Background: Systemic lupus erythematosus (SLE)-associated hepatitis ("lupus hepatitis") was one of the most frequent causes of liver function abnormalities in patients with SLE. Lupus hepatitis (LH) is commonly treated with conventional treatment, including non-steroidal anti-inflammatory drugs, corticosteroids, and immunomodulators. However, in refractory cases, other treatment options may be required.Methodology: We report the case of a patient with lupus hepatitis refractory to both conventional therapy and belimumab who was successfully treated with telitacicept, a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor.Literature review was performed on PubMed search forum.Result: The specific search term was "telitacicept", 23 papers were searched, among them 10 case reports/series articles reporting telitacicept treatment were elected.Apart from our literature reporting the effectiveness of telitacicept in treating LH, there is no report on it in treating LH.Conclusion: This case suggests that telitacicept should be an effective and safe treatment for LH refractory, even to those who failed to belimumab based on the standard treatment, and can reduce the dosage of glucocorticoids.However, further investigations, particularly prospective randomized controlled trials, are warranted to verify our findings and ensure patient safety.

BACKGROUND:Pulmonary embolism (PE) is a severe and acute cardiovascular syndrome with high mortality among patients with autoimmune inflammatory rheumatic diseases (AIIRDs). Accurate prediction and timely intervention play a pivotal role in enhancing survival rates. However, there is a notable scarcity of practical early prediction and risk assessment systems of PE in patients with AIIRD. METHODS:In the training cohort, 60 AIIRD with PE cases and 180 age-, gender-, and disease-matched AIIRD non-PE cases were identified from 7254 AIIRD cases in Tongji Hospital from 2014 to 2022. Univariable logistic regression (LR) and least absolute shrinkage and selection operator (LASSO) were used to select the clinical features for further training with machine learning (ML) methods, including random forest (RF), support vector machines (SVM), neural network (NN), logistic regression (LR), gradient boosted decision tree (GBDT), classification and regression trees (CART), and C5.0 models. The performances of these models were subsequently validated using a multicenter validation cohort. RESULTS:In the training cohort, 24 and 13 clinical features were selected by univariable LR and LASSO strategies, respectively. The five ML models (RF, SVM, NN, LR, and GBDT) showed promising performances, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.962-1.000 in the training cohort and 0.969-0.999 in the validation cohort. CART and C5.0 models achieved AUCs of 0.850 and 0.932, respectively, in the training cohort. Using D-dimer as a pre-screening index, the refined C5.0 model achieved an AUC exceeding 0.948 in the training cohort and an AUC above 0.925 in the validation cohort. These results markedly outperformed the use of D-dimer levels alone. CONCLUSION:ML-based models are proven to be precise for predicting the onset of PE in patients with AIIRD exhibiting clinical suspicion of PE. TRIAL REGISTRATION:Chictr.org.cn : ChiCTR2200059599.

The association between diabetes mellitus (DM) and risk of osteoarthritis (OA) is inconsistent based on published observational studies. This study aimed to conduct a two-sample Mendelian randomization (MR) analysis to explore the causal link between glycated hemoglobin (HbA1c) level and OA risk. Genome-wide association studies (GWAS) summary statistics were obtained from the publicly available Integrative Epidemiology Unit (IEU) OpenGWAS database. A series of screening processes were performed to select qualified instrumental single-nucleotide polymorphisms (SNPs) strongly related to exposure. The inverse-variance-weighted method, weighted-median method, and MR–Egger method were performed to ensure robust and reliable results. The MR–Egger intercept test, Cochran’s Q test, and the leave-one-out sensitivity analysis were utilized to assess the horizontal pleiotropy, heterogeneities, and stability of these genetic variants for OA. Odds ratio (OR) and 95

Objective This study aimed to determine the effect and safety of telitacicept, an antagonist of BLyS/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE) who failed treatment with belimumab and in whom telitacicept was administered combined with conventional therapy. A review of published reports on telitacicept for SLE was also performed. Methods A retrospective review was performed of the records of patients seen in the Department of Rheumatology at the Wuhan Hospital of Chinese and Western Medicine, Wuhan, China, with refractory SLE who had failed treatment with belimumab. The terms “systemic lupus erythematosus” and “telitacicept” were used to identify patients reported in the English medical literature. Results Identified were 14 refractory SLE patients, 3 males (21%) and 11 females (79%). The median age was 32.9 years. The median disease duration was 8.9 years. Patients in this cohort received telitacicept for an average of 34.1 weeks (17–62 weeks) and the total SLE responder index 4 (SRI-4) response rate was 78.9% ( n = 11). The mean SLE Disease Activity Index (SLEDAI) score declined from 8.6 at baseline (95% confidence interval [CI] 7.87–9.28) to 4.29 at the endpoint (95% CI 3.4–5.16). All cases (100%) had hypocomplementemia at baseline, and 7 cases (50%) reported normal C3 and C4 levels at the follow-up endpoint. At the observation endpoint, the 24‑h urinary protein value of the 13 cases with proteinuria (baseline 24‑h urinary protein > 0.5 g/d) displayed a reduction, and 3 values turned negative. Although some patients had low serum total immunoglobulin (Ig) levels, subnormal IgG levels, and absolute counts of peripheral blood lymphocytes after treatment, no serious infection was reported. One case was refractory lupus hepatitis confirmed by liver pathology, and upon change to change to telitacicept treatment, liver function returned to normal. Conclusion This is the first case series in SLE patients who accepted telitacicept treatment after failed treatment with belimumab. Our case series and review of the literature show that telitacicept combined with the original standard treatment may significantly improve disease activity while reducing prednisone use. No major safety issues were seen in this group of patients. Telitacicept may be a promising drug for the treatment of refractory lupus hepatitis.

