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It's October the 9th, 2026. This is the RheumNow podcast.
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Hi, I'm Dr. Jack Cush, executive editor of RheumNow.com.
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This week on the podcast, steroids are easy to start, hard to stop.
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When it comes to vaccination, hold the methotrexate, but not the JAK or biologic.
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We're going to weigh in on Avakapan and end with age-old messages on old age patients.
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Kind of a cute beginning, don't you think? It's what happens when you use AI.
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Let's begin with some regulatory announcements.
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The FDA has approved the BTK inhibitor from Novartis, remibrutinib, called Remibrutinib — branded as Rapsidio.
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It's the first drug approved for dermographism not controlled by antihistamines.
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Dermographism is a key feature in Still's disease, by the way.
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The drug is already approved for chronic spontaneous urticaria.
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Interesting, because we have looked at remibrutinib in many of our diseases and not had a lot of success in rheumatoid and lupus and whatnot.
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BTKs were all the rage a few years ago. It's good to see that they did find a home somewhere.
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Merck announced its results with its investigational drug, an anti-TL1A — that's a tumor necrosis factor-like ligand 1A — it's a pro-inflammatory cytokine, and theirs is an anti-inflammatory compound called tulisokabart, MK-7241.
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They had a positive clinical trial. Again, all the rage with these TL1A drugs that are in development.
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This is the next wave, sort of the next TNF inhibitor that'll be used in IBD and derm conditions and rheumatology, and rheumatoid — except so far, you know, more buzz than actual data.
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Anyway, this data on tulisokabart, phase 2, showed positive results in moderate to severe hidradenitis at week 16 — a HiSCR50 response of 72% versus 35% in the placebo.
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That's encouraging. That's the good news in hidradenitis.
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There was another one that just recently released — I think it's from Spire Pharmaceuticals — that had its TL1A drug that didn't work out quite as well as they had hoped for, and I'm not sure they're going to go forward with that.
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But there are a number of these in development. You should be looking for them.
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Biogen announced its 52-week data on its AMETHYST trial.
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We previously talked about the AMETHYST trial and the 24-week data.
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We had a nice interview with Joe Morola on this.
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From 24 weeks to 52 they all go into open label.
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This is a phase 2/3 study of the plasmacytoid dendritic cell inhibitor litifilimab in cutaneous lupus erythematosus patients.
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93 patients between week 24 and 52 — the results got better.
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The main outcome being CLASI IGA 0 to 1 — that's cutaneous lupus activity by the investigator global assessment, clearing of the skin — and that's cutaneous lupus skin with either little or no skin involvement.
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It went from about 14% up to 27%. Similarly, the CLASI-70, a high-level skin response, also continued to get better and was 29% at week 52.
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So this is encouraging data. I think we're going down the path of seeing drugs being approved for just cutaneous lupus, and I think that'll be a nice advantage.
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Argenx discontinued its phase 3 trial with efgartigimod as a subcutaneous drug.
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A neonatal receptor antibody knocks down a lot of autoantibodies and immunoglobulin levels and whatnot.
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It was being tested in moderate to severe Sjögren's syndrome.
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They halted — the data safety monitoring board, let's call it an independent safety monitoring committee — was evaluating the continuation of the trial because there were a high number of people that did not meet the primary endpoint at week 48 of a clinical estimated improvement.
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And anyway they affirmed that and the study was discontinued.
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Whether this gets further evaluation in rheumatic disease — this particular drug from Argenx, efgartigimod, it's approved for other conditions including myasthenia gravis etc. One
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of the company officials — I like their quotes — "Sjögren's disease is one of the most heterogeneous and complicated diseases in immunology."
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I've been saying that for a while. It's hard to get a drug approved in Sjögren's, partly because it's a complicated disease, partly because the assessment of it is really complicated, and there'll be high placebo response rates.
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Getting a delta above that is going to be very difficult.
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Anyway, that's a sobering piece of news.
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Data on rheumatoid arthritis this week came from a retrospective Kuwait registry on RA looking at over 2,600 patients.
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They took a particular look at what they called young RA and older RA — or early RA and older RA, or late-onset RA — the dividing line being 60 years of age.
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88% of their patients were under 60 and 11.5% were late-onset RA.
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The takeaway from this was that there wasn't a lot of differences between the two groups.
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Yes, age; yes, disease duration based on definition alone.
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But late-onset RA had more age-related comorbidities — 2 versus 0.9.
