QD 67 - Part 3, EULAR RA Treatment Guidelines Save
QD Clinic - Lessons from the literature
Part 3 2020 EULAR Recommendations for the Management of Rheumatoid Arthritis
MTX, GC & T2T
Features Dr Jack Cush
https://youtu.be/TzZxMKw92Ds
Transcription
QD clinic is brought to you by RheumNow Live. RheumNow Live where the audience matters. Did you know that at RheumNow Live, have sixteen hours of CME, and nearly five hours of that sixteen hours is devoted specifically to q and a between the audience and the panel, the panel being the faculty in each of the sessions we're going to have on the various disorders, rheumatoid, we have two on rheumatoid, psoriatic arthritis, ankylosing spondylitis, lupus, etcetera. So, again, be part of the audience. I think you'll enjoy it.
In this edition, we're going to talk about, again, EULAR twenty twenty recommendations on the management of rheumatoid arthritis. This is part three in a series where we're going to review the specific recommendations. Yesterday, we reviewed recommendations one through three, and now today we're gonna review four through eight. But first, before we do that, recognize that in considering your treatment options, the UR guidelines will point to something called poor prognostic factors. And is this an issue when you're managing your patients with rheumatoid arthritis?
Many of you would say yes. What are poor prognostic factors? There's a number of them that's been previously defined, but includes persistence of disease activity despite therapy. Second, high, usually very high elevations of sed rate and or CRP. Next is a sustained high swollen joint count.
Third is high titers. Fourth is high titers of rheumatoid factor and high titers of CCP antibodies. The presence of erosions obviously, is an important factor. And then lastly, failure of two or more disease modifying therapies. Any combination of these would constitute someone who has a poor prognostic factors or list of factors that will weigh on the outcome and may require more aggressive therapy.
So let's get into the fourth recommendation on the document provided by the analyst for rheumatic disease. Number four, methotrexate should be part of the first treatment strategy. This was in the prior guideline. Obviously, methotrexate first. It's methotrexate or die.
If someone has RA, they need to be on methotrexate unless there's a strong contraindication. Why? It's our best drug. We have a tremendous amount of experience with this drug. We know what it will do.
We know how long it takes. We know how to dose it. It is not just the first drug to start. It's the anchor drug upon which you build other therapies going forward. Someone doesn't respond to methotrexate and you're gonna add on.
Turns out, if you take methotrexate away and just add on another therapy without methotrexate, they don't do as well as keeping them on methotrexate. Yes. That's the drug that they didn't respond to. So it's the anchor drug whether you're going to add on glucocorticoids, a conventional DMARD, a biologic DMARD, or a synthetic targeted synthetic DMARD. Again, what's the dose?
I start at fifteen milligrams. Some people still start at ten or seven point five. Recommendations say the goal is to get to point three milligrams per kilogram and that you should escalate the doses every four to six weeks trying to get to a target dose. In The US and and The EU, that's generally a dose of twenty to twenty five milligrams per week. In Southeast Asia, it's a lot less being around ten milligrams or a little bit more.
Obviously, starting methotrexate mandates that everyone should be on folic acid. Folic acid has been proven to, number one, reduce the amount of discontinue discontinuations. Number two, reduce the amount of LFT elevations. And number three, no, it doesn't lower oral ulcers and nausea, but and again, that's how everybody uses it. How you use folic acid or folinic acid is up to you.
There are many regimens. They all work. And lastly, because methotrexate is so important, and because patients will read about it and think it's a cancer drug, patient education is very important. I love to say that methotrexate is a drug that we love and that patients hate because of what they read and what they're worried about. A few caveats on methotrexate.
When you're gonna be at fifteen milligrams or above, you either need to switch from PO to sub q, or what I do is go to split oral dosing. So at fifteen milligrams or higher, oral dosing has variable, absorption. But if you keep that at seven and a half to ten milligrams and then do it bid on every Wednesday, you get almost a 100% absorption just as you would if you went to a parenteral administration. Second, the things that screw up the use of methotrexate by patients are two key features. One, oral ulcers, queasiness, GI manifestations.
The treatment there is vitamin A. Eight thousand units a day, it works incredibly well. Stop me and ask me about it, I'll tell you about it. Second, the methotrexate blas. Taking methotrexate in the next day or thirty six hours they have the blas.
