Team: B-Cell Busters

Base article: Müller F, Taubmann J, Bucci L, Wilhelm A, Bergmann C, Völkl S, Aigner M, Rothe T, Minopoulou I, Tur C, Knitza J, Kharboutli S, Kretschmann S, Vasova I, Spoerl S, Reimann H, Munoz L, Gerlach RG, Schäfer S, Grieshaber-Bouyer R, Korganow AS, Farge-Bancel D, Mougiakakos D, Bozec A, Winkler T, Krönke G, Mackensen A, Schett G. CD19 CAR T-Cell Therapy in Autoimmune Disease – A Case Series with Follow-up. N Engl J Med. 2024 Feb 22;390(8):687-700. doi: 10.1056/NEJMoa2308917. PMID: 38381673.

Authors: Vanderbilt Rheumatology Fellowship Program

1. Yash Pershad, medical student, Vanderbilt University School of Medicine
2. Genessis Maldonado, MD, Fellow, Division of Rheumatology and Immunology, Vanderbilt University Medical Center
3. Tyler Reese, MD, Assistant Professor of Medicine, Division of Rheumatology and Immunology, Vanderbilt University Medical Center

Team Overview: 

CAR T-cells just pulled off the biggest cross-division upset in rheumatology history. After revolutionizing the oncology league, these engineered cellular superstars crossed over to autoimmunity with style.

In this groundbreaking series, 15 players with refractory autoimmune disease (8 SLE, 3 myositis, 4 systemic sclerosis) who had struck out with conventional therapies got drafted into the CAR T-cell program. The results? Nothing but net—every single patient broke free from immunosuppressive drugs and scored long-term remission with manageable side effects.

What makes this squad special isn’t just their full-court press targeting B cells. Unlike other B-cell depleting veterans like rituximab, these CD19 CAR T-cells take down both B cells and plasmablasts. These T-cells have hustle and heart—they dive straight into the tissues and eliminate targets without waiting for backup from other immune system teammates. By deploying this deep bench of CD19-targeted CAR T-cells, they don’t just temporarily put autoimmune B cells in the penalty box like rituximab—they completely retool the immune roster, potentially leading to long-term tolerance. Their defensive IQ is off the charts—they preserve those crucial vaccine-memory plasma cells while eliminating the troublemakers. That’s the kind of smart, selective defense that wins championships.

The study evaluated the efficacy and safety of this game-changing therapy using disease-specific assessment tools. For systemic lupus erythematosus (SLE), disease activity was measured using the SLEDAI-2K score. Idiopathic inflammatory myositis (IIM) was assessed through serum creatine kinase levels, the Manual Muscle Test-8 (MMT-8), and the ACR-EULAR Total Improvement Score. In systemic sclerosis (SSc), disease severity was monitored using the modified Rodnan skin score (mRSS). Secondary endpoints included tracking the duration of clinical remission, persistence of CAR T cells, and incidence of adverse events, ensuring a comprehensive evaluation of the therapy’s long-term impact.

Admittedly, it is still early in the season with only 15 players on the roster—some may call this a fluke from a small-market team. But the implications for future patients are undeniably championship-caliber. CAR T-cell therapy represents a paradigm shift with the potential to revolutionize how we manage autoimmune disease.

Related content on theMednet.org:

How do you envision incorporating CAR-T therapy into your clinical practice?

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Team: Obinutuzumab’s Got Game 

Base article: Furie RA, Aroca G, Cascino MD, Garg JP, Rovin BH, Alvarez A, Fragoso-Loyo H, Zuta-Santillan E, Schindler T, Brunetta P, Looney CM, Hassan I, Malvar A. B-cell depletion with obinutuzumab for the treatment of proliferative lupus nephritis: a randomised, double-blind, placebo-controlled trial. Ann Rheum Dis. 2022 Jan;81(1):100-107. doi: 10.1136/annrheumdis-2021-220920. Epub 2021 Oct 6. PMID: 34615636; PMCID: PMC8762029.

