2026 Resolutions (1.9.2026) Save
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Happy new year. It's January 9th, 2026, and this is the RheumNow podcast. Hi, I'm Jack Cush, executive editor of RheumNow.com. It's 2026. It's going to be a better year. It's going to be a better podcast. I'll give you my resolutions at the end of this. That means you got to stick around for a bit.
So, this week on the podcast, we're going to talk about bendability and its use in clinic, a better way to treat RA that involves getting outside of yourself or outside, and a novel advance in GLP-1 agonists. You know, GLP-1 agonists are called the incretins. I thought incretins were little men who jumped out of spaceships and were stealing my flip-flops, but that's another story.
So the first report is on preeclampsia and its association with antiphospholipid antibodies. Thought this was interesting. 100 women with severe preeclampsia were compared to 40 controls — just pregnant women without preeclampsia — and they assessed patients for antiphospholipid antibodies. They found them much more frequently in those with preeclampsia, 34% versus 10%. That's a 4-and-a-half-fold increased risk for APL positivity with severe preeclampsia. The preeclampsia occurred both early and late in pregnancy, so it did have predictive value. It might be something you might want to look at if you have a preeclampsia in a patient, or conversely, a patient who has antiphospholipid antibodies could be at risk for preeclampsia going forward.
Johnson and Johnson announced some topline results of a phase 2b JASMINE study, which assessed the efficacy and safety of nipocalimab in lupus patients. Nipocalimab is an FcRn blocker that has been shown in other studies to reduce autoantibody production and disease activity. It's been shown to have efficacy in Sjögren's and maybe in RA — quasi results in RA. This study was in lupus, where it met its primary endpoint at week 24, which is a significant reduction in the SRI-4 response versus those on placebo. No new safety signals, no granular data. This is going to be presented later on at another meeting. These are topline results.
Another study appeared this week about CAR T cells. You know, there are a lot of CAR T cell drugs in development. I think there's at least 40 companies doing about 80 studies right now on CAR T cell therapy in autoimmune diseases. And we're talking about this like it's the next coming of, you know, a savior in rheumatology. But really we've got very little data and we're about 3 to 5 years away from getting good data that we can hang our hat on. Right now we have these small reports.
And here's a report called the CASTLE study. It's a phase 1/2A CAR T cell trial of 24 patients with refractory lupus, scleroderma, and myositis. And it's — let me look at the numbers here — 10 with lupus, nine with scleroderma, and five with myositis. Again, they were treatment refractory and they're getting this autologous CD19 CAR T cell therapy called MVCART19.1. The primary goal of the study, being a phase 1/early 2 study, was safety, and they had no cytokine release syndromes, no CRS grade 2 or higher, no ICANS safety concerns at week 24, and that was all good.
More importantly, they did assess efficacy outcomes — 22 out of the 24 patients met a predetermined efficacy response. So in lupus, nine out of 10 met DORIS remission. Nine out of nine scleroderma patients had no progression of scleroderma — I guess that's their skin score. And four out of five had a major or moderate response on myositis outcomes. The bottom line is that all these patients did go off of glucocorticoids and were off of immunosuppressors for the first six months. If you look at the graph that we showed you in the tweet on that, the complete response is really at 6 months, but responses are lost over time variably. Again, they only had a one-time treatment. So again, another bit of early encouraging data, but I would tell you to be skeptical still, because we don't have really great data, really controlled data.
Arthritis Care and Research had a nice report on generalized joint hypermobility syndrome. It was a meta-analysis and systematic review of 46 studies in 23,000 patients, and they looked at the utility of the Beighton criteria in making the diagnosis of hypermobility syndrome. Using the usual Beighton criteria, it was about 2% in the populations that were studied. It was more prevalent in younger adults, about 5% in young adults between 18 and 25. And we know hypermobility is sort of a pediatric rheumatology problem, more so than an adult rheumatology problem, but young adults can have this too. Young adult patients presenting with what looks like what you think might be axial spinal arthritis, early disease or non-radiographic axial spinal arthritis, or fibromyalgia — you should probably be doing the Beighton score on these people. And you know what that is? There's five
maneuvers. It's the fourth finger that goes back more than 90°. It's your thumb flexed onto the surface of the forearm. It's hyperextension of the elbows, hyperextension of the knees, and being able to bend over and put your palms on the floor. That's nine points. The criteria for hypermobility is six points out of nine. But what they showed was that the number of points necessary to make the diagnosis changes according to age. So six points is right for young people 18 to 25, but they propose five points or more if you're 26 to 65. And then if you're over 65, it's four points that you need to make the diagnosis. I don't know that I agree with that, but they did the research, at least the meta-analysis. It's something that should be considered. And I would tell you that if you're like me, you probably don't test enough for hypermobility syndrome in patients who have ill-defined complaints and no evidence of synovitis or bony hypertrophy.
