The first round of RheumMadness 2025 had three blowouts and one MASSIVE upset. See how the Blue Ribbon Panel voted below, along with written explanations for how they made their picks. You can also check out how your bracket is doing on the tourneytopia website.

What’s next? Tomorrow, we will release a new podcast episode with our leadership team’s reaction to the first round results.  Results from additional rounds will be released as follows:

• Round 2 (the Entheseal Eight): April 3
• Round 3 (the IgG Four): April 5
• Round 4 (the Interleukin Two): April 7

First Matchup: CD40L in Sjogren’s defeats APIPPRA

The Blue Ribbon Panel unanimously chose CD40L in Sjogren’s over APIPPRA in a 7-0 blowout.  Hear their justification below:

• What could be more “innovation”-like than a medication where there is an unmet need? While prevention is better in the long term, from a purely immediate, practical standpoint, the urgency to help those already ill might be considered as higher priority than intercepting something that isn’t there yet – and already has many options in case it does manifest.
• I find the use of CD40L for Sjogren’s to be more innovative and fulfilling a greater need than the ABA for Pre-RA. The response to the ABA was too small and likely not worth the expense. I also noted that the study was drug funded. This should not make a difference but of course it does.
• I chose CD40L in Sjogren’s based on the quality of the report and visual aid and the desperate need for any therapies that provide relief to Sjogren’s patients. The article for the abatacept in pre-RA is great, but the visual aid is not nearly as informative as its competitor AND I do not see any insurers paying for abatacept for RA prevention any time soon, so clinical applicability of the chosen article is also not clear.
• SS is underrepresented in clinical research and drug discovery, the inclusion of the high symptom burden participant group, and trial of new class of therapeutic based on underpinning immune pathways that lead to escape of immune tolerance.
• APPIPRA study not a novel as also the ARRIA study in same issue of the Lancet – both could have been included in scouting report?
• Great matchup of two innovative concepts. Pre-RA prevention is incredibly exciting and the idea of stopping RA that sustains after discontinuation is incredibly novel… however, CD40L wins for two major reasons. 1) There is no approved targeted therapies for Sjogren’s  2) They included symptom burden in the analysis. Despite only early research, the idea of finding mechanisms to help the symptom burden in Sjogren’s pushes out the round 1 win.
• The CD40 ligand study in Sjögren’s disease stood out as one of the few trials to demonstrate a meaningful improvement in sicca symptoms, addressing a long-standing unmet need in treatment. The visual representation was particularly creative, with the Sjögren’s horse wordplay adding a clever touch that made the study more engaging. Additionally, the flowchart outlining treatment groups, interventions, and outcomes was clear and easy to follow, effectively guiding the reader through the study’s design. The infographic and scouting report introduced an innovative option in Sjögren’s treatment with clarity and accessibility.
• Novel targeted and effective therapy in Sjogren’s disease would be a game changer for these patients across the board, especially considering the dearth of effective agents for patients with Sjogren’s disease. While both are great trials, considering the number of options we have for RA therapy vs the lack of options for management of Sjogren’s disease at this time, I went with CD40L in Sjogren’s disease.

Second Matchup: TYK2 in SLE defeats long-term anifrolumab

The Blue Ribbon Panel unanimously chose TYK2 in SLE over long-term anifrolumab in another 7-0 blowout.  Hear their justification below:

• Sticking with the “innovation” theme – while Anifrolumab is new, it is already in many guidelines. Deucravacitinib offers an “innovation” approach because it is in oral form. If you are paying out of pocket, an oral medication helps you avoid needing to go to the hospital for infusion schedules, which is an additional cost, loss of time and needing to leave work.
• I find the fact that TYK2 works and is oral to be innovative. It is also an interferon blocker similar to anifrolumab.  I wonder if there will be studies in the future comparing the use of anifrolumab and TYK2 inhibitors.
• TYK2 in SLE is the winner here for me due to the quality of the visual aid, all the basketball puns in the report, and the novelty of TYK2 inhibitors in SLE (thus, being a more innovative option than tried and true Saphnelo).
• TYK2 is new class of ORAL treatment for SLE and showed improvements over placebo in all outcome measures over almost a year, with GREAT AE profile (not many!) This definitely beats a LTE, with risk of bias
• With lots of recent innovation in SLE, it is great to have this match-up of good therapies. With JAK inhibitors disappointing in lupus, the TYK2 data is exciting in its broad efficacy and safety.
• Both studies were important and engaging, but the TYK2 inhibitor stood out as an intriguing potential treatment, particularly because it is an oral medication with a novel mechanism of action for lupus treatment. The study’s graphic was clear and effectively conveyed key points, making it easy to follow. The report itself was engaging, almost reading like an advertisement, drawing in our attention and making the findings feel exciting. The creative puns and basketball references added a fun and memorable touch, making the presentation even more memorable.
• Since Anifrolumab already had strong data in it’s favor, the concept of an oral agent like Deucravacitinib being clinically efficacious against multiple end points is a promising novel avenue to explore!

