SGCAPS

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?

 

Back to the full list of scouting reports

Pred Dose in SLE

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, 2nd 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, 2nd 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.

 

Back to the full list of scouting reports

HCQ Screening Cost

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?

 

Back to the full list of scouting reports

TYK2 in SLE

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?

 

Back to the full list of scouting reports

Anifrolumab extension

Team: Lupus Legends: The Anifrolumab Edition

Base article: Kalunian KC, Furie R, Morand EF, Bruce IN, Manzi S, Tanaka Y, Winthrop K, Hupka I, Zhang LJ, Werther S, Abreu G, Hultquist M, Tummala R, Lindholm C, Al-Mossawi H. A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Arthritis Rheumatol. 2023 Feb;75(2):253-265. doi: 10.1002/art.42392. Epub 2022 Nov 11. PMID: 36369793; PMCID: PMC10098934.

Authors: The Medical University of South Carolina Fellowship Program

  1. Rachael Werner, MD, PhD, 3rd year fellow
  2. Gretchen Santana, MD, 2nd year fellow
  3. Rashi Vora, MD, 2nd year fellow
  4. Megan Donaldson, DO, 1st year fellow
  5. Maggie Smythe, MD, 1st year fellow
  6. Brandon Lew, MD, 1st year fellow
  7. Jennifer Schmidt, MD, Associate Program Director
  8. Faye Hant, DO, Program Director

Team Overview: 

In the heated competition of chronic illness treatments, “A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of anifrolumab in Active Systemic Lupus Erythematosus” is the undisputed MVP!

For patients, this trial shows that anifrolumab can offer relief during the overtime of managing chronic conditions. This trial shows strong data in using anifrolumab to reduce steroid usage, at least off the court.

For researchers, this trial offers invaluable insights on how long-term treatment options like anifrolumab can shape the future of chronic illness management. This study isn’t just a win for lupus—it shines a spotlight on interferon-targeted therapies which are also being explored in conditions like dermatomyositis and systemic sclerosis (1, 2). Plus, it’s a great gameplan for running long-term placebo-controlled trials.

In the competition of managing systemic lupus erythematosus (SLE), anifrolumab has emerged as a key player. This phase III long term extension (LTE) trial was like the championship finals, where patients who completed the initial TULIP trial were either continued on anifrolumab 300 mg, switched from 150mg to 300mg dosing or remained on the bench with placebo.

This trial showed that anifrolumab maintained a strong defense against serious adverse events (SAEs), with an exposure-adjusted incidence rate (EAIR) of 8.5 per 100 patient-years, outscoring the placebo team’s 11.2. Similarly, when it came to adverse events leading to treatment discontinuation, anifrolumab had fewer fouls and less time on the sidelines (EAIR of 2.5 compared to placebo’s 3.2).

In the infection zone, both teams were evenly matched, with non-opportunistic serious infections occurring at comparable rates. On the offense, anifrolumab excelled by reducing the need for glucocorticoids and improving SLE disease activity. This strategic move helped anifrolumab outscore placebo in overall disease management.

In conclusion, this LTE study was the longest placebo-controlled clinical trial in the SLE arena, and it reinforced anifrolumab’s favorable benefit-risk profile. Whether you’re advancing treatments, improving patient outcomes, or looking for a new research breakthrough, anifrolumab is THE player to watch for patients with moderate-to-severe SLE receiving standard therapy. Don’t sit on the bench—this is the one to watch for patients now and in the future!

Related content on theMednet.org:

How will you utilize newly FDA approved anifrolumab for SLE in your practice?

 

References:

  1. Shaw, K. S., Hashemi, K. B., Castillo, R. L., Rainone, E., Ho, A. W., Kahn, P. J., Oza, V. S., Femia, A., & Vleugels, R. A. (2024). Anifrolumab in recalcitrant cutaneous dermatomyositis: A Multicenter Retrospective Cohort study. Journal of the American Academy of Dermatology91(6), 1217–1219.  https://doi.org/10.1016/j.jaad.2024.07.1491
  2. Khanna, D., Denton, C. P., Assassi, S., Kuwana, M., Allanore, Y., Domsic, R. T., Kleoudis, C., Xu, J., Csomor, E., Seo, C., Albulescu, M., Tummala, R., Al-Mossawi, H., Kalyani, R. N., & Del Galdo, F. (2024). A randomised, parallel-group, double-blind, placebo-controlled phase 3 study to Determine the effectiveness of the type I interferon receptor antibody, Anifrolumab, In SYstemic sclerosis: DAISY study design and rationale. Clinical and Experimental Rheumatology. https://doi.org/10.55563/clinexprheumatol/s8qcyu

 

Back to the full list of scouting reports

Oral anti-IL-23

Team: The Oral Biologic Frontier

Base article: Bissonnette R, Pinter A, Ferris LK, Gerdes S, Rich P, Vender R, Miller M, Shen YK, Kannan A, Li S, DeKlotz C, Papp K. An Oral Interleukin-23-Receptor Antagonist Peptide for Plaque Psoriasis. N Engl J Med. 2024 Feb 8;390(6):510-521. doi: 10.1056/NEJMoa2308713. PMID: 38324484.

