Generic Tofacitinib (6.26.2026)

It's June 26, 2026. This is the RheumNow podcast and I'm Dr. Jack Cush, executive editor of RheumNow.com. This week on the podcast, generics, more on CAR-T and AI.

I'm going to begin with a quote from my favorite blog by Seth Godin. SethGodin.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 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 got to be in it to win it. If you're not using AI, you are part of the distant past. You're in the rear view mirror. If you read House of God, you're eat my dust, Eddie."

I think the big news of the week happened on June the 4th, not a month ago, and that was Brea Ridge Pharmaceuticals received FDA approval for their generic version of tofacitinib. This was both the 5 milligram and 10 milligram tablets. Not the 11 milligram XR version, but five and ten milligrams for both adult and pediatric use, for all the indications and all the warnings for which tofacitinib has been given. This is a game changer. The price is going to drop, the availability should increase. What would you do if tofacitinib were the same price as methotrexate?

Well, don't worry, it's not going to 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 is 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-23 inhibitor in patients with psoriatic disease, both psoriasis and psoriatic arthritis. This is a literature review, 34 studies looking at IL-23 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 certain enough about whether, if you inhibit IL-6 or 23 or 17 or IL-8, 10 — you know, any kind of biologic or new small molecule — 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, the United States, and Canada, where the risk is really low. 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 opportunistic 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 comes up 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 a JAK inhibitor your next choice. Everything else is fair game, including IL-23 inhibitors. I think that's good news.

The 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 — 38 patients, 24 of them had large B cell lymphomas, 14 of them had follicular B cell lymphomas. They were treated with CTL019, which has a trade name now. The 10-year survival — and these are bad patients with a deadly disease — the 10-year survival was 32%. 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 32% with large B cell. It was 47% with follicular lymphoma. That's good. Persistent neutropenia, grade two or three, was 5%. A risk of secondary malignancy was seen in 21%. B cell aplasia persisted in 44% of those who responded.

The point of this is, you know, this is being used outside of rheumatology. Here's where it started, really — 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. Um, affects the musculoskeletal system. I've had — again I practiced in Dallas. We have a lot of people that are Hispanic, a lot of people that travel, a 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 1,800 cases of confirmed and probable cases. 61% of whom reported travel, 80% 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 73% claim such exposure. 62% were in contact with animals. 40% — 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. Um, think about that.

Uh, I like this study. It was a 4-week proof of concept study about IL-6 inhibition in just depression patients. There's no arthritis. There's no autoimmune disease here. The biology of depression shows that IL-6 is up in these people, up in the brains. And so this led to this proof of concept study in 30 patients with depression who were either treated with placebo or tocilizumab usual dose. At 14 days, not much improvement. Let me just stop and say at 14 days after your first infusion of tocilizumab, how many people with RA have improved? Not many, you know. Systemic JIA, a lot, right? But all right, 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 tocilizumab is treatment, as far as depressive symptoms, depression severity, fatigue, anxiety, and quality of life. Remission was seen in 51% — depression remission, I didn't know that was possible — versus 31% on placebo. There's a tremendous placebo effect in all depression trials, but the delta there is 23%. Might you be getting consults for infusions of IL-6 therapy? It is possible, because you know the psychiatrists are not going to be prescribing it. It might happen.

Uh, I like this report from PLOS Medicine. Um, it's an Israeli study looking at a large number of first trimester pregnancies exposed to non-steroidals. So this was a database of over 250,000 singleton pregnancies. From that they found 20,22 — or 7.6% of the population — that were exposed to non-steroidals in the first trimester. Brave, because I don't think most doctors know that you can use non-steroidals 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 5% ibuprofen, 2% diclofenac, 1% naproxen. Um, when they did propensity scoring and matching and adjusted for maternal age, diabetes, obesity, smoking, folic acid use, other covariants, they looked at whether non-steroidals caused a problem as far as fetal malformations — that was the main readout. Main readout here: MCMs, major congenital malformations. Um, and overall no increased risk with congenital malformations when non-steroidals 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 — they usually don't have a comparator rate. You know, it's always like the rate of malformations in a cohort is usually like 3–4%, and the comparator rate is historic population-based and it's up to 3 to 5%. In this population in Israel, they found an 8.2% MCM rate in those exposed. It was 7% in the unexposed. Again, the adjusted relative risk is 0.99 and not significant. They looked at the individual kinds of malformations — whether it was musculoskeletal, urogenital, cardiac — also none of those were increased. We do know that you shouldn't be using non-steroidals in the last trimester, or certainly after week 32, because it causes ductus arteriosus problems in the fetus. But it's safe to use certainly in the first trimester, even in the second trimester. The ACR reproductive guidelines, I believe, say that yes, you can use standard non-steroidals — probably shouldn't use COX-2 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 non-steroidals, non-selective non-steroidals, non-COX-2, and says why not. Uh, 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, Dr. Cush? Why don't you use steroids in axial 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 94 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 entry numbers were TJC 10, SJC 3.6. These were almost 80% male, 32 years of age. Again, they were randomized to either placebo or glucocorticoids. At week 24, no significant difference between the two groups as far as ACR50, ACR70, or ASAS outcomes. And it's a modified SpA outcome, it's called PSARC. 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 this podcast. A study coming out of China looked at 340 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 DAS-28 scores. I think they started out with a DAS-28 of 4-something and it was minus 0.77 with AI, minus 0.27 with usual care. Many other things improved — functional status, medication adherence 90% versus 80%, patient satisfaction 96% versus 76%. Again, this is going to be a useful tool for the intercurrent care of your patients in the lead-up to 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 patients with newly diagnosed RA looked at the influence of income — low versus high income. The top quartile 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 under 65. I thought that was surprising. So maybe the converse is true — that being in sustained low income is 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 other study that I'm not going to have on this report.

