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It's October 30th, 2026. That's right, the day before Halloween.
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This is the RheumNow podcast, a special edition since it's the day before Halloween.
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And I'm Jack Cush wearing a goofy Halloween cap.
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This week on the podcast, new guidelines for PMR, certainty about good and bad beverages in gout, mixed results in lupus, non-lupus drugs save lupus lives, and big hips sink ships in psoriatic arthritis.
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If you can decipher that, you'll know everything about rheumatology.
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At the top, Novartis announced this past week that the European Commission has approved Cosentyx secukinumab for use in adults with polymyalgia rheumatica.
0:54
That would be adults with PMR not responding to or intolerant of glucocorticoids.
1:01
This makes secukinumab the first IL-17A inhibitor approved in Europe for PMR.
1:09
That's good news. I think we're awaiting the same sort of action by the FDA sometime in the next few weeks in the US, but we shall see.
1:23
A study of psoriasis and biologics from Italy shows that obesity does affect drug responses.
1:32
We know that. But I like the numbers on this.
1:36
562 plaque psoriasis patients treated with biologics.
1:41
A third of them, 34%, were obese. Obesity was associated with primary failure, not secondary failure, not failure due to toxicity, only primary failure.
1:53
The obese patients had primary failure 17% versus those that were non-obese, primary failure 6%.
1:59
That's a three-fold increase in primary failure due to obesity.
2:03
What they showed was for every five kilograms per meter squared BMI, there was a 37% increase in the failure rate.
2:16
The lowest failure rate was seen with IL-17 inhibitors and IL-23 inhibitors, especially compared to TNF inhibitors, about a 50% lower rate compared to TNF inhibitors.
2:28
And again, obesity did not associate with secondary failures or toxicity failures.
2:33
I found that to be a new wrinkle, a new bit of news to me.
2:38
And you know, the problem with therapies in psoriasis and psoriatic arthritis is we've got a lot of them.
2:44
Yes. But we also have what I think are somewhat disappointing survival statistics — when you go on a biologic, a new therapy, a JAK inhibitor, whatever, people don't usually respond and stay on the drugs long enough.
3:02
Is that because we have so many to choose from and we have a low threshold to change?
3:06
This study from the British Society of Rheumatology — they have a psoriatic arthritis registry of 815 patients.
3:12
And the good news was at 12 months with their index drug, new drugs, biologics, targeted synthetics, 24% had minimal disease activity.
3:23
Great. 24% had ACR 50. Great. But when you looked at the follow-up that they had, a median follow-up at 31 months, only two-thirds of patients were still on the index drug — it falls off pretty quick.
3:41
And not surprisingly, patients have to cycle.
3:44
Discontinuations were higher with the apremilast PDE4 inhibitors, were also higher in people who had high baseline activity, and patients who had poor patient-reported outcomes at baseline.
4:00
So the worse they were, the more likely they were to not do well.
4:05
Is that not the case for probably most of the diseases we take care of?
4:12
JAMA had a nice uveitis review that I put up that you should just look at.
4:17
About 40% of uveitis is linked to systemic disease, B27 and axial spondyloarthritis or spinal arthritis being the most common.
4:27
But they remind you, when you see uveitis — which peaks 20 to 40 years of age, half to two-thirds of it anterior uveitis — you need to actively worry about infection: TB, toxoplasmosis, herpes.
4:46
Anterior uveitis gets treated with topical steroids; posterior and panuveitis gets DMARDs first.
4:53
Methotrexate effective in 50%, mycophenolate 71%, adalimumab if they're refractory to conventional DMARDs.
5:03
I put that up because there was an interesting report on brepocitinib.
5:09
We've talked about the VALOR study and brepocitinib looking good in dermatomyositis — it's a TYK2/JAK1 inhibitor.
5:18
And they have two studies, CLARITY 1 and CLARITY 2, a phase three trial showing brepocitinib is effective in non-infectious uveitis.
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371 patients given either 45 milligrams of brepocitinib or placebo for 48 weeks.
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They had a steroid taper, and brepocitinib was highly effective when it came time to look at them at the end of 48 weeks.
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So that's good news. We need more drugs to be approved for uveitis.
5:54
There was a systematic review of cardiovascular outcomes in patients with IMIDs — immune-mediated inflammatory diseases — 11,000 patients from five studies, and they looked at patients who were treated with SGLT2 inhibitors.
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That includes drugs like Jardiance and the like.
6:21
In this group, 70% were lupus patients, 25% scleroderma.
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SGLT2 inhibitor use was associated with significantly lower all-cause mortality and heart failure risk.
