Glucagon-like peptide-1 receptor agonists and risk of sight-threatening retinopathy in Taiwanese population: A propensity based cohort study.

AIMS: To compare the risk of vision-threatening retinopathy between glucagon-like peptide-1 receptor agonists (GLP-1 RA) use and no use in patients with type 2 diabetes. METHODS: Using propensity score matching, we identified 27,506 pairs of GLP-1 RA users and non-users, 3904 pairs of GLP-1 RA and dipeptidyl peptidase-4 inhibitors (DPP-4i) users, 10,985 pairs of GLP-1 RA and sodium-glucose cotransporter-2 inhibitors (SGLT2i) users, 2542 pairs of GLP-1 RA and sulfonylurea, respectively, from Taiwan's National Health Insurance Research Database from January 1, 2009 to December 31, 2018. We used Cox proportional hazards models to compare the risk of vision-threatening retinopathy between GLP-1 RA use and other matched groups. RESULTS: In the matched cohorts, the time-varying exposure analysis showed that GLP-1 RA use was not associated with an increased risk of vision-threatening retinopathy compared to GLP-1 RA non-use (aHR 0.96, 95 % CI 0.89-1.03). New-user and active-comparator analyses showed that GLP-1 RA was associated with a significantly lower risk of vision-threatening retinopathy than DPP-4i (aHR 0.8, 95 % CI 0.66-0.97) but had no significant association with this risk compared to SGLT2i (aHR 1.09, 95 % CI 0.96-1.24) or sulfonylureas (aHR 0.79, 95 % CI 0.49-1.06). CONCLUSIONS: This nationwide cohort study showed that GLP-1 RA use was not associated with an increased risk of vision-threatening retinopathy compared to non- GLP-1 RA use, and GLP-1 RA could significantly lower the risk of vision-threatening retinopathy than DPP-4i.

Corrigendum: Risk of primary Sjogren's Syndrome following human papillomavirus infections: a nationwide population-based cohort study.

[This corrects the article DOI: 10.3389/fimmu.2022.967040.].

Abatacept versus tumor necrosis factor inhibitors on mortality and medical utilizations in the treatment of rheumatoid arthritis associated interstitial lung disease: a large-scale real-world retrospective cohort study.

Rheumatoid arthritis is a chronic inflammatory disease, and interstitial lung disease is one of the important extra-articular manifestations. There is limited evidence comparing abatacept (ABA) and tumor necrosis factor inhibitors (TNFi) regarding the risk of mortality among patients with rheumatoid arthritis associated interstitial lung disease (RA-ILD). The aim of this study is to investigate the risk of mortality in patients with RA-ILD treated with ABA compared to TNFi. This retrospective cohort study utilized TriNetX electronic health record database. We enrolled patients who were diagnosed with RA-ILD and had received a new prescription for either ABA or TNFi. Patients were categorized into two cohorts based on their initial prescription. The primary outcome was all-cause mortality, and secondary outcomes were healthcare utilizations, including hospitalization, critical care services, and mechanical ventilation. Subgroup analyses were performed on age, presence of anti-citrullinated peptide antibodies (ACPA), and cardiovascular risk. Among 34,388 RA-ILD patients, 895 were selected for each group (ABA and TNFi) following propensity score matching. The ABA group exhibited a higher all-cause mortality risk. (HR 1.296, 95% CI 1.006-1.671). Subgroup analysis showed a heightened risk of receiving mechanical ventilation in ABA-treated patients aged 18-64 years old (HR 1.853, 95% CI 1.002-3.426), and those with cardiovascular risk factors (HR 2.015, 95% CI 1.118-3.630). Another subgroup analysis indicated a higher risk of mortality among ABA-treated patients with positive-ACPA. (HR 4.138 95% CI 1.343-12.75). This real-world data research demonstrated a higher risk of all-cause mortality in RA-ILD patients treated with ABA compared to TNFi, particularly those aged 18-64 years, lacking cardiovascular risk factors, and positive-ACPA. ABA was associated with an increased risk of mechanical ventilation in patients aged 18-64 years and those with cardiovascular risk factors.

Association of maternal constipation and risk of atopic dermatitis in offspring.