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But that was mainly related to age and not any other factor when they did their analyses.
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They had similar levels of DAS-28 scores and CDAI scores.
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The late-onset patients had a marginally higher ESR — 41 versus 33 (those are mean values).
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The bottom line is age should not distinguish how people are going to be treated, right?
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Treat to target should be applied regardless of age.
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But studies really do show that most of us rheumatologists tend to wimp out a little bit on aggressive therapy in someone over the age of 60, 65, or 70.
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I don't think there's a good reason for that, and I would implore you not to do that.
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Another multi-center study looked at RA patients — 2,865 RA patients who had a mean disease duration of two years — that were treated with aggressive biologic or targeted synthetic drugs, and wanted to know what happened to their steroids.
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If you gave them all that really tough stuff, that really expensive drug, shouldn't you be able to withdraw steroids?
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Shouldn't those be steroid-sparing therapies?
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These people were treated with TNF inhibitors, IL-6 inhibitors, rituximab, abatacept, and JAK inhibitors.
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At the start of what is relatively early disease, 50% were on glucocorticoids.
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But at 3 and 6 months, only 26% and 37% had discontinued their glucocorticoids.
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Glucocorticoid discontinuation was more successful with JAK inhibitors than the other drugs — not by a lot, 24% versus 17%.
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Predictors of not stopping steroids: being on chronic steroids, having hypertension — that's kind of interesting.
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Patients treated with TNF inhibitors and abatacept and rituximab were more likely to stay on steroids compared to the JAKs, who were marginally better at getting off steroids.
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Something we probably should work at. Steroids are necessary, but they're acutely wonderful and chronically dangerous, are they not?
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We're in an era now of CAR-T cell craziness and cellular depletion therapies, which includes all kinds of CAR-T, NK CAR-T, allogeneic CAR-T, off-the-shelf CAR-T.
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But there's also these other drugs — the cell engagers, T-cell engagers, BiTEs and TriTEs.
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A report from last month looked at the T-cell engager linatumab — this is a CD3 and CD19 T-cell engager that's used for deep B cell depletion — was given to 15 patients with resistant, multi-drug-resistant RA.
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At week 12, nine out of 15 had a CDAI LDA response; only three out of 15 were in CDAI remission.
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This is a little bit like the CAR-T therapy reported at EULAR that showed success, but it wasn't that great.
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They did show, based on biopsies, good B cell depletion in four out of five biopsies of tissue, but not in the lymph nodes.
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And then later, 14 out of these 15 patients did flare.
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The good news is not much in the way of toxicity.
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There were no ICANS reports. There were three out of 15 patients with cytokine release syndrome grade one.
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Not too bad. There was one death a year after therapy, probably unrelated to this. So anyway, we're going to see more on these cellular depletion therapies including the T-cell engagers, B cell engagers, BiTEs, TriTEs, etc.
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A meta-analysis of IVIG in scleroderma. I've never used IVIG in scleroderma, and this report surprised me because 11 studies, 363 patients showed IVIG was safe — that I would have expected — but across the board it showed a significant improvement in modified Rodnan skin scores.
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It not only improved skin but it also improved GI manifestations in a significant way.
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And those people who had inflammatory myopathy also had a significant reduction in creatine kinase levels.
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Something to consider. I think that we are mounting some evidence that some therapies — we don't have great studies, right — but some of the therapies that we are using can have efficacy in systemic sclerosis patients.
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We have a bunch of reports on vasculitis and a few reports on Avakapan.
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Let's start with a discussion of PMR. A Danish national study of 51,000 PMR patients — half managed by primary care, half managed by secondary care MDs, I assume that's rheumatologists.
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The incidence of PMR is 112 cases per 100,000.
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That seems to be on par. Over a 10-year interval, the incidence of PMR in primary care went down but increased in secondary care — not sure why that was.
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Overall there was a decrease in number of PMR cases.
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The interesting thing here — remember the incidence rate is 112 per 100,000 — those PMR patients, how many of them develop GCA?
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You know, we always talk about should you look for GCA in PMR?
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I don't. It should be obvious when they have it.
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I'm not going to go searching for it in everyone.
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I think that's not cost effective. The rate that they found was five per 1,000 patient years.
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The bottom line was it's not many patients, and it developed within 68 days of a PMR diagnosis.
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The bad news from this study, though, that I am certain about is that after 5 and 10 years these PMR patients were still on prednisone — either 28% at 5 years and 22% at 10 years.