6:37
And again, these people were taking SGLT2 inhibitors for usually non-insulin-dependent diabetes, but they compared to a group of people not on these drugs with those diseases, and again there's a significant lowering, but no clear MI benefit.
6:56
We do know that these drugs are FDA approved and have established use in diabetes, heart failure, and CKD patients.
7:05
The question is, with this kind of data and other data I think that will follow, will lupus and autoimmune disease be an indication for SGLT2 inhibitors?
7:17
I mean, we're talking about that now when it comes to, for instance, psoriatic arthritis and getting GLP-1s, right?
7:25
Great effects on psoriatic arthritis. It's been effective in gout, rheumatoid, osteoarthritis.
7:34
But the controlled trials have been done now in psoriatic arthritis — that's probably going to lead to an FDA indication.
7:47
So your arsenal of drugs may extend outside of anti-inflammatory, anti-rheumatic, and immunosuppressive.
7:56
These drugs that will manage the cardiovascular consequences and the comorbidities that are deadly in our diseases are going to be important going forward. That's my opinion.
8:12
How good are we at comorbidities? You know, I started teaching about this back around 2000, and every rheumatologist I came in contact with said, "Yeah, comorbidity is a big problem — not my job, it's somebody else's job."
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But you know, 20 years later, many of you are very good at smoking.
8:31
Many of you are very good at lipids and diabetes, identifying the problem and starting treatment, and then maybe referring.
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Now you're getting better at obesity, knowing the hazards of obesity in all of our patients.
8:49
So this is a study of 2,200 inflammatory rheumatic disease patients and 140 rheumatologists.
8:57
And here lies the problem. Rheumatologists think that they're doing pretty darn good at identifying and managing comorbidities and screening for comorbidities — 72 to 92%, that includes screening for hypertension, osteoporosis, vaccines, and cancer.
9:15
When you ask the patients of those 140 rheumatologists, not so much — 12 to 33%.
9:23
There's always been this discordance about what you think you're doing and what they know you're doing.
9:29
And that's a communication gap, is it not?
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The truth is that rheumatologists do agree they have no structured process for comorbidity screening that's in place, and they point to time, responsibility, lack of reimbursement, not enough staff as all being factors as to why you're not doing it.
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Well, you should be doing it, because your patients see you, they think you're the one who knows the most about them, and they trust you more than anyone else.
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Many of your patients who you think are seeing primary care aren't seeing primary care.
10:08
So you've got to step up. You've got to identify the problems.
10:14
You've got to mandate that they have a primary care, and you need to use a screening tool. You can download one from RheumNow.
10:24
A study of scleroderma was published this week, and it looked at a new way — it's called spatial frequency domain imaging.
10:38
It's a non-invasive evaluation of skin, and they did it in 25 systemic sclerosis patients and 30 normal controls, and they showed it was effective and had correlations with modified Rodnan skin score and also correlations with histologic fibrosis.
10:57
But when you looked at the correlation coefficients, they weren't really — they were sort of on the weak to moderate side from the modified Rodnan skin score, and maybe moderate in histology and fibrosis.
11:13
So I like the idea of having a non-invasive automated way of assessing skin disease, because I don't know how many of you do modified Rodnan skin scores on every scleroderma patient.
11:28
I do. You know, you start in fingers, back of the hand, forearm, arms, chest, face, thighs, lower leg, and feet.
11:39
You score zero to three and add it up. You know, I just saw a guy this week who I've worried is going to have progressive disease, but the fact is he has sclerodactyly up to his elbows, no face involvement, and very little on his feet, but he's got Raynaud's.
12:01
And I'm treating him as if he has limited disease or CREST.
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He's getting methotrexate and he's been stable.
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His modified Rodnan skin score for the last five visits was 12, 14, 13, and 13.
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And I'm going to do it at every visit. But wouldn't it be great if I had another measure that could be done before they see me, out in the waiting room even?
12:28
Well, we're working our way towards that, are we not?
12:32
CAR T cell is all the rage, you know. Rheumatologists believe, based on the fabulous experiments of Schett and Erlangen, that it could be the answer — that we could get to a reset of a deranged immune system and patients will go into remission and won't need biologics or steroids or DMARDs.
12:54
Well, we know that that's not quite true with long-term follow-up of his original cohort, but there's still encouraging data.
13:03
So there was a survey this past week published, and it looked at German rheumatologists and asked their opinion on CAR T cell and T cell-redirecting therapies.
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The cohort size was large, the response rates were good.
13:25
This was a survey done in the last quarter, I think, of 2024.
