QD Video -Week 9 Save

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Free, live streaming right into your living room, office, or kitchen. Today's case is called class switching. It's prompted by a patient that I saw recently. She's a 40 year old with psoriatic arthritis. I must say the most god awful, mean, ugly, nasty psoriatic arthritis patient I've ever seen.

I put this up against any patient you've ever seen. And why can I say that? Well, at any one time this patient usually has on a good day, eight swollen joints, that's only on a 28 joint count, on a bad day, 16, plump, juicy, you know, like almost somewhere around plum size, not grape size, plum size joints. I mean, just god awful. She has taken and failed methotrexate, Plaquenil, Sulfazalazine, Enbrel, Remicade, Humira, Stellara, Rituxan, Arencia, Arava, cyclosporine, tacrolimus, Cimzia, Taltz, Cosentyx.

I'm sure I'm leaving something out. Failed them all. And the question is, how do you manage this patient? Well, again, she's 40, she's got severe psoriatic arthritis and really severe skin disease. I'm talking, you know, thirty to fifty percent BSA coverage with deep red scaly lesions that are painful.

Again, managed by me and psoriasis maven here in Dallas. It's her skin, it's her joints, it's both, know, and we get together and talk about it all the time. Her disease is complicated as you might imagine, bio obesity, fatty liver disease, some cirrhotic changes, diabetes, sleep issues, and even guess what, secondary fibromyalgia. So more recently, you know, I won't tell you the unbelievable combination regimen that she was taking for fear that you would either report me to the authorities or shut off this video and never listen to me again. But let's just say she was taking several biologic agents at the same time and was given, one IL-seventeen inhibitor along with a background of like Arava and cyclosporine and something else, and had no effect at all.

You know, a C. Dye score that was, you know, in the 30s was still in the 30s. And then unbeknownst to me after being on that for a solid ten weeks, she went to the dermatologist and was switched to the other IL-seventeen inhibitor and within two weeks all the skin, which I mean was truly ugly, I'll show you pictures if you want to see them someday, all went away. She was just left with this faint red erythema, scale was all gone. Six weeks later there was no erythema left.

She had normal looking skin, normal looking legs. She came back wearing high heels and she was crying because she was so proud of herself. She could wear high heels, meaning the severity of her skin led to edema, led to, you know, again, she couldn't wear normal shoes, she couldn't dress in a normal way. And along with this, her joints did fabulously well. Again, on another regimen that we won't talk about here, but the question is, can you switch if you fail one IL-seventeen inhibitor, should you try another?

This story says absolutely you should. But it's not just a story of IL-seventeen, but it's also a story of other classes of drugs. So we have five TNF inhibitors, you know that you can fail one TNF inhibitor and go to another and fifty-sixty percent of people are gonna respond. You can go to maybe a third and forty-fifty of people are gonna respond. You know class switching does work as long as it's not a primary failure, meaning they never responded.

But as I said with the other IL-seventeen inhibitor, the patient failed one meaning with primary non response and had a complete response to the other one. There are three IL-one inhibitors. Have I gone from one to the other to the other? Yes, have. And yes, with success.

There are two IL-six inhibitors. The third one got turned down by the FDA, but there's sorrelimab, Kevzara, and there's tocilizumab, Actemra. Can you switch from one to another? Absolutely, you can. I've got a recent example last week.

Patient failed one, failed a whole bunch of drugs just like this patient. And I'm telling you, the patient came back on a new IL-six inhibitor along with a new DMARD and joint counts that were in the teens eighteen, nineteen, 10 and swollen joints, C. Dye scores over 40. She came back with two swollen joints. I swear I almost cried because I didn't think it was possible.

But that's what class switching. And we have two JAK inhibitors, we have Xeljanz and now excuse me, and we may very well have a third one or a fourth one within a year or two. Can you switch from them? Been there, done that, it does work. I don't like switching, you know, amongst all five TNF inhibitors.

I've got a lecture that says you shouldn't do it. You should probably switch one and move on. If you're a primary non responder, probably should move on to another MOA because you have so many other MOAs. We only have one B cell inhibitor with rituximab and we only have one T cell T, stimulatory, molecule inhibitor in, Orenzia or abatacept. So there's no switching going on there just yet.

