The second round of RheumMadness 2025 (the entheseal eight) is full of more upsets!   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.

To hear a full round up of how participants voted, give our most recent RheumMadness podcast episode a listen.

Results from additional rounds will be released as follows:

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

First Matchup: CD40L in Sjogren’s defeats BiTEs

Another massive upset!  The Blue Ribbon Panel chose CD40L in Sjogren’s over BiTEs in a in a 4-3 vote.  This was shocking, as 58% of participants thought BiTEs would win this round, compared with 34% choosing CDL40L and 8% sticking with APIPPRA.

Hear the opinion of the panelists in favor of CD40L in Sjogren’s below:

• Both studies were innovative, with the BiTE study showing promise as a new treatment approach. However, 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 treatment need. It also provided a stronger level of evidence. At this stage, we believe the CD40 ligand study offers more immediate guidance for physicians and benefits for patients. The study’s visual presentation was particularly compelling, using the Sjögren’s horse wordplay to add a creative and memorable touch. Overall, the infographic and scouting report presented an innovative treatment option for Sjogren’s in a way that was both engaging and easy to interpret.
• This match-up is an early scouting of two exciting young prospects with a match-up of a case report against a phase 2 trial. Both have great potential, though the more robust findings in the dazodalibep brings this one further, especially when bolstered by the exciting inclusion of subjective and objective endpoints in Sjogren’s disease.
• Tough decision, but at this time I am leaning towards CD40L in Sjogren’s due to currently limited options to help treat Sjogren’s disease patients.
• This is a close call for me – both fit what im looking for in terms of the theme of Innovation. Im going for CD40L because there is an unmet need (like absolutely nothing solid) while SLE already has a lot of players on the field.

In contrast, here’s the opinion of those who voted for BiTEs:

• CD40L for Sjogren’s is good but there is potential to dramatically improve the treatment of several autoimmune diseases with BiTes. In fact, one of the studies looked at the use of BiTes in Sjogren’s. I feel BiTes have the potential to do the greatest good for the greatest number of people.
• What a difficult match-up! Both reports are excellent and the visual aid for CD40L inhibitor is fantastic. However, BiTEs is such an exciting and promising treatment, that appears to be more accessible and safe that CAR-T cell, that I had to pick that.
• LOVE BITES! The idea is so elegant The antibodies are “off the shelf.” The toxicity is low. THEY WORKED. The CD40L study is preliminary and the results heterogeneous – unlikely to be a game changer. BITEs all the way

Second Matchup: TYK2 in SLE defeats Oral anti-IL23

The Blue Ribbon Panel chose TYK2 in SLE over Oral Anti-IL23 in a 6-1 vote.  This was not an upset, as 49% of participants chose TYK2 in SLE, 36% chose oral anti-IL23, and 14% chose the long-term extension of anifrolumab.

Hear those in favor of TYK2 in SLE below:

• While oral IL-23 has great benefit for skin disease in psoriasis, the TYK2 wins this one as it hits not only skin but multiple lupus domains.
• Oral anti-IL23 drugs would be the second oral drug for psoriasis. So it is not quite as innovative as TYK2 for SLE. The joint and skin manifestations of SLE can be very difficult to treat and a new oral drug that is steroid sparing would be welcome. We may be pleasantly surprised that more good things will come with this unique drug.
• Novel therapy in SLE to help better control disease would be great, considering the limited options at this time.
• Another difficult match-up . Both reports and visual aids are great. Picking TYK2 as a more impactful paper. We do not have enough safe effective treatments in SLE, while psoriasis now has drug that achieve complete skin clearance potentially (e.g., bimekizumab).
• This one was difficult for me – because both fit the criteria of Innovative-“ness” and both have the potential to be scalable. I’m just going to vote for TYK2 only because I think the oral anti-IL23 is too early a contender.
• Both are great studies with exciting results and new class BUT the unmet need in SLE is greater (and the morbidity of SLE > PsA) and the TYK2 look so good. PsA has plenty of effective treatments already and I guess PO is nice but……a new agent for SLE – champion

In contrast, here’s the lone dissenting opinion in favor of Oral Anti-IL23

• Both studies were innovative and aimed at expanding treatment options in Rheumatology which would benefit both providers and patients. Although, the oral anti-IL-23 study focused solely on cutaneous involvement, it introduced an oral treatment with efficacy comparable to standard therapy and has a better safety profile than other available oral medications. The graphic was exceptionally well-designed, making complex information easy to digest. Adding the little players was a clever and engaging touch, allowing for a quick comparison of treatment options and clearly highlighting the advantages of this new oral medication over existing alternatives.

Third Matchup: Pred dose in SLE defeats SGCAPS

Another upset!  The Blue Ribbon Panel overwhelmingly favored pred dose in SLE, voting for them over SGCAPS in a 6-1 blowout.  However, 49% of participants chose SGCAPS compared with 36% picking pred dose in SLE and 14% for HCQ screen cost.

