Tofacitinib versus thalidomide for mucocutaneous lesions of systemic lupus erythematosus: A real-world CSTAR cohort study XXVII.

OBJECTIVE: Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE. METHODS: This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points. RESULTS: At 3 and 6 months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group. CONCLUSIONS: Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile.

Efficacy and Safety of Risankizumab in Patients with Psoriatic Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Currently, the cause of psoriatic arthritis (PsA) is unknown, and the effectiveness of current drug treatments is unsatisfactory. In March 2019, the US Food and Drug Administration (FDA) approved risankizumab, a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, for the treatment of PsA in adults. This study aimed to conduct a meta-analysis of double-blind, randomized, placebo-controlled trials to evaluate the effectiveness and safety of risankizumab in moderate-to-severe PsA. METHODS: We conducted a thorough search of relevant databases from the establishment of the databases to October 1, 2023. We conducted a meta-analysis using Stata 12.0 and utilized I2 and Egger tests to assess heterogeneity and publication bias among the studies. Bias assessment was performed using the risk bias map and bias risk summary diagram generated by Revman5.4 software. The review protocols were registered on PROSPERO (CRD42023451894) and adhered to the preferred reporting item of system evaluation (PRISMA) guideline. RESULTS: Six randomized controlled trials (RCTs) involving 5038 patients with PsA treated with either risankizumab or placebo were included in the analysis. At 24 weeks, the risankizumab group demonstrated a significantly higher American College of Rheumatology-20 (ACR20) response rate compared to the placebo group (RR 1.760, 95% CI 1.568-1.977, P < 0.001). Additionally, the risankizumab group showed a significantly higher Minimal Disease Activity (MDA) response rate compared to the placebo group (RR 1.827, 95% CI 1.048-3.184, P < 0.05). The risankizumab group also exhibited improvement in Short Form 36 Questionnaire (SF-36) score (SMD 0.51, 95% CI 0.33-0.69, P < 0.001), with significantly lower Health Assessment Questionnaire Disability Index (HAQ-DI) score (SMD - 0.27, 95% CI - 0.37 to - 0.17, P < 0.001) and higher Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score (SMD 0.27, 95% CI 0.20-0.35, P < 0.001) compared to the placebo group. Moreover, the risankizumab group had a significantly lower Psoriasis Area and Severity Index (PASI) score (SMD - 6.12, 95% CI - 10.02 to 2.23, P < 0.001). A study by Mease et al. indicated that patients receiving risankizumab generally demonstrated numerical improvements in the Leeds Enthesitis Index (LEI), although the small sample size limits the evidence. Further research is necessary to provide evidence-based guidelines. There were no significant differences in the incidence of serious adverse events (SAE) and serious treatment-emergent adverse events (STEAE) between the risankizumab and placebo groups (RR 0.76, 95% CI 0.45-1.28, P = 0.31; RR 0.99, 95% CI 0.49-1.99, P = 0.97, respectively), and the overall incidence of adverse events (AE) was not comparable (RR 1.10, 95% CI 0.63-1.94, P = 0.73). CONCLUSION: Risankizumab showed superior efficacy across multiple outcome measures compared to placebo, with no significant increase in adverse events. Our findings endorse risankizumab as an excellent treatment option for PsA, offering valuable insights for clinicians and patients when choosing appropriate therapeutic interventions. TRIAL REGISTRATION: Retrospectively registered (CRD42023451894, 16 August 2023).

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Genetically determined type 1 diabetes mellitus and risk of osteoporosis.

BACKGROUND: Observational evidence suggests that type 1 diabetes mellitus (T1DM) is associated with the risk of osteoporosis (OP). Nevertheless, it is not apparent whether these correlations indicate a causal relationship. To elucidate the causal relationship, a two-sample Mendelian randomization (MR) analysis was performed. METHODS: T1DM data was obtained from the large genome-wide association study (GWAS), in which 6683 cases and 12,173 controls from 12 European cohorts were involved. Bone mineral density (BMD) samples at four sites were extracted from the GEnetic Factors for OSteoporosis (GEFOS) consortium, including forearm (FA) (n = 8,143), femoral neck (FN) (n = 32,735), lumbar spine (LS) (n = 28,498), and heel (eBMD) (n = 426,824). The former three samples were from mixed populations and the last one was from European. Inverse variance weighting, MR-Egger, and weighted median tests were used to test the causal relationship between T1DM and OP. A series of sensitivity analyses were then conducted to verify the robustness of the results. RESULTS: Twenty-three independent SNPs were associated with FN-BMD and LS-BMD, twenty-seven were associated with FA-BMD, and thirty-one were associated with eBMD. Inverse variance-weighted estimates indicated a causal effect of T1DM on FN-BMD (odds ratio (OR) =1.033, 95 % confidence interval (CI): 1.012-1.054, p = 0.002) and LS-BMD (OR = 1.032, 95 % CI: 1.005-1.060, p = 0.022) on OP risk. Other MR methods, including weighted median and MR-Egger, calculated consistent trends. While no significant causation was found between T1DM and the other sites (FA-BMD: OR = 1.008, 95 % CI: 0.975-1.043, p = 0.632; eBMD: OR = 0.993, 95 % CI: 0.985-1.001, p = 0.106). No significant heterogeneity (except for eBMD) or horizontal pleiotropy was found for instrumental variables, suggesting these results were reliable and robust. CONCLUSIONS: This study shows a causal relationship between T1DM and the risk of some sites of OP (FN-BMD, LS-BMD), allowing for continued research to discover the clinical and experimental mechanisms of T1DM and OP. It also contributes to the recommendation if patients with T1DM need targeted care to promote bone health and timely prevention of osteoporosis.

