Latest ArticlesTo excavate and analyze signals of immune checkpoint inhibitors (ICIS) related adverse events of acute kidney injury through data mining methods based on the big data of FAERS, and to provide a reference for the safe clinical use of ICIS drugs.
Case reports were collected from April 2011 to March 2021 with immune checkpoint inhibitors (ICIS) as the first suspected drug and acute kidney injury (AKI) as the preferred term. Reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN) and multi-item gamma Poisson shrinker (MGPS) were used to study the relationship between ICIS and acute kidney injury. The incidence time, mortality and hospitalization rate of acute kidney injury were further studied.
1 528 cases of acute kidney injury were included. The proportion of people aged over 65 was the highest, reaching 65.38%. Males were about twice as large as females (64.66% vs 31.87%). Patients with chest cancer reported the most acute kidney injury (32.98%), followed by skin cancer (26.11%) and urogenital cancer (18.72%). Acute kidney injury was most reported in nivolumab monotherapy (54.78%). Cimepritimab had the strongest signal in immune checkpoint inhibitor monotherapy, which may be related to the patient population. The median onset time of acute kidney injury was 49 days in immune checkpoint inhibitor monotherapy regimens (interquartile range [IQR] 1~1 720).
The mechanism of action of immune checkpoint inhibitors differs from traditional cytotoxic and targeted drugs. The proper balance between activation and inhibition of immune molecule function is the key to a strong immune response, and sufficient attention should be given to its efficacy and safety.
Lupus nephritis (LN) is a common and serious organ damage of systemic lupus erythematosus (SLE), and is one of the main causes of death in SLE patients. Conventional medication has limited efficacy and many adverse reactions. With the continuous deepening of research on the molecular mechanism of LN, therapeutic drugs and methods targeting specific pathogenic targets are constantly emerging, attracting great attention from clinical doctors and immunologists. Based on the pathogenesis of LN, this article reviews the clinical application and progress in related clinical research of targeted therapy drugs for LN, in order to provide a basis for clinicians to more accurately diagnose and treat SLE and LN, reduce LN kidney damage, and maintain long-term remission of the disease.
Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocyte infiltration of exocrine glands, which may involve multiple systems. At present, the glandular treatment of SS is mainly localized, and the treatment regimen for systemic involvement is mainly based on those for other autoimmune diseases, and there is no approved targeted drug. In this study, we systematically reviewed the current treatment regimens for SS and summarized the drugs that are undergoing clinical trials and may be applied to SS in the future, including drugs targeting BAFF, CD40, Treg/Th17, BTK, JAK-STAT, and mesenchymal stem cells. Targeted drugs and combination therapy should be the focus of future research.
To review the application and recent research progress of phosphodiesterase 4 (PDE4) inhibitors in rheumatic autoimmune diseases.
Through a review of recent relevant literature and guidelines, we explored the latest research progress of PDE4 inhibitors in rheumatic autoimmune diseases such as psoriatic arthritis, Behçet's syndrome, rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and systemic sclerosis, focusing on their clinical efficacy, safety, and mechanisms of action.
PDE4 inhibitors demonstrated significant clinical efficacy in rheumatic autoimmune diseases, often accompanied by manageable adverse reactions like nausea and diarrhea.
PDE4 inhibitors are safe and effective drugs for treating rheumatic autoimmune illnesses and can improve the quality of life. They hold promising prospects for clinical applications.
The management of rheumatoid arthritis (RA) during the peri-conceptional period necessitates consideration of maternal disease control and its impact on fetal growth, as well as the administration of vaccinations to both mothers and infants. Currently, only tumor necrosis factor-α (TNF-α) inhibitors possess adequate empirical evidence supporting their safety during preconception and lactation periods. Discontinuation of Fc structural domain-containing TNF-α inhibitors is required in the third trimester, only certolizumab pegol stands out as a viable option throughout pregnancy. The available research data on other biological agents for RA remains insufficient to establish their safety in pregnancy. The impact of biological agents on vaccination and vaccine response, especially for live attenuated vaccines, should be considered in both mothers and infants.