Um, I like this report this week. A large population-based study showed the connection between obesity and low back pain. And we know there's a connection, but I like the numbers here. The study found that for weight gain you have a 7% increase in low back pain for every one unit of BMI that you increase, or every 10 lbs. That's very instructive. 10 lbs of weight, or 30 lbs of weight gained by your patient, they now have a 21% higher risk of chronic low back pain. I like that.
Um, a VA study looked at RA patients with calcium pyrophosphate deposition disease, CPPD. So this is older men at the VA, their average age around 65. They found 64 patients amongst their RA population — 2.3% — who had ICD-9 and ICD-10 codes for both RA and CPPD. The ones who had CPPD were older. They had more comorbidity, especially osteoarthritis, more spinal disease, diabetes, but less RF positivity. And if they were seropositive RA patients with CPPD, they were less likely to achieve low disease activity and used more prednisone and more biologic or targeted synthetics. They were also more likely to have death and total joint replacement. But the takeaway on this article was: if you have RA and CPPD, maybe you should be rethinking your diagnosis of RA, especially if they're seronegative. Think about it. I think it's good advice.
Um, I like this report that appeared recently in J Rheum. It's from Adelaide University in Australia, talking about green space exposure reducing the risk of RA. What is green space? You know, isn't that a band? Maybe I'm getting that confused. But we do know there's plenty of evidence out there about toxic exposures and increasing the risk of RA. It starts with diet and obesity. It's obvious with smoking. It's obviously being near pollution and hydrocarbons and solvents and whatnot. Tons of studies showing an increased risk of RA. That's substantial, right? You could very well say — and we should have this whole specialty of environmental rheumatology — that we should be making ourselves knowledgeable in this, because it's all about lifestyle, is it not? But anyway, this full-read article in J Rheum, the lead author is Stanhope, shows that exposure to green space — that's gardens, fields, being outdoors, being around greenery, being away from toxic exposures — has in three studies been shown to have a protective effect against developing RA. So could you not prevent RA by going green? This again underscores the importance of lifestyle in both the assessment of our patients and the counseling of our patients.
A UK group did an interesting study of almost 1,850 RA patients who were starting on a biologic or targeted synthetic. They found that 30% or so were on steroids at the beginning of therapy. And they followed them over a year and then even beyond. And they saw that two-thirds of patients were still on steroids and largely didn't change or wean their dose. What's going on? Why are you using very expensive, very potent drugs? The main reason is to get control of the disease. The secondary reason is to get them off of steroids. But we don't do that. And this is a call for — we probably need to pay more attention to this. I think the article was meant to point out that we're not vigilant in basically limiting or weaning steroids, and that maybe we should be doing better, or maybe that the therapies that we're using aren't as complete as we think they are.
Japan has more experience with this phenomenon of methotrexate-associated lymphoma and lymphoproliferative disorders. This report I put up this week: 38 RA patients who developed a methotrexate-related — meaning they got methotrexate and they developed an associated LPD, lymphoproliferative disorder. Of the 38, 22 spontaneously regressed when they stopped the methotrexate, but 16 were non-spontaneous regressors. Of those 16, a third of them — five — died. If you were a
non-regressor, meaning that it was going to continue the lymphoproliferative disorder, you were more likely to have high LDH levels at the start of therapy and at diagnosis. They were more likely to have lower lymphocyte recovery after you stop methotrexate. And clearly they had a higher mortality risk. You know what? I think this is really interesting, but I've never seen this and I've treated as many people with methotrexate as you have and I think I'm looking just like you are. I have some of my colleagues here in the US I do know have seen a case or two of this but I've never seen it. But it's still something to be notable of since you are the world's experts in methotrexate. Are you not?
Speaking of methotrexate, here's a study that I don't know what to do with. You know there's a few, a handful of studies about methotrexate and its use in polymyalgia — PMR — either refractory disease or in new onset disease. And I'm going to show you one and by the way I'm on the fence. I don't believe that it really works based on the data I've seen. I've seen more recent studies where it just really doesn't seem to work. This is a relatively small study, 58 patients, but it was a randomized controlled trial. These are new PMR patients with less than eight weeks of steroids. And they were then either given 25 milligrams per week of methotrexate or placebo. And they had a weaning protocol for the steroids over 24 weeks. At week 52, the endpoint being glucocorticoid-free remission seen in 80% that were on methotrexate, only 40% on placebo. Yes, this is significant at 0.0042. Do I believe it? Well, I got to because they published it. Seems like their methodology is fine. They're faulted for a relatively small study, right? I need to see big studies — 200 plus — well-designed trial, maintenance of blind, and at least a 24-week if not 52-week endpoint. So again, take with that what you will, but I wanted you to be aware of it.
