Poets Know It (3.13.2026) Save
Transcription
Hello everyone. It's Friday the 13th, 2026 March. This is the RheumNow podcast. I'm Jack Cush with RheumNow and let's get into the podcast.
Fiber. Should you be using fiber in your diet? Does it have medical benefits? I was flipping through the journal Nutrients recently — you should wonder why — and found an interesting study on knee OA that using a prebiotic fiber inulin, they looked at its effects on knee OA outcomes. So this is a study of 117 older adults. I think the mean age was like 67. They had knee OA and they either treated them with six weeks of inulin, I think 20 grams a day, or physiotherapy exercise, or both, or placebo. And they were looking at a number of different outcomes. And they basically showed that both the inulin and the physiotherapy exercise significantly improved pain over placebo. And yes the exercise was better than the inulin, but the inulin nonetheless was significant at p 0.045. It also improved pain sensitivity and grip strength, and that was associated — inulin only, that is — with an improvement in short-chain fatty acids and GLP-1, suggesting a connection between the gut and strength.
Anyway, I like this because it kind of follows up to what we talked about at — was it ACR — that inulin improved DMARD responses in RA, especially methotrexate responses. There's something here. Although again, this is not a gigantic study or incredibly well-done study and not a great journal, but nonetheless, I think there's something here.
AI — we're being talked to and talked about AI and its role in medicine. Found an interesting study on AI and different sorts of neural models in diagnosing different conditions. This study from an endocrine journal was about the diagnosis of acromegaly, and acromegaly as you know has coarse facial features, and often there are studies of AI diagnosing acromegaly just by facial photographs. In this study, they did hand photographs, specifically dorsal hand photographs — guess looking for large hands, coarse features in the hands — but then also ventral, a fist sign where the externally placed thumb, and that you couldn't — if you have the fist sign, you make a fist but your fingernails are still showing, whereas a normal person can bury their fingernails in the center crease of the fist, as I'm showing you here.
Anyway, using this, the AI model was able to diagnose acromegaly with sensitivity and specificity of 90%, same for positive predictive value, AUC 0.96, and it outperformed specialist diagnosis. This is a study of 700-plus patients — 317 acromegaly and 399 controls from 15 Japanese centers. The point being that diagnosis can be done by AI from visual photographs. It's been done in dermatology, by the way. There's no reason it can't be done in rheumatology. And we talked before about the crease signs decreasing in people with synovitis and other ways of doing visually aided diagnosis with computer modeling and AI. I think this is going to be a tool that we'll be using 10 years from now.
I think maybe there are a few really big headline results this week. Maybe this is the biggest one, and that is UCB announced in a press release topline results of their BE BOLD study. It's a head-to-head study of their IL-17A/F inhibitor bimekizumab going head-to-head against the IL-23 inhibitor risankizumab. This was a fairly large 553-patient study of PsA patients where the primary endpoint in a 24-week study was ACR50 responses at week 16. They just gave the topline results, and the 553 PsA patients were either biologic-naive or had failed one prior TNF, and they met their primary endpoint — that was an ACR50 with bimekizumab being superior to risankizumab. These are just the topline results, that's why I got a tweet and not a full article, because I couldn't write much more than I could write in a 300-character tweet. And I think we'll see this either as a late-breaking abstract at EULAR in June or maybe we have to wait until ACR.
But this is kind of — we don't have many head-to-head trials, do we, in rheumatology. In dermatology they've got a dozen of them, and that's why they can say in psoriasis that this is better than that and whatever. And again the psoriasis data has changed a lot in the last few years, has it not — with the IL-17s outperforming the TNFs, and then the IL-23s come up and they're outperforming IL-17s, and then the dual inhibitors come up and they're outperforming or going head-to-head, and that's just in psoriasis. Here, head-to-head for the first time in PsA — it's kind of an interesting result.