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Rheumatologists were 95% willing to refer their patients to specialized centers for depleting therapy, cellular therapy, CAR T cell therapy.
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But the rheumatologists said maybe 5% or less of their patients are severe enough to be suitable for this cellular therapy alternative.
13:55
They cite a number of barriers: high cost, limited experience, limited numbers of appropriate patients.
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And so I don't know how this is going to go.
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I mean, right now there are, I don't know, 50 to 100 trials in rheumatology looking at CAR T and like therapies.
14:15
They're all struggling with enrollment, and it's for these reasons.
14:19
You may not have enough patients. You may not have enough faith.
14:22
When they did the survey, they asked the rheumatologists some knowledge questions about depletion therapies, and on a possible score of 0 to 10, they scored a 4.86.
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So your knowledge is good, not great. This is still a challenge.
14:42
The development of these drugs, recruitment for these trials, and your buy-in is still a challenge.
14:49
You know, we had the announcement a few weeks ago that Novartis suspended its CAR T cell trials — I think it was eight or nine trials — based on a few deaths.
15:01
BMS, prior to that announcement, had held up its trial because they were doing some safety considerations, but there's been no new news about the restart of those CAR T cell studies.
15:14
We'll find out at ACR maybe what's really going on.
15:19
Artiva this week — Artiva is a company that's been developing something called AlloNK, an allogeneic NK cell depleting therapy, and they're doing it in RA and autoimmune disease, a phase 2 trial.
15:31
They had two deaths, different reasons and whatnot.
15:37
It's a minority of the patients, but it basically killed the trial.
15:42
So they have suspended the development of AlloNK.
15:48
They halted a phase three trial of AlloNK and they're downsizing this particular type of development.
15:56
We're going to see some hurdles in cellular depletion therapy development because these trials are difficult to do. But that's the news from this week.
16:09
You know, we subscribe to everything here at RheumNow.
16:15
The Journal of Physiotherapy Research International reported this week that TENS — transcutaneous electrical nerve stimulation — does not work in knee OA.
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A sham-controlled trial of 96 patients with knee OA, all of them were treated with exercise, and half received TENS and the other half got a sham TENS, and showed no difference in the outcomes at one month.
16:41
They used a formal score, the KOOS score — that's the knee injury and osteoarthritis outcome score — that is a reliable validated measure.
16:53
Moreover, it didn't matter which group you were in.
16:56
The ones that got better didn't achieve the minimally clinically important difference, the MCID.
17:05
So yeah, TENS doesn't seem to work here.
17:08
A review article from a nutrition journal looked at the risk of hyperuricemia and gout with certain therapies.
17:16
This is a meta-analysis of 52 studies, and yeah, it showed that alcohol had basically a two-fold increased risk of gout and a 50% increased risk of hyperuricemia.
17:29
The same could be found for sugar-sweetened, high-fructose corn syrup sodas and beverages — that increases gout 37% and increases uric acid elevations 48%.
17:41
The same was seen with tea. Tea also will increase the risk of gout 29%.
17:51
Again, this is putting all this data together from 52 studies.
17:58
While tea may increase your gout risk, coffee will decrease your gout risk — and decrease it by 46%.
18:10
The journal Advances in Rheumatology had a report this week from PANLAR looking at TB and latent tuberculosis burden in Latin America.
18:21
They reviewed the PANLAR registry that had 590 IMID patients taking a wealth of the drugs that you and I use.
18:30
Half are on glucocorticoids, 44% were on biologic DMARDs — TNF inhibitors, 29% JAK inhibitors, 27% were on conventional DMARDs.
18:43
590 patients — why were only 430 of them screened for TB?
18:49
Uh-oh. That's a problem. That's an oversight.
18:51
I know that. And by the way, I did a survey of rheumatologists back in 2012 that basically showed the same number.
19:00
Now, if I just hit you over the head — new patient, going to start on TNF inhibitor — yeah, you're going to say I'm going to screen for TB.
19:09
But if you make it a complex case and you bury it amongst all the choices that you have to make in a busy first visit, it's often missed.
19:15
So in their study, only 430, or 73%, had TB screening.
19:21
But of that number of 430, there was 14% who had evidence of latent tuberculosis.
19:29
That's very high. And maybe even higher, because they're probably on TNF inhibitors and maybe other drugs, but the main drug that drives TB risk here is TNF inhibitors — much more than JAKs, or IL-6, or abatacept. A lot more.
19:47
At 12 months they did a repeat TB screening in only 99 of the 430, and they had five new LTBI cases — meaning, well, why did they have to rescreen?
20:00
They should have rescreened, first off. You don't do annual testing — that's a special kind of stupid.
