Generic Tofacitinib (6.26.2026) Save

It's 06/26/2026. This is the RheumNow podcast, and I'm doctor Jack Cush, executive editor of rheumnow.com. This week on the podcast, generics, more on CAR T, and AI. I'm gonna begin with a quote from my favorite blog by Seth Godin, Seth sethseth'sblog.com. It's a blog about marketing, business, life, being smart about decision making.

And he's really talking about AI, and he's talking about why, too many of us are not adopting AI, not getting into AI, not experiment experimenting with it, and that's a gigantic mistake. His quote is, when you make the choice to avoid becoming the most experienced person in the room, whatever room you're in, you're making a bet about your future. You gotta be in it to win it. If you're not using AI, you are part of a distant past. You're in the rearview mirror if you read house of god, your eat my dust, Eddie.

I think the big news of the week, happened on June 4, not a month ago, and that was Breckenridge Pharmaceuticals received FDA approval for their approval of the generic version of tofacitinib. This was the both five milligram and ten milligram tablets, not the eleven milligram XR version, but five and ten milligrams for both adult and pediatric use for all the indications that tofacitinib has an indication, all the warnings for which tofacitinib has been given. This is a game changer. The drop the price is going to drop. The availability should increase.

What would you do if met if tofacitinib were the same price as methotrexate? Well, don't worry. It's not gonna be because there's a trend in recent years that when expensive drugs go biosimilar or generic, they still stay expensive. Although the price is cut substantially. But maybe competition will really drive it down.

You know, in India and Southeast Asia, outside The United States, tofacitinib is generic, is available, and is cheap, really cheap. How's this going to change how you practice? Are you able to get generic tofacitinib? Let me know. A report looked at the risk of TB with an IL-twenty three inhibitor in patients with psoriatic disease, both psoriasis and psoriatic arthritis.

This is a literature review, 34 studies, looking at IL-twenty three inhibition in psoriasis. No new cases in all the literature, but there was one case of LTBI, latent TB reactivation. In eight, PSA studies, no new cases of LTBI or new active TB. So I put this up to underscore the point that even though the package inserts for most biologics say that you should test for TB prior to the use of the drug. By the way, none of them say you should test for it repeatedly or do it annually.

That's a special kind of stupid. There's no reason to do that. You only retest when risk changes. Right? So you should test for it.

And the reason it's in the package insert is not because of the biology, it's because it was done in the clinical trials and people weren't on were not certain enough about if you inhibit IL six or IL 23 or IL 17 or IL eight, IL 10, you know, you know, any kind of biologic or new small molecule that maybe you could cause TB because a lot of these studies are done in distant lands where TB risk is much higher than it is in Western Europe, Australia, and United States and Canada, where the risk is really low. Right? But you do it because it's in the package insert. What's the real risk? It's no risk.

That's what this study shows. No risk. All the risk of TB and operatively infection comes when you inhibit TNF. TNF, TNF, TNF, that's what you worry about. If a drug has any effect on either gamma interferon, greater issue with alpha interferon, now maybe you have a risk of TB.

But whenever the story of TB and people call me and say, what can I use? I don't know what to use. Just don't use a TNF inhibitor. Don't make anifrolumab your next choice. Everything else is fair game, including IL-twenty three inhibitors.

I think that's good news. New England Journal published yesterday, a series on the long term outcomes of CD19 CAR T cell therapy in aggressive refractory relapsing B cell lymphomas. Thirty eight patients, twenty four of them had large B cell lymphomas, fourteen of them had follicular, B cell lymphomas. They were treated with, CTL-nineteen. It's got a trade name now.

The ten year survival, and these are bad patients with a deadly disease. The ten year survival was thirty two percent. That's good news because that's an increase in survival over what would have been expected. That's not fabulous news, meaning it's not curing everyone. It was thirty two percent with large B cell.

It was forty seven percent with follicular lymphoma. That's good. Persistent neutropenia grade two or three was five percent. A risk of secondary malignancy was seen in twenty one percent. B cell aplasia persisted in forty four percent of those who responded.