Another interesting study looked at does it matter when you use your TNF inhibitor, how early you use it? This is a Swiss study, good data, 3,300 axial spondyloarthritis patients who either received their first TNF inhibitor very early in the first year
um that was 400 plus patients. um early in the first one to two years that was 200 patients or greater than after two years that was um 2500 patients after they did the adjustments for age sex B27 smoking etc. um there was no difference in overall outcomes when it came to um the end points that they looked at which was retention on TNF or ASDAS scores. It didn't matter whether you got it in the first 12 months or after 24 months. And I kind of find that um maybe surprising, but you know, we we reported this from ACR. The Leid's group looked at um what happened if you use a TNF inhibitor very early as first therapy in RA and there was a benefit to it but mainly in the first I think it was first year or five years and only when it came to um minimizing the numbers of difficult to treat RA patients. Uh and I took away from that that yes you should use your best drug first. Um, why that didn't pan out here, um, might have to do with the end points that they looked at, TNF inhibitor retention and ASDAS scores. Um, maybe it would be different if they looked at the number who had damage or who had difficult to treat uh, axSpA, but I think this is um, a novel study.
Another study looking at uh persistence on therapy comes from Korean national uh insurance claims data uh 13-year study where they looked at um 1,660 um axSpA patients who um were either treated with an IL-17 inhibitor or a TNF inhibitor. And they found that um overall treatment uh durations on each of these drugs meaning was was probably was equal actually. However, if they looked at um people who discontinued for primary non-response, that was more likely with TNF inhibitors, suggesting therefore that an IL-17 inhibitor may have greater durability um when um used in this Korean cohort. Again the was higher significantly higher IL-17 versus TNF um about 54% higher and that was significant.
How often do you get fibromyalgia in uh axial spondyloarthritis? You know we see a lot of fibromyalgia and if you're not seeing any fibromyalgia in any of your rheumatic disease patients you're missing a ton cuz I'm not. And I think that this number um you know it's really really high in Sjögren's um it can be 30 40% in RA in this study of uh the DESIR uh cohort this is an axSpA early uh axSpA cohort study they did um annual FiRST studies that's a fibromyalgia survey to identify the disease fibromyalgia found in 22% at baseline. Those who had fibromyalgia and axSpA were less likely to be B27 positive, less likely to have X-ray sacroiliitis. Although in the end they all had the same number MRI sacroiliitis. They um these patients had less self-reported disease activity um less quality of life u measures more disability. They were more likely to be treated with TNF inhibitors than those that did not have fibromyalgia, which is troublesome, is it not? And that number is substantial. 64% if you had fibromyalgia SpA, got a TNF inhibitor versus 41% if you didn't have fibromyalgia and had um axSpA. And then what is that? Is that them having more pain, having more complaints, having more visits, getting more attention, gets you more prescriptions? Hard to know, but secondary fibromyalgia is a significant complication in the management of our patients regardless of the diagnosis.
Um, sleep's a big issue, is it not? Especially in fibromyalgia. Well, here in this study, it's an English longitudinal study of aging. They looked at um those who developed uh rheumatoid arthritis and they showed that those who developed rheumatoid arthritis, I think the number was like over 600 people in the study, they had significantly higher um moderate to poor quality sleep compared to those who had good quality sleep. And the all and and and again it raised the risk with moderate sleep quality 23% poor sleep quality raised it 50%. Now is it really causing RA or is it really causing depression that then gets diagnosed as RA correctly or wrongly them's the data you'll have to figure it out.
We've been talking about um PAs in the last uh few months. Um a recent study of physician assistant workforce showed that it grew in the United States by 28% from 2020 to 2024. That's a 28% growth in the number of physician assistants. That's outnumbering the growth of physicians. Um as of 2024, the number reached almost 190,000. It increased in every state uh in the union. The least in Alaska where was only 10% increase and the most in South Carolina where there was a 48% increase um up to almost 3,000 in 2024. As of 2024 um as I said the number was 189,188 physician assistants. That amounts to 55.6 PAs per 100,000 population. It's important. Uh, another big thing I tweeted about this week, not going to get into here, is that physician assistants and their society want them to be renamed as physician associates. Um, there's a nationwide push for this. The AMA is against it. There are three states in the union that are in favor have actually passed legislative changes for that. Oregon, New Hampshire, and
somewhere else. I can't remember off the top of my head, but nonetheless, um, they're in the news. Uh, I don't know if I said this last week or not, so I'm going to say it again this week. I think strength is really, really important. Um, and so much so, I think we should make that like one of our top goals in all of our patients. Getting stronger is getting better.