Another really important study was published this week about metformin, using a novel co-twin study of 1,261 pairs of people, half of whom were treated with metformin because they had diabetes. That half also had higher glucose levels, A1C levels, higher BMIs. The other half did not. The other twin did not. So basically what they showed was, even though the metformin people did have higher BMIs and diabetes, being on metformin they had less incident osteoarthritis in the periphery. That means hand, knee, and hip osteoarthritis with a 40% reduction at 10 years. The rate at 10 years was 6.7% in the treated twins on metformin versus 9.7% in the non-treated twin as far as osteoarthritis. And again, the non-treated twin did not have the higher BMI. But the treated twin had a lower incidence of OA. I think that's a really well done and important study.
Nordic registry study of non-steroidals. We don't get to talk a lot about non-steroidals. It was basically the first 20 years of my career in rheumatology from '84 to 2004 — or 2000 I should say — when I started doing biologic trials. I did a lot of non-steroidal trials and we used a lot of non-steroidals back then. So this is three Nordic countries, about 750,000 patients, and they found that these are OA patients and they found that non-steroidal use was being used by up to 40% under age 60. About 50 to 58% started the non-steroidal before the OA was officially diagnosed. Overall, non-steroidal use increased annually up until about age 55 and then it seems to decline, probably reflecting our concern about non-steroidal use in the elderly. But what they point out in this study is one, that non-steroidals are being used especially in younger OA patients, and that OA patients in general have a substantial risk of GI complications especially if on non-steroidals, reinforcing the fact that OA and non-steroidals are your invitation to aggressively question the patient about GI symptomatology and complications.
We reported Wednesday, Thursday about the Lilly phase 3 TOGETHER PsA trial. This again topline results, press release, no formal data — formal data to be presented at a meeting upcoming in 2026. This is a PsA trial, 271 patients who either received the IL-17 inhibitor ixekizumab, or the other group — and these are active PsA patients who are also obese — got ixekizumab plus tirzepatide, Zepbound. The combination of the GLP-1 along with the IL-17 inhibitor. And guess what? At week 36, the combination was better in the outcomes. And they chose as an outcome a combined outcome of an ACR50 — high bar — plus at least 10% weight loss from the weight loss drug. So that combined outcome was achieved in 32% on combination therapy versus 0.8% on ixekizumab alone. More importantly, forget about the weight loss part. What happens when you use the GLP-1 in patients with psoriatic arthritis?
Does it affect the ACR50 responses? And guess what? ACR50s were better with the combo. 34% ACR50 on combo versus 20% on exacerbation alone. Now again there was weight loss involved. I don't have the actual numbers to know how much, but that opens the door for the possibility that maybe these GLP-1 incretin therapies have some effect on inflammation and immunology more so than just weight loss. Could be that if they lost a substantial amount of weight they would also do better as far as their ACR50. So I thought that that was important.
I want to point you to a really nice article on reproductive health in the lupus clinic. It's written by nurse practitioner June Chu from the NIH. It's a really nice article in keeping with our program from last month and this month. You'll be seeing a lot of news and information about nurse practitioners and physician assistants.
I want to end with two things. Let's end with an Ask Cush Anything question. This is from Dr. Lauren Johnson. Hi, Dr. Cush. My name is Lauren Johnson. I'm a rheumatologist in Spokane, Washington. I have a question regarding EC4d testing in lupus. My patient is a 50-year-old woman who was diagnosed with lupus in California based on an Avise panel showing a positive EC4d of 52, the upper limit being 15. She also has a high titer IgG beta-2 glycoprotein 1 of 149, a persistently low C4 level ranging from 10 to 23. And in 2017, she had an ANA of 1 to 640. But since then, she's had a negative ANA by IFA. ANA subsets have been consistently negative, including a far double-stranded DNA test, and my initial evaluation with her did not show any signs of clinical lupus. Hematology evaluated her and did not think she had APS. Neurology is also treating her with IVIG therapy for GAD-positive autoimmune encephalitis, but this diagnosis has also been questioned. She had anaphylaxis to hydroxychloroquine and unfortunately she had sepsis due to cellulitis in 2017 and she's been off of all therapy since that time. My question is: in this ANA-negative patient without other clear signs of lupus, would you rely on EC4d testing as a diagnostic tool? And if so, would you try immunosuppression? Thank you.