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Hence the line, "Oh, I'm only going to give you prednisone for two years and you'll be off of it," is not true.
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More realistically it's five years, and you've got to work hard at getting them off of that.
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An Italian study looked at secukinumab in difficult-to-treat GCA patients — only 36 patients.
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You know, the story of secukinumab in GCA was that the TITAN study from five or six years ago was a very positive phase 2 trial, but the phase 3 trial — the GCA CAPTAIN study — didn't work; secukinumab failed to meet its primary endpoint.
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But then conversely, Novartis reported that when secukinumab was used in PMR recently in phase 3, that looked good.
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So here's a small, uncontrolled, 36-patient difficult GCA study — and they were given this drug because they either had relapsing disease.
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72% of them had previously received tocilizumab.
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They basically showed clinical remission in 85% at 3 months and 83% at 12 months.
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Steroid-free remission was achieved in 28% at 12 months.
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43% were able to discontinue their steroids.
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So this is uncontrolled, and this is at odds with the phase 3 GCA CAPTAIN study, and you have to wonder whether this is going to have legs or not.
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I do think we're going to see IL-17 inhibition in PMR.
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I don't know about in GCA, but I certainly would like to see it.
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I think we need more options for steroid-sparing therapy.
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I often teach that GCA is a condition of old white people.
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I worked at a VA clinic where it's old white, mostly males and some females — a lot of GCA.
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In my university practice, a lot of Caucasian older people, a lot of GCA.
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At Parkland, the county hospital, a lot of Hispanics and a lot of African-Americans — very rare to see GCA.
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But everyone argues with me when I say that, saying, "No, no, you can have it in non-whites."
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Well, here's a report coming out of Martinique of 43 biopsy-proven GCA patients from the Caribbean.
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These are Caribbean blacks, who are often very mixed race.
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The incidence rate was 1.76 per 100,000 — that's about half the rate that you see in Caucasians of northern European ancestry, three to four per 100,000.
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But they did see, from 1993 to 2014, a four-fold increase in reported cases.
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They were old — mean age 76. They were more female, 4:1 female to male.
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Presenting features: 65% headache, jaw claudication 33%, scalp tenderness 37%, anterior ischemic optic neuropathy 26%, and PMR was seen in a third of the patients.
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The mean survival of these people — again they're older, mean age 76 — was 13 years.
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So slightly different, but it happens, and if you suspect it in a non-white patient who is elderly, do the biopsy, because that's the only way you're going to prove the diagnosis.
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Two reports on Avakapan. As you know, Avakapan was removed from the market in Europe by the EMA over safety concerns and inappropriate reporting and a rare event that affects the liver.
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And it's up for review by the FDA. I think the FDA is waiting to see more reports in the literature like these two reports I'm going to tell you about.
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There's a bunch of reports at ACR that are upcoming that I'm reading the abstracts on right now.
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Most of these reports are actually not damning and not indictful, and may not support removal from the market in the United States.
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So here's a retrospective real-world report from a UK vasculitis center that looked at ANCA-associated vasculitis patients treated with either cyclophosphamide or mycophenolate or rituximab.
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133 of them received Avakapan, 458 did not.
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At one year, the Avakapan patients had a non-significant two-fold increase in ALT — that wasn't that much different between the Avakapan-plus and the Avakapan-minus groups: 16% versus 11%, not significant.
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If you looked at three-fold elevations of ALT, it got a little closer to significance, but still not significant — 11% versus 6%, P-value 0.064.
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No difference in other liver enzymes, alkaline phosphatase, bilirubin.
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And patients on Avakapan were less likely to meet Hy's Law, which means there's a 10% chance of death from liver cause.
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It was low in both groups. So that's encouraging information.
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Another retrospective study looked at 387 ANCA-associated vasculitis patients on glucocorticoids and immunosuppressants who either got Avakapan or not — 52 Avakapan versus 335 non-Avakapan.
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Now, both these studies don't tell you why they're on Avakapan, so there's a channeling bias in some of these reports.
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But I would think if they go on Avakapan, it's either because they're worried about steroids or because the patients have more aggressive disease.
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Anyway, in this cohort of 387 AAV patients, Avakapan was associated with less severe infections — about a 78% significant reduction at one year — and that was because they used less steroids.
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And if you looked at those on Avakapan versus not on Avakapan, no difference in relapse rates. Again, I think that's encouraging data.
