MTX Fails Knee OA (6.6.2025) Save

It's 06/06/2025. This is the RheumNow podcast. Hi. I'm doctor Jack Cush, executive editor of roomnow.com. This week, we got a few new revelations, a few sort of basic rheumatology things, and I think some important numbers to remember.

Let's begin with the numbers on vaccination. MMWR last week put out a report about their vaccines in children program, which began in 1994. That program basically allows all children to receive vaccines at no cost. Since 1994, they have prevented this program has prevented over five hundred and eight million vaccination related illnesses. It's prevented thirty two million hospitalizations, and has prevented one point one million deaths.

The direct savings of this program has been 540,000,000,000, and societal save savings is over $700,000,000,000. Again, these are numbers that come from the CDC. And if you think the CDC is biased, well, then maybe you won't believe these numbers. But I think these are important numbers to realize, especially as vaccines are falling under a lot of scrutiny. A nice basic piece comes from the Canadian Medical Journal where they reported a case of parvovirus b nineteen presenting with arthritis.

And while we may all teach that or have heard about that, I must say I really haven't seen much of that in my career. They go on to point out that the B nineteen virus is more likely to be associated with arthropathy than it is with the classic slap cheek rash. It's seen in adults who get this infection, up to sixty percent will get musculoskeletal complaints, mainly in the form of a symmetric polyarthralgia that can look a lot like RA. A subset of those will have inflammatory polyarthritis, mainly affecting PIPs and MCPs, other joints also. But those are the main ones, So it kinda looks like RA.

The interesting thing about this is that it's a self limiting condition in the vast majority of individuals with resolution of symptoms in three to four weeks. Maybe as much as one in five will go on to have symptoms and arthritis that can last, months to years. Actually, now that I remember, I had one patient and I was perplexed by this one patient because she had clearly serologically proven, parvo b nineteen, and I managed her for a while with nonsteroidals and steroids, but she continued to have symptoms. And you know what? She stayed as RA.

So did parvo b nineteen unmask what was going to be RA anyway, looking for a trigger? Or can parvo b nineteen in a very few people settle into RA? You can tell me next time you see me. A systematic review of JAK inhibitors, the systemic sclerosis. We've covered this a few times at ACR and EULAR, and next week is EULAR.

I'll be going, we'll be covering the meeting, watch for what we're going to say and do. But, in the past, we've talked about reports about JAK inhibitors being used in systemic sclerosis. In this meta analysis of 18 articles, eighty seven patients, not a lot. So these are single case reports and a few series, small series, that, age was highly varied. Most of the JAK inhibitor use was eighty plus percent tofacitinib, and they were the JAK was either being used to manage either skin disease, progressive systemic sclerosis in the skin with ILD or progressive skin disease with GI manifestations, forty five percent and thirty nine percent.

In this meta analysis, and this could be a reporting bias, eighty seven percent improved and only six percent relapsed. A high amount of adverse events, but they were not all that serious. Twenty percent had infections, although those were mostly minor. We do need controlled trials. I think it would be exciting to see if this really panned out in a large phase two trial.

Report this week about Blau syndrome, a rare auto inflammatory disorder with a triad of granulomatous dermatitis, arthritis, and uveitis that if unrecognized can lead to blindness. This Blau syndrome I know about because it's one of the auto inflammatory syndromes resulting from a NOD two gain of of function mutation with a variant of NOD two gene. This condition mainly affects young young children, two to four years. Treatments are meta analysis was looking at the treatments. In fact, look at two different sort of studies meta analyses.

One said that biologics work. The other one said that the biologic, especially TNF inhibitors, are probably good at controlling the joints. But one meta analysis said, you know what, it doesn't seem to matter, there's no preferred therapy and we need a better therapy, especially with regard to the uveitis. So that can be a real challenge. Another nice revelation this week is this report of ninety systemic sclerosis patients where they did a lot of testing and they found that IL-forty is elevated in systemic sclerosis.

So they compared 90 sclerodermas to 90 controls, healthy controls. They had skin biopsy in five patients versus healthy controls, and they found that IL-forty was significantly up regulated in the skin and it correlated with disease activity measures for scleroderma, the ESSG. It also correlated with GI manifestations, also with ILA TGF and TGF beta. It is a cytokine that has been linked to a number of disorders mainly because it seems to be pro inflammatory. It comes from activated B cells and polys.