Muscular strength — this is a JAMA Open Network prospective cohort study of older women. 5,472 older women showed that when they measured muscular strength by grip strength and chair stand times — I think it's repeated chair stand times — that those who achieved their goals had lower overall mortality, either a 15% or 33% lower mortality with different measures of strength. If you're strong, you hurt less. If you hurt less, you do more. If you do more, you live longer. Strength should be the goal.
Uh, last week we had — um, maybe the week before — we had an announcement about a complete response letter that the FDA issued to AstraZeneca regarding their application, their BLA, to get a new indication for anifrolumab, also known as Saphnelo, based on the SC TULIP study where anifrolumab was shown to be effective in cutaneous lupus. Um, in the EMA it's actually got approved for cutaneous lupus, but the FDA is saying, "Whoa, whoa, whoa, wait a second." They issued a complete response letter and now they say that the reason for this was that there are concerns about the way the data was analyzed, especially with regard to the key analyses, and that they are expecting that it needs to undergo a review, and that a decision on this extended indication is going to happen in the first half of 2026. Such is the case with these complete response letters. Again, a complete response letter doesn't mean that oh, you had a complete response and you're doing great. No, it means like halt, wait — this means we need to reanalyze this issue.
While it was just announced just this past month, it was originally — this complete response letter went to the company back in October. And the manufacturer AstraZeneca has been, I guess, working with the FDA on the key analyses of the SC TULIP study.
Um, the other big announcement I think this week was the FDA approved deucravacitinib, the selective TYK2 inhibitor made by BMS, for use in psoriatic arthritis. Um, it's approved for the treatment of adults with active psoriatic arthritis based on the pivotal phase 3 trials — the POETYK PSA-1 and the POETYK PSA-2 clinical trials. Um, that POETYK PSA-1 was 670 biologic-naive patients. The POETYK PSA-2 was 624 PsA patients that had — could have received biologics. Um, and in both studies deucravacitinib at 6 milligrams once a day was superior to placebo at its primary endpoint being an ACR20, and also at secondary endpoint of the MDA — minimal disease activity — at week 16. These are both 52-week trials with a primary endpoint at week 16.
So this is a new indication being added to deucravacitinib, also known as a TYK2 inhibitor. The dose, as you know, is 6 milligrams once a day with or without food. It is not recommended in the package insert for use with other potent immunosuppressants. Um, in these patients there is an infection warning that you should avoid its use in patients with active or serious infections. If a serious infection develops, discontinue deucravacitinib until the infection resolves, is what the package insert says. I would — I personally wouldn't do that, but that's my problem. Um, I stop biologics and new therapies when people are hospitalized or when I know that it's a truly serious infection.
Uh, and I guess maybe they're saying that when it's a serious infection, they should be tested for latent or active TB prior to initiating therapy. Is there a real risk of TB with TYK2 inhibition? Well, there isn't a lot of data on it, but as I've said here many, many times before, the greatest risk of TB is when you inhibit TNF. JAK and TYK inhibitors are not very good at inhibiting TNF. Has TB been reported in people receiving JAK and TYK inhibitors? Yes, because most of the trials done these days are done in parts of the world where TB is prevalent. It's not so prevalent in the United States, Western Europe, Australia, where TB rates are incredibly low. Anyway, the package insert says you got to do it. You got to do it.
Um, there have been reports of zoster and herpes simplex infection on a TYK2, just like you would expect on a JAK, and that they do get elevated LFTs, triglycerides, and asymptomatic CPK-emia has been reported, but the package insert says that there have been reports of rhabdomyolysis with CPK elevation, and obviously stopping the drug is advised in these rare situations.
The other big report from this week was from the New England Journal — obinutuzumab, the novel new — new for us rheumatology — anti-CD20 monoclonal antibody, was tested in patients with
active SLE without nephritis. As you know, obinutuzumab was approved in October for use in lupus nephritis based on trials proving its efficacy in lupus nephritis. This New England Journal article was a study of people without lupus nephritis and they basically — it's 303 lupus patients who were treated. The primary endpoint was an SRI-4 at week 52 where obinutuzumab 77%, placebo 53%, the difference was 23% and that was highly significant. Most of the patients going into this trial had a SLEDAI scores of like 13. That's pretty high. Most of them had like 80–90% had mucocutaneous disease and musculoskeletal disease but we don't see any classic skin endpoint outcomes or we don't see any like ACR 20 or CLASI output outcomes when you read the paper. Nonetheless, it was significant in non-renal lupus patients. And I think that whether that gets added to the indication, we'll just have to wait and see.