Genetic evidence for causal effects of leukocyte counts on risk for rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by the accumulation of leukocytes and inflammatory mediators within the synovial tissue. Leukocyte counts are proposed to play a role in the pathogenesis of RA. However, the causality remains unclear. To investigate the causal relationship between various leukocytes and RA by implementing two-sample univariable Mendelian Randomization (MR) and multivariable MR. MR analysis was performed using respective genome-wide association study (GWAS) summary statistics for the exposure traits (eosinophil counts, neutrophil counts, lymphocyte counts, monocyte counts, basophil counts, and white blood cell counts) and outcome trait (RA). Summary statistics for leukocytes were extracted from the Blood Cell Consortium meta-analysis and INTERVAL studies. Public GWAS information for RA included 14,361 cases and 43,923 controls. Inverse variance weighted, weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier, and multivariable MR analyses were performed in MR analysis. Univariable MR found elevated eosinophil counts (OR 1.580, 95% CI 1.389-2.681, p = 1.30 × 10-7) significantly increased the risk of RA. Multivariable MR further confirmed that eosinophil counts were a risk factor for RA. Increased eosinophils were associated with higher risk of RA. Further elucidations of the causality and mechanisms underlying are likely to identify feasible interventions to promote RA prevention.

Chinese registry of rheumatoid arthritis (CREDIT): III. The transition of disease activity during follow-ups and predictors of achieving treatment target.

AIM: The Chinese Registry of Rheumatoid Arthritis (CREDIT) is the first nationwide multi-center prospective rheumatoid arthritis (RA) registration cohort in China. This study aimed at presenting disease activities transition during follow-ups and identifying predictors to treatment response. METHOD: Patients who had baseline, 3- and 6-month follow-up data from November 2016 to April 2018 were recruited. Then, we selected patients who did not reach remission (REM)/low disease activity (LDA) at baseline to investigate the predictors for treatment response. RESULTS: There were 979 patients included (83.00% female, mean age 51.8 and median duration 3.84 years). REM/LDA rate at baseline, 3-, and 6-month follow-up were 34.02%, 59.35% and 68.23%. Additionally, early RA has more chance to achieve targets than established RA (6 months: 59.79% vs 48.13%, P = .002). High baseline Disease Activity Score of 28 joints (DAS28) (early RA: odds ratio [OR] 1.319, P = .019; established RA: OR 1.337, P < .001), biologic disease-modifying anti-rheumatic drugs (bDMARD)/targeted synthetic DMARD combined conventional DMARD therapy (early RA: OR 9.023, P = .046) and prednisolone usage (early RA: OR 2.526, P < .001) are positively associated with Clinical Disease Assessment Index (CDAI) decreasing at 3 months. Low baseline DAS28 (REM/LDA: early RA: OR 0.650, P < .001; established RA: OR 0.612, P < .001. REM: early RA: OR 0.743, P = .021; established RA: OR 0.674, P < .001), young age (REM: early RA: OR 0.977, P = .048) and decrease of CDAI at 3 months (REM/LDA: early RA: OR 7.185, P < .001; established RA: OR 8.752, P < .001. REM: early RA: OR 5.602, P < .001; established RA: OR 4.955, P < .001) predict REM/LDA at 6 months. CONCLUSION: Disease activity decreased during follow-ups. Disease duration, baseline disease activity, age, treatment strategies, and CDAI decreasing were associated with treatment response.

Gonadotropins facilitate potential differentiation of human bone marrow mesenchymal stem cells into Leydig cells in vitro.

Infertility due to low testosterone levels has increased in recent years. This has impacted the social well-being of the patients. This study was undertaken to investigate the potential of gonadotropins in facilitating differentiation of human bone marrow mesenchymal stem cells (BMSCs) into Leydig cells in vitro. BMSCs were isolated, cultured, and their biological characteristics were observed. BMSCs were induced with gonadotropins in vitro and their ability to differentiate into Leydig cells was studied. The level of expression of 3-beta hydroxysteroid dehydrogenase (3ß-HSD) and secretion of testosterone were determined using flow cytometry and enzyme-linked immunosorbent assay, respectively, and the results were compared between the experimental and control groups. The cultured BMSCs showed a typical morphology of the fibroblast-like colony. The growth curve of cells formed an S-shape. After inducing the cells for 8-13 days, the cells in the experimental group increased in size and showed typical characteristics of Leydig cells, and the growth occurred in spindle or stellate shapes. Cells from the experimental group highly expressed 3ß-HSD, and there was a gradual increase in the number of Leydig cells. The control group did not express 3ß-HSD. The level of testosterone in the experimental group was higher than the control group (p < 0.05). Additionally, the cells in the experimental group secreted higher levels of testosterone with increased culture time. The expression of Leydig cell-specific markers in the experimental group was significantly higher (p < 0.05). With these findings, BMSCs can be considered a new approach for the treatment of patients with low androgen levels.