QD 70 - The Reluctant Rheumatologist & Pegloticase Save
QD Clinic - Lessons from the clinic
The Reluctant Rheumatologist and Pegloticase
When do you consider using pegloticase?
Transcription
This is QD Clinic, and I'm doctor Jack Cush. QD Clinic is brought to you by RheumNow Live, a next generation medical meeting. Our case this week begins with the reluctant rheumatologist and peglodecase. Saw a 60 year old white male who had a lot of comorbidities and a history of gout. Not surprising, this patient had hypertension, diabetes, chronic renal disease, was on many different medicines.
He had been diagnosed with gout ten years ago, has had many attacks over the years, a history of sort of incomplete control with the attacks going from acute and intermittent to chronic and additive, and now he's at the point of having chronic tolfacius gout, involves the hands, the feet, the elbows, occasionally the knees. And when we saw him recently, he was on four hundred milligrams of allopurinol. His uric acid level was 6.8, and he was still having intermittent attacks and a lot of pain. And a lot of his pain, as you might imagine, is related to inflammatory damage and secondary pain and periarticular pain. But then he seems to have, warmth and inflammation in some joints as well.
The question is, how do you manage him? He's at the stage of having a chronic inflammatory polyarthritis because of his urate deposition disease evidenced by some big bulky, you know, walnut to pear size, not pear size, almost pear size, collections of of tophi, elbows, feet, hands, knees. It's, you know, obviously, deforming and, and hard for him. The issue is, in discussion with the other rheumatologists managing this case, is that there's a reluctance to start this man on peglodecase. Yes, you could step up his allopurinol, and yes, you could be one of the few rheumatologists out there that, you know, would use a dose higher than four hundred or three hundred.
But the facts are that rheumatologists aren't as great as we think we are at managing gout. We just like podiatrists and renal docs and internists largely only use three hundred milligrams a day. We seldom ever, use combination therapy. Very few of you have actually used peglodecase, although the numbers of peglodecase use in the last ten years that it's been approved has actually gone steadily up. But many of you have never used it for fear of side effects, anaphylaxis, tales told around the campfire or clinic fire, whatever.
And, and I'm here to tell you that I'm not afraid to use it. I've tried to use it a number of times and had problems either with the patient or the insurance or the patient being really sick and thinking they're too sick to get this infusion. And then, and I have used it, and it's really, I think a very effective way. The issue here is the argument that was presented to me by the other rheumatologists in discussion was, well, if we increase his dose up to six hundred, even up to eight hundred milligrams, we can start to get him to a hypouricemic state where he can lower his levels enough that you can dissolve some of those, tophi. The problem is the tophi are the tip of the iceberg.
He has a tremendous total body rate load. When you see tophi at all, what you're not seeing can be magnified 10 times fold, a 100 fold. And if you want to prove it, then do do do the dual energy CT scans, the deck scans that show urate deposits lighting up. The problem with, I think, the use of this therapy is an overestimation of anaphylaxis. You know, infusion reactions, I think it's like six, seven percent.
And very few of those, you know, less than one in ten of those actually meet the NIH definition for anaphylaxis. So while reactions do occur, the main reaction is because you're mobilizing all this urate, you get more gout attacks and patients feel sick. So the drug was approved ten years ago, done in studies where you give eight milligrams every, two weeks or every four weeks. The response rates are basically forty to fifty percent of patients. There's a dramatic lowering of serum uric acid levels from whatever they were down to undetectable on this drug.
The real issue is whether or not you, can fight the problem of anti drug antibodies and their anti PEG antibodies, which can get in the way in the long term success, could contribute to some of the toxicity. And I think that this trend right now is, to use a background of either methotrexate, azathioprine, or mycophenolate. There's a study going on right now with mycophenolate being done at UAB by Ken Saag. I've used azathioprine. We have a recent report in the room now about the use, a published report about the use of methotrexate and people going on this.
Why would they use these DMAR drugs? Not to treat the chronic synovitis, but to suppress the development of an anti drug, anti PEG antibody that can get in the way of long term success. Patients need to be infused. It's not a slow infusion. It's a fairly easy infusion though.
They get premedicated with antihistamines and Solu Medrol more so than hydrocortisone. It's done every two weeks. You have to get a uric acid level prior to the next infusion because you wanna see uric acid levels declining, going down, and staying down. But then if uric acid starts coming back up, well, that's basically anti PEG antibodies getting in the way, and now you're gonna have a rise in uric acid. And that means, oops, we shouldn't use the drug.
You can prevent that anti drug antibodies, anti peg antibodies by using, again, azathioprine, methotrexate, probably mycophenolate, and patients will have long term success. How long do you go? As long as it takes to make them disease free and to reduce their total body urate load, which adds to their risk of renal toxicity, cardiovascular toxicity, etcetera. I am fairly liberal with the use of steroids when we're starting out therapy because infusion reactions are very common and, patients should either be on a low dose of steroids or be very quick to use twenty milligrams of steroids at the first hint of a gout flare. Again, rheumatologists, the experts in all diseases are somewhat reluctant to use, peglodecase and I don't think that's really necessary.
Look for your next patient. I want to tell you about RheumNow live and a session I'm going to be in that's going to be on Saturday. It's the second step session on, rheumatoid arthritis. In my session, we have the opening lecture being done by Bruce Cronstein from NYU, famous for his work in adenosine. Bruce is gonna talk about the mechanisms involved in the efficacy and benefits and toxicities of methotrexate.