Lastly, I like the report from a nephrology journal about managing gout in CKD patients. It was chock-full of nuts — I mean, chock-full of good guidance. And it was a very well-written paper. I gave you a synopsis of it on RheumNow. But for the full report on, like for instance, what to do in transplant patients and dialysis patients and acute gout and whatnot — who should get urate-lowering therapy? The ACR and EULAR have put out guidelines. The ACR says that you should use urate-lowering therapy if the patient with gout has subcutaneous tophi, has radiographic gout, has two or more flares per year — that being gout flares. But urate-lowering therapy isn't recommended for those who have their first gout flare. But wait — if they have their first gout flare and they also have moderate to severe CKD, yes, they should get urate-lowering therapy. Or if their uric acid is greater than nine, yes, they should. Or if they have nephrolithiasis, yes, they should. So there are situations when you should start urate-lowering therapy in the face of CKD if that was the first gout flare.
As you know, uricosuric drugs are not recommended for use in patients with CKD, especially stage three and beyond, because you're going to cause a greater risk of nephrolithiasis and possibly kidney damage. They go into this issue of start low, go slow. And you know that's why the new guidelines say everyone gets a starter dose of 100 milligrams allopurinol and then after that you elevate it. But if you read the paper — or you read the paper by Lisa Stamp who did the start low go slow study — you know if they've got really bad CKD stage five, the dose is like 50 milligrams given like once a week or every other — twice a week — and as you get more and more renal function going from like five cc's per minute to 10 to 15 to 30, you might go to 50 twice a week or 50 every other day as your starting dose. It's not until you get to CKD stage 2 with a creatinine clearance of 60 to 90 that the 100 mg per day is the starting dose.
It's a good reference. Again, NSAIDs are contraindicated in CKD, but not contraindicated would be colchicine, oral steroids, arthrocentesis, and intraarticular injection of corticosteroids — all those don't need renal adjustments except colchicine does. Right? You don't want to use full-dose colchicine in people who have again significant CKD. It's a good reference. It's one worth downloading or sharing with your trainees.
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Fiber. Should you be using fiber in your diet? Does it have medical benefits? I was flipping through the journal Nutrients recently — you should wonder why — and found an interesting study on knee OA that using a prebiotic fiber inulin, they looked at its effects on knee OA outcomes. So this is a study of 117 older adults. I think the mean age was like 67. They had knee OA and they either treated them with six weeks of inulin, I think 20 grams a day, or physiotherapy exercise, or both, or placebo. And they were looking at a number of different outcomes. And they basically showed that both the inulin and the physiotherapy exercise significantly improved pain over placebo. And yes the exercise was better than the inulin, but the inulin nonetheless was significant at p 0.045. It also improved pain sensitivity and grip strength, and that was associated — inulin only, that is — with an improvement in short-chain fatty acids and GLP-1, suggesting a connection between the gut and strength.
Anyway, I like this because it kind of follows up to what we talked about at — was it ACR — that inulin improved DMARD responses in RA, especially methotrexate responses. There's something here. Although again, this is not a gigantic study or incredibly well-done study and not a great journal, but nonetheless, I think there's something here.
AI — we're being talked to and talked about AI and its role in medicine. Found an interesting study on AI and different sorts of neural models in diagnosing different conditions. This study from an endocrine journal was about the diagnosis of acromegaly, and acromegaly as you know has coarse facial features, and often there are studies of AI diagnosing acromegaly just by facial photographs. In this study, they did hand photographs, specifically dorsal hand photographs — guess looking for large hands, coarse features in the hands — but then also ventral, a fist sign where the externally placed thumb, and that you couldn't — if you have the fist sign, you make a fist but your fingernails are still showing, whereas a normal person can bury their fingernails in the center crease of the fist, as I'm showing you here.
Anyway, using this, the AI model was able to diagnose acromegaly with sensitivity and specificity of 90%, same for positive predictive value, AUC 0.96, and it outperformed specialist diagnosis. This is a study of 700-plus patients — 317 acromegaly and 399 controls from 15 Japanese centers. The point being that diagnosis can be done by AI from visual photographs. It's been done in dermatology, by the way. There's no reason it can't be done in rheumatology. And we talked before about the crease signs decreasing in people with synovitis and other ways of doing visually aided diagnosis with computer modeling and AI. I think this is going to be a tool that we'll be using 10 years from now.