But you know, have I seen people go from cyclosporine to abatacept and get better? Absolutely, I have. So I would, again, this is a lecture in favor of, maybe not lecture, but a report in favor of switching within a class that it is possible. I think the important thing is to have very defined endpoints to bring the patient back and see that they are responding within four to six weeks. If not, bail and move on to another drug.

Tune in tomorrow for more QD videos. Welcome to QD Clinic brought to you by roomnow.live, a great new meeting for rheumatologists. You can register and for free if you wanna watch it from home. Check it out. Today's case from the clinic is shingles happens.

A 71 year old male who I've been following for a few years who has psoriasis, pretty bad, psoriatic arthritis, pretty bad, previously taken a TNF inhibitor and about five months ago switched to ustekinumab. Done really, really well, skin and joints really just doing fabulous, but three weeks ago he comes down with shingles. Right side, dermatomal, really severe blistering lesions, a lot of pain, didn't call me, went to his primary care, was managed with Valtrex and is now going to pain management because of the severe neuropathic pain going on for three weeks. This is a disaster. It happens in the elderly.

It's really quite significant as far as morbidity goes. It's something that patients really, really dislike. Could this have been prevented? It could have been. He was not given a shingles vaccine prior to this and we'll review that in a second.

So he's dealing with three weeks of nine out of 10 pain, burning, numbness, shooting pains. He's got a lot of numbness, he might well be left with postherpetic neuralgia. And again, how should we have handled this maybe going forward? Well, in my experience that most of my patients who are getting shingles vaccines is being brought up by their primary care doctors. It can be brought up certainly in the rheumatology visit, and it should be your responsibility if they're going go on a drug, especially a JAK inhibitor and where the risk goes up significantly.

So what are the risks? Who's at risk? Clearly those who are older. You know, it starts when you're 60, it gets higher when you're 70, it's really high when you're 90, if you live that long. And clearly the drugs used to, prevent this, the either the Zostavax or the new Shingrix vaccines are indicated after the age of 50, but insurance companies will only usually pay for it after the age 60.

That's when the discussion should be had. Patients who are immunosuppressed. I don't particularly view my patients on a TNF inhibitor or an IL-seventeen inhibitors being immunosuppressed. I think their inflammation drives their risk. So what are the real life risk numbers for people as they get older?

People in the population, the risk of getting, herpes zoster is about five cases per thousand. Osteoarthritis patients, meaning those who are older, it's about ten cases per thousand, one per hundred. Rheumatoid arthritis patients, it's probably less than fifteen per thousand. It's a little bit higher, but not that much higher. Rheumatoid arthritis patients on TNF inhibitors, it's also not that much higher.

It's about fifteen to seventeen per thousand. The highest numbers are seen in severely immunosuppressed lupus and severely immune immunosuppressed, GPA patients who are taking cyclophosphamide, high dose steroids, There the rates are somewhere around forty five per thousand patients, and that's about the same rate that you see with the JAK inhibitors where the rates are about thirty five to forty five per thousand. So clearly going on a JAK inhibitor increases the risk. I don't know that going on other biologics substantially increases the risk. Certainly it might be higher when you're using, cytotoxic agents or when you're having someone go on rituximab, the numbers could in fact be higher.

The question is if you have someone at risk, are you going to recommend? Again, the old rule was to use the live virus vaccine, Zostavax, and the rule was that you need to be off of a biologic for two to four weeks, preferably four weeks, give the vaccine, and then, restart the biologic therapy like a TNF inhibitor at least two weeks later. So there's a period that you must be off. If someone's never been on a biologic and you want to give it, you give the vaccine, you wait two weeks, you can start the new therapy. Again, those at risk that where these rules are in place would be for biologics, especially TNF inhibitors, but all the biologics and also the JAK inhibitors.

Does that apply to methotrexate, hydroxychloroquine, sulfasalazine, cyclosporine, or Rava? No, it doesn't. It turns out that regular oral DMARDs, you can go ahead and give live virus vaccines without impunity. Right? But now it's a new era.