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Two reports on Still's disease. A study of 64 patients looked at macrophage activation syndrome in Still's disease — 55 of these were systemic JIA, nine were adult Still's.
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They were all treated with glucocorticoids.
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75% received anakinra. 52% received cyclosporine.
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Complete remission of the 64 was seen in only seven patients.
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Partial remission was seen in 64% of the 64 patients.
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Steroids were tapered in 78% in a median of 40 days.
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The good news is that the one-year survival probability of these Still's disease-related MAS patients was 93%.
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The bad news is MAS recurred 31% of the time, and 11% died.
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That's better than some other reports of MAS in kids or adults with Still's where the number can be as high as 39% mortality rate.
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This is a serious and bad complication of Still's — identification, aggressive treatment.
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They only looked at anakinra. There are a lot of other drugs including emapalumab, the gamma interferon monoclonal antibody inhibitor that is very, very effective and has recently been FDA approved.
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Another report looked at a potential biomarker in Still's — looking at serum IL-1RA levels.
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This was studied in 46 adult Still's patients that were not previously treated with anakinra, which, as you know, is an IL-1RA inhibitor.
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They found that IL-1RA levels were significantly higher in Still's versus controls, but they did not differ between active and inactive Still's.
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Hence, it's not going to be a good biomarker.
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They don't have a great definition of inactive versus active Still's, by the way — it's kind of up to the investigator.
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The inactive patients had no rash, no fever, but they had occasional lymphadenopathy, hepatomegaly, occasional elevations of ferritin.
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So no difference in IL-1RA levels between inactive and active — I don't know that that's going to hold up, but I know you're really interested in Still's disease like I am.
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A New England Journal report this week looked at retatrutide, a new investigational incretin GLP-1-like agent.
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This is a triple receptor agonist therapy that targets GIP, GLP-1, and glucagon receptors.
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It's thought to be maybe better GI-tolerated, maybe better at weight loss.
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In this study of about 2,000 people, the highest dose of this drug was associated with 25% weight loss — that is superior to tirzepatide and semaglutide in this study.
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They gave this drug, retatrutide, as either 4 milligrams, 9 milligrams, or 12 milligrams once a week, or placebo.
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The end of study is 80 weeks. The study did include 574 patients with moderate to severe osteoarthritis with radiographic evidence of OA, and 243 people with sleep apnea.
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Of the 574 with OA, WOMAC pain scores were significantly better with the new triple receptor agonist drug retatrutide compared to placebo — roughly about minus 3.5 versus minus 1.9 drop in WOMAC scores.
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Similarly, the sleep apnea was improved on the incretin therapy versus placebo.
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This is going to be on the market — it's not yet on the market, but it's going to be.
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And I think there's another report on this at ACR that you'll be hearing about.
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Last is a report just published in JAMA from Jeff Curtis and colleagues that looked at what do you do in patients who are going to get COVID vaccination or boosters of COVID vaccination — should you hold the biologic or the JAK inhibitor?
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We do know in very well-done studies with influenza, and some studies with JAKs, that you want to hold methotrexate for one or two weeks.
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I like one week. If you're on methotrexate, it will impair vaccine responses, but if you hold it for a week or two, the vaccine responses are as you'd expect, and there's no flare with methotrexate.
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What happens in the case of COVID vaccination or revaccination — what do you do with the JAK or the biologic?
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In this study they tested whether you should hold either the biologic or the JAK inhibitor for two weeks.
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They showed in a study of 840 patients with inflammatory arthritis — including RA, PsA, and axial spondyloarthritis patients — that holding the biologic or the JAK did not impair vaccine humoral responses.
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So that seemed like it was a good thing to do.
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But it did increase flare risk — with a two-fold odds ratio, 2.27, increase in flare risk — mostly seen when you held the JAK inhibitor, which would be the shortest-acting of all the drugs being used.
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So I think the bottom line is I would still hold a JAK inhibitor for a week.
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I don't know about a long-acting biologic — like an IL-17 inhibitor or a TNF inhibitor — it doesn't seem to make much sense, holding it for a week does very little because they have such long half-lives.
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But I think this is important to look at, especially JAK inhibitors and how that should be handled.
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Anyway, that's it for this week on the podcast.
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By the way, registration for RheumNow Live is open.
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We're posting the agenda and speakers next week.
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I think you're going to like the program.
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I'm really excited about it. You will be, too. Tune in next week.
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