The point of this is, you know, this is being used outside of rheumatology. This is where it started, really was in lymphoma and oncology. And these are major strides, but they are not without risk. And that's what we should be looking for as we develop CAR T cell therapies in rheumatology. Brucellosis, a great line from a Warren Zevon song, obscure, I know, affects the musculoskeletal system.

I've had I again, I practiced in Dallas. We have a lot of people that are Hispanic, a lot of people that travel, lot of people go back to Mexico or Central America. I've diagnosed two cases of brucellosis, one in the spine, one in the peripheral joint. Half of the cases of brucellosis do affect the spine and the SI joint. You should think about it.

Anyway, this is relevant as the CDC put out a series of brucellosis in The United States between 2010 and 2014. Almost eighteen hundred cases of confirmed and probable cases. Sixty one percent of whom reported travel. Eighty percent of those were international travel. And in most cases, the exposure was either being around animals, but more it was actually consuming unpasteurized dairy products or uncooked meats.

Both about seventy three percent claim such exposure. Sixty two percent were in contact with animals. Forty percent I don't know what that was. I left off the rest of the sentence. The point is brucellosis, you should be diagnosing, once or twice in your career, and you should be thinking about it when they don't respond to your usual medicines or when it's unilateral, although it can be bilateral sacroiliitis.

Think about that. I like this study. It was a four week proof of concept study about IL six inhibition in just depression patients. There's no arthritis. There's no autoimmune disease here.

The biology of depression shows that IL six is up in these people, up in the brains, and so this led to this proof of concept study in thirty patients with depression who were either treated with placebo or tocilizumab usual dose. At fourteen days, not much improvement. Let me just stop and say, at fourteen days after your first infusion of tocilizumab, how many people with RA, have improved? Yeah. Not many.

You know, j systemic JNA, a lot. Right? But in depression, not much improvement by day 14. But over time, looking out to a year, you know, months to a year, significant improvement when atosilizumab treatment as far as depressive symptoms, depression severity, fatigue, anxiety, and quality of life. Remission was seen in fifty one percent, depression remission, I didn't know that was possible, versus thirty one percent on placebo.

There's a tremendous placebo effect in all depression trials, but the delta there is twenty three percent. Might you be getting consults for infusions of IL six therapy? It is possible because you know that psychiatrists are not gonna be prescribing it. It might happen. I like this report from, PLOS Medicine.

It's an Israeli study looking at a large number of first trimester pregnancies exposed to nonsteroidals. So this was, a database of over two hundred and fifty thousand singleton pregnancies. From that, they found twenty thousand two hundred and two or seven point six of the population that were exposed to nonsteroidals in the first trimester. Brave, because I don't think most doctors know that you can use nonsteroidals during pregnancy, and most doctors, you know, rant, don't use any drugs or talk to me about drugs. Anyway, the drugs that were used in pregnancy in these Israeli patients who are pregnant was five percent ibuprofen, two percent diclofenac, one percent naproxen.

When they did propensity scoring and matching and adjusted for maternal age, diabetes, obesity, smoking, folic acid use, other key covariates. They looked at whether nonsteroidals caused the problem as far as fetal malformations. That was the main readout here, MCMs, major congenital malformations. And overall, no increased risk with congenital malformations when nonsteroids were used in the first trimester of life. The rate and I can tell you because I've done a lot of this research in the past, the they usually don't have a comparator rate.

They, you know, it's always like the rate of malformations in a cohort is usually like three, four percent, and the comparator rate is historic, population based, and it's up to three to five percent. In this population in Israel, they found eight point two percent MCM rate in the those exposed. It was seven percent in the unexposed. Again, the adjusted relative risk is point nine nine and not significant. They looked at the individual kinds of malformations, it's musculoskeletal, urogenital, cardiac, etcetera.