But what I liked about this was it seemed to be pretty impressive. I'd like to see this studied in other cohorts of scleroderma patients. A nice case report this week, a reminder that isoretinoin can cause sacroiliitis, it is rare. In a review of sixty seven patients in the literature who had this rare complication, They were all young, 21 years, had a median onset of disease of one to two years, but with a median of two point five months after receiving or starting isoretinoin. The main manifestations were seventy percent with back pain, low back pain, and forty five percent with hip pain.

Diagnosed by MRI, they often have bone marrow edema. They do not have erosions. They recover once you stop the isoretinoin. Eighty plus percent will recover. A few of those in my day.

So a registry study of 17,000 psoriasis patients looked at the drugs that they received and really asked the question, do the drugs that are used to treat psoriasis also treat psoriatic arthritis? I think you know the answer to that, but in the dermatology literature, think this was JAMA Dermatology, they found that in this cohort of seventeen thousand PSO patients that, nineteen percent had PSA. So biologics were being used in forty five percent of psoriasis patients at baseline, more so if they also had psoriatic arthritis, sixty six percent, right? It turns out that in the psoriasis patients, there was about nine percent who were put on a drug that would work for both. The point is that because they're treated for psoriasis doesn't mean that that drug, that biologic is going to work for psoriatic arthritis, and that's something you should be teaching primary care and dermatology.

Another look at GLP-1s, you're going to see lots of literature on this, a five year cohort study looked at obese type two diabetics treated either with semaglutide or with sitagliptin, which is Januvia, and they showed that the ones who are on the diabetics who are obese that were on the semaglutide, the GLP-one agonist, had a significantly lower risk of osteoporosis, thirty nine percent lower, and a significantly lower risk of gout, thirty seven percent lower, compared to being on sitagliptin. Interestingly, this study, argues with the results of other small studies that says that it might benefit knee, or hip osteoarthritis. This study did not show a lower incidence of knee or hip osteoarthritis. A retrospective VEXUS study of 59 patients looked at their treatments, and if you're treating VEXUS, you might struggle with what is the best therapy. These patients were ninety eight percent male, supposed to be mostly male, mean age 71 years, and nearly half of them had myelodysplasia in process.

Treatments that they used were tocilizumab, anakinra, azacitidine, baricitinib, and prednisone in just a few. The best responses in this cohort was seen with azacitidine, which is I think a hematologic drug, and tocilizumab. Put that away in your cap, it may come in handy. A nice, revelation again this week in calcium pyrophosphate deposition disease. We actually have, coming from a gene wide association study.

The cohort was the Million Veterans Program, which is a study of 550,000 veterans. In this study, they found that there were two genes that were linked, possibly linked to RNF 144 b and ENPP one. ENPP one, they know something about. It's got something to do with phosphorylation. They really don't know what r f one forty four b is, but again, the association here has been seen in Americans, which is calcium pyrophosphate, but those genes are specifically, associated with those of European and African ancestry.

Interesting. Right? So I I again, these same genes are found in our society, but also, in those continents as well. So it's we're getting closer to a better understanding of calcium pyrophosphate disease and its clinical associations. We reported in the past that there's a rising incidence of autoimmune disease.

I'm going to talk about autoimmune disease in the next three reports. First, a review of vitiligo, and that as we know is an immune mediated disease that has significant psychosocial impact, quality of life impact. Patients with this are profoundly affected. A review of the therapies basically says, number one, the only FDA approved therapy for vitiligo is ruxolitinib. It's a JAK1 inhibitor used for hematologic indications, but that other JAK inhibitors have been studied in several studies, mainly tofacitinib and baricitinib showing the same benefits, and that's encouraging.

I did not know that other drugs are out there that have been tested with positive results, but these are not FDA approved. Simvastatin, metformin, and afamilanotide. Afamilanotide. You can look at the citation if you're interested in the drug. I can't pronounce it.