***NOTE: This team was originally based on the phase II study results.  In February of 2025, the phase III results of the REGENCY trial was published in the New England Journal of Medicine (click for link).

Authors: University of Michigan Fellowship Program

1. Annie Carlton, MD, PhD, rheumatology fellow, University of Michigan
2. Rocio Bautista Sanchez, MD, rheumatology fellow, University of Michigan
3. Rishika Chin, MBBS, rheumatology fellow, University of Michigan
4. Lauren He, MD, rheumatology fellow, University of Michigan
5. Arati Kelekar, MBBS, rheumatology fellow, University of Michigan
6. Marianne Kerski, MD, rheumatology fellow, University of Michigan
7. Yasmin Khader, MD, rheumatology fellow, University of Michigan
8. David Riccardi, MD, rheumatology fellow, University of Michigan

Team Overview: 

Picture this: a 30-year-old female patient with systemic lupus erythematosus (SLE) and lupus nephritis (LN) on hydroxychloroquine, mycophenolate, and a stubborn prednisone requirement with persistent proteinuria despite your best efforts. What do you do next?

Obinutuzumab is an anti-CD20 monoclonal antibody with greater antibody-dependent cellular toxicity than traditional B cell depleting agents. In this double-blinded, placebo-controlled trial, adults with SLE and class III or IV LN with proteinuria (UPCR >1, eGFR≥30) who were treated with obinutuzumab were more likely to achieve complete renal response defined by UPCR<0.5, normal Cr (within 15% of baseline), and inactive sediment. Importantly, the greatest benefit was seen in those with baseline UPC>3 and class IV LN. Secondary outcomes were also impressive with greater improvement in eGFR, less rescue therapies, and rapid sustained depletion of CD19 cells in the obinutuzumab group. There were similar numbers of adverse events in both groups.

For a disease that has been described as far back as the 13th century, there has been a stagnant arsenal of medications in the rheumatologist’s toolbox for decades. Obinutuzumab reflects an exciting movement in SLE research today to expand therapeutic targets. This trial specifically includes patients we are most concerned about – those with marked kidney disease. While CAR-T is an innovative topic, it is not something that you pull from your bench to tag in when the game is on the line today. For that reason, we think the NOBILITY trial with obinutuzumab is the most important article for patients and providers.

***NOTE: The team overview above refers to the phase II study results.  In February of 2025, the phase III results of the REGENCY trial was published in the New England Journal of Medicine (click for link).

Related content on theMednet.org:

In the treatment of lupus nephritis, which patients may benefit from the use of rituximab or other B-cell depleting agents during induction?

What are the potential barriers to the widespread use of obinutuzumab in proliferative lupus nephritis?

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Team: RheumaNavigators

Base article:  Rivellese F, Nerviani A, Giorli G, Warren L, Jaworska E, Bombardieri M, Lewis MJ, Humby F, Pratt AG, Filer A, Gendi N, Cauli A, Choy E, McInnes I, Durez P, Edwards CJ, Buch MH, Gremese E, Taylor PC, Ng N, Cañete JD, Raizada S, McKay ND, Jadon D, Sainaghi PP, Stratton R, Ehrenstein MR, Ho P, Pereira JP, Dasgupta B, Gorman C, Galloway J, Chinoy H, van der Heijde D, Sasieni P, Barton A, Pitzalis C; STRAP collaborative group. Stratification of biological therapies by pathobiology in biologic-naive patients with rheumatoid arthritis (STRAP and STRAP-EU): two parallel, open-label, biopsy-driven, randomised trials. Lancet Rheumatol. 2023 Nov;5(11):e648-e659. doi: 10.1016/S2665-9913(23)00241-2. PMID: 38251532.