Also, none of those were increased. We do know that you shouldn't be using nonsteroidals in the last trimester or certainly after week thirty two because it causes ductus arteriosus problems in the fetus. And but it's safe to use certainly in the first trimester, even in the second trimester. The ACR reproductive guidelines, I believe, says that, yes, you can use, standard nonsteroidal. Probably shouldn't use COX two inhibitors because there isn't enough research and there's some indication that there could be risk there, but there's not enough known.

But regular nonsteroidals, nonselective nonsteroidals, non COX-two answers, why not? So I thought that was, something that you should think about when treating your pregnant patients. Oh, I don't know about you, but I teach residents and fellows that we don't use steroids. They often actually, they often ask, you use steroids in everything, doctor Cush. Why don't you use steroids in ankylosing spondylitis?

And I always say cavalierly, Well, because they don't work. And I don't think I could really point to a study, although I've read that in chapters. Anyway, I found a study, a double blind, randomized, placebo controlled study of ninety four patients with spondyloarthritis, and they had to have peripheral arthritis. These patients did not have psoriatic arthritis. So it's just SPA only with peripheral arthritis who had two or more swollen joints.

I think on average, they had like seven tender and an average of four or five, actually, the the the entry numbers were TJC 10, SJC two, three point six. These were almost eighty percent male, 32 years of age. Again, they were randomized to either placebo or, glucocorticoids. At week twenty four, no significant difference between the two groups as far as ACR fifty, ACR seventy, or SRC, p s a r c, outcomes, and it's modified per SPA. It's called a p s p a r c.

It's another combined measure of outcome. But again, this is proof that steroids in low doses don't work in patients with ankylosing spondylitis. I mentioned AI at the top of the podcast. A study coming out of China looked at three forty RA patients, who were managed by rheumatologists and post discharge were either managed in usual care ways, almost no follow-up, patient calls in with a problem, whatever, Or nurse led AI interactive programs where AI would follow the patient, interact with the patient post discharge, and then the nurse would act on what AI was finding. Big difference here.

Usual care was far inferior to AI platform care where the AI group had significantly better improvement in dash 28 scores. I think they started out with a dash 28 of four point something, and it was minus point seven seven with AI, minus point two seven with, usual care. Many other things improve, HAC, and functional status. Medication adherence, ninety percent versus eighty percent. Patient satisfaction, ninety six percent versus seventy six percent.

Again, this is gonna be a useful tool for the intercritical, intercurrent care of your patients in the lead up of the the the follow-up visit to you. AI is going to dominate the picture on information at your disposal that you or your team can respond to. Think about it. Do it. Or as Nike says, just do it.

A Korean study of over 50,000 patient patients with newly diagnosed RA looked at the influence of income, low versus high income, I think it was the top turtle of sustained high income status had a significant protective effect in all RA outcomes. So, you know, who was it? Joan Rivers who said, I've been rich. I've been poor. It is better to be rich when people say money isn't everything.

Here's an example where money is a big deal. And by the way, the real improvement was seen in RA patients 65. I thought that was surprising. So maybe the converse is true. That is that, you know, obviously, being a low income and sustained low income, that that's a significant risk factor.

Anyway, it's worth getting a second job if you have RA. Oh, but can you work if you have RA? That's a whole another study that I'm not gonna have in this report. About live virus use in, your JIA patients? A systematic review of nine studies in seven hundred and forty three patients showed that if you use the MMR virus vaccine, it's a live virus vaccine, no increase in flares, overall great safety, good immunogenicity in the short term.

But if the patient was on a biologic, the protection was incomplete or less durable over time, especially for measles and rubella, not so much with mumps. These were looking at five year post MMR, outcomes, especially as far as seroprotection. No. They didn't have enough patients, I think, in this and enough follow-up to know what what would happen as far as if there's a loss of protection, do they get those infections and whatnot. These were JIA patients.