Authors:  The Chicago Collaborative

  1. Maja Ivanovic, MD, first-year rheumatology fellow, University of Chicago
  2. Daming Shao, MD, first-year rheumatology fellow, University of Chicago
  3. Michael Macklin, MD, Assistant Professor of Medicine, University of Chicago
  4. Anu Pandit, MD, first-year rheumatology fellow, Northwestern University
  5. Laura Arneson, MD, Assistant Professor of Medicine, Northwestern University
  6. Aliya Ahsan, MD, first-year rheumatology fellow, Loyola University
  7. Mohit Gupta, MD, second-year rheumatology fellow, Loyola University
  8. Melissa Briones, MD, Associate Professor, Rheumatology, Loyola University

Team Overview: 

Psoriasis is a multisystem, immune-mediated inflammatory disorder at the intersection of dermatology and rheumatology. Extensive skin involvement or concurrent arthritis may require an aggressive approach, beyond topical agents, phototherapy, or conventional synthetic DMARDs. The veteran oral options in this arena, apremilast and JAK/TYK2 inhibitors, have limitations in their efficacy and safety.

This phase 2 dose-finding randomized clinical trial introduces a promising prospect: the novel oral treatment JNJ-77242113, which exerts strong defense by inhibiting IL-23 and downstream cytokine production involved in plaque psoriasis. In this study, 255 patients with moderate-to-severe plaque psoriasis were randomized to receive the rookie therapeutic with doses of 25 mg daily, 25 mg twice daily, 50 mg daily, 100 mg daily, 100 mg twice daily, or placebo for 16 weeks. The primary endpoint was 75% reduction from baseline in the Psoriasis Area and Severity Index score (PASI 75). At 16 weeks, the young phenom, JNJ-77242113, outmaneuvered placebo, demonstrating a significant dose-response relationship, with 79% of patients reaching PASI 75 in the highest-dose group.

The stats show that this novel oral IL-23 receptor antagonist is a rising star. By combining the ease of oral administration with significant therapeutic efficacy, it opens the door to an arena of safer and more convenient treatments for psoriasis and has strong potential for psoriatic arthritis as well. The success of this therapy is a harbinger of the rising players capable of oral inhibition of cytokine targets more broadly, heralding an era where patients will not have to compromise efficacy for ease of use – a slam dunk for us all!

Related content on theMednet.org:

What circumstances would drive you to consider using an oral IL-23 inhibitor over parenteral options for management of psoriasis/PsA?

 

Back to the full list of scouting reports

Bispecific T-cell engagers

Team: Bispecific T-Cell Engagers (BiTEs), aka “Other Drugs BiTE the Dust”

Base article: Alexander T, Krönke J, Cheng Q, Keller U, Krönke G. Teclistamab-Induced Remission in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2024 Sep 5;391(9):864-866. doi: 10.1056/NEJMc2407150. PMID: 39231352.

Authors: 

  1. Marwin Groener, Rheumatology Fellow, The Johns Hopkins University School of Medicine
  2. Maximilian F. Konig, Assistant Professor of Medicine, The Johns Hopkins University School of Medicine

Team Overview: 

CAR-T cell therapies promise to change the game of rheumatology. But an upcoming rookie (and MVP in oncology) is our No.1 draft pick this year: Bispecific T cell-engaging antibodies.

Originally scouted by hematologists, these bispecific antibodies bind the T cell receptor-CD3 complex on any T cell with one end and a B cell surface protein (e.g. CD19 or BCMA) on B cells with the other. This dual engagement results in the destruction of B cells by the patient’s own (unmodified) T cells.

In this case study (1), teclistamab, a BCMAxCD3 bispecific T cell engager, was used to treat a patient with refractory SLE (lupus nephritis, hemolytic anemia, rash, oral ulcers, and arthritis). By six weeks, all laboratory (hypocomplementemia, anti-dsDNA) and clinical abnormalities had resolved. Her SLEDAI-2K decreased from 20 to 0, and drug-free complete remission was sustained at 16-week follow-up.

Unlike CAR-T cell therapy, bispecific antibodies offer the potential for deep depletion and “immune reset” of the B-cell compartment without the requirement for apheresis and cell engineering, without cytotoxic conditioning therapy (“lymphodepletion”), and without any risk of secondary malignancies! Like CAR-T cell therapy, side effects included cytokine release syndrome, hypogammaglobulinemia (treated with IVIg), and mild infections.