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

• While the SGCAPs study proposed a scoring system to guide the management of GCA. The steroid dosing study in lupus nephritis provided stronger evidence as a systematic review. It addressed a crucial and frequently debated question in rheumatology. The optimal steroid dosing in LN patient is a challenge we often encounter in clinical practice, making the study particularly relevant. The graphic was exceptionally well-designed, engaging, and fun presenting the suggested dosing in a clear way. It made the information easy to remember and ready for application in real-world scenarios.
• Prednisone in lupus nephritis tackles one of the most fundamental problems in rheumatology – balancing the incredibly challenging risk/benefits of our love/hate medication. This is widely applicable with very high utility. SGCAPS is a great study, though difficulty in ultrasound reliability without proper experience and training makes it less broadly applicable.
• Pred dose SLE, We need as much evidence as possible that we no longer need large doses of corticosteroids. This is a welcome study. I found the SGCAPS intriguing but am concerned that other than large medical centers, there will not be adequate number of people with expertise to do the ultrasounds in a timely basis. This may be another case of disparity in care by where you live.
• Steroid mindfulness (pred dose in SLE) wins. SGCAPS report is excellent and their visual tool is one of the best in this competition. However, being thoughtful about prednisone dosing is what any rheumatologist in any practice setting can and MUST do; while ultrasound is a luxury not available to most of us, at least in the US.
• Innovation won’t be important if it won’t be scalable. While ultrasound use has been around for ten years, many countries still have yet to make it a standard part of curriculum. Therefore I don’t see the SGCAPS affecting clinical practice. While the Pred dose in SLE doesn’t seem new… and is a part of clinical intuition, it’s innovative in the sense that it did a rigorous analysis of current practice.
• The Pred dose in SLE study provides essential information to inform shared decision making for SLE. The SGCAPS just makes everyone who cannot access ultrasound for GCA feel bad!

In contrast, the lone panelist in favor of SGCAPS said this:

• Both of these are great trials- landmark paper about damage accrual in SLE patients on Prednisone vs new tool to help guide GCA management. It is definitely a tough call! I am leaning towards SGCAPS, the challenges of reliable GCA diagnosis guiding subsequent immunosuppressive therapy in elderly populations could benefit from innovative strides at this time.

Fourth Matchup: Obinutuzumab in LN defeats the STRAP trial

The blue ribbon panel chose obitnutuzumab in lupus nephritis over the STRAP trial in a 5-2 vote.  Of the remaining options, most participants agreed with 29% picking obinutuzumab versus 19% favoring STRAP in this round (nothing that 52% still thought CAR-T would still be in it and win this round!).

Those in favor of obinutuzumab in LN said this:

• The STRAP trial is a good idea but the results were underwhelming. The added expertise to do the synovial biopsies and the expense of reading these biopsies limits the potential as a future “guiding light”. Obinutuzumab looks exciting for SLE. This was my choice but I still have some reservations as there were no comparisons. I would like to know how many patients in the trial had previously been on voclosporin or belimumab. And how obinutuzumab compares to these two drugs.
• While I was initially leaning heavily towards the STRAP trial as it could potentially change the whole RA management landscape, I feel we need to use this time to gather stronger and more convincing data. Between these two trials, I favor the Obinutuzumab in LN intervention in terms of applicability. Both are great and monumental shifts in Rheumatology!
• I absolutely love it that our European colleagues are participating and, as a person not terribly well versed in American spots, I appreciate them just not sticking to basketball puns. The visual tool is beautiful too. However, as a practical clinician, I am picking Obinutuzumab as I see it using in my practice much sooner than synovial biopsies.
• Innovation won’t be important if it won’t be scalable. Obinutuzumab has the potential for a broader and more immediate clinical workflow impact & can be readily integrated to practice
• The STRAP trial sounds so enticing in the protocol but lack difference in ACR20 response and no actionable findings. Finding a B cell depletor that actually improves rates of remission in Lupus nephritis – GOLD

In contrast, the two panelists in favor of STRAP said this:

• Although the STRAP trial was ultimately negative, we were impressed by the team’s forward-thinking approach in selecting an article that discussed precision medicine and the opportunity to make our targeted therapies truly targeted. While the scouting report and graphic weren’t basketball-oriented, they still demonstrated more creativity compared to the Obinutuzumab in LN article. It’s clear that a lot of effort went into the STRAP trial presentation.
• In a bracket of innovation, STRAP trial breaks the mold of our other traditional drug trials by seeking to find new ways to compare our existing medications. I love the design of using synovial biopsies to better understand patient phenotype and strive for a future of patient-centric care.

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

1. Follow us on Bluesky
2. Follow us on Instagram
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).

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
2. Follow us on Instagram
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).