But still, this is a valuable report. We saw a report this week from the Endocrine Society meeting that was meeting somewhere in The United States that there was an abstract presented that type two diabetics taking semaglutide, the GLP one agonist, have a fifteen percent lower risk of fractures. It's an EHR study of twenty six thousand patients taking semaglutide or other controlled medicines. There are other previous studies that have made the same point that, protection against fractures is linked to a, weight loss, especially if it's rapid, and b, to to certainly, with the use of GLP one agents. Again, this is another issue as to why you, the rheumatologist, are going to have to be proficient in these drugs if not prescribing them to your patients at some point.

Right now, there's only a minority of you who are doing this. You know, there are a minority of rheumatologists who actually have weight loss clinics, And they're labor intensive. The drugs were were a little bit scary, but, you know, other than you saying you should to your patients, you should exercise without giving them specific exercises. And you should lose weight and go on a diet without giving a diet. You know, it's now gotten easier to manage the obesity, and the effects are dramatic.

Think about it. A retrospect a retrospective study looked at, PRP, platelet rich plasma injections, another goofy intervention invented by orthopedics, given to athletes in trouble who will take anything to win Wimbledon or compete in the playoffs. A retrospective study of a hundred and sixteen patients with bilateral knee OA, not too bad. Kellgren Lawrence scores are one and two, meaning it's not bone on bone, Kellgren Lawrence four. And they were treated with three PRP injections, a total of fifty eight patients, or nonsteroidals.

The patients could have had, intra articular prior treatment with hyaluronic acid. After five years, no significant difference in outcomes as far as, global pain Womack scores SF-thirty six. By the way, both groups with bilateral knee OA, followed five years did worsen, but PRP did nothing long term. Well, you you might say, well, I don't get it for long term. Well, people often expound on that there are probably long term benefits to this, and this shows that they're clearly not.

There may be there's argument about short term benefits to PRP as there might be short term benefits to hyaluronic acid, but is it worth the intra articular intrusion and risk? I think not. I don't do either. I wouldn't do either unless the patient recommends it. Now they are asking for PRP.

I'm sending it to one of my orthopedic colleagues. I think if you haven't downloaded, you should look at the RheumNow article on low back pain. It comes from it's a JAMA review. It's a comprehensive review, I must say. It reviews a lot of things.

It's almost as good as an ACR UR guideline, epidemiology, pathophysiology, diagnosis, evaluation, treatment, and they're specifically looking at non specific low back pain, meaning they're excluding all the discogenic disease, all of the, inflammatory spondyloarthritis, and this is based on one eight publications 100 over a twenty five year period. Some of the tenants of this review are really, I think we do a good job of covering the main highlights in the RheumNow article, you could look at that or you could download the JAMA article. They are very clear in stating upfront that you must actively exclude axial spondyloarthritis, especially in males under the age of 40, especially if they have inflammatory back pain, where, you know, the risk was the the risk of, I think of of ankylosing spondylitis, axial spondylitis, jumps threefold if they're young, and and if they have inflammatory back pain, and then jumps to, like, ninety percent if they got b 27. Anyway, actively excluded. Routine imaging for nonspecific low back pain is not recommended.

No point in doing it. Unlikely to find something, more unlikely to find something that means anything or that you can tailor therapy after. It's just looking good for the patient or appeasing your own guilt about what you don't know, about how to manage that situation. The guideline or actually many guidelines have said this, but this review article says that. They are clear in stating again what guidelines have said, exercise and cognitive behavioral therapy are best evidence treatment for a non specific chronic low back pain.

And there is no superiority for one exercise over the other. They are very clear in stating that bed rest is a no no. Patients with back pain should be active and moving and not lying in bed. That's a bad idea. They do worse.

We got another article this week on cognitive behavioral therapy, especially when the patient is self directed. Patients are taught to do self directed CBT. It's better than physician directed CBT. Why are we not using more CBT in rheumatology? I used a fair amount only because the practice next door to me, and not that there were a lot of medical practices in my building, was, a psychotherapist that did CBT, and patients definitely benefited from it.

Nonsteroidals remain the only evidence based first line pharmacologic option for acute and chronic nonspecific low back pain. They point out no evidence of benefit with acetaminophen, steroids, gabapentinoids, muscle relaxants. And of course, they're averting you from use of opioids. Opioids and invasive interventions have minimal benefit, but they, do have some significant risk, in low back pain and therefore should be avoided. Again, nonsteroidal is our first line, especially according to NICE and WHO recommendations.