Objectives: Atopic dermatitis (AD) is a chronic and relapsing dermatologic disease that can affect individuals of all ages, including children and adults. The prevalence of AD has increased dramatically over the past few decades. AD may affect children's daily activities, increase their parents' stress, and increase health expenditure. Constipation is a worldwide issue and may affect the gut microbiome. Some research has indicated that constipation might be associated with risk of atopic disease. The primary objective of this retrospective cohort study was to extend and to explore the link between maternal constipation and risk of atopic dermatitis in offspring. Methods: Using the Longitudinal Health Insurance Database, a subset of Taiwan's National Health Insurance Research Database, we identified 138,553 mothers with constipation and 138,553 matched controls between 2005 and 2016. Propensity score analysis was used matching birth year, child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and antibiotics usage, with a ratio of 1:1. Multiple Cox regression and subgroup analyses were used to estimate the adjusted hazard ratio of child AD. Results: The incidence of childhood AD was 66.17 per 1,000 person-years in constipated mothers. By adjusting child's sex, birth weight, gestational weeks, mode of delivery, maternal comorbidities, and received antibiotics, it was found that in children whose mother had constipation, there was a 1.26-fold risk of AD compared to the children of mothers without constipation (adjusted hazard ratio [aHR]: 1.26; 95% CI, 1.25-1.28). According to subgroup analyses, children in the maternal constipation group had a higher likelihood of AD irrespective of child's sex, birth weight, gestational weeks, mode of delivery, and with or without comorbidities, as well as usage of antibiotics during pregnancy. Compared to the non-constipated mothers, the aHR for the constipated mothers with laxative prescriptions <12 and ≥12 times within one year before the index date were 1.26; 95% CI, 1.24 -1.28 and 1.40; 95% CI, 1.29-1.52, respectively. Conclusion: Maternal constipation was associated with an elevated risk of AD in offspring. Clinicians should be aware of the potential link to atopic dermatitis in the children of constipation in pregnant women and should treat gut patency issues during pregnancy. More study is needed to investigate the mechanisms of maternal constipation and atopic diseases in offspring.

Endometriosis and Sjögren's syndrome: Bidirectional associations in population-based 15-year retrospective cohorts.

INTRODUCTION: Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder affecting salivary and lacrimal glands, while endometriosis involves uterine-like tissue growth outside the uterus, causing pelvic pain and infertility. Investigating their intricate relationship using real-world data is crucial due to limited research on their connection. MATERIAL AND METHODS: This population-based cohort study included patients with endometriosis and controls without endometriosis. Propensity score matching was used to balance baseline differences in demographic and clinic characteristics between the two groups. Cox proportional hazards model were used to estimate the effect of endometriosis on the risk of new-onset pSS over time. A symmetrical cohort study, including patients with pSS and propensity score-matched controls without pSS, was conducted to investigate the effect of pSS on the risk of endometriosis over time. To elaborate on the mechanisms linking endometriosis and pSS, Ingenuity Pathway Analysis was performed to identify activated pathways in eutopic endometrium from patients with endometriosis and parotid tissues from patients with pSS. RESULTS: A total of 15 947 patients with endometriosis and 15 947 propensity score-matched controls without endometriosis were included. Patients with endometriosis presented a significantly greater risk of pSS compared to non-endometriosis controls (adjusted hazard ratio, aHR = 1.57, 95% CI = 1.29-1.91, p < 0.001). In the symmetrical cohort study, which included 4906 pSS patients and 4,906 propensity score-matched controls without pSS, patients with pSS were found to be at a significantly higher risk of endometriosis compared to non-pSS controls (aHR = 1.51, 95% CI = 1.12-2.04, p = 0.012). Ingenuity Pathway Analysis showed that the underlying cellular mechanisms involved autoimmune-related pathways, including activation of dendritic cell maturation, and chronic inflammatory pathways, including the fibrosis signaling pathway. CONCLUSIONS: These findings support a bidirectional association between endometriosis and pSS, which may be driven by dendritic cell maturation and fibrosis signaling pathways.

Cataract Development Among Pediatric Patients With Uveitis.