Hi, Dr. Cush. Thanks, Lauren. That's a really hard question and a hard case and I'm glad you're managing it. As a skilled rheumatologist, they need guidance on this. No, I would not use immunosuppressive therapy on this patient because this patient doesn't have lupus. This patient doesn't meet old criteria and new criteria for lupus. This patient has autoimmune features, right? And you see plenty of ANA-positive consults that you're not going to put on therapy. You don't necessarily have to meet criteria to go on hydroxychloroquine or something else. But at the same time, those criteria are instructive in making decisions, hard decisions like this. So, number one, never treat a lab test. Number two, hang your hat on hard and fast clinical findings that are truly indicative of the disease you wish to treat or the disease the patient is concerned about.
You know, this patient is an in-betweener. She doesn't fit neatly into any box. She clearly has autoimmune disease evidenced by the EC4d, the positive Avise panel, the beta-2 glycoprotein antibodies, the low C4 levels, the intermittent ANAs, and being diagnosed with GAD-65 autoimmune encephalitis. But you ask, should she be treated? Well, if she's getting IVIG or gamma globulin therapy, that's probably more potent than anything that you would do to try to control autoimmune disease. Although they probably don't know what they're treating and you wouldn't know what you're treating. Let someone else play with the gamma globulin, and I look at this as a positive-test consult — whether it's an at-risk person with arthralgia who has a positive CCP, or it's someone with autoantibodies being considered with MCTD or lupus. I only treat what I see, and I think that if she develops serositis, give her a drug for serositis and say maybe this is lupus. But again she doesn't meet criteria, and the best you can do — I'd say, because of the autoimmune features, she may be at risk. But the good news here is: one, she hasn't progressed despite having these symptoms for how long? That's good news. If she's going to have an aggressive autoimmune disease, don't you think it would have reared its ugly head by now? Two, that she's already on treatment and that you as an experienced autoimmune specialist are going to follow her for what she has. Until then, she gets symptomatic management without stepping into immunosuppressives, biologics, and expensive therapies.
Again, we want to thank Lauren for what I thought was a really interesting case. Remember, February 7th and 8th is RheumNow Live in Dallas. We hope you're going to be there. Registration's filling up. I think we have maybe 40 seats
left for in the room. We hope that you'll go to RheumNow.live and register. It's going to be a great meeting. I was talking to — we're talking to Dr. Mike McClung, who's like the world's greatest on osteoporosis, and he's going to do a fabulous talk, the keynote speech on Saturday afternoon on 50 years of osteoporosis. You don't want to miss it. He's too good to miss.
On Sunday, we have this great session called Staying Ahead of Spondyloarthritis. Dennis Poddubnyy, who's like a world leader in spondyloarthritis, is going to talk about diagnosing axial disease. And then we have Jessica Walsh and Katherine Bakewell going to be on stage together talking about treatment and complications of spine arthritis. And that's going to be a really fabulous session.
And then right after that, there's going to be these two talks on myositis by Rohit Aggarwal from Pittsburgh. He's the man on myositis, talking about asymptomatic elevation of CK and what to do about it, and then an update on the myositis autoantibodies and how they should be used. We hope to see you in Dallas. Go to RheumNow.live to register.
Um, oh, what about my New Year's resolutions? Here we go. Number one, RheumNow in 2026 is going to have more authors, more invited authors doing more invited commentaries and perspectives. Two, RheumNow is going to have a Spanish version of its website available to those of you who like Spanish over the English. Number three, we're going to be covering more meetings. We're sending more of our faculty, who are so good at covering ACR and EULAR and RheumNow Live, to all the other meetings and asking them to write reports and do tweeting from the meeting. Follow us on social media — whether on LinkedIn or Twitter, you'll see a lot.
And the last thing is we're going to be fully invested in artificial intelligence on RheumNow. We're already using it for a number of different things, especially for quizzes and surveys. We find it really useful. And I think — oh my god, he's going to use AI and AI is going to take over. No, it's not. You know, at RheumNow we are the authority. We are the experts. We provide the perspectives on the information, articles, and news reports that we find, but we're going to now use AI to expand the data and the info that we receive and how we present that to you. And AI is also really good at organizing information into more presentable, more digestible forms. AI will not be writing our articles. Don't worry, our authors and I will be, and we'll be fully transparent about when we do use AI.
