RheumNow Podcast Heartbreak Of Methotrexate %2811.16.18%29 Save

Doctor. Jack Cush, Executive Editor of roomnow.com. It is 11/16/2018. This RoomNow podcast is brought to you by roomnow.live, a new and exciting meeting held in Fort Worth, Texas on March 22 through '24 next year 2019. Go to roomnow.live to learn more about this great meeting, the program, the distinctive TED Talks and maybe even register.

So this week we have what to do in your, anticoagulated patients who are going to have dental work. How about scleroderma? Wouldn't it be great to have, a scleroderma maven hold your hand and whisper in your ear how to best manage your systemic sclerosis patients? And lastly, what about heart stopping news for methotrexate, meaning the results of the New England Journal article called the CERT study. I tweeted this week about polypharmacy mainly because I had a patient who came to me not knowing what medicines they were on, not knowing the doses, and their patient was on a lot of medicines and yet really didn't know and it did happen to be an elderly patient.

This is a very worrisome phenomenon, very risky situation. My definition of polypharmacy is when the patient's med list goes on to a second page or is on the back to the first page, and can't be all sort of neatly put together. Also when the patient can't remember the name of the drugs that they're on or the doses that they're taking or God forbid, why they're even taking a medicine. There are formal definitions such as the use of many different medicines used to concurrently treat a single disease or coexistent and related diseases. Clearly, if polypharmacy is a high risk scenario, especially in the elderly, your job is to guard against it.

Your job is to write a new prescription and stop too. Your job is to identify it. Yes, you'll know it when you see it, it's just like pornography, and when you see it, you really should set the goal of reducing that person's drug list by at least 50%. That's probably the best thing you could do for any of your patients. I did have another tweet up this week about what to do in a CCP positive RA patient who has a tender six swollen joints, has a DAS score of 5.1 gets put on methotrexate and TNF inhibitor and quickly goes into remission.

So at six months, they're in remission, at month twelve, they're in remission, at month eighteen, they're back to see you, and guess what, the TJC is zero, the SJC is zero, what do you do with their drugs? The options were do nothing, continue the same methotrexate and TNF inhibitor, or actually get the patient off of all drugs, or to wean the methotrexate and stop the methotrexate, or lastly to wean and or stop the TNF inhibitor. Well, only four percent of people said try to get the patient off all drugs. A third of you said it would be unwise to do anything, stick with what's working, be conservative, it is too early to stop any medicine. Twenty three percent, it would be wise to wean and then ultimately stop the methotrexate, and forty percent, the largest number said, try to wean or space out the TNF inhibitor, continue the methotrexate and then maybe stop it.

Clearly, you're driven by conservatism, by don't mess with what works, and by finances and or safety, making your choices. I think based on the data, the smart thing would be to wean and or stop methotrexate and continue them on the most powerful drug. If you stop TNF inhibitors, many of them will continue to do well, but there will be a radiographic benefit. You're more likely to be able to stop methotrexate without affecting radiographic benefit and still maintain the same efficacy, but it's a cost issue, for many of you. An interesting study of ANCA associated vasculitis looked at patients in four different clinical trials, a total of three fifty four patients, and looked at long term outcomes.

Specifically, percent developed end stage renal disease and nineteen percent died. So the predictors of these bad outcomes were not surprisingly disease activity at month three and six. So measures of these activity for ANCA associated vasculitis can predict who's going to do bad. Problem is that most of us don't have a measure that we usually use. In clinical trials, it's the Birmingham Vasculitis Activity Score.

You could do the same, your own composite score, and customize the BVAS to your practice or use acute phase reactants, organ specific symptomatology and a hack, and again, you'll know when they're in remission and doing well and that's a good sign for the future. But I think this is an important message. Another very large database study looked at gout and the risk of incident chronic kidney disease or CKD. Over forty thousand patients followed over time. If you had gout, guess what, you had nearly double the risk of developing CKD.

But maybe the other important part of this research showed that if those patients were put on urate lowering therapy, there was a forty percent reduction in the risk of developing CKD, suggesting the importance of urate lowering therapy. We have tweeted and talked about here before that chronic urate lowering therapy also reduces the risk of cardiovascular events in gout patients. Now we're showing you the same except in this case, the risk of future renal disease. Another very large study, 52,000 patients with psoriasis from 28 different studies of meta analysis looked at sexual dysfunction in psoriasis patients showed a surprisingly high rate of sexual dysfunction, nearly half patients admitting to sexual dysfunction, and somewhere between thirty and eighty percent of patients, admitting to erectile dysfunction. These findings were most likely be associated with who?

The elderly, those with anxiety, depression, and those who had genital psoriasis. Not surprising, but it's one of those things we don't often talk about, especially with our psoriasis and psoriatic arthritis patients that it may be worth bringing up. It is important to ask patients with psoriasis and psoriatic arthritis if they have psoriatic lesions scaling, down there in the genital and or rectal area, crack of the butt as well, umbilicus, again, the places you don't generally look when you're examining patients. Another scenario came up this week in practice about what to do with one of my lupus patients who's going to have all teeth removed for severe dental caries and how to manage that patient's immunosuppression, azathioprine, and anticoagulation. Well, data is very clear on what to do with the DMARR therapy, it should be continued throughout.

Steroids should be continued and there's no need for stress doses of steroids in patients undergoing major surgery or even minor surgery. In this case, we're talking about minor surgery. Is it minor if you remove all the teeth? It's minor if it's someone else, it's major if it's me. But what to do about this patient's Plavix?