I think maybe there are a few really big headline results this week. Maybe this is the biggest one, and that is UCB announced in a press release topline results of their BE BOLD study. It's a head-to-head study of their IL-17A/F inhibitor bimekizumab going head-to-head against the IL-23 inhibitor risankizumab. This was a fairly large 553-patient study of PsA patients where the primary endpoint in a 24-week study was ACR50 responses at week 16. They just gave the topline results, and the 553 PsA patients were either biologic-naive or had failed one prior TNF, and they met their primary endpoint — that was an ACR50 with bimekizumab being superior to risankizumab. These are just the topline results, that's why I got a tweet and not a full article, because I couldn't write much more than I could write in a 300-character tweet. And I think we'll see this either as a late-breaking abstract at EULAR in June or maybe we have to wait until ACR.
But this is kind of — we don't have many head-to-head trials, do we, in rheumatology. In dermatology they've got a dozen of them, and that's why they can say in psoriasis that this is better than that and whatever. And again the psoriasis data has changed a lot in the last few years, has it not — with the IL-17s outperforming the TNFs, and then the IL-23s come up and they're outperforming IL-17s, and then the dual inhibitors come up and they're outperforming or going head-to-head, and that's just in psoriasis. Here, head-to-head for the first time in PsA — it's kind of an interesting result.
Another interesting study looked at does it matter when you use your TNF inhibitor, how early you use it? This is a Swiss study, good data, 3,300 axial spondyloarthritis patients who either received their first TNF inhibitor very early in the first year
um that was 400 plus patients. um early in the first one to two years that was 200 patients or greater than after two years that was um 2500 patients after they did the adjustments for age sex B27 smoking etc. um there was no difference in overall outcomes when it came to um the end points that they looked at which was retention on TNF or ASDAS scores. It didn't matter whether you got it in the first 12 months or after 24 months. And I kind of find that um maybe surprising, but you know, we we reported this from ACR. The Leid's group looked at um what happened if you use a TNF inhibitor very early as first therapy in RA and there was a benefit to it but mainly in the first I think it was first year or five years and only when it came to um minimizing the numbers of difficult to treat RA patients. Uh and I took away from that that yes you should use your best drug first. Um, why that didn't pan out here, um, might have to do with the end points that they looked at, TNF inhibitor retention and ASDAS scores. Um, maybe it would be different if they looked at the number who had damage or who had difficult to treat uh, axSpA, but I think this is um, a novel study.
Another study looking at uh persistence on therapy comes from Korean national uh insurance claims data uh 13-year study where they looked at um 1,660 um axSpA patients who um were either treated with an IL-17 inhibitor or a TNF inhibitor. And they found that um overall treatment uh durations on each of these drugs meaning was was probably was equal actually. However, if they looked at um people who discontinued for primary non-response, that was more likely with TNF inhibitors, suggesting therefore that an IL-17 inhibitor may have greater durability um when um used in this Korean cohort. Again the was higher significantly higher IL-17 versus TNF um about 54% higher and that was significant.
How often do you get fibromyalgia in uh axial spondyloarthritis? You know we see a lot of fibromyalgia and if you're not seeing any fibromyalgia in any of your rheumatic disease patients you're missing a ton cuz I'm not. And I think that this number um you know it's really really high in Sjögren's um it can be 30 40% in RA in this study of uh the DESIR uh cohort this is an axSpA early uh axSpA cohort study they did um annual FiRST studies that's a fibromyalgia survey to identify the disease fibromyalgia found in 22% at baseline. Those who had fibromyalgia and axSpA were less likely to be B27 positive, less likely to have X-ray sacroiliitis. Although in the end they all had the same number MRI sacroiliitis. They um these patients had less self-reported disease activity um less quality of life u measures more disability. They were more likely to be treated with TNF inhibitors than those that did not have fibromyalgia, which is troublesome, is it not? And that number is substantial. 64% if you had fibromyalgia SpA, got a TNF inhibitor versus 41% if you didn't have fibromyalgia and had um axSpA. And then what is that? Is that them having more pain, having more complaints, having more visits, getting more attention, gets you more prescriptions? Hard to know, but secondary fibromyalgia is a significant complication in the management of our patients regardless of the diagnosis.
