Study in focus 1: Baricitinib in auto-inflammatory type 1 interferonopathies

Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) and Aicardi-Goutieres syndrome (AGS) are monogenic auto-inflammatory disorders. They may have early onset of symptoms and have a prominent interferon (IFN) response gene signature (IGS).  Janus kinase (JAK) signal transducer and activator of transcription (STAT) pathway is the principal signal transduction pathway for IFNs. Thus Baricitinib, a specific JAK 1/2 inhibitor, was studied to treat these patients.

This study involved a total of 9 patients (5 CANDLE, 3 SAVI, and 1 AGS). They received baricitinib in the range of 8 to 12 mg. The median duration of exposure to baricitinib was 52.1 weeks. The clinical parameters, laboratory results, and dose-dependent decrease in IFN biomarkers and IGS was studied. Also, the physician’s global assessment of disease activity was assessed. A decrease from baseline was noted in CANDLE and SAVI but increased in AGS. These findings suggest that baricitinib could be a potential therapeutic agent in patients with auto-inflammatory interferonopathies.

Study in focus 2: Maternal and infant outcomes of pregnancy associated with anti-SSA/RO antibodies

Anti-SSA/RO is a serological marker used to help in the diagnosis of Sjogren’s syndrome and systemic lupus erythematosus (SLE). A meta-analysis, including 18 studies (after all exclusion) comprising 1675 patients and 1920 pregnancies was done to assess the maternal and infant outcomes with anti-SSA/RO positive pregnancies. 50% of these pregnancies had a cesarean delivery and 26% had preterm labor. Other outcomes were spontaneous abortion (5%) and termination of pregnancy (4%).

As regards fetal outcomes, 4% had perinatal death and 3% intrauterine growth retardation. Cardiac outcomes noted were congenital heart block (7%), endocardial fibroelastosis (6%), and dilated cardiomyopathy (6%). Other outcomes included 19% cutaneous neonatal lupus erythematosus, 12% hepatobiliary disease, and 16% hematological manifestations. These adverse pregnancy outcomes of women with anti-SSA/RO antibodies serve as an indicator and guide for the diagnosis and subsequent treatment of these women for better maternal and infant health.

References:

1. Kanazawa N, et al. Efficacy and safety of baricitinib in Japanese patients with autoinflammatory type I interferonopathies (NNS/CANDLE, SAVI, And AGS). Pediatr Rheumatol Online J 2023; 21(1) : 38.
2. Sheng X, Song X, Xiong Y et al. Maternal and infant outcomes of pregnancy associated with anti-SSA/RO antibodies: a systematic review and meta-analysis. Pediatr Rheumatol Online J 2023; 21(1) : 22.