A recent report from ACR, this was abstract number 2,782 from Stony Brook, State University of New York at Stony Brook, looked at a study of their temporal artery biopsy patients, total twenty seven of them, and that twenty of them were on anticoagulation prior to the procedure. They have data on what happens when they remove the anticoagulants or continue the anticoagulants, and basically sixteen of the patients were studied and found that if you continue the anticoagulant, you had a very low risk, only three out of sixteen had a minor bleeding event, there were no major bleeding events in the patients who continue the anticoagulation suggesting that if the patient's need for anticoagulation is incredibly strong, recent PEs, very unstable atrial fibrillation, probably shouldn't stop the anticoagulation and it seems to be it might be safe to continue it. However, if it's not necessarily a major issue, you probably could stop it for a few days. Something like Plavix has a very short half life, stopping it for two days probably wouldn't matter that much. A meta analysis of RA patients looked at what happens when they get pregnant.

There's 10 different studies, two zero four RA patients looked at, RA activity and they showed that sixty percent of patients had improvement in their RA as based on a validated measure. Interestingly, postpartum, half of them flared. So I've always taught that it's not eighty percent of people who get better when they get pregnant if they have RA, that's not true at all. The data that I've looked at says at least a third of them get worse, forty percent might get better and in between doesn't change that much. This data, this meta analysis of the same or a subset of studies looks almost to be the same.

The point being that you should worry about disease activity and not be coaching everybody that they're going to get better if they get pregnant with their RA. I found an interesting report about off label use of rituximab in children with HENOX shown line purpura. As you know, HENOX shown line purpura is generally conservatively managed with no therapy and really no need for steroids and the palpable purpura lesions will ultimately pass in a lot of patients. But for those who have severe disease, especially if it's renal and or intestinal disease, The question is, what do you do? There really isn't any proven therapy.

This particular report was a collection, a retrospective review of eight patients at a single center who had received rituximab with great success and with very little toxicity, a favorable pilot report of how that might perform in HSP. In that report, they also reviewed the literature and found another, I think nine patients and eight reports. What was it? 10 patients and eight reports showing the same thing both in adults and children with favorable outcomes when rituximab was needed because of severe refractory disease. I'm not advocating that you use rituximab in HSP, I'm saying that if you have a bad case, you should look at this literature and come to your own conclusion.

What to do about systemic sclerosis? Well, an interesting report appears this week in Arthritis Care and Research published by Janet Pope and her colleagues about how to manage systemic sclerosis based on expert opinion. So a panel got together, looked at different scenarios and came up with some of the following. This is an excerpt of what was in that report. Renal crisis, ACE inhibitors, calcium channel blockers, and then later add an angiotensin receptor blocker and ARB.

Mild Raynaud's, almost eighty percent suggested you should use calcium channel blockers, phosphodiesterase five inhibitors, PDE5 inhibitors that includes sildenafil and tadalafil, and then later ARBs or maybe another calcium channel blocker. Severe Raynaud's, you would use the same and then obviously the PDE5 inhibitors and then move on to prostanoids if you needed to. Digital ulcers, two thirds of the experts recommended calcium channel blockers and PDE5, inhibitors. Interstitial lung disease, seventy percent of experts recommended microphenolate and that with more severe advancing disease, intravenous cyclophosphamide and or rituximab. Mild skin involvement, I don't think they had a recommendation.

For moderate skin involvement, they recommended methotrexate or microphenolate and that as the modified Rottmann's skin score got higher like 34 or higher, that was not just methotrexate but, mycophenolate and IV cyclophosphamide and maybe even hematopoietic stem cell, the same kind of regimen as was used in the Scott trial reported last year's ACR and this year's ACR. And lastly, inflammatory arthritis, methotrexate, low dose corticosteroids, hydroxychloroquine or toxamant tocilizumab. I'm a little surprised by corticosteroids and hydroxychloroquine as a recommendation, but that's what the experts say when they're holding your hand. Then lastly, the CERT study. The CERT study is a cardiovascular intervention trial in cardiology patients only, there's no arthritis involved here, and they were given either placebo or methotrexate.

So high risk individuals with prior MI, and these patients had to have metabolic syndrome and or diabetes to get in, they were not required to have an elevated CRP to get in, and unfortunately, methotrexate failed as a prevention agent in these high risk cardiovascular patients. The study was prematurely stopped past April, by the Data Safety Monitoring Board because when they looked at the data and I think over, four thousand seven and eighty six patients, they found the same rate of their primary endpoint, which was again either, a non fatal MI, stroke, cardiovascular death, unstable angina requiring revascularization. About two hundred patients in both groups suggesting that adding methotrexate wasn't going to add much to the study. These results are different than the CANTOZ trial which we've talked about and published on before. The CANTOZ trial was done with canakinumab, the same kind of trial, high risk patients except in that trial, you had to have an elevated CRP to get into that study.

Again, the CANTOZ, patients had a mean CRP of 4.5 milligrams per liter, whereas the CERT patients had a mean CRP level of 1.5. The CERT study showed no significant change in IL-one, IL-six or CRP levels, whereas the CANTO study showed a significant reduction in CRP and IL-six levels. And there were other benefits to the successful CANTHOS trial. It lowered gout risk, it lowered osteoarthritis, knee replacement, and hip replacement risk. There were a number of things.

Unfortunately though, the FDA has recently said, No, you can't have this indication to the makers of, canakinumab. And so they're in negotiation about what to do with the cardiovascular prevention aspect of the Kansas trial. But this methotrexate trial, the CERT study showed it didn't work as well. It probably could be because of design, it could also be because methotrexate may be not quite as potent as an IL-one inhibitor. But we do know that methotrexate is highly impactful in preventing cardiovascular deaths and death in RA patients.

Data from Choi and Wolf and a whole bunch of others have shown that. Anyway, that's it for this week on the RheumNow podcast. Check out roomnow.live and register for a meeting. You can go to the website and get the citations for these reports and others. Tune in, we'll see you next week.