But those are our resolutions for 2026. Maybe you should ask yourself: if RheumNow is using AI, why aren't I? Hm. Let's talk about it. We've got 2026 ahead to do
So, this week on the podcast, we're going to talk about bendability and its use in clinic, a better way to treat RA that involves getting outside of yourself or outside, and a novel advance in GLP-1 agonists. You know, GLP-1 agonists are called the incretins. I thought incretins were little men who jumped out of spaceships and were stealing my flip-flops, but that's another story.
So the first report is on preeclampsia and its association with antiphospholipid antibodies. Thought this was interesting. 100 women with severe preeclampsia were compared to 40 controls — just pregnant women without preeclampsia — and they assessed patients for antiphospholipid antibodies. They found them much more frequently in those with preeclampsia, 34% versus 10%. That's a 4-and-a-half-fold increased risk for APL positivity with severe preeclampsia. The preeclampsia occurred both early and late in pregnancy, so it did have predictive value. It might be something you might want to look at if you have a preeclampsia in a patient, or conversely, a patient who has antiphospholipid antibodies could be at risk for preeclampsia going forward.
Johnson and Johnson announced some topline results of a phase 2b JASMINE study, which assessed the efficacy and safety of nipocalimab in lupus patients. Nipocalimab is an FcRn blocker that has been shown in other studies to reduce autoantibody production and disease activity. It's been shown to have efficacy in Sjögren's and maybe in RA — quasi results in RA. This study was in lupus, where it met its primary endpoint at week 24, which is a significant reduction in the SRI-4 response versus those on placebo. No new safety signals, no granular data. This is going to be presented later on at another meeting. These are topline results.
Another study appeared this week about CAR T cells. You know, there are a lot of CAR T cell drugs in development. I think there's at least 40 companies doing about 80 studies right now on CAR T cell therapy in autoimmune diseases. And we're talking about this like it's the next coming of, you know, a savior in rheumatology. But really we've got very little data and we're about 3 to 5 years away from getting good data that we can hang our hat on. Right now we have these small reports.
And here's a report called the CASTLE study. It's a phase 1/2A CAR T cell trial of 24 patients with refractory lupus, scleroderma, and myositis. And it's — let me look at the numbers here — 10 with lupus, nine with scleroderma, and five with myositis. Again, they were treatment refractory and they're getting this autologous CD19 CAR T cell therapy called MVCART19.1. The primary goal of the study, being a phase 1/early 2 study, was safety, and they had no cytokine release syndromes, no CRS grade 2 or higher, no ICANS safety concerns at week 24, and that was all good.
More importantly, they did assess efficacy outcomes — 22 out of the 24 patients met a predetermined efficacy response. So in lupus, nine out of 10 met DORIS remission. Nine out of nine scleroderma patients had no progression of scleroderma — I guess that's their skin score. And four out of five had a major or moderate response on myositis outcomes. The bottom line is that all these patients did go off of glucocorticoids and were off of immunosuppressors for the first six months. If you look at the graph that we showed you in the tweet on that, the complete response is really at 6 months, but responses are lost over time variably. Again, they only had a one-time treatment. So again, another bit of early encouraging data, but I would tell you to be skeptical still, because we don't have really great data, really controlled data.
Arthritis Care and Research had a nice report on generalized joint hypermobility syndrome. It was a meta-analysis and systematic review of 46 studies in 23,000 patients, and they looked at the utility of the Beighton criteria in making the diagnosis of hypermobility syndrome. Using the usual Beighton criteria, it was about 2% in the populations that were studied. It was more prevalent in younger adults, about 5% in young adults between 18 and 25. And we know hypermobility is sort of a pediatric rheumatology problem, more so than an adult rheumatology problem, but young adults can have this too. Young adult patients presenting with what looks like what you think might be axial spinal arthritis, early disease or non-radiographic axial spinal arthritis, or fibromyalgia — you should probably be doing the Beighton score on these people. And you know what that is? There's five
maneuvers. It's the fourth finger that goes back more than 90°. It's your thumb flexed onto the surface of the forearm. It's hyperextension of the elbows, hyperextension of the knees, and being able to bend over and put your palms on the floor. That's nine points. The criteria for hypermobility is six points out of nine. But what they showed was that the number of points necessary to make the diagnosis changes according to age. So six points is right for young people 18 to 25, but they propose five points or more if you're 26 to 65. And then if you're over 65, it's four points that you need to make the diagnosis. I don't know that I agree with that, but they did the research, at least the meta-analysis. It's something that should be considered. And I would tell you that if you're like me, you probably don't test enough for hypermobility syndrome in patients who have ill-defined complaints and no evidence of synovitis or bony hypertrophy.