Rationale: Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple systems. Central nervous system (CNS) demyelinating syndromes are one of the rare neurological manifestations of SLE, whose diagnosis, treatment, and prognosis are rarely reported. Belimumab, an anti-BAFF monoclonal antibody, has been approved by the FDA for the treatment of SLE. We aimed to assess the effects of belimumab on demyelinating syndromes in patients with SLE. Patient concerns: Six patients with demyelination in SLE who were managed at Traditional Chinese and Western Medicine Hospital of Wuhan from March 2021 to March 2023, who received belimumab ≥ 5 times, were enrolled. Ten age- and sex-matched SLE patients with noutneuropsychiatric systemic lupus erythematosus (NPSLE) and normal controls were recruited to analyze potential biomarkers. Diagnoses: All patients were diagnosed with SLE based on the 2012 Systemic Lupus International Collaborating Clinics (SLICC) SLE classification criteria or the 2019 EULAR/ACR classification criteria. All SLE patients with CNS demyelinating syndromes were diagnosed by rheumatologists, neurologists, and radiologists. Interventions: These patients were administered belimumab combined with standard treatment (glucocorticoids and/or antimalarials and/or immunosuppressants [cyclophosphamide, mycophenolate, methotrexate, etc.]). Outcomes: Six patients were included in the study (100% female, mean [range] age at first demyelinating episode 42.8 [24–66] years). The most common extra-CNS features in these patients were rash, arthritis, alopecia, leukopenia, and hypocomplementemia. After Belimumab treatment, 3 of 6 (50%) patients achieved complete remission with decreased prednisone, 2 improvements, and 1 relapsed with uterine surgery. Compared with the baseline, 3.5 months post belimumab treatment, the disease activity score SLEDAI (21.5–5.5, P < .001), C3 and C4 increased, and extra-CNS symptoms improved rapidly. Moreover, The expression of lupus susceptibility gene PBX1 in CD19+ B cells was lowest in demyelinating syndromes with lupus patients compared with healthy volunteers and lupus patients without demyelination, and its relative expression negatively correlated with SLE disease activity. Conclusion: Belimumab could be an effective and safe option for the treatment of SLE demyelination. In addition, PBX1 might be a potential biomarker for the clinical diagnosis of lupus in patients with demyelinating syndrome.

Abstract Novel Coronavirus disease 2019 (COVID‐19) has spread rapidly around the world. Individuals with immune dysregulation and/or on immunosuppressive therapy, such as rheumatic patients, are considered at greater risk for infections. However, the risks of patients with each subcategory of rheumatic diseases have not been reported. Here, we identified 100 rheumatic patients from 18,786 COVID‐19 patients hospitalized in 23 centers affiliated to Hubei COVID‐19 Rheumatology Alliance between January 1 and April 1, 2020. Demographic information, medical history, length of hospital stay, classification of disease severity, symptoms and signs, laboratory tests, disease outcome, computed tomography, and treatments information were collected. Compared to gout and ankylosing spondylitis (AS) patients, patients with connective tissue disease (CTD) tend to be more severe after COVID‐19 infection (p = 0.081). CTD patients also had lower lymphocyte counts, hemoglobin, and platelet counts (p values were 0.033, < 0.001, and 0.071, respectively). Hydroxychloroquine therapy and low‐ to medium‐dose glucocorticoids before COVID‐19 diagnosis reduced the progression of COVID‐19 to severe/critical conditions (p = 0.001 for hydroxychloroquine; p = 0.006 for glucocorticoids). Our data suggests that COVID‐19 in CTD patients may be more severe compared to patients with AS or gout.

