Team: CD40L Inhibitor in Sjögren’s, aka the “Sjögren Horse”
Authors: Trainees associated with the Duke Rheumatology Fellowship
- Jamie Lim, third year medical student
- Hannah Concannon, third year medical student
- Robyn Guo Ku, third year medical student
- Eric A. Wilson, MD, third year internal medicine resident
- Lisa Criscione-Schreiber, MD, MEd, Professor of Medicine
- 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!
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