Um, I like this report this week. A large population-based study showed the connection between obesity and low back pain. And we know there's a connection, but I like the numbers here. The study found that for weight gain you have a 7% increase in low back pain for every one unit of BMI that you increase, or every 10 lbs. That's very instructive. 10 lbs of weight, or 30 lbs of weight gained by your patient, they now have a 21% higher risk of chronic low back pain. I like that.
Um, a VA study looked at RA patients with calcium pyrophosphate deposition disease, CPPD. So this is older men at the VA, their average age around 65. They found 64 patients amongst their RA population — 2.3% — who had ICD-9 and ICD-10 codes for both RA and CPPD. The ones who had CPPD were older. They had more comorbidity, especially osteoarthritis, more spinal disease, diabetes, but less RF positivity. And if they were seropositive RA patients with CPPD, they were less likely to achieve low disease activity and used more prednisone and more biologic or targeted synthetics. They were also more likely to have death and total joint replacement. But the takeaway on this article was: if you have RA and CPPD, maybe you should be rethinking your diagnosis of RA, especially if they're seronegative. Think about it. I think it's good advice.
Um, I like this report that appeared recently in J Rheum. It's from Adelaide University in Australia, talking about green space exposure reducing the risk of RA. What is green space? You know, isn't that a band? Maybe I'm getting that confused. But we do know there's plenty of evidence out there about toxic exposures and increasing the risk of RA. It starts with diet and obesity. It's obvious with smoking. It's obviously being near pollution and hydrocarbons and solvents and whatnot. Tons of studies showing an increased risk of RA. That's substantial, right? You could very well say — and we should have this whole specialty of environmental rheumatology — that we should be making ourselves knowledgeable in this, because it's all about lifestyle, is it not? But anyway, this full-read article in J Rheum, the lead author is Stanhope, shows that exposure to green space — that's gardens, fields, being outdoors, being around greenery, being away from toxic exposures — has in three studies been shown to have a protective effect against developing RA. So could you not prevent RA by going green? This again underscores the importance of lifestyle in both the assessment of our patients and the counseling of our patients.
A UK group did an interesting study of almost 1,850 RA patients who were starting on a biologic or targeted synthetic. They found that 30% or so were on steroids at the beginning of therapy. And they followed them over a year and then even beyond. And they saw that two-thirds of patients were still on steroids and largely didn't change or wean their dose. What's going on? Why are you using very expensive, very potent drugs? The main reason is to get control of the disease. The secondary reason is to get them off of steroids. But we don't do that. And this is a call for — we probably need to pay more attention to this. I think the article was meant to point out that we're not vigilant in basically limiting or weaning steroids, and that maybe we should be doing better, or maybe that the therapies that we're using aren't as complete as we think they are.
Japan has more experience with this phenomenon of methotrexate-associated lymphoma and lymphoproliferative disorders. This report I put up this week: 38 RA patients who developed a methotrexate-related — meaning they got methotrexate and they developed an associated LPD, lymphoproliferative disorder. Of the 38, 22 spontaneously regressed when they stopped the methotrexate, but 16 were non-spontaneous regressors. Of those 16, a third of them — five — died. If you were a
non-regressor, meaning that it was going to continue the lymphoproliferative disorder, you were more likely to have high LDH levels at the start of therapy and at diagnosis. They were more likely to have lower lymphocyte recovery after you stop methotrexate. And clearly they had a higher mortality risk. You know what? I think this is really interesting, but I've never seen this and I've treated as many people with methotrexate as you have and I think I'm looking just like you are. I have some of my colleagues here in the US I do know have seen a case or two of this but I've never seen it. But it's still something to be notable of since you are the world's experts in methotrexate. Are you not?
Speaking of methotrexate, here's a study that I don't know what to do with. You know there's a few, a handful of studies about methotrexate and its use in polymyalgia — PMR — either refractory disease or in new onset disease. And I'm going to show you one and by the way I'm on the fence. I don't believe that it really works based on the data I've seen. I've seen more recent studies where it just really doesn't seem to work. This is a relatively small study, 58 patients, but it was a randomized controlled trial. These are new PMR patients with less than eight weeks of steroids. And they were then either given 25 milligrams per week of methotrexate or placebo. And they had a weaning protocol for the steroids over 24 weeks. At week 52, the endpoint being glucocorticoid-free remission seen in 80% that were on methotrexate, only 40% on placebo. Yes, this is significant at 0.0042. Do I believe it? Well, I got to because they published it. Seems like their methodology is fine. They're faulted for a relatively small study, right? I need to see big studies — 200 plus — well-designed trial, maintenance of blind, and at least a 24-week if not 52-week endpoint. So again, take with that what you will, but I wanted you to be aware of it.