What about live virus use in your JIA patients? A systematic review of nine studies in 743 patients showed that if you use the MMR vaccine — it's a live virus vaccine — there was 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 5-year post-MMR outcomes, especially as far as seroprotection. They didn't have enough patients and enough follow-up to know what would happen as far as whether a loss of protection led to 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, where there was an abstract presented that type 2 diabetics taking semaglutide, the GLP-1 agonist, have a 15% lower risk of fractures. It's an EHR study of 26,000 patients taking semaglutide or other control medicines. There are other previous studies that have made the same point — that protection against fractures is linked to weight loss, especially if it's rapid, and certainly with the use of GLP-1 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. There are a minority of rheumatologists who actually have weight loss clinics, and they're labor intensive. The drugs were a little bit scary, but other than you saying 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 — it's now gotten easier to manage the obesity and the effects are dramatic. Think about it.
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 116 patients with bilateral knee OA. Not too bad. Kellgren-Lawrence scores were one and two, meaning it's not bone on bone — Kellgren-Lawrence 4. And they were treated with three PRP injections, a total of 58 patients, or non-steroidals. The patients could have had intraarticular prior treatment with hyaluronic acid.

After 5 years, no significant difference in outcomes as far as global pain VAS scores, SF-36. By the way, both groups with bilateral knee OA followed 5 years did worsen, but PRP did nothing long-term. Well, you might say, well, I don't give 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 argument about short-term benefits to PRP, as there might be short-term benefits to hyaluronic acid. But is it worth the intraarticular intrusion and risk? I think not. I don't do either. I wouldn't do either unless the patient recommends it. If they are asking for PRP, I'm sending them to one of my orthopedic colleagues.

I think if you haven't downloaded it, 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 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 the inflammatory spondyloarthritis. And this is based on 108 publications over a 25-year period.

Some of the tenets of this review — I think we do a good job of covering the main highlights in the RheumNow article. So you could look at that or you could download the JAMA article. They are very clear in stating up front that you must actively exclude axial spondyloarthritis, especially in males under the age of 40, especially if they have inflammatory back pain. The risk of ankylosing spondylitis, axial spondylitis, jumps three-fold if they're young and if they have inflammatory back pain, and then it jumps to like 90% if they've got B27. Anyway, actively excluding routine imaging for non-specific 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 the best evidence treatment for 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 it 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.

Non-steroidals remain the only evidence-based first-line pharmacologic option for acute and chronic non-specific 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, non-steroidals are first line, especially according to NICE and WHO recommendations. They also say — opioids can be used in severe 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 non-specific low back pain. A network meta-analysis shows spinal injections are no better than sham, and multiple RCTs have shown the same.

Interesting. I like this report from Iain McInnes, Professor Naggie, and others — a great set of European investigators. I think Bernard Combe is 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 going to test for, you know, um, anything, applesauce levels or particulate matter, uh, concentrations. And now you're going to apply that test to 500 patients and samples in the best study done almost 20 years ago. But you got the samples, you got the data, and you prove 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 are some of the points of their paper. CCP remains the gold standard. Um but they say you know maybe combinations of rheumatoid serologies can become an advantage. So the use of CarP antibodies or 14-3-3η or anti-PAD4 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 high specificity in RA but low sensitivity. But are you going to add these on? I mean I do a rheumatoid factor, a CCP, and I've played with 14-3-3η and it's sometimes useful. I don't do CarP and PAD4 and I don't know where to order scavenger receptor A 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, DR beta-1 alleles not useful. GWAS studies, polygenic risk scores are basically um investigations at this point.

The MBDA score, the multi-biomarker disease activity score, also known as Vectra, is maybe one of the most studied of the putative biomarkers. But I say putative because — and they give it hope — I don't give it hope because um again all their data is based on retrospective analyses. They've yet to do a prospective study. I've given it to them. I've given it to them um verbally. I've given it to them written out what the design should look like. Um they haven't done it. They invest in um reanalysis of other people's data and other putative biomarkers are doing the same nonsense.

In my opinion, MMP3 levels stand out as the most predictive of future erosive disease in RA.

They may spend a lot of time talking about pathotyping — doing either histological or transcriptomic um analyses of synovial tissues to then say whether what's going on in the joint is either um lymphoid, myeloid, diffuse myeloid, or fibroid — 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 synovial tissue biopsies.

They think that biomarkers in the future could be used to guide tapering. Um 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 um to do surveillance for comorbidities, uh and that would include CRP, um proBNP levels, um calprotectin, KL-6, MMP7, MUC5B, and are good examples, and there are other bone marker turnovers in um looking at osteoporotic disease.

I think that these are um 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 RheumNow 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. I hope you enjoy it. Take care.