Background/Purpose: The exact role of interleukin-17 in systemic sclerosis (SSc) has not been established. This trial assessed the pharmacokinetics (PK), safety, and efficacy of multiple subcutaneous doses of brodalumab 210 mg administered every 2 weeks in Japanese SSc patients with moderate-to-severe skin thickening.

Methods: In this open-label, multiple-dose, phase 1 study, eligible patients received 52‑week treatment. Primary endpoints were PK and safety. Secondary endpoints included change from baseline in the modified Rodnan Skin Score (mRSS) and Composite Response Index in Systemic Sclerosis (CRISS) score. Exploratory endpoints included lymphocyte subset testing.

Results: Eight patients were enrolled. Mean (SD) age was 53.6 (10.6) years, total mRSS was 23.1 (5.1), and SSc disease duration was 2.2 (1.9) years. Mean (SD) serum brodalumab trough concentration increased to 21.8 (16.7) μg/mL at week 2 and remained almost constant at week 52. Drug-related treatment-emergent adverse events were observed in three patients: oral candidiasis (n=3), vulvovaginal candidiasis (n=1), and arthralgia (n=1). A rapid and significant decrease in mRSS was observed as early as week 4 (p< 0.005), which continued until week 52 (p< 0.0001). At week 52, all patients achieved a CRISS score ≥0.6. The Th17/Treg balance showed a significant sustained Treg dominance over 52 weeks (p< 0.05). The significant decrease in the number of immunoglobulin G⁺ class-switched memory B cells and plasmablasts (p< 0.01) was accompanied by a significant increase in the number of transitional B cells (p< 0.05) by week 52.

Conclusion: Brodalumab demonstrated a rapid, sustained, and significant decrease in mRSS over 52 weeks in Japanese SSc patients with moderate-to-severe skin thickening, which could be attributed to its direct effects on fibroblasts and indirect effects via impacts on B and T cell subsets.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/pharmacokinetics-safety-and-efficacy-of-subcutaneous-brodalumab-for-systemic-sclerosis-with-moderate-to-severe-skin-thickening-a-single-arm-open-label-multi-dose-phase-1-trial/