I'll bet that you can't either. Alopecia areata is in the news and that the incidence of that has gone up in the last thirty years between 1990 and 2021. In 1990, the incidence worldwide incidence looks like it was twenty million people, but that by 2021, thirty one years later, it's now almost thirty one million affected globally. The highest incidence is seen in The United States and Canada, North America, where the incidence is over five hundred cases per 100,000. Other high prevalence countries would include, South America, Southeast Asia, and Australia.

Lowest incidence is seen in Africa and The Middle East. And another report of rising incidence of autoimmunity comes from The UK. It's a UK study, showing that autoimmunity is being found at higher rates in women who are pregnant. So this is a UK CPR, indeed it is a well known database that's mined for population based, associations. In their study of almost twenty one years, they found one hundred and eighty five thousand pregnancies, in one hundred thousand women who had autoimmune disease.

They looked for the prevalence of autoimmune disease amongst this cohort, compared it to those without autoimmune disease, and what they found is that in what's the year here? In '19 no, in 2020, in 2000, the incidence of autoimmune disease in pregnancy was three point five percent. By 2021, it's now up to four point seven percent. They're specifically looking for 17 autoimmune diseases, a wide array, including many of the drug things that you see, but the thing that they saw most in association with pregnancy was psoriasis had the highest prevalence. And if you consider psoriasis an autoimmune disease, and I do.

The greatest increase during this time period from 2002 to 2021 was for Hashimoto's thyroiditis followed by celiac disease, Graves' disease, and type one diabetes. To me, the big report this week that's kind of controversial is the report that showed up in JAMA on methotrexate failing in osteoarthritis. It's a report out of China, with an accompanying editorial by Nancy Lane, basically saying put the nail in the methotrexate osteoarthritis coffin, it doesn't work. It's not quite that simple. In this placebo controlled randomized trial of two fifteen patients with knee OA, they enrolled patients with knee OA that was inflammatory, meaning they had to have effusions and or synovitis on MRI.

And when they looked at the patients treated with placebo versus those with methotrexate, no significant difference as far as the one year outcomes. You might remember that last year, I think we reported a analyst of internal medicine article that said it does work in knee OA. And in this article, which is from MedPage today that reviews this, it basically says, if you look at the preponderance of data, you know, there's reports about methotrexate in hand OA suggesting it might work. And in knee OA, it kind of depends on whether there's an inflammatory component or not, and seems to always fail when there's inflammatory disease, or whether it's just degenerative OA, and occasionally it seems to work there. I studied this, when I was at UT Southwestern, I think around 1993 to 1995, I think I enrolled about 24 patients in a double blind randomized placebo controlled trial.

I was really jazzed by some of the results I was seeing, but I was blinded. After I unblinded it and looked at the data, there was no effect. We treated patients who only had DJD, no infusions, no warm joints, no positive MRIs, we didn't do MRIs, we had MRI data in a few, and they had to have normal sed rates and CRPs. Now I recognize that osteoarthritis can cause some of its damage by intermittent bouts of inflammation, and maybe methotrexate, and that was a basis for our study. Our thinking was that methotrexate would knock out those intermittent bouts and prevent ongoing pain or ongoing damage, and we didn't see it in our very small cohort.

I didn't report that by the way, because our cohort was so small. I thought I was going to have a hard time with that, and I thought, Who other than me is crazy enough to do a trial like this? Well, many people have done it since then, and I think that right now it's equivocal, and that's sort of an answer, a negative answer as to whether methotrexate works in knee OA. That's it for this week. Be sure to tune in next week for more information.

We're gonna be coming to you from EULAR in Barcelona. Be there, follow us, we're gonna have fun, we hope you enjoy it too. Specifically, what we're gonna do is, ULAR starts on Wednesday eleventh. Starting on Thursday, Friday and Saturday, we're gonna do a live day one, two report, day three report, day four report with a panel at 6PM Barcelona time. I think that's twelve noon, Eastern time here, and you can see those videos where we're gonna discuss what's happening at the meeting.

You can follow us on Twitter, and then when we get back from Barcelona, we're gonna have panel reports on RA, PSA, SPA, etcetera. Hope you enjoy our coverage. We'll talk next week. Bye.