CNS fatigue, can't get out of bed, don't feel like doing anything. Again, that's treated by taking with the methotrexate dextromethorphan. It produces a competitive inhibition of binding of methotrexate metabolites, excitogenic amines, to NMDA receptors in the brain. It prevents this methotrexate blase and other neurologic, and constitutional manifestations that follow methotrexate for thirty six hours. You can take it with the methotrexate dose, and then maybe the next day once or twice.
I use Mucinex DM. It's got thirty or fifty milligrams of DM in it. It works really, really well. Why not recommend a biologic since everyone thinks that's our best therapies? Well, studies have actually not shown that.
Head to head against methotrexate in brand new patients, biologic DMARDs do not perform better, and obviously they're a lot more expensive. The question is whether or not you should use an early biologic or a late biologic. That was actually in this week's room now, the VEDERA study, by Paul Emry's group showed there was no advantage to using very early, etanercept when starting methotrexate in early RA patients, and that the responses were basically the same as if you waited until they didn't respond for twenty four weeks and then added on, and patients quickly do catch up. That's item number four on the recommendation. Item number five reads as follows.
If patients with contraindications methotrexate or early intolerance occurs, you should be using leflinamide or sulfasalazine as your next best first treatment strategy. They perform equally well in head to head trials, certainly methotrexate and leflinomide. Sulfazalazine, maybe not so much, but then again it it's in the same bracket. Worldwide, leflinomide gets a tremendous amount of use because it's often the preferred drug to biologics and as opposed to North America where we use more biologics as second line. Plaquenil didn't make the list.
Hydroxychloroquine in that article said that has a limited place in the management of RA, especially early on, and mainly in its use in mild RA. Clinical trials done a long time ago continue to show or have shown that it is clinically weak as far as efficacy, but has no evidence of structural benefit as far as structural structural efficacy. So hydroxychloroquine is an add on drug, not your first line drug. Item number six, short term glucocorticoids should be considered when initiating or changing a conventional DMARD in different dose regimens and routes of administration, but should be tapered as rapidly and as clinically feasible as possible. Basically, what they're saying here is it's bridging therapy while you're waiting for the DMAR to take effect.
You know, your fastest effects are probably with the JAK inhibitors. Your slowest effects are going to be with sulfasalazine, Plaquenil, and Rituximab. Everything else is, you know, six to eight to twelve weeks. Maybe you need steroids during that period to get them over the hump. They didn't specifically say who shouldn't get steroids at the outset, They said they were kind of liberal in saying that everybody should get them when you're starting therapy.
And I think you need to keep in mind the short term benefit of glucocorticoids, but the long term hazards and risk. Again, are acutely wonderful and chronically dangerous is what I tell my patients. Item number seven. If the treatment target is not achieved with the first conventional DMARR, that's methotrexate, leflunomide, etc, in the absence of poor prognostic factors, other conventional DMARDs should be considered. This was in the 2016 recommendation and is carried forward.
What they're saying is that in the absence of poor prognostic factors, you can continue to use conventional DMARR therapy or combinations of conventional DMARDs as opposed to jumping into more expensive, more aggressive therapy with either biologics or targeted synthetics. So that's a very important, factor. It doesn't matter whether you switch to a conventional DMARDs or add on conventional DMARDs. It makes sense to add on if you ask me. But again, that's really your choice that to be made with the patient.
Item number eight, our last item for today is if a treatment target is not achieved with the first conventional DMARR therapy and poor prognostic factors are present, remember, erosion, CRP, many swollen joints, high titers, rheumatoid factor, see it, then a biologic DMARD or a a targeted synthetic DMARD should be added. And, again, not replaced, but should be added. I think these are all important factors. And, again, what's different about this from the 2,016 recommendations that said before that maybe you should use a TNF inhibitor first, and then after that, a targeted synthetic. Here, looking at the data, there is no particular advantage.
In fact, there are studies of JAK inhibitors outperforming not just methotrexate but outperforming, TNF inhibitors mainly adalimumab in sort of head to head fashion with a background of methotrexate suggesting that it doesn't matter whether you use a TNF inhibitor or JAK inhibitor, or other targeted synthetics. Right now, we only have JAKs, at this point. So it's either or. And, again, they they didn't say consider. They say add.