20:07
You only do retesting when risk changes: new exposures, maybe you needed to do it to start a new biologic.
20:19
But they found five new LTBI cases. Of the five, there were only two that had active TB. So there's a lesson to be learned here.
20:26
In the United States, if you're born in the United States, and in England and Western Europe and Scandinavia and Australia, the risk of TB is very, very low.
21:48
Incidence rates are about, you know, in the general population about one per 100,000 per year.
21:48
In an RA population it's going lower and lower — every five years it's probably around five per 100,000.
21:49
Put them on a TNF inhibitor, that risk doubles if you're from these low-risk areas.
21:49
But if you're from Latin America, the population risk is 30 to 60, and if you're on a TNF inhibitor it can go up two- to nine-fold.
21:49
If you're from a high-risk endemic area — that's Southeast Asia, all of Russia, Africa — all being higher, higher, higher than Latin America, and all of those are gigantically high compared to the United States, Canada, England, Germany, Austria, etc. But again, do you need to do repeat testing?
21:49
Not unless risk changes, or unless you're mandated to do so by an idiot guideline that your insurance company is adhering to.
21:49
And then again, the risk of getting TB is much lower, is it not?
21:52
Okay, it's really about identifying latent TB.
21:54
So I hope you found that helpful. I liked it from a numbers standpoint.
21:58
A lot of interesting articles this week, including an article by Eric Dein on IVIG and scleroderma — interesting, some evidence but no good studies, right?
22:09
And a good article by Brian Jaros looking at how to best treat Takayasu's. You should look at that.
22:16
Two articles I want to bring up because they're pretty popular.
22:22
One is a New England Journal article on ianalumab, the BAFF-depleting monoclonal antibody.
22:28
Ianalumab is an IgG1 monoclonal antibody that depletes — has a dual mechanism for depletion of B cells.
22:34
It targets BAFF and it works via ADCC. At ACR last year they reported the NEPTUNE 1 and NEPTUNE 2 trials.
22:46
Lot of buzz, a lot of excitement, you know, definite improvement, met its primary endpoint.
22:49
You know, finally we got a biologic that looks good.
22:53
Well, it showed up in New England Journal, all the data, and it still looks good.
22:58
It still met its primary endpoint, which was the change in SLEDAI over 48 weeks.
23:06
But if you look at the graphs, you know, the change in SLEDAI over 48 weeks happens at the end — it doesn't happen right out of the gate when you compare it to placebo.
23:15
So NEPTUNE 1 had two arms: placebo versus ianalumab.
23:20
And this is a parenteral therapy given monthly.
23:28
And then NEPTUNE 2 trial was a medium dose versus — monthly versus every-3-month ianalumab versus placebo.
23:39
And they both worked at week 48. The p-value in NEPTUNE 1 was 0.05 and the p-value in NEPTUNE 2 was 0.04. So congratulations on all of that.
23:56
But there are mixed results here. When they looked at a bunch of secondary outcomes — something called the SSSD and the SPRE and other measures that are important to patients — ianalumab was numerically better than placebo but not significantly so.
24:14
So when they looked at the SLEDAI responders — to be a SLEDAI responder you had to drop your SLEDAI score, a composite score of many measures, by five points or more — SLEDAI responders in the NEPTUNE 1 study was 57% versus 48%.
24:31
Looks good but not significant. NEPTUNE 2 study the SLEDAI responses were 60%, 60.5% for the two dose arms versus 55% in placebo — also not significant.
24:46
So why did this not look great? And I think the answer is quite simply that these are two very large trials — altogether 779 patients were enrolled in these studies and treated.
25:01
The SLEDAI response is the primary endpoint.
25:04
It's a composite measure with a score that goes from zero to 123.
25:09
The mean entry SLEDAI score at baseline in both NEPTUNE 1 and 2 was around 12 plus or minus five or six, meaning they had mild disease for the most part.
25:26
How many of them had more than mild disease?
25:29
An SLEDAI greater than 13 — that doesn't sound like moderate disease to me, but about a third of patients.
25:35
So I think the main fault of this trial was that they enrolled relatively mild patients and asked them to, you know, do an Olympic kind of performance.
25:48
Novartis has already started another phase three trial with more severe patients.
25:53
That's called the THEA study, that's currently enrolling.
25:58
We'll probably see that maybe 2028, 2029, I don't know.
26:02
But we'll get that. The question is, with this data that they have — and this is two phase three trials, that's enough for the FDA to make a consideration — the FDA has had this data for a while.
26:15
They're supposed to make a regulatory decision on ianalumab by the end of this year.