Authors: EMEUNET

1. Yvonne Tan, BSc, MD, MSc, Clinical Research Fellow, University of Manchester, United Kingdom, Clinical research fellow
2. Jean-Guillaume Letarouilly, MD, PhD, Service de rhumatologie, CHU Lille, Univ. Lille, Lille, France, Attending
3. Guillermo Carvajal Alegria, MD, PhD, Department of Rheumatology, Tours University Hospital, Tours University, Tours, France, Associate Professor
4. Milena Bond, Department of Rheumatology, Teaching Hospital of the Paracelsus Medical University, Hospital of Bruneck  (ASAAA-SABES), Bruneck, Italy, PhD candidate.
5. Francesca Crisafulli, Rheumatology and Clinical Immunology Unit, ASST Spedali Civili  of Brescia, University of Brescia, Brescia, Italy, Attending
6. Magda Osipyan, Department of Rheumatology, Vardanants Medical Center, Yeveran, Armenia, Associate Professor
7. Alejandro Gomez Gomez, MD, PhD, Department of Rheumatology, Hospital Universitari Vall d’Hebron, Barcelona, Spain, Attending
8. Krystel Aouad, MD, MSc, MPH, Department of Rheumatology, Saint George Hospital University Medical Center, Saint George University of Beirut, Lebanon, Assistant Professor

Team Overview: 

The STRAP trial is like setting sail with a “golden compass” to navigate the uncharted waters of rheumatoid arthritis (RA) treatment, with personalized medicine as the ultimate destination. A total of 223 RA patients across 26 centres in the UK and Europe embarked on this quest, none having previously used biological therapies. Each patient underwent a “mystical” synovial biopsy to reveal their B cell type—either “B cell-poor” or “B cell-rich”—intended to serve as a guiding light.

Three biological “armors”—rituximab, etanercept, and tocilizumab—were chosen as companions, each patient randomly assigned to one. The hope? That this “golden compass” of B cell types would direct researchers to the ideal treatment for each patient. However, the journey proved more complex than anticipated. After 16 weeks, the B cell profiles did not reveal the anticipated answers. Rituximab was not the “guiding star” as there was no difference in ACR 20 response (primary endpoint) compared with the other two “armors”: tocilizumab or etanercept. Yet, the “golden compass” provided valuable information as there was a lower response to rituximab in patients with a “pauci-immune” (low immune cell) profile, and B cell-rich patients treated with rituximab faced an increased risk of joint damage.

Yet, there was a silver lining: all three treatments held steady in terms of safety, acting like steadfast allies in Lyra’s world and protecting patients equally well across B cell profiles. Although the STRAP trial did not provide a definitive answer, it became a compass pointing researchers toward deeper questions in RA treatment. The journey to precision medicine continues, with the “golden compass” guiding the way through RA’s vast, uncharted landscape and setting the course for future discovery. The compass is set, and the adventure awaits.

Related content on theMednet.org:

Does synovial biopsy provide diagnostic value in undifferentiated inflammatory arthritis?

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Team: Ultrasound Avengers / Halo Heroes

Base article: Sebastian A, van der Geest KSM, Tomelleri A, Macchioni P, Klinowski G, Salvarani C, Prieto-Peña D, Conticini E, Khurshid M, Dagna L, Brouwer E, Dasgupta B. Development of a diagnostic prediction model for giant cell arteritis by sequential application of Southend Giant Cell Arteritis Probability Score and ultrasonography: a prospective multicentre study. Lancet Rheumatol. 2024 May;6(5):e291-e299. doi: 10.1016/S2665-9913(24)00027-4. Epub 2024 Mar 27. PMID: 38554720.

Authors: Medical College of Wisconsin Fellowship Program

1. Sabahat Usmani, MD, first-year rheumatology fellow, Medical College of Wisconsin
2. Fatima Hassan, MD, first-year rheumatology fellow, Medical College of Wisconsin
3. Mahum Mirza, MD, second-year rheumatology fellow, Medical College of Wisconsin
4. Bonit Gill, MD, second-year rheumatology fellow, Medical College of Wisconsin
5. Micheal Putman, MD, Rheumatology Fellowship Program Director, Medical College of Wisconsin

Team Overview: 

The HAS-GCA Score team is a formidable force in the RheumMadness tournament. This “dynamic duo” combining the Southend Giant Cell Arteritis Probability Score (SGCAPS) with the halo count using ultrasonography forms a diagnostic powerhouse, pairing clinical expertise with high-resolution imaging. Together, they create a streamlined, evidence-based approach to diagnosing GCA, offering significant advantages over traditional methods.