Importance: The long-term estimated risk of development of cataracts among pediatric patients with uveitis is not clear. Objective: To describe factors associated with the development of cataracts among pediatric patients with uveitis. Design, Setting, and Participants: This cohort study used the international TriNetX database to enroll pediatric patients with and without uveitis from January 1, 2002, to December 31, 2022. The nonuveitis cohort consisted of randomly selected control patients matched by age, sex, race and ethnicity, and specific comorbidities. Exposure: Diagnosis of uveitis, identified using diagnostic codes. Main Outcomes and Measures: The primary outcome was the risk of developing cataracts among the uveitis group compared with the nonuveitis comparison group, with hazard ratios (HRs) and 95% CIs reported. Results: A total of 22 687 pediatric patients with uveitis (mean [SD] age, 10.3 [5.6] years; 54.2% male) and 22 687 comparators without uveitis (mean [SD] age, 10.3 [5.6] years; 54.5% male) were enrolled in the study. The risk of cataracts was increased among pediatric patients with uveitis up to a follow-up duration of 20 years (HR, 17.17; 95%CI, 12.90-22.80) from the index date. Subgroup analyses revealed an elevated cataract risk across age groups: 0 to 6 years (HR, 19.09; 95% CI, 10.10-36.00), 7 to 12 years (HR, 27.16; 95% CI, 15.59-47.20), and 13 to 18 years (HR, 13.39; 95% CI, 8.84-20.30); both female sex (HR, 13.76; 95% CI, 9.60-19.71) and male sex (HR, 11.97; 95% CI, 8.47-16.91); and Asian (HR, 13.80; 95% CI, 3.28-58.07), Black or African American (HR, 10.41; 95% CI, 5.60-19.36), and White (HR, 15.82; 95% CI, 11.05-22.60) race. Furthermore, increased cataract risks were also observed among those with and without a history of immunosuppressive agents (with: HR, 26.52 [95% CI, 16.75-41.90]; without: HR, 17.69 [95% CI: 11.39-27.40]), a history of steroid eye drop use (with: HR, 29.51 [95% CI, 14.56-59.70]; without: HR, 16.49 [95% CI, 11.92-22.70]), and a history of intraocular procedures (with: HR, 11.07 [95%CI, 4.42-27.71]; without: HR, 14.49 [95% CI, 10.11-20.70]). Conclusions and Relevance: In this cohort study of pediatric patients with uveitis, an elevated risk of cataracts following a uveitis diagnosis was found compared with pediatric patients without uveitis. The findings suggest that pediatric patients with uveitis should be monitored for cataract development.

Early clinical response associates with long-term outcomes with ixekizumab in radiographic axial spondyloarthritis.

BACKGROUND: The Assessment of SpondyloArthritis international Society-European Alliance of Associations for Rheumatology recommendations for axial spondyloarthritis (axSpA) management include patient assessment for biological disease-modifying antirheumatic drug (bDMARD) treatment response after at least 12 weeks of treatment. The current treat-to-target strategy for axSpA is to achieve inactive disease (ID; Axial Spondyloarthritis Disease Activity Score (ASDAS) <1.3) or at least low disease activity (LDA; 1.3≤ASDAS<2.1).To investigate the association between treatment response at week 12 and/or week 24 and attainment of the ASDAS<2.1 treat-to-target recommendation at week 52 in bDMARD-naïve patients with radiographic (r-)axSpA treated with ixekizumab (IXE). METHODS: This post hoc analysis included patients randomly assigned to IXE 80 mg every 4 weeks from COAST-V (NCT02696785), a phase 3 trial in bDMARD-naïve patients with r-axSpA. The proportion of patients who achieved ASDAS<2.1 at week 52 was measured among those who attained or not clinically important improvement (CII, ∆ASDAS≥1.1) response, and among those with ID, LDA and high or very high disease activity at week 12 and/or week 24. Non-response was assumed for missing data. RESULTS: Amongst 81 patients, 47 (58.0%) achieved ASDAS CII at week 12, with 70.2% (n=33) achieving ASDAS<2.1 at week 52. At week 24, 52 (64.2%) patients achieved ASDAS CII, with 71.2% (n=37) achieving ASDAS<2.1 at week 52. Of the 24 patients who did not achieve ASDAS CII at either week 12 or week 24, 5 (20.8%) achieved ASDAS<2.1 at week 52. CONCLUSION: This analysis reinforces the current recommendation that continuing treatment in those achieving ASDAS CII at week 12 and/or week 24 increases the likelihood of obtaining ID/LDA at week 52. TRIAL REGISTRATION NUMBER: NCT02696785.