Um, sleep's a big issue, is it not? Especially in fibromyalgia. Well, here in this study, it's an English longitudinal study of aging. They looked at um those who developed uh rheumatoid arthritis and they showed that those who developed rheumatoid arthritis, I think the number was like over 600 people in the study, they had significantly higher um moderate to poor quality sleep compared to those who had good quality sleep. And the all and and and again it raised the risk with moderate sleep quality 23% poor sleep quality raised it 50%. Now is it really causing RA or is it really causing depression that then gets diagnosed as RA correctly or wrongly them's the data you'll have to figure it out.
We've been talking about um PAs in the last uh few months. Um a recent study of physician assistant workforce showed that it grew in the United States by 28% from 2020 to 2024. That's a 28% growth in the number of physician assistants. That's outnumbering the growth of physicians. Um as of 2024, the number reached almost 190,000. It increased in every state uh in the union. The least in Alaska where was only 10% increase and the most in South Carolina where there was a 48% increase um up to almost 3,000 in 2024. As of 2024 um as I said the number was 189,188 physician assistants. That amounts to 55.6 PAs per 100,000 population. It's important. Uh, another big thing I tweeted about this week, not going to get into here, is that physician assistants and their society want them to be renamed as physician associates. Um, there's a nationwide push for this. The AMA is against it. There are three states in the union that are in favor have actually passed legislative changes for that. Oregon, New Hampshire, and
somewhere else. I can't remember off the top of my head, but nonetheless, um, they're in the news. Uh, I don't know if I said this last week or not, so I'm going to say it again this week. I think strength is really, really important. Um, and so much so, I think we should make that like one of our top goals in all of our patients. Getting stronger is getting better.
Muscular strength — this is a JAMA Open Network prospective cohort study of older women. 5,472 older women showed that when they measured muscular strength by grip strength and chair stand times — I think it's repeated chair stand times — that those who achieved their goals had lower overall mortality, either a 15% or 33% lower mortality with different measures of strength. If you're strong, you hurt less. If you hurt less, you do more. If you do more, you live longer. Strength should be the goal.
Uh, last week we had — um, maybe the week before — we had an announcement about a complete response letter that the FDA issued to AstraZeneca regarding their application, their BLA, to get a new indication for anifrolumab, also known as Saphnelo, based on the SC TULIP study where anifrolumab was shown to be effective in cutaneous lupus. Um, in the EMA it's actually got approved for cutaneous lupus, but the FDA is saying, "Whoa, whoa, whoa, wait a second." They issued a complete response letter and now they say that the reason for this was that there are concerns about the way the data was analyzed, especially with regard to the key analyses, and that they are expecting that it needs to undergo a review, and that a decision on this extended indication is going to happen in the first half of 2026. Such is the case with these complete response letters. Again, a complete response letter doesn't mean that oh, you had a complete response and you're doing great. No, it means like halt, wait — this means we need to reanalyze this issue.
While it was just announced just this past month, it was originally — this complete response letter went to the company back in October. And the manufacturer AstraZeneca has been, I guess, working with the FDA on the key analyses of the SC TULIP study.
Um, the other big announcement I think this week was the FDA approved deucravacitinib, the selective TYK2 inhibitor made by BMS, for use in psoriatic arthritis. Um, it's approved for the treatment of adults with active psoriatic arthritis based on the pivotal phase 3 trials — the POETYK PSA-1 and the POETYK PSA-2 clinical trials. Um, that POETYK PSA-1 was 670 biologic-naive patients. The POETYK PSA-2 was 624 PsA patients that had — could have received biologics. Um, and in both studies deucravacitinib at 6 milligrams once a day was superior to placebo at its primary endpoint being an ACR20, and also at secondary endpoint of the MDA — minimal disease activity — at week 16. These are both 52-week trials with a primary endpoint at week 16.