We have a new shingles vaccine that's not live. It's an inactive virus. It's two shots. You have to be given two to six months after the first shot. It's about the same cost as the original Zostavax vaccine, which is almost $300, $320 something like that.

And it's the difference here though are substantial. One, you can give the live virus vaccine to almost anyone including people on biologics. Although that research has not been done, there does not appear to be any new signals and that drug that drug has been out there and selling really really well for a long time. We've not heard any disasters of the adjuvant inactive virus vaccine, the Shingrix causing reactivation or worsening of lupus or RA or whatever the underlying inflammatory disorder is. So you can give it to people who are on DMARDs, oral DMARDs, conventional DMARDs, and even on biologics, we've done that.

But again, there is no formal guideline that says you can do that. That's just my experience, my recommendation. I know there are others who are very concerned that the manufacturers of Shingrix haven't done their due diligence in doing studies in our immunosuppressed patients, and I also chime in and say they should, they're getting off easy by not doing it. But until such time, we're gonna have to go with, what seems to be best, based on what we know of the drug and of the patients. So I would recommend that patients who are on or going on, more advanced therapies, biologics and, the JAK inhibitors or other small molecule inhibitors be given this after the age of 60, especially if it's going to be a JAK inhibitor.

Definitely after the age of 70, this my guy was 71 years old. And then again, it's easy to take. There are more, side effects with the Shingrix vaccine. Nuisance side effects, flu like symptoms, myalgias, feeling, crummy, that sort of thing. And that's probably from the adjuvant.

I haven't heard of any patients say it was horrible. There have been about, you know, ten to twenty percent of patients who are complaining of some symptoms. I guess the other thing that you need to know is the Zostavax was a good vaccine. It lasts for four years. Its efficacy waned with the increasing age of the person receiving it.

So it was much better when given to 50 and 60 year olds than to 70 and 80 year olds. But the Shingrix vaccine, the newer vaccine, is far more effective, doesn't wane or change with age, doesn't change as far as protection against postherpetic neuralgia as you get older. That's why it seems to be a superior product. Think So about this when you're faced with the issue of shingles in your patients. More tomorrow on QD Clinic.

Hi. This is QD Clinic brought to you by RheumNow Live. A fabulous meeting coming up in a few weeks. Let me just tell you the faculty. Mike Holers, John O'Shea, Mike Weinbach, Len Calabrese, me, Lisa Samaritano, Eric Madison, Ted Pincus, Fred Wolf, Maddie Feldman, Arti Kavanaugh, Philip Conahan, Eric Ritterman, Elaine Husney, John Ravelle, Gayord Chet, Ron Van Vollenhaven, Philip Sio, Carol Langford, Paul Monarch, and I think I left a few out.

It's a killer faculty. Rheumnow. Live to register. Today's case is secondary loss of efficacy and what to do about it. 25 year old gal with rheumatoid arthritis, probably about five, six years, comes in.

She's had been doing well. Actually, I guess it's only three years because she's been on a TNF inhibitor for about two, two and a half years. She's on one of those first line TNF inhibitors you have to use. Was doing great. Had a few aches and pains at her last visit six months ago.

Says that since the last six weeks, she's been worse with pain all over. I thought it was gonna be sort of secondary pain or fibromyalgia pain, but lo and behold on joint exam, she's got a ton of joints. Mean, I think her joint count was 11 tender, 10 swollen. It was a little bit surprising. And she says that she's been very compliant with the medicine taking it as prescribed.

And so the question is, what do you do? Do you treat this as a flare? Do you treat this as secondary loss of efficacy? I call this a secondary loss of efficacy and I treat it by changing her drug. What am I gonna change her to?

Was previously on methotrexate, a TNF inhibitor, and did well just on a TNF inhibitor. I could have added back methotrexate, I changed her TNF inhibitor just to another TNF inhibitor, and why did I do that? Well, let's go over some of the data on loss of efficacy. Primary loss of efficacy is a drug that never works. So people who've never been on TNF inhibitor who are on methotrexate and then go on a TNF inhibitor, it's the sixtyfortytwenty response.

