How does inflammation kill neurons, and what can we do about it? Check out our latest paper where we consider this question: rdcu.be/e4nfP.
assessed only with brain imaging, but spinal cord lesions can also develop without relapse in a low but non-negligible proportion of patients, with a study from our center reporting that only 50% of those with new SC lesions had new subclinical brain lesions: journals.sagepub.com/doi/10.1177/...
in observational "real-world" studies where this is even more difficult to assess well). PIRMA improves on this, but just wanted to point out some limitations that I've been thinking about and struggling with for a while. Also, I feel like I'm opening up a can of worms here, but PIRMA typically is
Completely agree that PIRMA is a huge improvement over PIRA, since considering PIRA to be non-inflammatory progression disregards what we've known for decades about subclinical focal lesion development in MS. I just feel that over the past years PIRA has dominated the literature (including
PIRMA is then, since CDP is a cleaner outcome with less underlying assumptions.
patient immune to PIRMA by definition (thus most disability worsening will be defined as RAW/MAW, even if there is underlying non-inflammatory progression). But in HET patients, since inflammatory disease activity is very infrequent, PIRMA=CDP for the most part, so I'm not sure what the point of
2) For the reasons in my prior post, I think that the main utility is for patients on HET, since the likelihood of MRI inflammatory disease activity is very low. In LET/MET you can't really disentangle "non-inflammatory" from "inflammatory" progression, since relapses and MRI activity make a
1) Defining a relapse is rather arbitrary and may not necessarily reflect an inflammatory event (I still find it challenging in clinical practice to define a relapse, since we often see patients with mild exam worsening without MRI activity and with histories that are equivocal)
Definitely agree that PIRMA makes more sense than PIRA if one is trying to study non-inflammatory progression (and an unfortunate trend in the literature is people equating PIRA to non-inflammatory progression which is inappropriate), but I think there are still significant limitations:
They show that in a simulated scenario where there is no difference in PIRA between a treatment and control arm (n=800 each), a mistaken finding of a harmful effect of treatment on PIRA is found once relapse reduction reached 60%" (estimated HR = 1.26, CI = 1.03–1.48).
The central finding of this paper seem to all be due to a bias associated with having less relapses/lesions with HET vs MET. By definition, you can't have PIRA or PIRMA if you're having relapses or new lesions. This is nicely shown in this paper: pubmed.ncbi.nlm.nih.gov/40554392/
Overjoyed to share our new work exploring the antigen specificity of CSF-expanded CD8+ T cells in #multiplesclerosis #EBV in @natimmunol.nature.com #immunology 🧪🧵1/
www.nature.com/articles/s41...
Media: do not lead with the false government framing of what happened
Alex from our time working together, while he was in nursing school. Later, he moved to ICU, working as a nurse to support critically ill Veterans. He had such a great attitude. We’d chat between patients about trying to get in a mountain bike ride together. Will never happen now
The FDA explains its rejection of the multiple sclerosis drug tolebrutinib in a Complete Response Letter (CRL). "A favorable benefit-risk profile could not be established for any patient subpopulation" download.open.fda.gov/crl/CRL_NDA2...
New press release from Sanofi - tolebrutinib did NOT meet it's primary endpoint in PP-MS trial
www.sanofi.com/en/media-roo...
They were presented at ECRIMS. See poster here
#ICYMI We were joined by Dr. Elias Sotirchos to discuss vaccines in the setting of immunocompromised patients. www.youtube.com/watch?v=7VCE...
This program was made possible with support from Alexion Pharmaceuticals
#MedSky Vaccines play a crucial role in protecting immunocompromised patients & help prevent the spread of diseases.
Join us on March 25th for a discussion led by Dr. @esotirchos.bsky.social
To register, visit us02web.zoom.us/webinar/regi...
#URGENT: #MultipleSclerosis research funding at risk: contact Congress today!
The Continuing Resolution to fund the government cuts funding by 57%
The #MS Society has an action alert urging Members of Congress to oppose these cuts here nmss.quorum.us/campaign/113...
Please take action and #share!
Pleased to write this editorial with Larry Steinman about a potential novel antibody in MS
www.neurology.org/doi/10.1212/...
Original manuscript here:
www.neurology.org/doi/10.1212/...
In these situations, especially if live CBA is not available for follow-up testing in patients with high suspicion for MOGAD or AQP4+ NMOSD, clinical and imaging phenotypic characteristics need to be relied on more heavily to help guide appropriate management.
We must recognize though that fixed CBAs may be the only assays readily accessible, especially in resource-limited settings.
These results support that using exclusively fixed CBAs may miss many cases resulting in misdiagnosis and consequently suboptimal treatment, but also has significant implications for characterizing "double-seronegative" NMOSD.
Live CBA had markedly better sensitivity, especially for MOG-IgG testing, with very good specificity for both live and fixed CBA (notably specificity was 100% for AQP4-IgG by both assays).
Excited to share out study (led by Yana Said and in collaboration with colleagues at the Mayo Clinic) reporting our real-world clinical experience with paired fixed and live CBA testing for MOG-IgG and AQP4-IgG.
onlinelibrary.wiley.com/doi/10.1002/...
A bill to break up UnitedHealth, CVS, Cigna and more has been introduced by a bipartisan group of U.S. senators and representatives.
The legislation would force insurers to sell their pharmacy businesses.
It aims to combat PBMs, pharma middlemen who drive up costs.
A multi-center, randomized-controlled, open-label, rater-blinded, pragmatic trial “Treatment of Inflammatory Myelitis and Optic Neuritis with Early vs Rescue Plasma Exchange” that is planned to commence in the United States in 2025.