Should be a fabulous lecture. Alvin Wells is gonna be talking about updates in imaging and new guidelines for imaging in rheumatoid arthritis including ultrasound. And then I'll be talking about differences in seronegative and seropositive and telling you things you didn't know about seronegative RA that will scare you to death. RoomNow live. You can still register at roomnow.live.
Talk to you tomorrow.
He had been diagnosed with gout ten years ago, has had many attacks over the years, a history of sort of incomplete control with the attacks going from acute and intermittent to chronic and additive, and now he's at the point of having chronic tolfacius gout, involves the hands, the feet, the elbows, occasionally the knees. And when we saw him recently, he was on four hundred milligrams of allopurinol. His uric acid level was 6.8, and he was still having intermittent attacks and a lot of pain. And a lot of his pain, as you might imagine, is related to inflammatory damage and secondary pain and periarticular pain. But then he seems to have, warmth and inflammation in some joints as well.
The question is, how do you manage him? He's at the stage of having a chronic inflammatory polyarthritis because of his urate deposition disease evidenced by some big bulky, you know, walnut to pear size, not pear size, almost pear size, collections of of tophi, elbows, feet, hands, knees. It's, you know, obviously, deforming and, and hard for him. The issue is, in discussion with the other rheumatologists managing this case, is that there's a reluctance to start this man on peglodecase. Yes, you could step up his allopurinol, and yes, you could be one of the few rheumatologists out there that, you know, would use a dose higher than four hundred or three hundred.
But the facts are that rheumatologists aren't as great as we think we are at managing gout. We just like podiatrists and renal docs and internists largely only use three hundred milligrams a day. We seldom ever, use combination therapy. Very few of you have actually used peglodecase, although the numbers of peglodecase use in the last ten years that it's been approved has actually gone steadily up. But many of you have never used it for fear of side effects, anaphylaxis, tales told around the campfire or clinic fire, whatever.
And, and I'm here to tell you that I'm not afraid to use it. I've tried to use it a number of times and had problems either with the patient or the insurance or the patient being really sick and thinking they're too sick to get this infusion. And then, and I have used it, and it's really, I think a very effective way. The issue here is the argument that was presented to me by the other rheumatologists in discussion was, well, if we increase his dose up to six hundred, even up to eight hundred milligrams, we can start to get him to a hypouricemic state where he can lower his levels enough that you can dissolve some of those, tophi. The problem is the tophi are the tip of the iceberg.
He has a tremendous total body rate load. When you see tophi at all, what you're not seeing can be magnified 10 times fold, a 100 fold. And if you want to prove it, then do do do the dual energy CT scans, the deck scans that show urate deposits lighting up. The problem with, I think, the use of this therapy is an overestimation of anaphylaxis. You know, infusion reactions, I think it's like six, seven percent.
And very few of those, you know, less than one in ten of those actually meet the NIH definition for anaphylaxis. So while reactions do occur, the main reaction is because you're mobilizing all this urate, you get more gout attacks and patients feel sick. So the drug was approved ten years ago, done in studies where you give eight milligrams every, two weeks or every four weeks. The response rates are basically forty to fifty percent of patients. There's a dramatic lowering of serum uric acid levels from whatever they were down to undetectable on this drug.
The real issue is whether or not you, can fight the problem of anti drug antibodies and their anti PEG antibodies, which can get in the way in the long term success, could contribute to some of the toxicity. And I think that this trend right now is, to use a background of either methotrexate, azathioprine, or mycophenolate. There's a study going on right now with mycophenolate being done at UAB by Ken Saag. I've used azathioprine. We have a recent report in the room now about the use, a published report about the use of methotrexate and people going on this.
Why would they use these DMAR drugs? Not to treat the chronic synovitis, but to suppress the development of an anti drug, anti PEG antibody that can get in the way of long term success. Patients need to be infused. It's not a slow infusion. It's a fairly easy infusion though.
They get premedicated with antihistamines and Solu Medrol more so than hydrocortisone. It's done every two weeks. You have to get a uric acid level prior to the next infusion because you wanna see uric acid levels declining, going down, and staying down. But then if uric acid starts coming back up, well, that's basically anti PEG antibodies getting in the way, and now you're gonna have a rise in uric acid. And that means, oops, we shouldn't use the drug.
You can prevent that anti drug antibodies, anti peg antibodies by using, again, azathioprine, methotrexate, probably mycophenolate, and patients will have long term success. How long do you go? As long as it takes to make them disease free and to reduce their total body urate load, which adds to their risk of renal toxicity, cardiovascular toxicity, etcetera. I am fairly liberal with the use of steroids when we're starting out therapy because infusion reactions are very common and, patients should either be on a low dose of steroids or be very quick to use twenty milligrams of steroids at the first hint of a gout flare. Again, rheumatologists, the experts in all diseases are somewhat reluctant to use, peglodecase and I don't think that's really necessary.
Look for your next patient. I want to tell you about RheumNow live and a session I'm going to be in that's going to be on Saturday. It's the second step session on, rheumatoid arthritis. In my session, we have the opening lecture being done by Bruce Cronstein from NYU, famous for his work in adenosine. Bruce is gonna talk about the mechanisms involved in the efficacy and benefits and toxicities of methotrexate.
Should be a fabulous lecture. Alvin Wells is gonna be talking about updates in imaging and new guidelines for imaging in rheumatoid arthritis including ultrasound. And then I'll be talking about differences in seronegative and seropositive and telling you things you didn't know about seronegative RA that will scare you to death. RoomNow live. You can still register at roomnow.live.
Talk to you tomorrow.
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