Sixty percent are going have an ACR20. That means forty percent of patients will have a primary loss of or lack of efficacy. Those who respond and then lose response over time, those are called secondary loss of efficacy. So the numbers on primary loss are between forty and thirty The 2016 accelerate study done by Roy Fleishman and others compared head to head adalimumab versus cerdulizumab and showed in an open label randomized study that seventy percent of people responded right out of the gate at their endpoint, meaning that thirty percent were primary non responders. In that study they did a crossover.

So primary non responders were then switched to a second or the alternative TNF inhibitor and they showed that about fifty percent of those patients or fifty five percent of those patients responded. That means overall a total, secondary response of about forty percent of patients. So you'll lose quite a bit in primary non responders. The data on people who switch usually secondary loss of efficacy, secondary non responders, about fifty percent or more will respond to the second TNF inhibitor but then it goes down so you go from your first TNF inhibitor sixty forty twenty, that's ACR twenty, fifty, and 70 responses respectively, to your second TNF inhibitor where it's now gonna be fifty thirty fifteen, and a third one would likewise go down to 40, you know, 20, 10. But those are all in people who, again, don't respond to the first and then go on to the second.

So, like, if you're a primary nonresponder, you probably shouldn't be changing to another TNF inhibitor. Your levels of response are going be lowered. Instead of 40%, you can do 50 60% if you use another MOA or a small molecule inhibitor like one of the JAK inhibitors. I think, you know, the finer points of this are what to do when you're a secondary, this patient had her first TNF inhibitor, she's a secondary loss. The data on going to a second inhibitor, second TNF inhibitor are good, as far as the outcomes when you are switching for either toxicity reasons or for a secondary loss of efficacy.

So this patient who goes on a second TNF inhibitor actually has a sixtyfortytwenty chance of doing well with her second TNF inhibitor. But again, I want to remind you if she was going to, if she goes, if this was because she never responded to the first one, her chances wouldn't be sixty, forty, 20, it might be forty or fifty percent for an ACR 20 response with the second drug. That's why I'm saying if you're a primary non responder, go to another MOA. If you're a secondary non responder, you can use a second. I don't know about using a third.

That doesn't seem smart to me. That's the story with secondary, loss of efficacy. Let me know what you do when you see me. Welcome to QD Video brought to you by RheumNow Live. It's a master class for those who want to master rheumatology.

Check it out at roomnow.live. Our case today is the coexistence of RA and gout. Is it possible? Just saw an 80 year old gentleman who's had rheumatoid arthritis for about the last ten years. He's also had the diagnosis of gout.

He's currently on a 100 of allopurinol, Actually, two hundred allopurinol. I just increased it to three hundred. He's on five milligrams of prednisone and currently taking leflinamide. Although he's been on methotrexate and in biologics in the past, now at his current age, he's trying to avoid the biologics because of cost issues. Anyway, he's on allopurinol and he's on Arava.

Arava, as you know, is a drug that also can lower uric acid levels by being a mild or weak uricosuric drug. So I don't know about you, but when I'm teaching people, I've always said that you can't have gout and rheumatoid arthritis. Usually when you see as a consultant gout and rheumatoid arthritis, it's because one or the other is the wrong diagnosis made by people in primary care or people less skilled than you. And that's entirely possible because rheumatoid factor is seen in twenty million Americans. Hyperuricemia, you know, if gout is in eight point three million Americans and nephrolithiasis is in twenty million Americans.

Hypouricemia has got to somewhere in between those numbers. So it's not uncommon to have RA in a random, elevated uric acid or have gout in a random elevated rheumatoid factor. But it turns out that when you look at this, it does happen and every rheumatologist will tell you they got a few patients where they're pretty certain they have gout and RA or they're a little concerned that this could be gout or RA and they're sort of straddling the fence on management. My patient, I'm not straddling the fence, clearly RA, RA erosions, rheumatoid factor and CCP, clearly gout with sporadic gout like attacks and hyperuricemia up to a uric acid of 10. Again, definitive way would be to tap the joint and show there's crystals there as well.

