0:01
Hi everyone. It's October 23rd, 2026. This is the RheumNow podcast.
0:08
Hi, I'm Dr. Jack Cush, executive editor of RheumNow.com.
0:11
What do you do when you find two different crystals in one joint?
0:17
Should you worry about cryptococcus having a twofold higher risk with JAK inhibitors?
0:21
You know, there are patients out there that have myositis and scleroderma, and a Sjögren's patient who has early damage has a much greater than twofold risk of lymphoma.
0:35
It's double trouble week on the RheumNow podcast. Welcome.
0:40
A few FDA announcements. The FDA has approved the new drug application for Evoxac, which is approved, as you know, as an oral pill for dry mouth of Sjögren's syndrome.
0:58
The company called Cassette has been granted the right to sell oral liquid Evoxac as an alternative treatment option for those with dry mouth symptoms and Sjögren's.
1:11
This is going to be available at the end of this year.
1:12
It's not available right now, but I thought it was interesting.
1:16
It's a new formulation of Evoxac and that might benefit a few people who have, as is often the case, which Sjögren's patients have — a problem swallowing pills.
1:26
The FDA is currently reviewing the Sun Pharma IL-23 inhibitor tildrakizumab.
1:32
We've seen trials on that. There have been phase three trials in Spire 1 and Spire 2 in PsA.
1:37
So they're reviewing the application and the PDUFA date, the action date, is coming up next week, October 29.
1:47
We'll be watching that and maybe we'll have another IL-23 inhibitor approved for psoriatic arthritis.
1:54
It's getting crowded out there, is it not?
1:59
You know, many of you are using AI. I listened to a few presentations yesterday at medical schools where the overlying message was don't worry, doctors always have jobs, AI will never replace you.
2:12
Turns out that that may not be true, but that was the message.
2:17
You know, doctors are needed for the empathy and everyone was apologizing — don't worry, AI is here but you'll always have a job.
2:24
You know what, AI makes you better. It makes you a much better physician.
2:31
I use it all the time. I use it for organization, for step one research.
2:38
And I saw this paper this week about Open Evidence.
2:43
I think this was published in JAMA — a study of nearly a million US clinicians which included 560,000 MDs who submitted, in a two and a half year period, 271 million AI clinical queries in this two and a half years.
3:05
MDs on average that used Open Evidence were submitting 371 queries a month.
3:15
About a third of it was for treatment insights, 14% was for diagnostic insights.
3:24
The people who were the higher users of this AI tool, Open Evidence, were young MDs, oncologists, hematologists, internists, and family medicine.
3:39
If you're not using Open Evidence, as Lenny Calib and I have been for a few years, I think you should be looking at it.
3:47
It's a good way — and I'll do research where I'll ask the same question of ChatGPT or Claude.ai and Open Evidence to see what they come up with.
3:59
Okay, the thing about AI — well, you say, you know, they lie and there's that hallucination thing where it makes stuff up.
4:09
If you're an expert in rheumatology, you'll spot the nonsense that AI will throw out at you.
4:15
I was in a chat ring with a bunch of my high school friends and one guy who's very much involved with the Atlanta Falcons says, "Hey, what happened?
4:24
I heard that we lost a game. ChatGPT says that Savo High School lost, you know, 45-13."
4:33
And I said, "ChatGPT is wrong. Sable won that game."
4:37
So it does make mistakes, but it is incumbent upon you to be expert enough to spot them.
4:42
Otherwise, it's going to make you much more efficient in my opinion.
4:51
A study on 418 patients with microscopic polyangiitis — I talked about this last week.
4:56
The value of CBC information in this REVEAL study.
5:01
High baseline neutrophil to lymphocyte ratio greater than 10 was associated with significantly higher disease activity measured by the Birmingham Vasculitis Activity Score, a higher risk of alveolar hemorrhage, renal dysfunction, reduced survival, and higher infection-related mortalities.
5:19
All from the CBC at first or baseline visit.
5:24
Again, the other interesting thing about that study was a low NLR in those patients predicted a higher risk of ILD and UIP-type ILD.
5:38
So again, it behooves us to figure out a way to program this information coming out of your CBC every day.
5:47
Otherwise, you've got to get your calculator out and do the math.
5:51
Okay. Cryptococcus is rare. I found a study that says it's rare.
5:59
It's a retrospective Trinetx analysis of RA patients who were starting either a JAK inhibitor or a TNF inhibitor — over 32,000 people in each group — and they looked at the risk of cryptococcus: JAKs versus TNF, JAKs versus non-TNF, TNF versus non-TNF.
6:19
Turns out that cryptococcus was seen very rarely, less than 2% — 2% of people, that's two per thousand.
6:30
I like to teach that things like cancer, TB, fungal infections are like one in a thousand, one in 10,000 risk.
6:37
I've never seen a cryptococcal infection in RA.
6:42
I have seen cryptococcal meningitis complicate lupus, but they're rare events.
6:48
In this study, they showed that there were significantly higher risk of cryptococcal infections in RA — a twofold higher risk in two different of those comparisons.
7:01
So that just means that, you know, JAKs don't have much in the way of opportunistic infections other than — as you know — shingles, and that's because of its inhibition of interferon.
7:13
But other than shingles, you know, TB doesn't really happen here.
7:16
But it looks like from this analysis — against Trinetx, which is good and bad depending on what kind of mood you're in that day — you might consider that JAKs might have an increased risk for cryptococcal infections.
7:31
Speaking of opportunistic infections, a Thai study looked at pediatric SLE patients.
7:37
You know, they have more severe disease, do they not?
7:40
And they looked at 177 pediatric SLE. 38 developed an opportunistic infection.
7:47
38 out of 177 — my goodness, that's like a 16-17% risk.