SGCAPS, the seasoned veteran, excels in stratifying patients into risk categories based on clinical features, laboratory findings, and imaging results. However, subtle cases of GCA can sometimes pose a challenge for this tool. Enter ultrasonography: the rising star in diagnostic imaging. With its ability to identify vascular abnormalities such as the hallmark “halo sign,” ultrasonography can detect even the most elusive signs of GCA, improving diagnostic accuracy. By combining these two methods, the team enhances the reliability of diagnosis while reducing unnecessary reliance on invasive temporal artery biopsies (TABs), which can be both time-consuming and uncomfortable for patients.

Despite their impressive strengths, the HAS-GCA Score team is not without its limitations. One major concern is the reliance on ultrasound expertise, which may not be available in all clinical settings, particularly in resource-limited environments. Additionally, the performance of these diagnostic tools may vary depending on the patient population or healthcare system. Nonetheless, their innovative approach holds great promise. With precision and synergy, the HAS-GCA Score team has the potential to revolutionize GCA diagnostics and improve patient outcomes, making them a top contender in the RheumMadness tournament.

Related content on theMednet.org:

How do you make the decision to empirically treat for GCA when a patient is referred but cannot be immediately seen in clinic?

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Team: Steroid dose in SLE

Base article: Figueroa-Parra G, Cuéllar-Gutiérrez MC, González-Treviño M, Sanchez-Rodriguez A, Flores-Gouyonnet J, Meade-Aguilar JA, Prokop LJ, Murad MH, Dall’Era M, Rovin BH, Houssiau F, Tamirou F, Fervenza FC, Crowson CS, Putman MS, Duarte-García A. Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials. Arthritis Rheumatol. 2024 Sep;76(9):1408-1418. doi: 10.1002/art.42920. Epub 2024 Jun 28. PMID: 38766897.

Authors: Washington University in St. Louis Fellowship Program

1. Sambhawana Bhandari, MD, 2^nd year rheumatology fellow, Washington University in St. Louis School of Medicine
2. Ariella Coler- Reilly, MD PhD candidate, Washington University in St. Louis School of Medicine
3. Alfred Kim, MD PhD, Associate Professor, Division of Rheumatology, Washington University in St. Louis School of Medicine
4. Lacey Feigl-Lenzen, Rheumatology fellowship program coordinator, Washington University in St. Louis School of Medicine
5. Sarah Goodman, MD, 2^nd year rheumatology fellow, Washington University in St. Louis

Team Overview: 

Glucocorticoids, our savior and the bane of our existence! Since their dramatic debut in 1948, transforming the life of a patient with rheumatoid arthritis and earning Hench, Kendall, and Reichstein the Nobel Prize, they have remained a cornerstone of rheumatic disease management (1). However, overutilization leads to infections and damage accrual, even at lower doses (2,3). Closing the evidence gap on optimal prescribing is crucial, and glucocorticoid-free induction therapies are emerging as safer alternatives (4). This meta-analysis included 50 RCT arms with data from 3,231 lupus nephritis (LN) patients to assess how different glucocorticoid doses influence complete response (CR), serious infections, and mortality.

Key Results:

• Rates of CR: 19.5% (95% CI 7.3–31.5) at 25 mg/day vs 34.6% (95% CI 16.9–52.3) at 60 mg/day
• Rates of serious infections: 3.2% (95% CI 2.4–4.0) at 25 mg/day vs 12.1% (95% CI 9.3–14.9) at 60 mg/day
• Rate of death: 0.2% (95% CI 0.0–0.4) at 25 mg/day vs 2.7% (95% CI 0.0–5.3) at 60 mg/day

This study is foundational as LN poses high mortality risks, and current glucocorticoid practices lead to severe side effects. By analyzing protocolized practices across many trials, this study highlights the impact of steroid dosing on kidney outcomes and safety emphasizing the need for personalized tapering strategies to prevent complications like infections and death. Limitations include variability in trial designs, participant populations, and tapering regimens, which may affect generalizability, as well as a lack of data on infection risk factors.

