Reefer Madness (12.12.2025)
Dr. Jack Cush reviews the news, journal and regulatory reports from this past week on RheumNow.com. B cell drugs in SLE and ITP, biomarkers in GCA & PSS and great videos by APPs.
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Phase 1 trial of IL-6 targeting immunotherapy (PPV-06) in 24 pts w/ inflammatory knee osteoarthritis (KOA) demonstrates safety, Abs that neutralize IL-6, decreasing CRP values and improved clinical outcomes, determined by changes in KOOS scores https://t.co/urZupN62Kw https://t.co/sru1SnsOig
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Dr. John Cush @RheumNow( View Tweet )
Treating Refractory Still's Disease
A full read systematic review article examined treatment options for difficult to manage systemic juvenile idiopathic arthritis, or Still’s disease. It classified these refractory disease patients as those with either (1) persistent arthritis, (2) recurrent or difficult-to-treat
Retrospective review of 113 AOSD pts, median age 45yrs, ferritin 4626 (IQR 1169–14,239). Advanced Rx (IVIG, IL-1, IL-6) required in 15 (13.3%), NOT predicted by ferritin levels, either measured continuously or by quartiles. Ferritin is not a reliable biomarker in AOSD. https://t.co/pHEPeIf9u2
Dr. John Cush @RheumNow( View Tweet )
PET Uptake in Large Vessel GCA – Does tocilizumab help?
Giant cell arteritis (GCA) is the most common form of adult vasculitis in the United States and can be subdivided into those with cranial only symptoms, those with large vessel vasculiti/PMR, and those with mixed features. Non-invasive imaging is key in detecting large vessel
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I've always (very) simplistically considered post-CAR-T CRS and HLH/MAS in the same bucket, and there certainly are substantial similarities.
It raises the obvious question - can we borrow therapies?
@CarolineDiorio @ChildrensPhila in the #ACR25 BCRC pre-meeting @RheumNow https://t.co/2HkHxpl89u
David Liew @drdavidliew( View Tweet )
Mateo Faxas et al. TriNetX study, propensity score matched. 3000 patients. Arrythmia risk is higher with IL-6i vs TNFi in diabetic RA patients. V Tachy (HR 1.4), PPM need (HR 1.4) significantly higher. AF, SVT, VF all numerically increased. @RheumNow #ACR25 Abstr#2283 https://t.co/U2Tk38Mobg
Richard Conway @RichardPAConway( View Tweet )
#1726 IA from immune checkpoint inhibitors (ICI) is a distinct autoimmune entity: T cell-driven but not antibody-mediated
irAE arthritis shows hyperactive, cytotoxic CD8+ T cells & metabolic reprogramming, unlike RA. IL-6, IL-12 & IFNα fuel this process. @RheumNow #ACR25
Mrinalini Dey @DrMiniDey( View Tweet )
Biomarkers in Stills disease and MAS. #ACR25 @RheumNow
IL 6 may not be helpful compared to CRP, and IL 1 beta is difficult to measure
IL-18 seems to be the best one. https://t.co/u3oBTd4eaP
Bella Mehta @bella_mehta( View Tweet )
IL- 18 go together sometimes with glycolytic enzymes such as aldolase
Also MAS may not be a switch on and off mechanism.
Lastly MAS with Stills may have increased IL18 levels but not in other disease like SLE
#ACR25 @RheumNow https://t.co/BW1fD7usBT
Bella Mehta @bella_mehta( View Tweet )
What do we know about IL-18
Normal levels less than 500
Non specific 500 to 15000
Stills (quiet) 2000 to 10000
Mas/glares 20000 and more
@RheumNow #ACR25 https://t.co/ZAltAD5Q8V
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Bella Mehta @bella_mehta( View Tweet )
Kuzkina et al. Efficacy of IL-6i with olokizumab on depression in RA. There appear to be some benefit but anti-depressants still needed. Group 1 is olokizumab alone, other 2 groups have anti-depressants also. @RheumNow #ACR25 Abstr#1323 https://t.co/h2ExYQgKTL
Richard Conway @RichardPAConway( View Tweet )
#0853 Olink proteomics in anti-Ro+ pregnancies identifies macrophage-derived IL-6 & CCL3 as serum predictors of foetal AV block
These pro-inflammatory proteins predicted fAVB independent of maternal diagnosis or Ab titres, pointing to new pathogenic pathways. @RheumNow #ACR25
Mrinalini Dey @DrMiniDey( View Tweet )
#1627 SLR informing the 2025 @eular_org recommendations for PMR & LVV 🔍
141 studies (30 RCTs) reviewed: new & further evidence for IL-6, JAK & B-cell-targeted therapies. Data will underpin updated management guidance. @RheumNow #ACR25
Mrinalini Dey @DrMiniDey( View Tweet )
Upadacitinib in GCA doesn't just affect IL-6, it alters IFNg, known to be important in vascular change in GCA.
