Volume 6, Issue 2

Background and Objectives Biologic therapy has been used for Behçet’s Syndrome after first-line immunomodulation, but in the absence of high-quality evidence or predictive biomarkers. BIO-BEHÇET’S was a randomized controlled clinical trial to compare the two most widely used biologics for Behçet’s Syndrome at that time, infliximab versus interferon-α2a, and identify potential biomarkers for response. Methods A total of 79 patients with active Behçet’s Syndrome were randomized to either infliximab (REMICADE) or interferon-α2a (ROFERON) according to the UK national treatment pathway, and follow-up with symptom-directed examination undertaken at Weeks 12 and 24. The head-to-head trial included an exploratory analysis on the potential role of single nucleotide polymorphisms (SNPs) and urinary metabolomic to act as biomarkers for drug response. Genotypic analysis was performed to determine whether four SNPs in IFNL3 and IFNL4 – selected based on known effects – impacted primary and secondary outcomes. For metabolomic analyses, urine samples were analyzed by nuclear magnetic resonance spectroscopy and principal component analysis. Results Genetic data suggested potential association between outcomes and carriage of rs4803221 or rs7248668 variants in the IFNL3 (IL-28B) gene locus for interferon-α2a patients; however, with the relatively small sample, statistical significance was lost when corrected for multiple testing. Metabolomic analysis identified potential markers of metabolic response to infliximab. Conclusion BIO-BEHÇET’S suggests there is potential for a novel metabolomic biomarker that can identify response to infliximab in patients with Behçet’s Syndrome. Further work will characterize the appropriate metabolite (s) from existing samples to inform future prospective trials to study this in more detail clinically.

Background and Objectives No prior studies have directly compared sirolimus with the standard of care (SoC) for lupus nephritis (LN) patients. This study aimed to compare the efficacy and safety of sirolimus with mycophenolate mofetil (MMF) for the treatment of LN. Methods A real-world cohort study based on the Chinese SLE Treatment and Research (CSTAR) registry was conducted. Patients with active LN who were prescribed either sirolimus or MMF were enrolled. Propensity score matching was applied to ensure comparable baseline disease conditions. SLE disease activity indices, serological parameters, steroid doses, renal efficacy, and adverse events were evaluated at 3-month, 6-month, and 12-month follow-ups. Results Data from 53 patients in each group were analyzed. Sirolimus demonstrated clinical effectiveness comparable to MMF, as evidenced by similar rates of lupus nephritis remission and lupus low disease activity state (LLDAS) /remission or a clinical response (reduction of SLE Disease Activity Index 2000 [SLEDAI-2K] ≥4 and increase in physician’s global assessment [PhGA] < 0.3), as well as changes in 24-hour urine protein level, SLEDAI-2K score, PhGA score, and steroid tapering effect ( P ≥ 0.05 at all follow-up timepoints). Notably, sirolimus group exhibited greater improvements in complement levels compared to MMF group at 3, 6, and 12 months. Ten adverse events in sirolimus group and one in MMF group were reported, with no severe adverse events. Conclusion Sirolimus demonstrated comparable efficacy to MMF in the treatment of LN and glucocorticoid tapering, with additional benefits in serological improvement. Furthermore, sirolimus was well tolerated in LN patients, supporting its potential as a therapeutic option for LN.

Background and Objectives Pulmonary arterial hypertension (PAH) is a life-threatening condition that requires optimized medical therapy to maintain a low-risk profile. This study assessed the effects of initial PAH-specific combination therapy with tadalafil/sildenafil on clinical and functional outcomes in a real-world setting. Methods We conducted a multicenter retrospective study of 85 patients diagnosed with connective tissue disease-associated PAH (CTD-PAH) via right heart catheterization from 2009 to 2023. Data on treatment regimens and efficacy measures, including 6-min walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenicity 2 (sST2), World Health Organization (WHO) functional class, risk stratification, treat-to-target status and survival, were collected. Results Patients receiving initial combination therapy with endothelin receptor antagonists (ERAs) and phosphodiesterase-5 inhibitors showed varied improvements. The tadalafil plus ERAs combination significantly reduced NT-pro BNP levels and improved risk status ( P < 0.05). Notable enhancements in 6MWD, soluble ST2, and WHO functional class were observed in the tadalafil plus ERA group ( P < 0.001), but not in the sildenafil group ( P > 0.05). Additionally, 1-year treat-to-target rates were higher in the tadalafil plus ERA group (73.5%) than in the sildenafil group (45.6%, P = 0.005). Conclusion These findings suggest that tadalafil combined with ERAs leads to better improvements in exercise capacity, functional class, and treatment goals compared to sildenafil-based regimens, offering valuable insights for optimizing CTD-PAH treatment.

Background and Objectives The latest prevalence data for rheumatoid arthritis (RA) is essential for effective disease control and management. Although numerous studies examine the global burden of RA, recent data specific to China has been lacking. The aim of this study is to evaluate the variations of RA burden in mainland China from 1990 to 2021 utilizing data from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) study 2021. Methods We conducted a retrospective analysis of RA burden in China based on the GBD 2021 study. We collected data on RA prevalence, incidence, and disability adjusted life years in China from 1990 to 2021, then calculated the estimated annual percentage change (EAPC) to summarize the overall trends. Results In 2021, the total numbers of prevalent cases, incident cases, and disability-adjusted life years (DALYs) for RA in China were 4,755,500, 247,300, and 833,800, respectively; From 1990 to 2021, the rates of incidence, prevalence, and DALYs of RA showed an increasing trend, with EAPCs of 0.61, 0.59, and 0.17, respectively. Throughout this period, the RA burden was notably higher in females than in males. In 2021, RA incidence rates among individuals aged 15–44, 45–59, and 60–85+ followed an approximate 1∶1∶1 ratio. Projections using the Bayesian Age-Period-Cohort (BAPC) model indicated that by 2045, compared to 2021, the total incident cases, prevalent cases, and DALYs of RA in China are expected to increase by 15.7%, 13.2%, and 4.2%, respectively. Conclusion Over the past 32 years, the RA burden in China had continued to increase, and is expected to rise substantially over the next decade. Therefore, it is necessary to strengthen the prevention and management of RA, with priority given to the female population and young patients.