They also say, what else? Opioids can be used in severe refractory cases, refractory cases under strict monitoring, but there is significant safety risk. And then invasive interventions, spinal injections, radiofrequency denervation, spinal cord stimulation, spinal fusion are not recommended for nonspecific low back pain. Network meta analysis shows spinal injections are no better than sham, and multiple RCTs have shown the same. Interesting.

I like this report from Ian McGinnis, professor Nagy, and others, a great set of, European investigators. I think Bernard Combs on that too asking it's a review of biomarkers in RA. You know, it is the holy grail. We're thinking if we can just have a biomarker, we'll know what to do. Some of you think we have biomarkers, and there are companies out there trying to play the biomarker marketing game.

In my mind, it's not a biomarker unless it's been shown in a prospective trial to have predictive value that would help me in making decisions. If you have a test, you know, you're gonna test for, you know, anything, applesauce levels or particulate matter, concentrations. And now you're going to apply that test to 500 patients and samples in the best study done almost twenty years ago. But you got the samples, you got the data, and you proved something from that analysis. You just predicted the past.

You didn't predict its value as a be used proactively as a biomarker. So here's some of the points of their paper. CCP remains the gold standard. But they say, you know, maybe combinations of rheumatoid serologies can become an advantage. So car the use of CARB P antibodies or fourteen three three ADA or anti PAD four or anti scavenger receptor a.

I'm not familiar with that one. May prove that some people with seronegative disease have RA because of their close, their high specificity in RA but low sensitivity. But are you gonna add these on? I mean, I do a rheumatoid factor in a CCP, and I've played with fourteen three three ADA, and sometimes useful. I don't do CARD p and and PAD four, and I don't know where to order SRA antibodies.

But they say that this can be an advantage. I think that they're prompting the audience to know that research is ongoing here. They also say genetic studies are really of no value. You know, HLA DR4 typing Doctor beta one o alleles, not useful. GWAS studies, polygenic risk scores are basically, investigations at this point.

The MBDA score, the Multi Biomarker Disease Activity Score, also known as Vectra, is maybe one of the most studies of the putative biomarkers. But I say putative because and they give it hope. I don't give it hope because, again, all their data is based on retrospective analysis. They have yet to do a prospective study. I've given it to them.

I've given it to them, verbally. I've given it to them written out what the design should look like. They haven't done it. They invest in, reanalysis of other people's data. And then other putative biomarkers are doing the same nonsense, in my opinion.

MMP three level stands out as the most predictive of future erosive disease in RA. The they may spend a lot of time talking about pathotyping, that doing either histological or transcriptomic, analyses of synovial tissues to then say whether what's going on in the joint is either, lymphoid myeloid, diffuse myeloid, or pauci immune might help guide therapies. And there are a few studies out there where this has been modestly, moderately effective. We're not yet at the stage of doing small tissue bios biopsies. They think that biomarkers in the future could be used to guide tapering.

There's some evidence that MBDA and ACPA levels and calprotectin levels can help predict who you can safely taper. And lastly, that maybe you should be using biomarkers, to do surveillance for comorbidities, and that would include CAR P, proBNP levels, calprotectin, KL6, MMP7, MUC5B, and ILD are good examples, and there are other bone marker turnovers in, looking at osteoporotic disease. I think that these are, smart ways to think about the future. They are not yet ready for prime time, but this is what we're hopeful about. That's it for this week on the podcast.

Make sure you go to the website to check out these citations and more. Hope that you're looking at the Room IQ quiz every Saturday morning. And next month, starting in two weeks, we have a month of gout. It's gout, more than a flare. Gout is a systemic disease.

We are planning. We are writing. We are videoing. We're making podcasts. It's a campaign month, totally devoted to gout in the month of July.

Hope you'll be there. Hope you enjoy it. Take care.