Effectiveness of janus kinase inhibitors in relapsing giant cell arteritis in real-world clinical practice and review of the literature.

BACKGROUND: A substantial proportion of patients with giant cell arteritis (GCA) relapse despite standard therapy with glucocorticoids, methotrexate and tocilizumab. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway is involved in the pathogenesis of GCA and JAK inhibitors (JAKi) could be a therapeutic alternative. We evaluated the effectiveness of JAKi in relapsing GCA patients in a real-world setting and reviewed available literature. METHODS: Retrospective analysis of GCA patients treated with JAKi for relapsing disease at thirteen centers in Spain and one center in United States (01/2017-12/2022). Outcomes assessed included clinical remission, complete remission and safety. Clinical remission was defined as the absence of GCA signs and symptoms regardless of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values. Complete remission was defined as the absence of GCA signs and symptoms along with normal ESR and CRP values. A systematic literature search for other JAKi-treated GCA cases was conducted. RESULTS: Thirty-five patients (86% females, mean age 72.3) with relapsing GCA received JAKi therapy (baricitinib, n = 15; tofacitinib, n = 10; upadacitinib, n = 10). Before JAKi therapy, 22 (63%) patients had received conventional synthetic immunosuppressants (e.g., methotrexate), and 30 (86%) biologics (e.g., tocilizumab). After a median (IQR) follow-up of 11 (6-15.5) months, 20 (57%) patients achieved and maintained clinical remission, 16 (46%) patients achieved and maintained complete remission, and 15 (43%) patients discontinued the initial JAKi due to relapse (n = 11 [31%]) or serious adverse events (n = 4 [11%]). A literature search identified another 36 JAKi-treated GCA cases with clinical improvement reported for the majority of them. CONCLUSIONS: This real-world analysis and literature review suggest that JAKi could be effective in GCA, including in patients failing established glucocorticoid-sparing therapies such as tocilizumab and methotrexate. A phase III randomized controlled trial of upadacitinib is currently ongoing (ClinicalTrials.gov ID NCT03725202).

Factors associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus.

BACKGROUND: Pregnancies in Systemic lupus erythematosus (SLE) are considered high risk and associated with maternal and obstetric complications. OBJECTIVES: To determine the most important predictors for each of the main adverse pregnancy outcomes in SLE patients. METHODS: Patients with SLE were retrospectively analysed from 1990 to 2020. Maternal and fetal complications in pregnant women with SLE were retrieved. We compared clinical and analytical characteristics of SLE patients with adverse pregnancy outcomes to controls with SLE diagnosis without adverse pregnancy outcomes. Qualitative data were analysed by Chi-square test and Fisher's exact test. Continuous variables were analysed by using Student's t test. Multiple logistic regression was performed to determine the predictive factors for adverse pregnancy outcomes with adjustment of confounding factors. RESULTS: 135 multiparous women were included (42% with adverse pregnancy outcomes). A total of 57 pregnancies (42%) were linked to adverse outcomes. The occurrence of abortion was correlated with anti-DNAds (ß = 0.71, p = 0.04), renal involvement (ß = 0.28, p 0.03), antiphospholipid antibodies (APA) (ß = 0.29, p 0.03), erythrocyte sedimentation rate (ESR) elevation (ß = 0.81, p = 0.02) and C-reactive protein (CPR) elevation (ß = 0.91, p = 0.01). Stillbirth was also correlated with renal involvement (ß = 0.26, p = 0.04), APA (ß = 0.22, p = 0.03) and ESR elevation (ß = 0.53, p = 0.02). Preeclampsia was correlated with direct Coombs positivity (ß = 0.42, p = 0.01), serositis (ß = 0.31, p = 0.02), ESR elevation (ß = 0.52, p = 0.03) and CPR elevation (ß = 0.32, p = 0.04). Neonatal Lupus was correlated with anti-RNP (ß = 0.16, p = 0.03) and anti-Ro/SSA (ß = 0.16, p 0.02). CONCLUSIONS: The most unfavourable pregnancy outcome in women with SLE was spontaneous abortion. Renal involvement, anti-DNAds positivity, antiphospholipid antibody positivity, anti-Ro/SSA, elevated ESR and a younger age at disease onset increased the risk of pregnancy complications.