Another really important study was published this week about metformin, using a novel co-twin study of 1,261 pairs of people, half of whom were treated with metformin because they had diabetes. That half also had higher glucose levels, A1C levels, higher BMIs. The other half did not. The other twin did not. So basically what they showed was, even though the metformin people did have higher BMIs and diabetes, being on metformin they had less incident osteoarthritis in the periphery. That means hand, knee, and hip osteoarthritis with a 40% reduction at 10 years. The rate at 10 years was 6.7% in the treated twins on metformin versus 9.7% in the non-treated twin as far as osteoarthritis. And again, the non-treated twin did not have the higher BMI. But the treated twin had a lower incidence of OA. I think that's a really well done and important study.
Nordic registry study of non-steroidals. We don't get to talk a lot about non-steroidals. It was basically the first 20 years of my career in rheumatology from '84 to 2004 — or 2000 I should say — when I started doing biologic trials. I did a lot of non-steroidal trials and we used a lot of non-steroidals back then. So this is three Nordic countries, about 750,000 patients, and they found that these are OA patients and they found that non-steroidal use was being used by up to 40% under age 60. About 50 to 58% started the non-steroidal before the OA was officially diagnosed. Overall, non-steroidal use increased annually up until about age 55 and then it seems to decline, probably reflecting our concern about non-steroidal use in the elderly. But what they point out in this study is one, that non-steroidals are being used especially in younger OA patients, and that OA patients in general have a substantial risk of GI complications especially if on non-steroidals, reinforcing the fact that OA and non-steroidals are your invitation to aggressively question the patient about GI symptomatology and complications.
We reported Wednesday, Thursday about the Lilly phase 3 TOGETHER PsA trial. This again topline results, press release, no formal data — formal data to be presented at a meeting upcoming in 2026. This is a PsA trial, 271 patients who either received the IL-17 inhibitor ixekizumab, or the other group — and these are active PsA patients who are also obese — got ixekizumab plus tirzepatide, Zepbound. The combination of the GLP-1 along with the IL-17 inhibitor. And guess what? At week 36, the combination was better in the outcomes. And they chose as an outcome a combined outcome of an ACR50 — high bar — plus at least 10% weight loss from the weight loss drug. So that combined outcome was achieved in 32% on combination therapy versus 0.8% on ixekizumab alone. More importantly, forget about the weight loss part. What happens when you use the GLP-1 in patients with psoriatic arthritis?
Does it affect the ACR50 responses? And guess what? ACR50s were better with the combo. 34% ACR50 on combo versus 20% on exacerbation alone. Now again there was weight loss involved. I don't have the actual numbers to know how much, but that opens the door for the possibility that maybe these GLP-1 incretin therapies have some effect on inflammation and immunology more so than just weight loss. Could be that if they lost a substantial amount of weight they would also do better as far as their ACR50. So I thought that that was important.
I want to point you to a really nice article on reproductive health in the lupus clinic. It's written by nurse practitioner June Chu from the NIH. It's a really nice article in keeping with our program from last month and this month. You'll be seeing a lot of news and information about nurse practitioners and physician assistants.
I want to end with two things. Let's end with an Ask Cush Anything question. This is from Dr. Lauren Johnson. Hi, Dr. Cush. My name is Lauren Johnson. I'm a rheumatologist in Spokane, Washington. I have a question regarding EC4d testing in lupus. My patient is a 50-year-old woman who was diagnosed with lupus in California based on an Avise panel showing a positive EC4d of 52, the upper limit being 15. She also has a high titer IgG beta-2 glycoprotein 1 of 149, a persistently low C4 level ranging from 10 to 23. And in 2017, she had an ANA of 1 to 640. But since then, she's had a negative ANA by IFA. ANA subsets have been consistently negative, including a far double-stranded DNA test, and my initial evaluation with her did not show any signs of clinical lupus. Hematology evaluated her and did not think she had APS. Neurology is also treating her with IVIG therapy for GAD-positive autoimmune encephalitis, but this diagnosis has also been questioned. She had anaphylaxis to hydroxychloroquine and unfortunately she had sepsis due to cellulitis in 2017 and she's been off of all therapy since that time. My question is: in this ANA-negative patient without other clear signs of lupus, would you rely on EC4d testing as a diagnostic tool? And if so, would you try immunosuppression? Thank you.