So this is a new indication being added to deucravacitinib, also known as a TYK2 inhibitor. The dose, as you know, is 6 milligrams once a day with or without food. It is not recommended in the package insert for use with other potent immunosuppressants. Um, in these patients there is an infection warning that you should avoid its use in patients with active or serious infections. If a serious infection develops, discontinue deucravacitinib until the infection resolves, is what the package insert says. I would — I personally wouldn't do that, but that's my problem. Um, I stop biologics and new therapies when people are hospitalized or when I know that it's a truly serious infection.
Uh, and I guess maybe they're saying that when it's a serious infection, they should be tested for latent or active TB prior to initiating therapy. Is there a real risk of TB with TYK2 inhibition? Well, there isn't a lot of data on it, but as I've said here many, many times before, the greatest risk of TB is when you inhibit TNF. JAK and TYK inhibitors are not very good at inhibiting TNF. Has TB been reported in people receiving JAK and TYK inhibitors? Yes, because most of the trials done these days are done in parts of the world where TB is prevalent. It's not so prevalent in the United States, Western Europe, Australia, where TB rates are incredibly low. Anyway, the package insert says you got to do it. You got to do it.
Um, there have been reports of zoster and herpes simplex infection on a TYK2, just like you would expect on a JAK, and that they do get elevated LFTs, triglycerides, and asymptomatic CPK-emia has been reported, but the package insert says that there have been reports of rhabdomyolysis with CPK elevation, and obviously stopping the drug is advised in these rare situations.
The other big report from this week was from the New England Journal — obinutuzumab, the novel new — new for us rheumatology — anti-CD20 monoclonal antibody, was tested in patients with
active SLE without nephritis. As you know, obinutuzumab was approved in October for use in lupus nephritis based on trials proving its efficacy in lupus nephritis. This New England Journal article was a study of people without lupus nephritis and they basically — it's 303 lupus patients who were treated. The primary endpoint was an SRI-4 at week 52 where obinutuzumab 77%, placebo 53%, the difference was 23% and that was highly significant. Most of the patients going into this trial had a SLEDAI scores of like 13. That's pretty high. Most of them had like 80–90% had mucocutaneous disease and musculoskeletal disease but we don't see any classic skin endpoint outcomes or we don't see any like ACR 20 or CLASI output outcomes when you read the paper. Nonetheless, it was significant in non-renal lupus patients. And I think that whether that gets added to the indication, we'll just have to wait and see.
Lastly, I like the report from a nephrology journal about managing gout in CKD patients. It was chock-full of nuts — I mean, chock-full of good guidance. And it was a very well-written paper. I gave you a synopsis of it on RheumNow. But for the full report on, like for instance, what to do in transplant patients and dialysis patients and acute gout and whatnot — who should get urate-lowering therapy? The ACR and EULAR have put out guidelines. The ACR says that you should use urate-lowering therapy if the patient with gout has subcutaneous tophi, has radiographic gout, has two or more flares per year — that being gout flares. But urate-lowering therapy isn't recommended for those who have their first gout flare. But wait — if they have their first gout flare and they also have moderate to severe CKD, yes, they should get urate-lowering therapy. Or if their uric acid is greater than nine, yes, they should. Or if they have nephrolithiasis, yes, they should. So there are situations when you should start urate-lowering therapy in the face of CKD if that was the first gout flare.
As you know, uricosuric drugs are not recommended for use in patients with CKD, especially stage three and beyond, because you're going to cause a greater risk of nephrolithiasis and possibly kidney damage. They go into this issue of start low, go slow. And you know that's why the new guidelines say everyone gets a starter dose of 100 milligrams allopurinol and then after that you elevate it. But if you read the paper — or you read the paper by Lisa Stamp who did the start low go slow study — you know if they've got really bad CKD stage five, the dose is like 50 milligrams given like once a week or every other — twice a week — and as you get more and more renal function going from like five cc's per minute to 10 to 15 to 30, you might go to 50 twice a week or 50 every other day as your starting dose. It's not until you get to CKD stage 2 with a creatinine clearance of 60 to 90 that the 100 mg per day is the starting dose.
It's a good reference. Again, NSAIDs are contraindicated in CKD, but not contraindicated would be colchicine, oral steroids, arthrocentesis, and intraarticular injection of corticosteroids — all those don't need renal adjustments except colchicine does. Right? You don't want to use full-dose colchicine in people who have again significant CKD. It's a good reference. It's one worth downloading or sharing with your trainees.
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