I saw the rheumatologist last week and after 5 months of Benepali she says it's not working and stop taking it immediately. For about 10 weeks Benepali was really good and I felt a lot better but for the last 2 months have increasingly been going back to as bad as it's ever been. She reckons my body has produced the anti-bodies, in spite of taking 15 MTX alongside... so no point trying any more anti TNF drugs she says.
I felt very hopeful starting biologics, especial during the wonderful time when they worked but it's hard to maintain optimism for the next one she wants me to try..Tocilizumab. Apparently it goes for a new target. How many targets are there? This one is the IL-6 protein it says in the leaflet. Does this mean the anti TNF is just left to get on with it ?
She also mentioned Jak inhibitors....
In less than 2 years I will have tried 4 different drugs, none of which seem to have worked. It's getting easy to imagine reaching the end of the line.
( Could it be good thing, the ability to produce anti-bodies so speedily ? Immune system still taking an interest in what's going on )
I am going to have a depot steroid injection on Monday and take some time off during the drugs intermission, walk by the sea..
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Im sorry I dont know about biologicals as on NSAIDS & DEMARDS totaling 9 but so far helping me to function, albeit limited with pain, but told I dont qualify for anything else. Someone on here will be able to discuss with you knowledgably.
Oh dear..... having just started on a biologic and it working well (I think) this is my nightmare.
You could imagine the immune system like a machine full of different cogs whirring around, and our machine has got out of control so the cogs are whirring too fast. Anti-TNFs stop one particular cog from going too fast, So that slows the whole machine. Sadly something has put a dose of oil on that cog so it's whirring away again....
But the are other cogs, and the other biologics target these different one....one called IL-6 (interleukin 6), and also interleukin 1, one is B cells, one is T cells, and also the JAK (janus kinase). Altogether there are 6 different types of biologics at the moment, that target 6 different types of cogs. And more being developed all the time so hopefully you'll find the right one for you.
Am I correct in thinking that anti-TNFs such as enbrel target more than one of these cogs? As you are probably aware I was prescribed baricitinib in the hope that it would reduce the risk of getting an infection, which I'm prone to, compared to other anti-TNFs. I'm not 100% sure I heard the immunologist that I was referred to correctly, but think he said something to the effect that JAK Inhibitors target just one specific cog as mentioned in your post , whereas other anti-TNFs target more than one. I can't swear to it, but think the words he used was they tend to blanket bomb the immune system. Just to clarify as I'm not the best at explaining stuff in writing, I'm talking about one specific anti-TNF, let's say benapali, stopping more than one of these cogs whirring too fast.
Thought I wasn't too far off from hearing him right, thanks helixhelix.
Glad about that, as they think there's a chance that might help reduce the risk of getting an infection, at least that's my understanding of it. The main reason my rheumy likes it is if I should get an infection and have to stop taking baricitinib then it leaves the body pretty sharpish, much faster than other meds apparently.
thanks Helix. That's enlightening and somehow encouraging as well as being a great description. So if the cog is vital enough then slowing that particular one down disrupts the whole thing ?
How do you learn all this ?
I tried to ask the rheumatologist about it and she looked bemused & told me at length how we all respond differently but I may have put it in a very confusing way.
It's only a rough analogy for some horrendously complicated science.... but yes my non-scientific understanding is if you can influence a cog in the immune system chain it will have knock on effects.
Thank you for your superb posts, they are always so helpful. Whether you are a science nerd or not, you are an angel to be helping us all, greatly appreciated
Hi Rosey, A walk by the sea is my idea of pure bliss! Enjoy it! As for biologics, great description by HH ! I also understand that the Immune system still taking an interest as you said isn't all bad. It's main function is to fight infection and alot of the cells produced are doing good. There are one or two that do the wrong thing and that's where the drugs come in. Do you have a choice of your next biologic? I'm on Baracitinib 4mg per day. It's been more successful than Benepali for me. I still have days of swelling and my legs /feet ache every day but think that's more to do with Fibro. Try not to get too disheartened. I'm not far behind you! I am positive you will find that one! Keep going and stay strong. We are always here. Xx
Hi Shalf. Thanks for your support. I was not offered a choice and did not think to ask for one. She said the Tocilizimab is very similar to Benepali in terms of risks and side effects. Yes the sea is always soothing even when you can only sit and watch it.
