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Elias Sotirchos @esotirchos.bsky.social · 08/10/2026

Interesting article Joe! However, I remain perplexed as to how as a field we continue to allow people to claim that they are studying "multiple sclerosis" (in this case they even go beyond that and claim to study "advanced MS") when the study only includes EAE data..... MS!=EAE

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NEJM.org @nejm.org · 01/07/2026

Among patients with newly diagnosed relapsing multiple sclerosis, rituximab was noninferior to ocrelizumab in preventing new or enlarging lesions on MRI. The risk of serious adverse events was similar in the two groups. Full phase 3 OVERLORD-MS trial results: nej.md/3QJuaep

A graph from an Original Article published in the New England Journal of Medicine article titled "Rituximab versus Ocrelizumab in Newly Diagnosed Relapsing Multiple Sclerosis." The figure shows graphs of the primary end point. Panel A indicates no new or enlarging lesions on T2-weighted MRI, while Panel B shows a noninferiority test. The trial name, OVERLORD-MS, is in parentheses after the title.

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Jenna Norton @jenna-m-norton.bsky.social · 30/04/2026

Sharing this screen grab from a friend at NIH (with permission). This is a checklist program officers have to complete before a grant can be awarded. The first question: "Is this grant All Clean/Clear in the NIH Text analysis Tool?" 🧵1/3

Screen grab of an NIH grants checklist showing the first question is: "1. Is this grant All Clean/Clear in the NIH Text analysis Tool?"

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Elias Sotirchos @esotirchos.bsky.social · 17/02/2026

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/...

journals.sagepub.com

Sage Journals: Discover world-class research

Subscription and open access journals from Sage, the world's leading independent academic publisher.

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Elias Sotirchos @esotirchos.bsky.social · 17/02/2026

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

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Elias Sotirchos @esotirchos.bsky.social · 17/02/2026

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

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Elias Sotirchos @esotirchos.bsky.social · 16/02/2026

PIRMA is then, since CDP is a cleaner outcome with less underlying assumptions.

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Elias Sotirchos @esotirchos.bsky.social · 16/02/2026

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

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Elias Sotirchos @esotirchos.bsky.social · 16/02/2026

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

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Elias Sotirchos @esotirchos.bsky.social · 16/02/2026

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)

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Elias Sotirchos @esotirchos.bsky.social · 16/02/2026

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:

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Elias Sotirchos @esotirchos.bsky.social · 16/02/2026

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).

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Elias Sotirchos @esotirchos.bsky.social · 16/02/2026

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/

pubmed.ncbi.nlm.nih.gov

Uncovering a bias in estimated treatment effects on PIRA in multiple sclerosis clinical trials - PubMed

Italian Ministry of University and Research.

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Don Moynihan @donmoyn.bsky.social · 24/01/2026

Media: do not lead with the false government framing of what happened

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Dimitri Drekonja, MD, MS @dimitridrekonja.bsky.social · 24/01/2026

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

Alex Pretti from his early days working at the VA

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brandon-beaber.bsky.social @brandon-beaber.bsky.social · 06/01/2026

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...

download.open.fda.gov

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Elias Sotirchos @esotirchos.bsky.social · 16/12/2025

They were presented at ECRIMS. See poster here

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The Sumaira Foundation (TSF) @thesumairafdn.bsky.social · 15/04/2025

#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

youtube.com

Immunizations for the Immunocompromised

YouTube video by The Sumaira Foundation

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LPJ Lab - Neuroimmunometabolism @lpjlab.org · 10/03/2025

#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!

nmss.quorum.us

URGENT: MS Research Funding at Risk – Contact Congress Today

ACTION NEEDED TODAY

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Joe Sabatino @jsabatino37.bsky.social · 13/02/2025

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/...

neurology.org

Neurology® Journals

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Elias Sotirchos @esotirchos.bsky.social · 05/02/2025

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.

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Elias Sotirchos @esotirchos.bsky.social · 05/02/2025

We must recognize though that fixed CBAs may be the only assays readily accessible, especially in resource-limited settings.

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Elias Sotirchos @esotirchos.bsky.social · 05/02/2025

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.

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Elias Sotirchos @esotirchos.bsky.social · 05/02/2025

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).

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More Perfect Union @moreperfectunion.bsky.social · 12/12/2024

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.

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

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.

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

Regardless though, a randomized controlled clinical trial is needed to further inform the use and timing of PLEX for treatment of severe demyelinating attacks. This is why we are pursuing (together with co-PI Dr. John Chen from Mayo), the TIMELY-PLEX trial:

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

Performing additional analyses, including a formal comparison of 1st-line PLEX recipients vs those who received only corticosteroids, accounting/matching for relevant variable such as demographics, attack severity etc can help provide further insight into these findings.

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

So unless we think that PLEX actually worsens clinical outcomes (which seems unlikely), it should be fairly clear that this is likely driven by selection bias.

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

Notably, in this study patients treated with only corticosteroids for their attacks had BETTER disability than those who received PLEX at the last follow-up, despite similar demographics and clinical characteristics.

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

This is a huge selection bias that is present in all retrospective studies of PLEX in NMOSD and MOGAD, since the analysis is restricted only to those who received PLEX.

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

PLEX is not done as a 2nd or 3rd-line therapy randomly, but because patients did not significantly improve or even worsened after 1st line therapy. Conversely, many of those who received PLEX as a first-line therapy may have improved with just corticosteroids.

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Elias Sotirchos @esotirchos.bsky.social · 04/12/2024

jnnp.bmj.com/content/earl... This is an interesting study. Need to be careful though with potentially overinterpreting this and other retrospective observational studies purported to prove the effectiveness of early PLEX. My detailed rapid response to this article here: jnnp.bmj.com/content/earl...

jnnp.bmj.com

Apheresis therapies in MOGAD: a retrospective study of 117 therapeutic interventions in 571 attacks

Background Incomplete attack remission is the main cause of disability in myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Apheresis therapies such as plasma exchange and immun...

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Stacey L. Clardy @staceylclardy.bsky.social · 20/11/2024

Time to strike the label “Lupus Myelitis” … Forever ✅ What say you, #MedSky #RheumSky #NeuroSky? 🧠🎙️ Neurology Podcast: Dr. @esotirchos.bsky.social discusses the underlying etiologies of myelitis in patients with rheumatologic disease. Listen now: bit.ly/48VRPwC

bit.ly

Myelitis Associated With Rheumatologic Disease

Dr. Stacey Clardy talks with Dr. Elias Sotirchos about the underlying etiologies of myelitis in patients with rheumatologic disease. Read the related article in . Disclosures can be found at Neurology...

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