7:52
3.4 events per 100 patient years. What in the world?
7:59
Most common opportunistic infections were Candida 27%, Aspergillus 13.5%, CMV 13.5%, with skin and lung being the most likely organ systems involved.
8:11
Other risk factors included getting pulse steroids — not low dose steroids or up to 10 milligram steroids, but pulse steroids — and a SLEDAI of greater than 11, or as you would expect, disease activity would be a higher risk.
8:27
Kids might be at higher risk, but kids may have more severe disease.
8:31
More severe disease may bring a risk of opportunistic infections.
8:36
Two reports on gout. The first report — 150 patients — is basically making the point that your patients with gout who are on allopurinol: if they have elevated LFTs, don't worry about it, monitor the LFTs, keep the allopurinol.
8:54
150 patients, 56 years of age, 21% on alcohol, 30% obese, 5% with metabolic-associated steatohepatitis.
9:08
They were all on allopurinol. 20% had an increased AST or ALT.
9:14
87% of those were mild. None of them were severe.
9:16
None of them led to drug discontinuation.
9:19
And again, you can continue the allopurinol without significant changes in AST and ALT, and I think that's comforting because that's kind of what I
9:31
do. When LFT elevations were found, allopurinol was not deemed to be the primary cause — there were things like obesity, taking statins at the
9:48
same time, etc.
9:48
Another study out of Tokyo looked at 107 patients, mean age 86, and they all had synovial fluid aspiration.
10:03
Most of them had urate crystals, but 16-17% of them had CPPD crystals also.
10:14
In this cohort of 107, there were a few people who had a history of gout and hyperuricemia — that was 17 out of the 107.
10:26
About 40% of them had a history of gout and hyperuricemia, which would explain the crystals maybe being together.
10:38
Nobody was treated for gout; they were all treated for CPPD.
10:49
Well, the good news is that the treatments are the same, are they not, for the most part?
10:54
But the point is that you need to look for the crystals yourself, and identification of both could have importance as to what happens further down the road.
11:06
This is a short follow-up study — it'd be interesting to know what happens to people after two years.
11:11
We did a report this week about scleroderma patients, systemic sclerosis patients who have myositis.
11:21
The cohort that we showed demonstrated that myositis when found in systemic sclerosis was associated with an increased risk of cardiac involvement including heart failure.
11:33
And basically those people had very little risk of ILD.
11:39
Not having myositis made you have a greater risk of ILD.
11:42
Pretty interesting part of the double trouble story here on the podcast.
11:50
An interesting study this week from JAMA about treating refractory carpal tunnel syndrome — and I guess they just had splinting.
11:59
So 39 patients, 63 carpal tunnel injections.
12:07
They either had ultrasound-guided hydrodissection with normal saline, no steroid; or people who just had steroid injection; or the third group had ultrasound saline hydrodissection and steroid.
12:27
The idea is that you give the saline, it's supposed to move around the median nerve and get it to a happier spot.
12:39
At week 24, the groups that got saline were superior to steroid alone — 86 and 90%.
12:48
Not much added benefit of using steroid on top of saline.
12:54
Are you willing to do that? I don't know.
12:58
I'd like to see this study repeated. It's only 39 patients, but I think it's interesting that you may not need to use steroids.
13:07
A Portuguese study looked at patients with primary Sjögren's disease and showed that early damage as assessed by survey questionnaires — the SSDDI and, I'm sorry, the SSDDI and the SSDI — these are things that look at what organs are involved in Sjögren's.
13:28
But if you have early organ involvement, hence damage, that they saw with those two different tools, either a 12-fold or a 14-fold increased risk of lymphoma.
13:42
208 patients, follow-up of 14 years, damage was seen in about 80% of people.
13:52
Mortality was linked to age but not to damage.
13:57
Lymphoma was linked to early findings of damage. Might want to consider that.
14:06
Two studies on RA. A Polish study compared the comorbidity frequency between RA and PsA.
14:12
In their cohorts, RA patients had an older age in general, especially at diagnosis — 61 years versus 44 years for PsA.
14:23
RA had higher, and maybe that older age could drive the higher rates of comorbidities.
14:33
RA patients had significantly more comorbidities — 74% in RA — including hypertension, ischemic heart disease, cardiovascular disease.
14:42
Comparing RA to PsA: hypertension 18% to 12%, ischemic heart disease 11% versus 6%, cerebrovascular disease 4 versus 2%.
14:54
You know, I've often thought that PsA, because of its association with obesity and metabolic derangement, probably had more comorbidities.
15:03
But there are other studies that do point out pound-for-pound, RA has got more comorbidity.
15:09
It's just one of the things that you're good at managing.
15:14
The Italian GIADA early RA registry of 134 patients looked at retention rates on JAK inhibitors.
15:24
Retention rates at 6 months: 81%. 12 months: 75%.
15:31
That's pretty good. At 24 months — uh-oh — 61%.
15:36
So it's not much better than TNF inhibitors if you were to do historic comparisons.
15:43
Who's not going to do well and stay on the JAK inhibitor?
15:48
Patients who start out with glucocorticoids at baseline, those who have high disease activity, those who have high pain scores — they're the ones who are going to bail out on the JAK inhibitor before two years.
16:01
That's it for the podcast. I want to remind you, RheumNow Live registration is open for the 2027 meeting.
16:11
It is January 30 and 31 in Dallas, Texas.
16:13
You can look at the agenda that's there.
16:16
You can register early — there's early bird registration.
16:20
We're going to have sessions on obesity, on CAR T cell, on JAK inhibitors, on lupus.
16:30
I think you're going to like the program. We'll see you there.
If you are a health practitioner, you may Login/Register to comment.
Due to the nature of these comment forums, only health practitioners are allowed to comment at this time.