This “off-the-shelf” therapy has the potential to become the Michael Jordan of rheumatology. Blinatumomab, a CD19xCD3 bispecific T cell engager (BiTE), was also successful in patients with rheumatoid arthritis (2), and teclistamab showed promise in systemic sclerosis, Sjögren’s disease, anti-MDA5-associated dermatomyositis (3). The future holds even more for this promising player that can be engineered to beat any opponent. Bispecific antibody therapies targeting autoreactive B cells in SLE (9G4xCD3 BiTE, 4), antiphospholipid syndrome (BaiTE, 5), and even autoreactive T cells in ankylosing spondylitis (TRBV9xCD3 BiTE, 6) were presented at ACR Convergence 2024, highlighting opportunities for precision targeting without increasing the infection risk.

Related content on theMednet.org:

What factors drive you to prioritize T vs B cell inhibition when choosing therapies for patients with refractory SLE?

References

  1. Alexander T, Krönke J, Cheng Q, Keller U, Krönke G. Teclistamab-Induced Remission in Refractory Systemic Lupus Erythematosus. N Engl J Med. 2024 Sep 5;391(9):864-866. PMID: 39231352.
  2. Bucci L, Hagen M, Rothe T, Raimondo MG, Fagni F, Tur C, Wirsching A, Wacker J, Wilhelm A, Auger JP, Pachowsky M, Eckstein M, Alivernini S, Zoli A, Krönke G, Uderhardt S, Bozec A, D’Agostino MA, Schett G, Grieshaber-Bouyer R. Bispecific T cell engager therapy for refractory rheumatoid arthritis. Nat Med. 2024 Jun;30(6):1593-1601. PMID: 38671240.
  3. Hagen M, Bucci L, Böltz S, Nöthling DM, Rothe T, Anoshkin K, Raimondo MG, Tur C, Wirsching A, Wacker J, Düsing C, Distler JHW, Kuwert T, Bozec A, Ramming A, Schett G, Grieshaber-Bouyer R. BCMA-Targeted T-Cell-Engager Therapy for Autoimmune Disease. N Engl J Med. 2024 Sep 5;391(9):867-869. PMID: 39231353.
  4. Liu J, Xia Y, Ferris D, Shaw E, Mog B, Pearlman A, Moritz B, Kaeo K, Gliech C, Awosika T, DiNapoli S, Nichakawade T, Li Y, Ge J, Glavaris S, Marcou N, Ahmedna T, Bugrovsky R, Jenks S, Bettegowda C, Goldman D, Petri M, Sanz I, Kinzler K, Zhou S, Vogelstein B, Paul S, Andrade F, Konig M. T Cell-Engaging Bispecific Antibodies to Target Autoreactive 9G4 Idiotope B Cells in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9).
  5. Xia Y, Liu J, Pearlman A, Mog B, Shaw E, Kaeo K, Gliech C, Moritz B, Awosika T, DiNapoli S, Glavaris S, Ge J, Nichakawade T, Marcou N, Paul S, Pardoll D, Bettegowda C, Goldman D, Petri M, Rosen A, Kinzler K, Zhou S, Vogelstein B, Konig M. Bispecific Autoantigen-T Cell Engagers (BaiTE) to Selectively Target Autoreactive B Cells in Antiphospholipid Syndrome [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9).
  6. Glavaris S, Pearlman A, Liu J, Ge J, Xia Y, Kaeo K, Awosika T, Gliech C, Nichakawade T, Marcou N, Bettegowda C, Pardoll D, Kinzler K, Zhou S, Vogelstein B, Paul S, Konig M. TRBV9-Targeted Bispecific T Cell-Engaging Antibodies to Reset the Autoreactive T Cell Compartment in Spondyloarthritis and HLA-DQ8 Celiac Disease [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9).

 

Back to the full list of scouting reports

Abatacept in pre-RA

Team: Abatacept for pre-RA, aka the “tendon ticklers”

Base article: Cope AP, Jasenecova M, Vasconcelos JC, Filer A, Raza K, Qureshi S, D’Agostino MA, McInnes IB, Isaacs JD, Pratt AG, Fisher BA, Buckley CD, Emery P, Ho P, Buch MH, Ciurtin C, van Schaardenburg D, Huizinga T, Toes R, Georgiou E, Kelly J, Murphy C, Prevost AT; APIPPRA study investigators. Abatacept in individuals at high risk of rheumatoid arthritis (APIPPRA): a randomised, double-blind, multicentre, parallel, placebo-controlled, phase 2b clinical trial. Lancet. 2024 Mar 2;403(10429):838-849. doi: 10.1016/S0140-6736(23)02649-1. Epub 2024 Feb 13. PMID: 38364839.