Like, make the change, buddy. It's time to put up and and and make the patient get better right quick. In tomorrow's episode, we're gonna talk about the toxicities that we need to consider before we go on to other traits, other treatments in patients with advanced disease or advanced therapeutics. Tune in for more on QD Clinic.
In this edition, we're going to talk about, again, EULAR twenty twenty recommendations on the management of rheumatoid arthritis. This is part three in a series where we're going to review the specific recommendations. Yesterday, we reviewed recommendations one through three, and now today we're gonna review four through eight. But first, before we do that, recognize that in considering your treatment options, the UR guidelines will point to something called poor prognostic factors. And is this an issue when you're managing your patients with rheumatoid arthritis?
Many of you would say yes. What are poor prognostic factors? There's a number of them that's been previously defined, but includes persistence of disease activity despite therapy. Second, high, usually very high elevations of sed rate and or CRP. Next is a sustained high swollen joint count.
Third is high titers. Fourth is high titers of rheumatoid factor and high titers of CCP antibodies. The presence of erosions obviously, is an important factor. And then lastly, failure of two or more disease modifying therapies. Any combination of these would constitute someone who has a poor prognostic factors or list of factors that will weigh on the outcome and may require more aggressive therapy.
So let's get into the fourth recommendation on the document provided by the analyst for rheumatic disease. Number four, methotrexate should be part of the first treatment strategy. This was in the prior guideline. Obviously, methotrexate first. It's methotrexate or die.
If someone has RA, they need to be on methotrexate unless there's a strong contraindication. Why? It's our best drug. We have a tremendous amount of experience with this drug. We know what it will do.
We know how long it takes. We know how to dose it. It is not just the first drug to start. It's the anchor drug upon which you build other therapies going forward. Someone doesn't respond to methotrexate and you're gonna add on.
Turns out, if you take methotrexate away and just add on another therapy without methotrexate, they don't do as well as keeping them on methotrexate. Yes. That's the drug that they didn't respond to. So it's the anchor drug whether you're going to add on glucocorticoids, a conventional DMARD, a biologic DMARD, or a synthetic targeted synthetic DMARD. Again, what's the dose?
I start at fifteen milligrams. Some people still start at ten or seven point five. Recommendations say the goal is to get to point three milligrams per kilogram and that you should escalate the doses every four to six weeks trying to get to a target dose. In The US and and The EU, that's generally a dose of twenty to twenty five milligrams per week. In Southeast Asia, it's a lot less being around ten milligrams or a little bit more.
Obviously, starting methotrexate mandates that everyone should be on folic acid. Folic acid has been proven to, number one, reduce the amount of discontinue discontinuations. Number two, reduce the amount of LFT elevations. And number three, no, it doesn't lower oral ulcers and nausea, but and again, that's how everybody uses it. How you use folic acid or folinic acid is up to you.
There are many regimens. They all work. And lastly, because methotrexate is so important, and because patients will read about it and think it's a cancer drug, patient education is very important. I love to say that methotrexate is a drug that we love and that patients hate because of what they read and what they're worried about. A few caveats on methotrexate.
When you're gonna be at fifteen milligrams or above, you either need to switch from PO to sub q, or what I do is go to split oral dosing. So at fifteen milligrams or higher, oral dosing has variable, absorption. But if you keep that at seven and a half to ten milligrams and then do it bid on every Wednesday, you get almost a 100% absorption just as you would if you went to a parenteral administration. Second, the things that screw up the use of methotrexate by patients are two key features. One, oral ulcers, queasiness, GI manifestations.
The treatment there is vitamin A. Eight thousand units a day, it works incredibly well. Stop me and ask me about it, I'll tell you about it. Second, the methotrexate blas. Taking methotrexate in the next day or thirty six hours they have the blas.
CNS fatigue, can't get out of bed, don't feel like doing anything. Again, that's treated by taking with the methotrexate dextromethorphan. It produces a competitive inhibition of binding of methotrexate metabolites, excitogenic amines, to NMDA receptors in the brain. It prevents this methotrexate blase and other neurologic, and constitutional manifestations that follow methotrexate for thirty six hours. You can take it with the methotrexate dose, and then maybe the next day once or twice.