Interleukin 23 versus interleukin 12/23 inhibitors on preventing incidental psoriatic arthritis in patients with psoriasis? A real-world comparison from the TriNetX Global Collaborative Network.

BACKGROUND: Managing psoriasis and its comorbidities, particularly psoriatic arthritis, often involves using IL-23 and IL-12/23 inhibitors. However, the comparative risk of these treatments still needs to be explored. OBJECTIVE: This study evaluates the risk of developing psoriatic arthritis in patients treated with IL23 inhibitors compared to IL-12/23 inhibitors. METHODS: This retrospective cohort study utilized data from the TriNetX, including adult patients diagnosed with psoriasis. Patients with IL-23 or IL-12/23 inhibitors treatment were included and propensity score matched. The primary outcome was the incidence of arthropathic psoriasis, analyzed using a Cox regression hazard model and Kaplan-Meier estimates. RESULTS: The study included matched cohorts of patients treated with IL-23 inhibitors (n=2,273) and IL-12/23 inhibitors (n=2,995). Cox regression analysis revealed no significant difference in the cumulative incidence of arthropathic psoriasis between the IL-23i and IL-12/23i cohorts (p = 0.812). Kaplan-Meier estimates confirmed similar cumulative incidences of arthropathic psoriasis in both cohorts over the study period. LIMITATION: Long-term follow-up studies are required to understand more of the effects of these interleukin inhibitors. CONCLUSION: No significant difference but a numerically lower risk of PsA in PsO patients treated with IL-23 inhibitors than with IL-12/23 inhibitors, underscoring their comparable efficacy in PsO management and follow-up.

Association of PCSK9 inhibitors with mortality: insights from a retrospective cohort analysis.

BACKGROUND AND AIMS: PCSK9 inhibitors are effective in reducing cardiovascular events, but their impact on all-cause mortality and medical utilization compared to statins is unclear. This study investigated PCSK9 inhibitor use and its impact on mortality and medical utilization versus statins, using TriNetX database data with up to 9 years of follow-up. METHODS AND RESULTS: This retrospective cohort study analyzed TriNetX data spanning July 1, 2015, to December 31, 2023, including 79 194 PCSK9 inhibitor users (alirocumab, evolocumab, inclisiran) and 5 437 513 statin users with hyperlipidemia. The primary outcomes were all-cause mortality and medical utilization, including hospital inpatient services, emergency department visits, critical care, and mechanical ventilation. Propensity score matching showed that PCSK9 inhibitor use was associated with a 28.3% lower risk of all-cause mortality (adjusted hazard ratio [aHR] 0.717, 95% CI: 0.673-0.763) and significant reductions in medical utilization (hospital inpatient services usage: aHR 0.692, 95% CI: 0.664-0.721; emergency department services: aHR 0.756, 95% CI: 0.726-0.788; critical care services: aHR 0.619, 95% CI: 0.578-0.664; and mechanical ventilation: aHR 0.537, 95% CI: 0.484-0.596) compared to statins. These findings were consistent across various demographics and clinical subgroups. The sensitivity analyses supported the robustness of the findings. CONCLUSION: PCSK9 inhibitors significantly reduced all-cause mortality and medical utilization compared to statins, suggesting their important role in dyslipidemia management, particularly for statin-naïve or intolerant patients. Further research, including randomized controlled trials, is needed to confirm these findings and explore the underlying mechanisms.

From psoriasis to psoriatic arthritis: epidemiological insights from a retrospective cohort study of 74,046 patients.

Introduction: To verify our hypothesis that psoriatic arthritis (PsA) is mainly genetically predetermined and distinct from psoriasis (PsO), we use the TriNetX database to investigate whether intrinsic factors outweigh externals in PsA emergence in PsO patients. Methods: We conducted three retrospective cohort studies utilizing information from the TriNetX network, whether (a) PsO patients with type 2 diabetes mellitus (DM) face an elevated risk of developing PsA compared to those without type 2 DM; (b) PsO patients who smoke face a higher risk of PsA; and (c) PsO patients with type 2 DM who smoke are more likely to develop PsA than those who do not smoke. Results: PsO patients with type 2 DM exhibited an elevated risk of developing PsA [hazard ratio (HR), 1.11; 95% CI 1.03-1.20], with the combined outcome demonstrating a heightened HR of 1.31 (95% CI 1.25-1.37). PsO patients with a smoking history exhibited an elevated risk of developing PsA (HR, 1.11; 95% CI 1.06-1.17), with the combined outcome demonstrating a heightened HR of 1.28 (95% CI 1.24-1.33). PsO patients with type 2 DM and a history of smoking were not found to be associated with an increased risk of developing PsA (HR, 1.05; 95% CI 0.92-1.20). However, the combined result revealed a higher risk of 1.15 (95% CI 1.06). Discussion: These findings suggested that intrinsic factors outweigh external factors in PsA emergence in PsO patients. Further studies may focus on genetic disparities between PsO and PsA as potential risk indicators rather than solely on phenotypic distinctions.