26:22
My guess is it might happen the week of ACR, but I'm just guessing. I have no inside track.
26:26
The last report I think was really important.
26:29
Last year, September 2023, we had a campaign on polymyalgia rheumatica.
26:38
My campaign advisory committee — four great people in PMR — one of their goals was to have PMR on the program the next year at ACR.
26:51
They did. To have new guidelines for PMR — and they have.
26:53
But now this is the BSR guidelines, and this is updating guidelines that are — I want to say 2009 or 2015.
27:05
2015, I think. Anyway, these are worth reviewing.
27:07
And you remember at EULAR this year, there were new EULAR guidelines on large vessel vasculitis, which included Takayasu's, GCA, and they threw in PMR as well.
27:21
What the BSR puts forward kind of aligns with that fairly well.
27:27
Number one, start low — starting dose prednisone 12.5 to 15, not 15 to 25.
27:35
Wherever you start, you can increase it up to a max of 25.
27:39
And once you have a response, you can begin tapering two to four weeks after symptom control.
28:03
They did say outright that starting doses below 10 milligrams a day or lower are incomplete and not even worth going for.
28:03
Standard taper is 2.5 milligrams every two to four weeks down to 10 milligrams, then 1 milligram every four to eight weeks thereafter.
28:40
I like the one from Richard Conway, which he makes monthly changes, kind of along the same line.
29:27
We've covered that here before. If steroid toxicity or risk is high, you can do a faster taper, which is 1 milligram every two to three weeks, aiming to stop within six months.
30:48
That's often what happens in the clinical trials.
31:08
The other thing that's new in these guidelines from the BSR is bone protection is mandatory.
31:50
These people are going to be on steroids a long while.
31:59
Don't wait for them to have a bad DEXA. Everyone gets protection by being on a bisphosphonate, calcium, vitamin D unless there's a contraindication. Get a DEXA. Follow them going forward.
31:59
Third new thing is methotrexate is a possible option.
31:59
I don't like this one at all. And they point to a small 58-patient PMR MAST study, which I have had problems with in the past.
31:59
That's 25 milligrams of methotrexate a week trying to achieve GC-free remission, and in a 52-week study it showed that it worked, but that trial had problems.
31:59
There are other methotrexate trials that have some problems, and the EULAR guideline said that you can use methotrexate for problematic steroid sparing with PMR and GCA.
31:59
And when asked what's the data, they basically said the rest of the world doesn't have IL-6 or JAK inhibition access that they can use.
31:59
So they're going with the next best thing even when the data is not all that great.
31:59
But this is a BSR guideline — congratulations if that's what you want to listen to.
31:59
Faster tapers are legitimate and can be done within six months.
31:59
In the MAST study, half the patients achieved GC-free remission within six months and being off steroids.
31:59
So it is possible. You can do fast tapers.
31:59
Maybe you should do a fast taper and challenge the hell out of everyone.
31:59
And then when you can't taper, well then you need steroid sparing, and then you'll be using steroid-sparing therapies faster.
31:59
But the bottom line is PMR patients are on steroids way longer than what you promise.
31:59
Everyone promises one to two years. The average is four to five.
31:59
IL-6 blockade or other steroid-sparing therapies is for refractory disease, not first-line therapy.
31:59
They think that these guidelines were kind of given to NICE and the UK population, especially to primary care, and they said that you should consider rheumatology referral because rheumatologists will talk about the earlier possible use of methotrexate in newly diagnosed patients.
32:00
They say that patients who are refractory and may need steroid-sparing therapy should be referred to rheumatologists, and that you should consider methotrexate in patients who have relapsed or who are at higher toxicity risk.
32:00
Read the article, get more insights into whether your standards of care with PMR are up to snuff according to the BSR.
32:00
Next week we go to Florida — Orlando, Florida — for ACR.
32:00
We'll be there. Come by the RheumNow booth.
32:00
Come by, get a rheumatology card, a pocket brain.
32:00
You can hand this out to your mentees. Get a RheumNow pen — you know, we give those out.
32:00
We've got plenty for you. Come by, get a picture.
32:00
Tell me what you like. Get a picture with me or my avatar.
32:00
That'll be at the booth. You won't — you can't imagine what they did to this big fat head of mine in the booth.
32:00
Go by and either take a picture with it or tell me what you think.
32:00
They gave me a temporary beard. They put things up my nose.
32:00
They gave me a Mexican mustache. It was not pretty.
32:00
But we hope to see you at ACR. It's going to be fun.
32:00
It's going to be a lot of great information.
32:02
Follow us at RheumNow.com. Take care. Adios.
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