Infection is a great challenge that threatens human health today. The immune system consists of cells, tissues, and molecules in the body that work together to protect against foreign pathogens, such as infections, to maintain health. Infection triggers an immune response, but dysfunction of T cells, B cells and NK cells has the potential to predispose patients to infection and reduce the clearance or suppression of pathogenic microorganisms. Since interleukin-2 (IL-2) has been shown to stimulate and up-regulate the function and number of CD4+ T cells and CD8+ T cells, it has been widely reported that IL-2 can increase anti-infective function and clinical efficacy in the treatment of a variety of chronic infectious diseases. This article reviews the possible mechanism of IL-2 in infection immunity and related clinical trials, aiming to provide a reference for the prevention and treatment of chronic infectious diseases with low dose of IL-2.
To analyze the clinical efficacy of rituximab by comparing the changes of clinical manifestations, immunological features, imaging tests and human lipopolysaccharids-binding protein (LBP) before and after rituximab treatment in patients with lupus mesenteric vasculitis (LMV).
A total of 10 patients diagnosed with secondary LMV of systemic lupus erythematosus (SLE) in the Department of Rheumatology and Immunology of Peking University People's Hospital from January 2011 to May 2023 who were treated with rituximab were enrolled. Their clinical characteristics, laboratory results, efficacy and prognosis data were analyzed, and the level of intestinal injury marker LBP before and after treatment was analyzed.
The clinical symptoms of 10 LMV patients were significantly improved after rituximab treatment, abdominal pain lessened or disappeared (P=0.003), gastrointestinal wall thickening and edema alleviated or disappeared (P=0.000), intestinal obstruction/perforation relieved (P=0.025), IgG declined (P=0.032), complement 3 rebounded (P=0.047), the percentage of B lymphocytes decreased (P=0.022), and SLEDAI scores decreased (P=0.005). LMV remission rate was 100%, while the recurrence rate was 10%. LBP concentration decreased significantly after rituximab treatment [(8.94±6.37) μg·mL-1 vs (2.89±3.21) μg·mL-1, P=0.04].
Rituximab combined with glucocorticoid therapy can effectively improve serum immunological features, imaging tests and intestinal damage in patients with lupus mesenteric vasculitis, and has good clinical effect. Human lipopolysaccharide-binding protein is expected to be an index for evaluating and monitoring intestinal injury in lupus mesenteric vasculitis.
To explore the effect of Qingre Lishi Huoxue method combined with iguratimod tablets on bone metabolism and observe the clinical efficacy in treating primary rheumatoid arthritis.
Ninety patients with RA of damp-heat paralysis type who were treated for the first time in the rheumatology department of our hospital from June 2021 to December 2022 were selected and randomly divided into two groups, 45 cases in each group. The control group was treated with iguratimod tablets, while the treatment group was treated with Qingre Lishi Huoxue method in addition. At 12 weeks of treatment, the effective rate of TCM syndromes in the two groups was observed, and the changes of BMD and bone metabolism levels were measured, including serum osteocalcin (BGP), type I procollagen N-terminal propeptide (PINP), β-collagen special series (β-CTX), 25-hydroxy vitamin D (25(OH)D), and parathyroid hormone (PTH); at the same time, disease activity indicators were evaluated, including joint swelling number (SJC), tenderness number (TJC), the patient global assessment (PGA), disease activity index 28-CRP (DAS28-CRP), anti-cyclic citrullinated peptide antibody (ACPA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and safety indicators such as blood and urine routine, liver and kidney function, and ECG.