If UPA in GCA has some cardiovascular concerns extrapolated from RA, it also has some plausible cardiovascular benefits too that TCZ may not
#ACR25 ABST0751 @RheumNow https://t.co/rMetLPP9z6
David Liew @drdavidliew( View Tweet )
From Eye on Cytokine Storm- Decoding MAS by Dr Grant Schulert : “IL-18 is highly elevated in SJIa and other autoinflammatory disorders…can amplify innate signaling as well as induce IFN-gamma”. @RheumNow #ACR2025 https://t.co/6e5yfeDepX
Gabriela Martinez Zayas, MD @MartinezZayasMd( View Tweet )
Muscle mass & JAKi? 15 active RA pts (+ sarcopenia risk) Rx w/ tofacitinib - signif. improved @1 mo. @6 mos muscle mass signif improved (+242 cm3, +4%, p=0·017) {less w/ NSAIDs); w/ signif creatinine incr (0.06 mg/dl) & decr in serum IL-6, IL-1 & TNF. No change in CK, myoglobin, https://t.co/taY7DisMOS
Dr. John Cush @RheumNow( View Tweet )
Review of IL-1 family cytokines in inflammation and immunity - including, IL-1, IL-18, IL-33, IL-36, IL-37, IL-38, IL-1Ra, etc. Full read -- Good Reference!! https://t.co/01o05qYPjU https://t.co/HLcfPM2cPw
Dr. John Cush @RheumNow( View Tweet )
Canakinumab in VEXAS - 47 males Rx w/ anakinra (44), canakinumab (9), or both(6). Response @1 mos: ANAK 34% vs CANK 100%; 22% vs 78% @ 3 mos. Drug survival was 54 mos CANK 300/m; 7 mo CANK 150/m; 1 mo ANAK. More ISR (47% v 0) & infx w/ ANAK https://t.co/Y3iSfajTal https://t.co/qTNamGDwVI
Dr. John Cush @RheumNow( View Tweet )
Join us Sept 23 @ 7PM ET for the next Rheum to Breathe Journal Club!
We’ll dive into two pivotal ILD studies:
📄 FIBRONEER (Nerandomilast in PPF) – NEJM 2025
📄 RECITAL (Rituximab vs Cyclophosphamide in CTD-ILD) – Lancet
Panelists: Dr. Toby Maher, Dr. Shervin Assassi
Moderator: https://t.co/BebFhDJ1mM
Dr. John Cush @RheumNow( View Tweet )
Study of 43 PsA pts starting bDMARD shows Calprotectin was elevated in PsA, decreased w/ biologics, but had no signif correlation w/ US synovitis. Baseline calprotectin, S100A12, IL-6, IL-17A, IL-23, CXCL10 were high. Calprotectin, S100A12, IL-6 decreased w/ Rx (p < 0.05).
Dr. John Cush @RheumNow( View Tweet )
ERS/EULAR guidelines for CTD-related interstitial lung disease
The European Respiratory Society (ERS) and European Alliance of Associations for Rheumatology (EULAR) have published clinical practice guidelines for the evaluation and management of connective tissue diseases (CTD) associated interstitial lung disease (ILD) in two simultaneous publications in
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APLAR 2025: What’s New in RA Management?
The unveiling of the updated 2025 recommendations for RA treatment, presented by Josef Smolen in the plenary session on the first day of the conference, sparked attention. Although not yet formally published, these updated recommendations represent a refined consensus that simplifies decision-
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Sjögren's Graduates (8.22.2025)
Dr. Jack Cush reviews the news, journal reports, FDA approvals, drug safety, and more from this week.
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Advances in Still's disease Rx:
- using IL-1 or IL-6 inhibitors 1st line
- New FDA approval of emapalumab (IFNg) for MAS
- unclear if biologics can cause lung probs in Stills https://t.co/zSqTcOSVGE https://t.co/8GhoamkV4N
Dr. John Cush @RheumNow( View Tweet )
Recent Blogs
How would you manage a patient with Overlap (anti-synthetase) syndrome, ILD, polyarthritis and myositis?
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