Third Matchup: Pred dose in SLE defeats HCQ screen cost

The Blue Ribbon Panel chose pred dose in SLE over HCQ screen cost 5-2.

Here’s what the panel had to say in favor of pred dose in SLE:

• It is true the HCQ screening is often either too much or too little. I wonder since we can now order HCQ blood levels if screening will not be as much of an issue. Verifying that we can safely get by with lower doses of corticosteroids to me is more important.
• Steroid dose wins hands down. The visual aid is absolutely amazing and the topic is SO important now and will only continue being more relevant in the future. Great job! Reduced screening in HCQ seems difficult to achieve in clinical practice (as people might forget to get their exam) and unlikely to get significant patient buy-in (patients are SO worried about retinopathy and mostly already see an eye doctor yearly). I appreciate the puns in the report, however.
• Pred dose paper gives valuable data to undertake shared decision making with patients in the trade off of better chance of good renal outcomes versus increased risk of infection and 10 fold incr risk of death. And highlights the unmet need in lupus nephritis. I am also not sure how generalisable the HCQ screen data are to other health care settings
• Compared to the hydroxychloroquine study, the steroid dosing study in lupus nephritis provided a stronger level of evidence as a systematic review, addressing a crucial and frequently debated question in rheumatology: the optimal steroid dose for both efficacy and safety. This is a topic we constantly encounter in clinical practice, making the study particularly relevant. The graphic was exceptionally well-designed and professional, effectively distilling the key findings into a format that was both engaging and informative. It presented the suggested dosing in a way that was clear at a glance, making it easy to remember and apply in real-world scenarios. The creative and fun approach to the infographic further enhanced its impact.
• Both are great trials, but in depth understanding of the impact of our glucocorticoid practices forges the path towards developing newer and effective steroid sparing therapies for life threatening rheumatologic conditions like lupus nephritis.

In contrast, the panelists who chose HCQ screen cost had this to say:

• The “innovation” aspect here is an invitation to rethink and improve current screening guidelines to be more.. optimal? more efficient and resource-conscious while maintaining patient safety. The prednisone study, while also relevant, is only refining what we already do rather than optimizing. I think the infographic was one of the best though.
• Innovative study and an innovative choice by the Lankenau Internal Medicine team. Innovation is not necessarily a novel, unique therapy, but challenging our assumptions and affecting the lives of wide swaths of rheumatology patients worldwide. This is a great approach to finding ways to innovative our day-to-day practice and optimize patient care.

Fourth Matchup: Obinutuzumab in lupus nephritis defeats CD-19 CAR-T

Ah, now the madness truly begins. This was a massive upset. The Blue Ribbon Panel chose obinutuzumab in lupus nephritis over CD19 CAR-T Cells in a 4-3 nail-biter.

Here’s what those in favor of obinutuzumab in lupus nephritis had to say:

• This was difficult because both fit the theme for “innovation”. However, i feel that Obinutuzumab is the Queen here. It can be readily integrated to current Rheumatology practice. CAR-T has problems of scalability, wide-spread application and long-term global feasibility. Access can also be difficult – You need specialized centers and infrastructure, you need doctors who have the training and proper funding.
• I know that CAR T cell therapy is very impressive but I find the expense and risk to be too great. It will only help a small number of people. Obinutuzumab is a novel way of blocking B cells and most likely has the potential to help a larger number of people.
• Great to have a novel therapy that has potential to enhance outcomes in lupus nephritis, where there is so much unmet need. Beside CAR T paper is still just a small case series……
• CD19 CAR T definitely created a paradigm shift in options for refractory and severe rheumatologic disease. However till we gather substantial data, we are favoring Obinutuzumab in terms of agents with strong evidence for current and practical utility in lupus nephritis.

In contrast, here’s what those in favor of CD19 CAR-T Cell Therapy had to say:

• As much as it pains me to have to pick CAR-T cells again, I think CD-19 CAR-T is the winner here. It is a ground-breaking therapy that has the promise of curing autoimmune disease. Additional points to the team for using AI to help with the visual aid! If Obinutuzumab was compared to, say, belimumab + MMF + prednisone, it would have been an awesome very clinically applicable trial. However, just on its own, it is not quite as innovative or promising as CAR-T cells. Kudos to the Obinutuzumab team for making a clearly readable visual aid that is  not too busy.
• CAR-T has garnered a lot of attention in the rheumatology field with only small trials and limited follow-up but has the clear potential to revolutionize our field with possibility of curing our most severe patients.
• The CAR-T therapy study perfectly aligned with the purpose of this scouting event as an innovative and forward-thinking study. While it was a small-sized case series, it offers hope for both providers and patients, hinting at a potential breakthrough that could revolutionize rheumatology. The scouting report itself was engaging and fun to read, making complex science feel exciting and accessible. We counted over 20 sports references, which added more creativity to the writing.

So, how’s your bracket doing? We want to know! Here’s how to connect with us:

1. Follow us on Bluesky
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3. Join the conversation on X, formerly known as Twitter using #RheumMadness.

Remember, you can also find practical Q&As about each topic on theMednet.org! Links are included in each scouting report (find them here).