At 12 weeks of treatment, the effective rate of TCM syndromes in the treatment group was significantly higher than that in the control group (χ2=5.07, P<0.05). The BMD level of the right forearm in both the treatment group and the control group was significantly improved compared with that before treatment (P<0.05). The BMD levels of the lumbar spine and left hip in the two groups were improved compared with those before treatment, but the difference was not statistically significant (P>0.05). The BMD level of the right forearm in the treatment group was significantly higher than that in the control group (P<0.05). The bone metabolism levels in the treatment group were significantly improved compared with those before treatment (P<0.05), however, for the control group only the levels of BGP and 25(OH)D were improved compared with those before treatment. The efficacy evaluation indexes in the treatment group were significantly improved compared with those before treatment (P<0.05), while in the control group, only TJC and ACPA were significantly decreased compared with those before treatment (P<0.05). The levels of ESR and CRP in the treatment group were significantly lower than those in the control group (P<0.05). Comparison of safety indicators showed that neither group experienced significant adverse reactions such as heart, liver, and kidney dysfunction or severe infections.
Qingre Lishi Huoxue method combined with iguratimod tablets can improve bone metabolism, promote bone formation, inhibit bone resorption, increase bone density, prevent and delay osteoporosis and even fractures while controlling RA disease and reducing inflammatory indicators, improve joint function, and improve the quality of life of patients, with good tolerance and safety.
To observe the adverse reactions of thalidomide in the reproductive system, such as menstrual disorders and ovarian reserve function, in women of childbearing age with rheumatic immune diseases and provide references for the safety of clinical medication.
A retrospective analysis was conducted on female patients aged 18~45 years with complete data who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University and received thalidomide treatment from January 2018 to June 2023. The occurrence of menstrual disorders and levels of anti-Müllerian hormone (AMH) during thalidomide use were observed to analyze the potential adverse effects on reproductive system function and risk factors.
A total of 214 patients were included, with an average age of (34.81±6.45) years. The dosage of thalidomide ranged from 25 to 75 mg·d-1, with a cumulative dose ranging from 750 to 81 000 mg. The treatment duration ranged from 1 to 36 months. The rate of menstrual cycle disorders in women of childbearing age during thalidomide use was as high as 79.59%, with a rate of amenorrhea of 18.37%. Univariate analysis showed a significant correlation between cumulative dose, treatment duration, and decreased AMH levels (P<0.05). The menstrual recovery rate after discontinuation of thalidomide was 62.5% in patients with AMH ≤ 2 ng·mL-1, while it was 100% in patients with AMH>2 ng·mL-1. The menstrual recovery time for both groups was within 1~2 months. Pearson correlation analysis showed a negative linear correlation between AMH and daily dose of thalidomide (r=-0.522, P<0.05), cumulative dose (r=-0.807, P<0.05), and treatment duration (r=-0.761, P<0.05). Cox regression analysis showed that a cumulative dose of thalidomide >9 g was an independent risk factor for adverse events in the reproductive system (HR=19.014, P<0.001).
The incidence of menstrual disorders and decreased ovarian reserve function is high in women of childbearing age using thalidomide. Therefore, the reproductive risks should be evaluated, and ovarian reserve function should be monitored to prevent ovarian dysfunction leading to amenorrhea and affecting fertility and quality of life.
To evaluate the possibility of hepatitis B reactivation in patients with hepatitis B infection-associated rheumatoid arthritis who were treated with TNF inhibitors.
Literature search method and inclusion and exclusion criteria were established, then the databases were searched, literature meeting inclusion criteria were collected, and relevant data was extracted for analysis.
A total of 14 studies involving 534 HBV-related rheumatoid arthritis patients were included. The overall comprehensive hepatitis B reactivation rate was 0.017 5 [95%CI: 0.005 4, 0.034 0], I2=67%, P<0.01. In the subgroup analysis, the reactivation rate of hepatitis B using glucocorticoids was 0.067 6 [95%CI: 0.039 6, 0.101 2], I2=89%, P<0.01. The reactivation rate of hepatitis B without glucocorticoids was 0.045 7 [95%CI: 0.016 4, 0.084 6], I2=69%, P<0.01.
The employment of TNF inhibitors in patients with HBV-related rheumatoid arthritis had a certain rate of hepatitis B reactivation. In the subgroup analysis, the rate of hepatitis B reactivation in the target population showed a distinct regional distribution, and the rate of hepatitis B reactivation in the glucocorticoid-using subgroup was higher than that in the glucocorticoid-not subgroup.
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