I didn't do it in this case, I have done that in the past. What I've gleaned from the literature on this subject is you can have the coexistence. Although I think it's still good to teach there is a negative association between the two, that's what you should be telling your primary care audience. So there are a few studies that show that amongst gout patients, RA occurs in two to three point eight percent. There's one study I saw that shows amongst gout patients, RA occurs, sorry, amongst RA patients, gout occurs in up to three percent of patients.

So it's out there. What's the profile of someone who gets gout in RA? Tend to be male, to be older, tend to have elevated creatinines. They also tend to just have one, autoantibody, not CCP and rheumatoid factor, they have one or the other and usually not in sky high levels, but they also have hyperuricemia. It's said that seventy five percent of these cases gout precedes the diagnosis of RA which again makes me think was that the right diagnosis or not?

Do you have documentation or not? Have you seen it? Again, I wouldn't say these coexist until you've seen it and you diagnose it. Hearsay is not something you need to deal with going forward. Again, patients tend to do better with their gout when their RA is controlled.

So can uncontrolled RA provoke gout attacks? No one really has answered that question, but I find it interesting that these two can coexist, especially when I've been saying for years, can't have gout and RA together. Those are my final words. I'm sticking to them until I'm proven otherwise. QD Clinic here brought to you by RheumNow Live, changing minds and practice in Downtown Fort Worth on March 22.

Be there live or online. Today's case is the power of patient choice. Just recently saw a 25 year old young gal who's had inflammatory arthritis in both knees with enthesitis with an elevated CRP and a low titer ANA, and I'm calling her a JIA JIA or a B27 positive peripheral spondyloarthritis. Doesn't seem to matter. She's been tried with nonsteroidal.

She's had her joints injected. She needed to move up to a DMARD. And the question is what DMARDs do I want to use? I wanted to use methotrexate. I gave her a range of possibilities, did not offer her a biologic at the outset.

I gave her a number of different DMARDs to choose from, and she took a prescription home and then called back and said, know, she talked it over with her husband, they don't really want to be on methotrexate. When I gave them the list of side effects, they preferred the side effects associated with hydroxychloroquine and so that's what she started. Again, didn't think that was a very good move because I thought she had enough inflammation that I wanted something was going to work maybe more completely, maybe more quickly but nonetheless, you know, I always like to go with what patients want to do, especially if I'm, if I was a 100% certain I try to talk her out of it, can't be a 100% certain. So we let her use hydroxy and she comes back after eight weeks and lo and behold, she has nothing. No enthesitis, no swollen knees and these were swollen knees with fairly good sized and warmth, totally gone, she's now back to running, she feels good, oh and by the way she's pregnant.

So it's probably a good thing, she didn't expect the pregnancy, she's on hydroxychloroquine, she's gonna continue it and then we'll see how she's doing as we get into the middle trimester. I'll see her back and we'll make the decision about hydroxychloroquine. Told her there's no rush to stop that. But I think what's remarkable about this case is the idea of patient choice. I think all studies should involve an additional arm.

Let's say you're doing a three arm study, drug A versus drug B versus placebo, I'd add a fourth arm. It'll be drug A versus drug B versus placebo versus patient choice. Because in my experience, and there's some literature to support this, when the patient chooses, they actually have better buy in, more compliance, they're motivated to get better, it seems like that they have an active participation in their own improvement. It works out incredibly well. I recently saw a patient who, was just a horrible case of rheumatoid arthritis.

I mean just god awful miserable and she had previously been treated with Actemra, Tocilizumab and a combination of a bunch of drugs did nothing to her. And she came back and we went over again this would have been like her thirty fifth choice as far as therapy. I mean I'm at the end of the rope really. And I offer her Kevzara, sorrelimab, the newer IL-six inhibitor. She came back in two months and nothing.

You know, she had like 15 swollen joints, incredible disability, all disappeared. But she chose, that's what she wanted to do. And I think that her buy in, many of her other choices I've given her in the past were given as sort of like this is last ditch effort. I gave her a number of different choices and that's the one that she wanted to do and it's amazing. So it goes to what we talked about the other day.

You can switch within classes, but again the most important switch in that patient and this first patient I talked about is giving the patient their choice. They actually stack the deck in favor of a response in my opinion. Tell me what you think.