April 2025 to July 2025
Author: Antony Psarras
Neutrophil Activation Markers and Rheumatoid Arthritis Treatment Response to the JAK1/2 Inhibitor Baricitinib
Kuley et al. (10.1002/art.43042) analysed markers of neutrophil activation, calprotectin, and neutrophil extracellular traps (NETs) using ELISA in plasma from patients with RA (n = 271) and healthy controls (n = 39). For patients with RA, neutrophil activation markers were measured at baseline, 12 weeks, and 24 weeks after receiving placebo and 2 mg and 4 mg baricitinib. Whole-blood RNA analyses from multiple randomised baricitinib RA trials were performed to study neutrophil-related transcripts (n = 1,651). Baseline levels of plasma neutrophil markers were elevated in patients with RA compared to healthy controls (P < 0.001). Receiving baricitinib reduced levels of soluble calprotectin at 12 and 24 weeks, especially in patients with RA responding to treatment. Whole-blood RNA analysis revealed similar changes in the predominant neutrophil markers calprotectin and Fcα receptor I upon reception of baricitinib in three randomised clinical trials involving patients at various stages of disease-modifying therapy.
Efficacy and Safety of Sodium–Glucose Cotransporter 2 Inhibitors for the Primary Prevention of Cardiovascular, Renal Events, and Safety Outcomes in Patients With Systemic Lupus Erythematosus and Comorbid Type 2 Diabetes: A Population-Based Target Trial Emulation
Sheng Kai Ma et al. (10.1002/art.43037) performed an emulated clinical trial in an insurance-based cohort in the United States, evaluating SGLT2i versus DPP4i for primary prevention of cardiovascular, renal, and other clinical outcomes among patients with both SLE and comorbid T2DM. SGLT2i recipients had significantly lower risks of incident acute kidney injury, chronic kidney disease, end-stage renal disease, heart failure, emergency department visits, and severe sepsis. Risks of all-cause mortality, lupus nephritis, myocardial, stroke, and hospitalisations did not differ. Genital infection risk was increased, but urinary tract infection risk did not differ. No significant difference was observed for diabetic ketoacidosis risk and fractures. In this emulated clinical trial, treatment with SGLT2i, compared to DPP4i therapy, was associated with significantly reduced risks of several cardiorenal complications among patients with both SLE and T2DM.
Development of Extramusculoskeletal Manifestations in Upadacitinib-Treated Patients With Psoriatic Arthritis or Axial Spondyloarthritis
Poddubnyy et al. (10.1002/art.43069) the development of extramusculoskeletal manifestations (EMMs) among patients with psoriatic arthritis (PsA) or axial spondyloarthritis (axSpA) treated with upadacitinib 15 mg. Most patients (87.1%–99.3%) did not have a history of EMMs at baseline. In PsA, development of uveitis and IBD were low regardless of treatment or prior EMM history; rates were similar with upadacitinib 15 mg and adalimumab. In r-axSpA, development of uveitis was numerically lower (E/100 PY) in patients treated with upadacitinib 15 mg (2.8) versus placebo (7.5) and in patients with no history of uveitis (upadacitinib 15 mg 0.6; placebo 1.2) versus a history of uveitis (upadacitinib 15 mg 2.1; placebo 6.2); occurrence of IBD and psoriasis were low regardless of treatment or history. In nr-axSpA, development of uveitis was low regardless of history but was numerically lower in patients treated with upadacitinib 15 mg (0.9) versus placebo (2.1); occurrence of IBD and psoriasis were low or absent. In patients with spondyloarthritis, development of EMMs was generally low with upadacitinib 15 mg. Uveitis was numerically lower in patients treated with upadacitinib 15 mg versus placebo, and particularly in r-axSpA. Regardless of treatment in r-axSpA, having a history of uveitis appeared to predispose patients for future uveitis events.
Safety and Efficacy of Ianalumab in Patients With Sjögren’s Disease: 52-Week Results From a Randomized, Placebo-Controlled, Phase 2b Dose-Ranging Study
Dörner et al. (10.1002/art.43059) studied the 52-week safety and efficacy of ianalumab from phase 2b dose-finding study in patients with Sjögren’s disease (SjD). Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks until week 24 (treatment period (TP1). At week 24, patients on 300 mg were rerandomized to continue 300 mg or receive placebo until week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, and patients on 5 and 50 mg directly entered posttreatment safety follow-up. During TP1, 190 patients were randomized (placebo = 49, 5 mg = 47, 50 mg = 47, 300 mg = 47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81 of 90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (EULAR Sjögren’s Syndrome Disease Activity Index, EULAR Sjögren’s Syndrome Patient Reported Index, patient global assessment, and physician global assessment change from week 24: −1.45, −0.46, −4.69, and −6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Conclusion: In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favourable safety profile up to two years of follow-up.
Outcome of Patients With Lupus Nephritis Treated With an Anti-CD40 Monoclonal Antibody According to Kidney Biopsy Features
Uzzo et al. (10.1002/art.43076) investigated whether the treatment effect of the anti-CD40 monoclonal antibody BI 655064 on kidney outcomes may be modified by the presence of glomerular monocytes, a target for this drug with a well-known role in lupus nephritis (LN) pathogenesis. One hundred one renal biopsies of patients with LN enrolled in the BI 655064 trial were scored centrally. A higher BI 655064 dose (180 or 240 mg) was associated with better outcomes of UP/UC and CRR when glomerular monocytes were present in kidney biopsy samples (odds ratio [OR] 3.66 [95% confidence interval (CI) 1.09–12.3], P = 0.04; OR 4.58 [95% CI 1.24–16.9], P = 0.02). A trend toward improved eGFR was also observed in these patients (at 52 weeks, P = 0.08). Conclusion: In LN kidney biopsy samples with glomerular monocytes, high-dose BI 655064 treatment improved proteinuria at 52 weeks and resulted in a higher CRR compared to biopsy samples without glomerular monocytes. Histologic features may guide the choice of treatment for individual patients with LN.
Antony Psarras
Antony is an NIHR Academic Clinical Lecturer in Rheumatology at the University of Oxford and Oxford University Hospitals. His research interest lies in immune regulation of autoimmune rheumatic diseases, particularly systemic lupus erythematosus (SLE). He is currently focusing on high dimensional single cell multi –omic approaches to investigate the immunometabolic reprogramming in preclinical autoimmunity and SLE. Antony is a member of the EMEUNET Newsletter Sub-committee.