Related content on theMednet.org:

What steroid regimen do you typically use for induction therapy in patients with lupus nephritis?

References

1. Conn et al, The Story Behind the Use of Glucocorticoids in the Treatment of Rheumatoid Arthritis, Seminars in Arthritis and Rheumatism, Volume 51, Issue 1, 2021, https://doi.org/10.1016/j.semarthrit.2020.09.016
2. Abe K, Ishikawa Y, Kita Y, Yajima N, Inoue E, Sada KE, Miyawaki Y, Yoshimi R, Shimojima Y, Ohno S, Kajiyama H, Ichinose K, Sato S, Fujiwara M. Association of low-dose glucocorticoid use and infection occurrence in systemic lupus erythematosus patients: a prospective cohort study. Arthritis Res Ther. 2022 Jul 28;24(1):179. doi: 10.1186/s13075-022-02869-9. PMID: 35902976; PMCID: PMC9330647.
3. Ugarte-Gil MF, Mak A, Leong J, Dharmadhikari B, Kow NY, Reátegui-Sokolova C, Elera-Fitzcarrald C, Aranow C, Arnaud L, Askanase AD, Bae SC, Bernatsky S, Bruce IN, Buyon J, Costedoat-Chalumeau N, Dooley MA, Fortin PR, Ginzler EM, Gladman DD, Hanly J, Inanc M, Isenberg D, Jacobsen S, James JA, Jönsen A, Kalunian K, Kamen DL, Lim SS, Morand E, Mosca M, Peschken C, Pons-Estel BA, Rahman A, Ramsey-Goldman R, Reynolds J, Romero-Diaz J, Ruiz-Irastorza G, Sánchez-Guerrero J, Svenungsson E, Urowitz M, Vinet E, van Vollenhoven RF, Voskuyl A, Wallace DJ, Petri MA, Manzi S, Clarke AE, Cheung M, Farewell V, Alarcon GS. Impact of glucocorticoids on the incidence of lupus-related major organ damage: a systematic literature review and meta-regression analysis of longitudinal observational studies. Lupus Sci Med. 2021 Dec;8(1):e000590. doi: 10.1136/lupus-2021-000590. PMID: 34930819; PMCID: PMC8689160.
4. Condon MB, Ashby D, Pepper RJ, Cook HT. Prospective observational single-centre cohort study to evaluate the effectiveness of treating lupus nephritis with rituximab and mycophenolate mofetil but no oral steroids. Ann Rheum Dis. 2013 Aug;72(8):1280-6. doi: 10.1136/annrheumdis-2012-202844. Epub 2013 Jun 5. PMID: 23740227.

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Team: Plaquenil Pioneers

Base article: Quist SW, Dorsthorst ST, Freriks RD, Postma MJ, Hoyng CB, van Asten F. Cost-effectiveness of hydroxychloroquine retinopathy screening: the current guideline versus no screening and reduced regimens. Eur J Health Econ. 2024 Aug 20. doi: 10.1007/s10198-024-01715-w. Epub ahead of print. PMID: 39162892.