BackgroundIn the ongoing COVID-19 pandemic, the susceptibility of patients with rheumatic diseases to COVID-19 remains unclear. We aimed to investigate susceptibility to COVID-19 in patients with autoimmune rheumatic diseases during the ongoing COVID-19 pandemic.MethodsWe did a multicentre retrospective study of patients with autoimmune rheumatic diseases in Hubei province, the epicentre of the COVID-19 outbreak in China. Patients with rheumatic diseases were contacted through an automated telephone-based survey to investigate their susceptibility to COVID-19. Data about COVID-19 exposure or diagnosis were collected. Families with a documented history of COVID-19 exposure, as defined by having at least one family member diagnosed with COVID-19, were followed up by medical professionals to obtain detailed information, including sex, age, smoking history, past medical history, use of medications, and information related to COVID-19.FindingsBetween March 20 and March 30, 2020, 6228 patients with autoimmune rheumatic diseases were included in the study. The overall rate of COVID-19 in patients with an autoimmune rheumatic disease in our study population was 0·43% (27 of 6228 patients). We identified 42 families in which COVID-19 was diagnosed between Dec 20, 2019, and March 20, 2020, in either patients with a rheumatic disease or in a family member residing at the same physical address during the outbreak. Within these 42 families, COVID-19 was diagnosed in 27 (63%) of 43 patients with a rheumatic disease and in 28 (34%) of 83 of their family members with no rheumatic disease (adjusted odds ratio [OR] 2·68 [95% CI 1·14–6·27]; p=0·023). Patients with rheumatic disease who were taking hydroxychloroquine had a lower risk of COVID-19 infection than patients taking other disease-modifying anti-rheumatic drugs (OR 0·09 [95% CI 0·01–0·94]; p=0·044). Additionally, the risk of COVID-19 was increased with age (adjusted OR 1·04 [95%CI 1·01–1·06]; p=0·0081).InterpretationPatients with autoimmune rheumatic disease might be more susceptible to COVID-19 infection than the general population.FundingNational Natural Science Foundation of China and the Tongji Hospital Clinical Research Flagship Program.

BackgroundAn outbreak of coronavirus disease 2019 (COVID-19) started in December, 2019. The epicentre, Wuhan in Hubei Province, was in lockdown. From Jan 23, 2020, most hospitals in Wuhan only focused on patients with COVID-19, and patients with chronic diseases could not visit their physicians in clinic and had no access to prescriptions. Smart System of Disease Management (SSDM) is a series of mobile applications for chronic disease management that includes both patient and physician interfaces. After training in clinic, patients regularly do a disease activity assessment, and input data from lab tests as well as their medication. The data is then synchronised to the mobile of the responsible physician. The physician can then do an online consultation and renew prescriptions on the basis of real-time data from his or her patients. We aimed to establish the feasibility and effects of SSDM in maintaining effective interactions between patients and physicians in Hubei province during the COVID-19 epidemic period.MethodsBased on the SSDM database, we did a multicentre retrospective cohort study of patients with rheumatic disease in Hubei province in China. SSDM had been widely used across China since 2015. To study the influence of interruption of routine care by the COVID-19 epidemic for patients with rheumatic disease, we included patients registered with SSDM from Hubei Province. Data on patient disease activities, online consultations, and prescription refilling, as well as surveys on satisfaction about the online service were extracted from Jan 23, 2020 to Feb 27, 2020, acting as the study group, and data from the same period during 2018 and 2019 were also extracted as a control. Inclusion criteria included a confirmed diagnosis of rheumatic disease and disease duration of at least 3 months. Patients were excluded from the study if they declined participation or discontinued before completion of the survey. For patients with rheumatoid arthritis, achieving a disease activity score with 28 joints (DAS28) of less than 3·2 was considered to be a treat-to-target (T2T) status. For patients with systemic lupus erythematosus, a disease activity index-2000 (SLESAI-2K) score of less than 4 was the main target of the lupus low disease-activity state (LLDAS). We compared the T2T and LLDAS prevalence during the epidemic period of 2020 with that of 2018 and 2019. All statistical analyses were done with Python version 3.7.4. We used descriptive and frequency statistics (percentage) to describe baseline demographic information and clinical information. Comparison of ratio variables between two groups was done with a χ2 test.FindingsBy Feb 27, 2020, a total of 173 560 adult patients (46 861 [27%] men and 126 699 [73%] women) with rheumatic disease from 860 hospitals across China registered and routinely used SSDM since 2015. Patients were encouraged to upload their data and do a disease activity self-assessment every 1–3 months. 10 441 (6%) of 173 560 patients (3237 [31%] with rheumatoid arthritis and 1566 [15%] with systemic lupus erythematosus) were managed by 176 rheumatologists from 42 hospitals in Hubei province. From Jan 23, 2020 to Feb 27, 2020, 69 rheumatologists from 28 hospitals provided 1451 patients with 1692 consultations and supplied 566 (39%) of them with continued medication, which included 55 commonly used therapeutic drugs for rheumatic diseases. 247 (8%) of 3237 patients with rheumatoid arthritis during the 2020 epidemic and 350 (9%) in same period during 2018 and 2019 did the DAS28 self-assessments, and T2T was 47% in 2020 compared with 50% in 2018 and 2019, (p=0·53). 293 (19%) of 1566 patients with systemic lupus erythematosus in 2020 and 210 (16%) in 2018 and 2019 did the SLESAI-2K self-assessments, and LLDAS was 60% in 2020 compared with 47% in 2018 and 2019 (p=0·03). Surveys showed that 100% of patients were satisfied with the interactions, which prevented the risk of cross-infection and discontinuation of medication.InterpretationPatients with rheumatism can maintain accessibility to good care in the era of the COVID-19 epidemic by using SSDM for consultations and medication refills. The clinical outcomes, at least for both rheumatoid arthritis and systemic lupus erythematosus, are not compromised.FundingNone.