Clinical Response to Baricitinib in Monogenic Lupus: Real-World Evidence from a Case Series of Seven Patients.

Abstract

Background: Monogenic lupus is a rare, early-onset form of lupus caused by high-penetrance genetic variants, with diverse clinical features and a central role for type I interferon (IFN-I) in its pathogenesis. Standard treatments are lacking, but Janus kinase (JAK) inhibitors show promise, especially in refractory cases.

Objective: To assess the safety and potential therapeutic benefits of baricitinib in children with monogenic lupus, based on real-world data from a single tertiary childhood lupus clinic.

Methods: We conducted a retrospective observational study of patients with genetically confirmed monogenic treated with baricitinib between January 2023 and May 2025. Clinical, laboratory, and genetic data were analysed at baseline, six months, and the most recent follow-up. Outcomes included SLE Disease Activity Index (SLEDAI), Physician/Parent Global Assessment (GA), and daily glucocorticoid (GC) dose, and adverse events were collected.

Results: Seven patients with mutations in C1q, DNase1L3, PRKCD, and NRAS were included. All had persistent disease activity despite multiple conventional and biologic therapies. Baricitinib was introduced as adjunct therapy. All patients tolerated baricitinib well, with no serious infections or adverse events reported. By six months, all patients showed improved disease activity, with SLEDAI scores decreasing from 14.2 to 4.1 by day 90 and remaining stable, PGA improving from 5.8 to 2.5 by day 180, and reduced daily GC doses.

Conclusion: Baricitinib was well-tolerated and associated with clinical improvement in patients with treatment-refractory monogenic lupus. These findings support its potential therapeutic role and highlight the need for larger, long-term studies.