Authors: Allegheny Health Network Adult Rheumatology Fellowship

  1. Conor O’Donnell, DO, Second year rheumatology fellow
  2. Saloni Goyal, DO, Second year rheumatology fellow
  3. Guru Prasad Parthiban, MD, First year rheumatology fellow
  4. Mara Banez, MD, First year rheumatology fellow
  5. Michael Lucke, MD, Program Director

Team Overview: 

Imagine your patient squaring off on the baseball diamond in the immunologic ballpark. Rheumatoid Arthritis (RA) is the pitcher and is ready to throw a citrullinated fast ball at your patient. Would you rather risk the long-term consequences of a strikeout, or give them the resources to prevent RA’s tendrils from infiltrating their pristine joint space? The APIPPRA trial showed that abatacept’s protective gear could stave off the inflammatory advances of rheumatoid arthritis.

This groundbreaking trial was the first of its kind to demonstrate a sustained delay in the development of RA and onset of clinical synovitis. In this multicenter placebo controlled clinical trial, abatacept showed improvement in pain scores, functional well-being, quality of life and subclinical synovitis at one year.

At 12 months, 29% of patients on placebo had development of clinical synovitis or progression to RA compared to 6% of patients on abatacept. Despite discontinuation of the abatacept in the treatment arm at 12 months, this difference was sustained at 24 months, with 38% in the placebo group compared to 25% in the abatacept group. There was no increase in side effects in the abatacept group compared to placebo.

Abatacept was a home run in potentially delaying the transition from pre-clinical RA to clinical RA, suggesting it may alter the risk state of pre-clinical RA. This low-risk, high-reward tool will empower your patient to seize victory in the battle against rheumatoid arthritis.

Related content on theMednet.org:

What is your approach to monitoring patients referred for high titer +RF and +CCP but without active symptoms of inflammatory arthritis?

 

Back to the full list of scouting reports

CD40L Inhibitor in Sjogren’s

Team: CD40L Inhibitor in Sjögren’s, aka the “Sjögren Horse”

Base article: St Clair EW, Baer AN, Ng WF, et al. CD40 ligand antagonist dazodalibep in Sjögren’s disease: a randomized, double-blinded, placebo-controlled, phase 2 trial. Nat Med. 2024;30(6):1583-1592. doi:10.1038/s41591-024-03009-3

Authors: Trainees associated with the Duke Rheumatology Fellowship

  1. Jamie Lim, third year medical student
  2. Hannah Concannon, third year medical student
  3. Robyn Guo Ku, third year medical student
  4. Eric A. Wilson, MD, third year internal medicine resident
  5. Lisa Criscione-Schreiber, MD, MEd, Professor of Medicine
  6. David Leverenz, MD, MEd, Program Director

Team Overview: 

Currently, there are no approved targeted therapies for Sjögren’s disease (SjD). Clinical heterogeneity has made the search for efficacious treatments challenging; however, SjD may be gearing up for its Cinderella story with the development of the CD40 ligand antagonist, Dazodalibep (DAZ).

In St. Clair et al’s recently published phase 2 trial, patients with SjD received three infusions of IV DAZ 1500 mg or placebo every 2 weeks, followed by four additional doses every 4 weeks. Authors pre-defined 2 distinct SjD populations to pick and roll their way around previous challenges with heterogenity. Population 1 included those with high systemic disease activity (ESSDAI ≥5), while population 2 included patients with high symptom burden (ESSPRI ≥5) and limited systemic organ involvement (ESSDAI < 5).

Primary endpoints – change from baseline ESSDAI score in population 1 and change from baseline ESSPRI score in population 2 at 169 days – were achieved in both populations. In population 1, ESSDAI scores decreased significantly more (P = 0.0167) in the DAZ group (−6.3 ± 0.6) than in the placebo group (−4.1 ± 0.6). Similarly, ESSPRI scores were significantly lowered (P = 0.0002) with DAZ treatment ( −1.8 ± 0.2) compared to placebo (−0.5 ± 0.2; P = 0.0002) in population 2. In both populations, these outcomes also surpassed the minimal clinically important improvement in ESSDAI score (3-point reduction) or ESSPRI score (1-point reduction).

Team Sjögren’s Horse is hopeful that larger, phase 3 trials will show that DAZ is a slam-dunk for SjD!

Related content on theMednet.org:

What is your approach to managing sicca symptoms in patients not responding or not tolerating conservative measures, pilocarpine, and cevimeline?

What is your approach to immunomodulatory treatment in patients with Sjogren’s syndrome who have active serologies (i.e. elevated ESR, hypergammaglobulinemia, hypocomplementemia) but minimal symptoms?

 

Back to the full list of scouting reports