Authors: Lankenau Internal Medicine Residents

1. Amanda Rodriguez, DO, Internal Medicine Resident, Lankenau Medical Center 
2. Emily Thoman, DO, Internal Medicine Resident, Lankenau Medical Center 
3. Michael Galperin, DO, Internal Medicine Resident, Lankenau Medical Center 
4. Sebastiano Porcu, MD, Internal Medicine Resident, Lankenau Medical Center 
5. Stephanie Giattino, MD, Associate Program Director, Internal Medicine Residency, Lankenau Medical Center 

Team Overview: 

Welcome to the court of hydroxychloroquine screening guidelines! Our starting player, hydroxychloroquine (HCQ), a fan favorite dropping buckets left and right in the treatment of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), can come with a catch: HCQ-induced retinopathy, an opponent no one wants to face (a real ankle breaker). Current screening guidelines from the American Academy of Ophthalmology, recommend all patients start with an eye screening in their first year of HCQ treatment, then annually after 5 years on HCQ therapy in low-risk patients.  While these guidelines are effective in catching HCQ-induced retinopathy, this rigorous screening adds to the already burdensome waitlists for Ophthalmology clinics and contributes to increased medical and societal costs, including worsened quality of life and productivity losses.

A team of researchers in the Netherlands set out to challenge these guidelines, and they certainly brought their “A-game” in this study, spotlighting 359 patients. For low-risk patients, it is more cost-effective to delay follow-up screenings to ten years after the initial screening and then switch to every two years. For high-risk patients, annual screenings are more efficient starting at five years, rather than the one-year mark. This strategic game plan can help keep patients in the paint with an effective treatment, while reducing wait times for Ophthalmology offices and improving screening cost efficiency. You hear that? That’s all net, baby!

Related content on theMednet.org:

How do you optimize retinopathy screening schedules for patients on hydroxychloroquine while also prioritizing cost-effectiveness?

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Team: TykTARC Influencers

Base article: Morand E, Pike M, Merrill JT, van Vollenhoven R, Werth VP, Hobar C, Delev N, Shah V, Sharkey B, Wegman T, Catlett I, Banerjee S, Singhal S. Deucravacitinib, a Tyrosine Kinase 2 Inhibitor, in Systemic Lupus Erythematosus: A Phase II, Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol. 2023 Feb;75(2):242-252. doi: 10.1002/art.42391. Epub 2022 Nov 11. PMID: 36369798; PMCID: PMC10100399.

Authors: UNC Rheumatology Fellows

1. Griffin Sonaty, MD, first-year rheumatology fellow, University of North Carolina
2. Saloni Patolia, MD, first-year rheumatology fellow, University of North Carolina
3. Aaron Smith, MD, first-year rheumatology fellow, University of North Carolina
4. Michael Cunningham, MD, assistant professor of rheumatology, University of North Carolina

Team Overview: 

Are cytokines interferon’ with your patient’s SLEDAI score? Is their BILAG beating belimumab? Are they too SLICC to respond to saphnelo? Is their skin too CLASI for chloroquine? Do you envy the casual charm and elegance of the orally bioavailable JAK inhibitors, but would like your treatments to be supported by more evidence of efficacy against lupus and less evidence of increased risk of thromboembolic disease? Step right up, step right up, we’ve got a med for you!

Say sayonara syringes! Orally bioavailable deucravacitinib targets Tyk2, a key kinase in interferon 1, IL-10, IL-12, and IL-23 signaling. A recent double-blinded placebo controlled randomized clinical trial with 363 patients showed that 48-weeks of treatment with oral twice daily deucravacitinib led to significant improvements in frequencies of SRI-4 response (34.1%57.1%), LLDAS (13.3%36.3%), CLASI-50 (16.769.6), and BICLA (25.647.3). No other lupus treatment has ever been shown to be clinically efficacious against such a broad spectrum of lupus clinical trial endpoints! Commonly trended lupus disease markers such as complements and dsDNA also significantly improved. Absolutely no major cardiovascular or thromboembolic events occurred!

In short, deucravacitinib slam dunks over SLEDAI, boxes out BILAG, stuffs SRI-4, levels LLDAS, crosses CLASI and does it all per os! Where other medications take a time out, deucravacitinib sinks from downtown!

*Treatment with deucravicitinib may be associated with increased risk of acneiform rash, upper respiratory infection, or urinary tract infection.

Related content on theMednet.org:

What is your experience with using oral deucravicitinib for conditions such as recalcitrant facial discoid lupus or recalcitrant lichen planus?

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