bursitis pain but it all seemed to merge into one at times. I couldn't lean forward to do anything without excruciating pain across my lower back which then took days to fade at all. It was a dose of that that had me admitted to hospital to deal with sacroiliacitis the quick way using infusions of pred and diazepam - it certainly worked quickly but I had a bad reaction to the i.v. diazepam so they had to stop that before the course was finished and I was sent for the slower option.

    I had cortisone shots into the trigger points plus the anaesthetist pain specialist did small amounts of manual mobilisation - you have to be wary, the mobilisation releases the cytokines and you feel as if you are having a flare of the PMR as they get into the system. In the UK I had used Bowen to mitigate the MPS, but that wasn't available here. However, I did get some physio at the hospital and she worked on the knots of muscle fibres. One day I got a student who did a real sports massage on the hard bits - and I have a friend here who is combined physio and sports massage trained so I've had a couple of sessions from her. I found that really helped - apart from needing 2 days to recover from the sore shoulders! I then went back to the pain specialist every month or so, then had a break of 6 months with a final session a year ago.

    I honestly don't know how you can access all of what I had here in the UK - Bowen certainly, a sports massage/physio is probably the best way to get the mobilisation work done. There is a BIG difference between just physio and sports physio. I had had similar work done years ago in Germany - just by the local physio who happened to be physio for the football team, but that did take a lot longer than the cortisone injections took this time. GPs can do some cortisone shots but what I had was effectively all over my back and is called needling in the US - no idea if anyone in the UK indulges in it.

    You really do have my sympathy because I know all about the pain - I don't think I will ever forget it and I definitely don't ever want to go there again. But it really did seem that once the specific spots were calmed down with cortisone injections the oral pred worked more effectively and a lower dose was possible. I've come across a few people now who have been put on "steroid sparers" and initially been able to reduce - and then wallop, another flare galloped over the horizon. I think that it also makes the body less responsive to the pred because of the yoyoing of the dose - the Americans warned about getting into that spiral several years ago. By the way - is it REALLY OA? I was told when I first developed PMR that it was all OA, the very dismissive rheumy claimed she could "feel it in the knee". Ten years later there is absolutely no evidence of OA in that knee that anyone here can find. I am sure it was bursitis, as was the hip.

    PS - Dasgupta did the initial study where they got 22 out of 23 patients into remission using leflunomide. I now know at least 3 other people who have been on it, for 2 of you it did nothing, for the other one it worked well for a few months but then life-threatening side effects appeared so he had to be taken off. He must be very disappointed.

  • Dear prmpro, I am new to pmr and struggling. I have been reading many posts here that all have such good and valuable information. My question is about the cortisone injections and manual treatments that brightened your picture. Since I don't know if I have anything except pmr causing shoulder pain, have you heard of any information that states that cortisone shot into affected painful area could help reduce the inflammation (along with the oral pred of course). I think Eileen alluded to the possibility of this now being considered by some. It does make sense to me to put the cortisone right into the inflamed area. Actually, I am desperate to try anything and all modalities that might help and won't hurt.

    Can you elaborate on 'manual treatments'. Are you referring to a specific type of massage? Thank you for your expert help. You have had this disease for a very long time. Do you have any good days? Can I hope to get over this pain someday, having just started on 15 mg of pred 4 days ago and having only some relief not total miracle relief like most state. Thank you.

  • Of course I have had good days - even in the early days without pred I had better days. It is the nature of the beast.

    If after a week of 15mg you haven't had a 70% improvement overall in symptoms then maybe you could ask your doctor to try 20mg. However - you have to do your bit too. Just because you are on pred does NOT mean you are now perfectly healthy and can start to catch up on all the things you haven't been doing because of the pain and stiffness. Do that and your symptoms will get worse not better because your body is intolerant of acute exercise - you have to be patient and you have to do your bit. Even now after 5 years on pred and down to 4mg there are things I do at my peril. Mainly housework ;-) - using a vacuum cleaner or sweeping brush is fatal!!!!!

    If you have bursitis in the shoulder then a local cortisone shot is likely to help that faster than waiting for oral pred to work - for me it took months on oral for the bursitis to fade, it did go eventually though. Don't however assume that a cortisone shot doesn't hurt - it can do. All I can say is, if you have a practitioner who will try it, go for it.

    By the way, some of us frequent all the forums ;-)

  • Good luck with the new drug. I start taking Mycophenolate today. Slightly anxious about it, I will post on the forum if I get any adverse reaction. Not expecting much for a while as I understand it takes 2 -3 months to take effect.

  • I started Mycophenolate almost 6 weeks ago as keep getting flare ups at 25 mg Pred. I have pmr & gca. Easier to take than Pred but just discovered at weekend I have shingles which is a side effect. Bloods need to be done weekly too.

  • Poor you having to deal with shingles. I had it at the back of my head about 20 years ago and ended up in hospital with cellulitis too. It is horrible and I certainly don't want it again! I didn't realise it was a possible side-effect, nor that you need a weekly blood test. That may be enough to put me off, but do keep us posted about whether it helps or not.

    PMR pro- The Othopaedic surgeon diagnosed OA of my knee from an X-Ray but I am also having an MRI scan of it next Friday, so, hopefully if there is anything else there, it will be seen.

  • The risk of shingles is raised with almost all immunosuppressants.

    No, I have to say, a weekly blood test would put me off! I have one vein you can get blood out of - bashing it weekly instead of monthly wouldn't do it any good at all! They spent over an hour looking for a vein in the other arm when I wanted to donate plasma and there was nothing else any good!

  • The blood tests are only weekly to begin with like all immunosupressants and then they go to 2 weekly and monthly if everything is ok.

    I don't think the risk of shingles is higher with MMF than any other type of immunosupressant. I took them for 3 months without any problems and if you go onto the VUK Health unlocked page and ask there are lots of people on there take them. MMF has revololutionised the lives of a lot of patients with vasculitis and the side effect profile is low.

    That said I do think PMRpro has given you food for thought. Personally speaking I would much rather take an immunosupressant than prednisolone! We are all different though and it's almost certain now that I don't have PMR so feel free to discount my opinion.

    I truly hope you do manage to feel better soon Suzy.

  • Hello suzy 1959 .. We have been in touch with each other in the past and I am so sorry that you are also going through a bad time .. I had to come off of Leflunomide and I'm now back on 15mg Methotrexate injections .. We are so similar in the way we have PMR .. What you describe when you go below 11mg steroid is how I am at 14-14.05, I wish I could get to 11 mg because that would be an achievement . Yes my PMR is definetly stubborn , frequent flares on the way and feeling like an alien because my body won't let me get down like other people . I hope you get some funding for the new medication.I've never heard of it. I am thinking of you hoping things improve for you soon ,like you I try and do careful reductions and after nearly 11 years with PMR I think I've tried every trick in the book and always eager to learn new tricks and pray that new medications can help . I see my nice Rheumatologist next week ,I hope he will be patient with me ,I'm expecting him to put me up higher on the methotrexate but with the giddiness and the bad fall I had before Christmas we will see. We have a whole new year in front so slow is the motto.. Good luck and hope you're feeling better soon.. trish29

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