Hi, Dr. Cush. Thanks, Lauren. That's a really hard question and a hard case and I'm glad you're managing it. As a skilled rheumatologist, they need guidance on this. No, I would not use immunosuppressive therapy on this patient because this patient doesn't have lupus. This patient doesn't meet old criteria and new criteria for lupus. This patient has autoimmune features, right? And you see plenty of ANA-positive consults that you're not going to put on therapy. You don't necessarily have to meet criteria to go on hydroxychloroquine or something else. But at the same time, those criteria are instructive in making decisions, hard decisions like this. So, number one, never treat a lab test. Number two, hang your hat on hard and fast clinical findings that are truly indicative of the disease you wish to treat or the disease the patient is concerned about.
You know, this patient is an in-betweener. She doesn't fit neatly into any box. She clearly has autoimmune disease evidenced by the EC4d, the positive Avise panel, the beta-2 glycoprotein antibodies, the low C4 levels, the intermittent ANAs, and being diagnosed with GAD-65 autoimmune encephalitis. But you ask, should she be treated? Well, if she's getting IVIG or gamma globulin therapy, that's probably more potent than anything that you would do to try to control autoimmune disease. Although they probably don't know what they're treating and you wouldn't know what you're treating. Let someone else play with the gamma globulin, and I look at this as a positive-test consult — whether it's an at-risk person with arthralgia who has a positive CCP, or it's someone with autoantibodies being considered with MCTD or lupus. I only treat what I see, and I think that if she develops serositis, give her a drug for serositis and say maybe this is lupus. But again she doesn't meet criteria, and the best you can do — I'd say, because of the autoimmune features, she may be at risk. But the good news here is: one, she hasn't progressed despite having these symptoms for how long? That's good news. If she's going to have an aggressive autoimmune disease, don't you think it would have reared its ugly head by now? Two, that she's already on treatment and that you as an experienced autoimmune specialist are going to follow her for what she has. Until then, she gets symptomatic management without stepping into immunosuppressives, biologics, and expensive therapies.
Again, we want to thank Lauren for what I thought was a really interesting case. Remember, February 7th and 8th is RheumNow Live in Dallas. We hope you're going to be there. Registration's filling up. I think we have maybe 40 seats
left for in the room. We hope that you'll go to RheumNow.live and register. It's going to be a great meeting. I was talking to — we're talking to Dr. Mike McClung, who's like the world's greatest on osteoporosis, and he's going to do a fabulous talk, the keynote speech on Saturday afternoon on 50 years of osteoporosis. You don't want to miss it. He's too good to miss.
On Sunday, we have this great session called Staying Ahead of Spondyloarthritis. Dennis Poddubnyy, who's like a world leader in spondyloarthritis, is going to talk about diagnosing axial disease. And then we have Jessica Walsh and Katherine Bakewell going to be on stage together talking about treatment and complications of spine arthritis. And that's going to be a really fabulous session.
And then right after that, there's going to be these two talks on myositis by Rohit Aggarwal from Pittsburgh. He's the man on myositis, talking about asymptomatic elevation of CK and what to do about it, and then an update on the myositis autoantibodies and how they should be used. We hope to see you in Dallas. Go to RheumNow.live to register.
Um, oh, what about my New Year's resolutions? Here we go. Number one, RheumNow in 2026 is going to have more authors, more invited authors doing more invited commentaries and perspectives. Two, RheumNow is going to have a Spanish version of its website available to those of you who like Spanish over the English. Number three, we're going to be covering more meetings. We're sending more of our faculty, who are so good at covering ACR and EULAR and RheumNow Live, to all the other meetings and asking them to write reports and do tweeting from the meeting. Follow us on social media — whether on LinkedIn or Twitter, you'll see a lot.
And the last thing is we're going to be fully invested in artificial intelligence on RheumNow. We're already using it for a number of different things, especially for quizzes and surveys. We find it really useful. And I think — oh my god, he's going to use AI and AI is going to take over. No, it's not. You know, at RheumNow we are the authority. We are the experts. We provide the perspectives on the information, articles, and news reports that we find, but we're going to now use AI to expand the data and the info that we receive and how we present that to you. And AI is also really good at organizing information into more presentable, more digestible forms. AI will not be writing our articles. Don't worry, our authors and I will be, and we'll be fully transparent about when we do use AI.
But those are our resolutions for 2026. Maybe you should ask yourself: if RheumNow is using AI, why aren't I? Hm. Let's talk about it. We've got 2026 ahead to do
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