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?

 

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