Real-World Assessment of Recommended COVID-19 Vaccination Waiting Period after Chemotherapy.

There is a knowledge gap concerning the proper timing for COVID-19 vaccination in cancer patients undergoing chemotherapy. We aimed to evaluate the suitability of the guidelines that recommend waiting at least three months after undergoing chemotherapy before receiving a COVID-19 vaccine. This retrospective cohort study used aggregated data from the TriNetX US Collaboratory network. Participants were grouped into two groups based on the interval between chemotherapy and vaccination. The primary outcome assessed was infection risks, including COVID-19; skin, intra-abdominal, and urinary tract infections; pneumonia; and sepsis. Secondary measures included healthcare utilization and all causes of mortality. Kaplan-Meier analysis and the Cox proportional hazard model were used to calculate the cumulative incidence and hazard ratio (HR) and 95% confidence intervals for the outcomes. The proportional hazard assumption was tested with the generalized Schoenfeld approach. Four subgroup analyses (cancer type, vaccine brand, sex, age) were conducted. Sensitivity analyses were performed to account for competing risks and explore three distinct time intervals. Patients receiving a vaccine within three months after chemotherapy had a higher risk of COVID-19 infection (HR: 1.428, 95% CI: 1.035-1.970), urinary tract infection (HR: 1.477, 95% CI: 1.083-2.014), and sepsis (HR: 1.854, 95% CI: 1.091-3.152) compared to those who adhered to the recommendations. Hospital inpatient service utilization risk was also significantly elevated for the within three months group (HR: 1.692, 95% CI: 1.354-2.115). Adhering to a three-month post-chemotherapy waiting period reduces infection and healthcare utilization risks for cancer patients receiving a COVID-19 vaccine.

Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus.

Importance: Lupus nephritis is a major complication of systemic lupus erythematosus (SLE). Randomized clinical trials have shown nephroprotective and cardioprotective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is). Objective: To investigate whether the use of SGLT2is is associated with the onset and progression of lupus nephritis and other kidney and cardiac outcomes in patients with SLE and type 2 diabetes. Design, Setting, and Participants: This multicenter cohort study used the US Collaborative Network of the TriNetX clinical data platform to identify patients with SLE and type 2 diabetes from January 1, 2015, to December 31, 2022. Data collection and analysis were conducted in September 2023. Exposures: Individuals were categorized into 2 groups by SGLT2i use or nonuse with 1:1 propensity score matching. Main Outcomes and Measures: The Kaplan-Meier method and Cox proportional hazards regression models were used to calculate the 5-year adjusted hazard ratios (AHRs) of lupus nephritis, dialysis, kidney transplant, heart failure, and mortality for the 2 groups. Results: From 31 790 eligible participants, 1775 matched pairs of SGLT2i users and nonusers (N = 3550) were selected based on propensity scores. The mean (SD) age of matched participants was 56.8 (11.6) years, and 3012 (84.8%) were women. SGLT2i users had a significantly lower risk of lupus nephritis (AHR, 0.55; 95% CI, 0.40-0.77), dialysis (AHR, 0.29; 95% CI, 0.17-0.48), kidney transplant (AHR, 0.14; 95% CI, 0.03-0.62), heart failure (AHR, 0.65; 95% CI, 0.53-0.78), and all-cause mortality (AHR, 0.35; 95% CI, 0.26-0.47) than SGLT2i nonusers. Conclusions and Relevance: In this cohort study of patients with SLE and type 2 diabetes, SGLT2i users had a significantly lower risk of lupus nephritis, dialysis, kidney transplant, heart failure, and all-cause mortality than nonusers. The findings suggest that SGLT2is may provide some nephroprotective and cardioprotective benefits.