Latest ArticlesThe 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.
The analytical target profile (ATP) of analytical procedure is the key content in the development of analytical procedure and even the whole life cycle management, and the content had been explicitly proposed in the latest release of ICH Q14 and USP <1220 in 2022. The steps of establishing ATP were discussed in detail in this paper based on the latest research progress in the whole life cycle of analytical procedure at home and abroad, which included: ① Collect relevant prior knowledge. ② Determine the performance characteristics of the procedure to be reported according to the relevant critical quality attribute (CQA) to be detected. ③ Study and formulate the acceptance criteria of corresponding performance characteristics. ④ Construct the ATP of existed analytical procedure using retrospective research. ⑤ Optimize and update the primary ATP. It is expected that the paper could provide reference for methodological researchers at home and abroad and bring convenience to the development and evaluation for the whole life cycle of analytical procedure.
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.
To analyze the characteristics of roxadustat utilization in our hospital's renal division, promote rational use of roxadustat, and provide evidence for a post-marketing study.
A retrospective study was conducted. The clinical data of hospitalized patients treated with roxadustat from July 1st, 2021, to June 30th, 2022, in the renal division of our hospital were collected and analyzed.
A total of 208 medical records were included. Twenty-two (10.6%) acute kidney injury patients with anemia without the diagnosis of chronic kidney disease were treated with roxadustat. The average single dose of dialysis patients was significantly higher than that of non-dialysis patients (77.85 vs 67.37 mg, P=0.03). Sixty-three patients (30.3%) received statins, and 27 (13.0%) received sevelamer. There was significant difference between hemoglobin levels at baseline and discharge (84.80 vs 89.43 g·L-1, P=0.007). No adverse events occurred in any patient.
The tolerability and safety were good in anemia patients in the renal division who were treated with roxadustat. However, there existed a few problems, such as off-label drug use, subtherapeutic dosage and drug-drug interactions. It is necessary to strengthen the intervention of clinical pharmacists and promote the rational use of roxadustat.
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 study the effects of cinobufagin and its main component alkaloids on the contraction of colonic smooth muscle in rats in vitro and their influence on abnormal expression of channel proteins related to diarrhea in vivo.
Normal rat colon tissue samples were put into the bath to connect with the displacement tension transducer. After the tension of the colon sample was stabilized, different doses of cinobufagin and alkaloid solution were given to the colon sample, and the changes of the contraction tension of the colon sample were recorded. The rats were given the clinically equivalent dose of cinobufagin and alkaloid solution by gavage for 7 consecutive days, and the rats were killed on the 8th day. Colon tissues were taken, and the expressions of calcium channel proteins CaV1.2, CaV1.3, sodium channel proteins NHE2, NHE3, aquaporins AQP3, AQP8 were detected by Western blot to observe the changes.
The tension of colon specimen did not change significantly when the original solution was <0.10 mg (drug content<0.09 mg); 0.10~18.74 mg stock solution (0.09~16.21 mg) increased the tension of colon specimen. If the original solution was >19.25 mg (drug content >16.64 mg), the tension of colon specimen decreased. When alkaloids was <0.06 μg, the tension of colon specimen had no obvious change; 0.06~23.41 μg alkaloid increased the tension of colon specimen. When alkaloids was >24.03 μg, the tension of colon specimen decreased. Compared with the normal group, the sodium channel proteins NHE2, NHE3 and aquaporins AQP3, AQP8 in the cinobufotalin group decreased significantly (P<0.05), while the calcium channel protein CaV1.2 increased significantly (P<0.05). Sodium channel protein NHE3 and aquaporin AQP3 were significantly decreased in the alkaloid group (P<0.05). There was no significant difference in the expression of other proteins (P>0.05).
In the study of diarrhea mechanism, the results of colon tension test in vitro showed that a certain dose of cinobufagin could promote intestinal peristalsis and increase the incidence of diarrhea, and it could inhibit intestinal peristalsis when the dosage was higher than a certain level. The detection results of diarrhea-related proteins in the colon showed that the administration of cinobufotalin and alkaloid solution would cause changes in diarrhea-related channel proteins, and the number of alkaloid solutions that had significant effects on channel proteins was less than that of the original solution, suggesting that there were other components in the purgative component besides the alkaloids.
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.
With the rising of investigational new drugs in clinical trials, the risk of adverse events is increasing as many aspects of the innovation medicine need to be explored. The first-in-human clinical trial (FIH) was retrieved in PubMed from January 1, 2009 to October 31, 2022. The types of drugs and the proportion of adverse drug reactions (ADRs) were analyzed. The number of innovative drugs in FIH during 2021-2022 was 37.4% of the number during 2009-2020. In terms of large molecule drugs, the proportion of ADRs reported in the period 2021-2022 is higher than the proportion in 2009-2020 (15.63% vs 12.66%). Importantly, the proportion of monoclonal antibodies with ADRs in 2021-2022 was also higher than that in 2009-2020 (27.59% vs 11.32%). Strengthen risk awareness and the risk of acute insight play significant important role in early warning and prevention of adverse events in FIH. At the same time, the key elements of emergency management and principles of emergency treatment are the essential cores of the entire emergency management strategy. It is crucial to formulate a feasible emergency management strategy which is worth exploring. The potential risk factors in FIH, the common adverse events of innovative drugs, the key elements of first aid management and the principles of first aid management are expounded on how to realize emergency management strategies.
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 analyze all clinical trials of ankylosing spondylitis (AS) up to December 31, 2022, so as to provide information reference for clinical studies related to AS drug treatment.
The website ClinicalTrials.gov was searched, then the items of the retrieved trials were described and analyzed.
There were 392 clinical trials of AS, with 59 countries/regions participating in the world, and the top three were the United States, China, and Germany. The primary objective of the trials was treatment (n=187), followed by prevention (n=9). Nearly two-thirds of the trials excluded children, and 97% of the trials were not gender restricted. Most studies were designed to be randomized, parallel-assigned, and unblinded. The largest number of interventional trials involved biological agents (n=201), followed by chemical agents (n=65), and a small number of trials (n=3) also investigated the therapeutic effects of stem cells.
Most of the clinical trials of AS registered on ClinicalTrials.gov are randomized, parallel-assigned, unblinded interventional trials based on therapeutic purposes. The participating countries and sponsors are mostly in the United States, and a majority of the trials are funded by pharmaceutical companies. At the same time, new biological agents targeting different targets have gradually become the mainstream, bringing new opportunities for the treatment of AS.
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