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?

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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?

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