I use Mucinex DM. It's got thirty or fifty milligrams of DM in it. It works really, really well. Why not recommend a biologic since everyone thinks that's our best therapies? Well, studies have actually not shown that.
Head to head against methotrexate in brand new patients, biologic DMARDs do not perform better, and obviously they're a lot more expensive. The question is whether or not you should use an early biologic or a late biologic. That was actually in this week's room now, the VEDERA study, by Paul Emry's group showed there was no advantage to using very early, etanercept when starting methotrexate in early RA patients, and that the responses were basically the same as if you waited until they didn't respond for twenty four weeks and then added on, and patients quickly do catch up. That's item number four on the recommendation. Item number five reads as follows.
If patients with contraindications methotrexate or early intolerance occurs, you should be using leflinamide or sulfasalazine as your next best first treatment strategy. They perform equally well in head to head trials, certainly methotrexate and leflinomide. Sulfazalazine, maybe not so much, but then again it it's in the same bracket. Worldwide, leflinomide gets a tremendous amount of use because it's often the preferred drug to biologics and as opposed to North America where we use more biologics as second line. Plaquenil didn't make the list.
Hydroxychloroquine in that article said that has a limited place in the management of RA, especially early on, and mainly in its use in mild RA. Clinical trials done a long time ago continue to show or have shown that it is clinically weak as far as efficacy, but has no evidence of structural benefit as far as structural structural efficacy. So hydroxychloroquine is an add on drug, not your first line drug. Item number six, short term glucocorticoids should be considered when initiating or changing a conventional DMARD in different dose regimens and routes of administration, but should be tapered as rapidly and as clinically feasible as possible. Basically, what they're saying here is it's bridging therapy while you're waiting for the DMAR to take effect.
You know, your fastest effects are probably with the JAK inhibitors. Your slowest effects are going to be with sulfasalazine, Plaquenil, and Rituximab. Everything else is, you know, six to eight to twelve weeks. Maybe you need steroids during that period to get them over the hump. They didn't specifically say who shouldn't get steroids at the outset, They said they were kind of liberal in saying that everybody should get them when you're starting therapy.
And I think you need to keep in mind the short term benefit of glucocorticoids, but the long term hazards and risk. Again, are acutely wonderful and chronically dangerous is what I tell my patients. Item number seven. If the treatment target is not achieved with the first conventional DMARR, that's methotrexate, leflunomide, etc, in the absence of poor prognostic factors, other conventional DMARDs should be considered. This was in the 2016 recommendation and is carried forward.
What they're saying is that in the absence of poor prognostic factors, you can continue to use conventional DMARR therapy or combinations of conventional DMARDs as opposed to jumping into more expensive, more aggressive therapy with either biologics or targeted synthetics. So that's a very important, factor. It doesn't matter whether you switch to a conventional DMARDs or add on conventional DMARDs. It makes sense to add on if you ask me. But again, that's really your choice that to be made with the patient.
Item number eight, our last item for today is if a treatment target is not achieved with the first conventional DMARR therapy and poor prognostic factors are present, remember, erosion, CRP, many swollen joints, high titers, rheumatoid factor, see it, then a biologic DMARD or a a targeted synthetic DMARD should be added. And, again, not replaced, but should be added. I think these are all important factors. And, again, what's different about this from the 2,016 recommendations that said before that maybe you should use a TNF inhibitor first, and then after that, a targeted synthetic. Here, looking at the data, there is no particular advantage.
In fact, there are studies of JAK inhibitors outperforming not just methotrexate but outperforming, TNF inhibitors mainly adalimumab in sort of head to head fashion with a background of methotrexate suggesting that it doesn't matter whether you use a TNF inhibitor or JAK inhibitor, or other targeted synthetics. Right now, we only have JAKs, at this point. So it's either or. And, again, they they didn't say consider. They say add.
Like, make the change, buddy. It's time to put up and and and make the patient get better right quick. In tomorrow's episode, we're gonna talk about the toxicities that we need to consider before we go on to other traits, other treatments in patients with advanced disease or advanced therapeutics. Tune in for more on QD Clinic.
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