Sorry to hear that rosey, bit soul destroying. I’ve been on benepali alone for about 11 weeks & feel so much better than on MTX and Hydroxychloroquine (less fatigue, more energy, sleeping through night). I know they can stop working & dread same: it’s my third drug in just over a year & first without awful side effects so really feel for you. Do hope the next one is your magic bullet🤞X beautiful beach: reminds me of Cornwall.
I know just how you feel, you start these drugs with so much hope invested, and it's really cruel when they don't work/ stop working/ produce side effects etc etc.
Please don't lose hope, I have been on many NSAIDs, and on my 5th biologic. As HH says, they all target different things, and it is so worth persevering till you find the right one/combination.
The biggest problem imho is that it takes so long for each treatment to kick in, and to discover whether it's the right one for you.
I hope, fingers crossed, that I have found it for me, and feel sure that you will get there too. One step at a time!
Thanks for your reply hatsheput. Yes I guess I am just in the hopes dashed phase but feeling more optimistic from these replies and ready to try the next thing. Maybe this will turn out to be my cog. I hope you will find you have got there now.
Hi Roseyx I have been injecting myself weekly with tocilizumab (Roactemra) for a year now and I can only tell you how it has affected me personally. It has been a miracle drug, reducing all my inflammatory markers and improving my red blood count, and all my blood results have markedly improved. It worked within a matter of weeks and my mobility, pain levels and joints have all improved. This treatment was agreed between my rheumatologist and cardiologist as a 5th line drug against my severe RA which had only responded for limited periods to multiple drug combinations in the past. Before starting this new drug I couldn’t walk or weightbear, was in agonising constant pain, used a wheelchair to get around and was desperate to find something to help. I have had RA for 35 years, have had 5 joint replacements, and suffer from heart failure all down to RA. My life has transformed and I hope that should you decide to start this treatment your outcome is as good as mine. It’s hard to be positive with a debilitating chronic disease however I take comfort from the fact that there are new treatments being offered all the time and I’ve always been open to try something new. Hope all goes well with you whatever you decide.
Hi Mcleish, thank you very much for posting your amazing story of improvement on tocilizumab. It's alway puts one's own concerns in perspective to hear how very bad RA can be for others. It's great that this drug has brought you so much relief after all these years.
I will be try & be open to what ever happens next and definitely intend to start tocilizumab but the rheumatologist says I have to clear out benepali for a couple of weeks first.
Hi roseyx hope you have an easy time and no flares off benapali. The reason I wrote was tocilizumab isn’t a drug of choice for most rheumatologist and I was also very wary about starting it. I’m glad I gave it a chance cos it’s been the best so far for me. Everyone’s RA responds differently and I so hope this works for you , I know how painfully frustrating it is to keep having to change meds. When myself and my sister were diagnosed treatments were limited and it wasn’t treated aggressively like it is now that’s why we both have had so many joint replacements. Only in the last 15 years have I seen a massive improvement in early intervention Keep well and take care of yourself there’s a treatment for you out there and you’ll hopefully get there soon.
The biology behind RA isn't understood very well... but one study found that there are elevated levels of a molecule called TNF in the joints of people with RA, so they created one group of biologics to block this molecule (TNF is know to be involved in inflammatory signalling between your immune cells).
There are some other molecules that we know are involved in the inflammatory pathway including JAK and IL6. So a different group of biologics block these molecules from signalling to immune cells to lead to inflammation.
The problem is that our bodies produce antibodies to ('naturally') block foreign molecules which our immune system thinks are bad. While you are on biologics your body might mount an antibody response against your biologic drug, producing an antibody which blocks the action of your biologic which was trying to block the initial inflammatory molecule (be it TNF/JAK/IL6). This is when your rheumatologist might move you to another class of biologics. This is also why you might be kept on a mixture of drugs like methotrexate in addition to your biologic - so your immune system sees loads of new molecules and might not be so quick to make an antibody against any one of them.
I was changed from enbrel to benipali was on it for a few months didn't work. explained to my rhuemy nurse and she arranged for me to go back to enbrel. She told a few more patients were changing back to their original biological . I'm know so much better. Iwas also told it could tske over 12 weeks to work with any new bio drug and if it doesnt work there are others to try. Go back and ask if you can try another one. I've also been on humera (sp) and changed back to enbrel so there is hope
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