E137: Obexelimab in IgG4-RD (INDIGO)

A new therapy for SLE! This one is a CD40-CD40L blocker, which has some nice new-things to inhibit. The study itself was a qualified success and the podcast got a bit more rant-y than it should have been, but hopefully you get a kick out of it.  Paper: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00691-4/fulltext  

Another day, another B cell drug. This one adds an interesting option for IgG4-RD, offering a "maybe less efficacious maybe less toxic" pathway. I could see folks being excited for this, especially in a disease where non-scary-manifestations are relatively common.  Also, check out boardsbank.com!  Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2601337

Big trial this week in the NEJM investigating the IL17 inhibitor secukinumab in PMR. Well worth a read, I would bet on FDA approval in the near future. Some interesting tidbits and of course a weird safety thing we now have to grapple with.  Be sure to go to boardsbank.com! Free rheumatology board review, >1000 questions!  Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2602567

Really interesting study this week comparing the IL17 inhibitor ixekizumab WITH the GLP1 inhibitor tirzepatide to ixekizumab alone. Raises some interesting questions about what worked here and whether or not it matters how it worked.    Paper: https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.70134 Newsletter: http://autoimmunedevreport.com/  

Great trial this week looking at brepocitinib in dermatomyositis. Looks like a winner, expect it will be approved. Where it fits in our approach to IIM is an open question, but nice to have another option.  Study: https://www.nejm.org/doi/10.1056/NEJMoa2503531 JC Companion: https://autoimmunedevreport.substack.com/  

Good RCT this week, investigating the CD20 B cell inhibitor obinutuzumab for SLE. Sign up for my newsletter if you would like to have a read-along companion piece!    Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2516150 Landing Page: https://ebrheum.com/ Substack: https://autoimmunedevreport.substack.com/

Quick podcast this week about a nifty head to head study that I had previously missed. Worth reading if - like me - you're still trying to figure out how the heck to manage osteoporosis.  Paper: https://pubmed.ncbi.nlm.nih.gov/28755782/

Today I cover the recent publication of the RESET-RA study, which evaluated vagal nerve stimulation to treat rheumatoid arthritis. Have a listen in full, but let me be clear upfront: I do not think this works and will not be referring any patients to receive it. This will forever be my pivotal example of the effect of unblinding, but would love to hear if you think different!    Paper: https://www.nature.com/articles/s41591-025-04114-7 Supplement (see S4): https://www.nature.com/articles/s41591-025-04114-7#Sec27    

Surprisingly (unbelievably?) impressive RCT evaluating the Blys/APRIL inhibitor "telitacicept" for patients with SLE (mixed SLE and SLE-LN). Very curious to see where the FDA goes with this one.    Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2414719

Ever wonder how often you really need to check "monitoring" labs? If so then this is the podcast for you! Bryant England mentioned this during his excellent Year in Review session at ACR Convergence 2025. I've been meaning to cover it and finally got around to doing so. Have a listen and share with friends!   Paper: https://pubmed.ncbi.nlm.nih.gov/40854212/