Impact of telemedicine on disease activity assessment: A case-crossover study nested within a cohort of patients with systemic lupus erythematosus.

INTRODUCTION: The utilisation of telemedicine has been rapidly growing among patients with rheumatic diseases, especially following the corona virus disease 2019 pandemic. Ease and convenience appear to dominate the reasons for this growth. However, the effects of this approach in patients with systemic lupus erythematosus (SLE) are yet to be revealed. In this study, we examined the effect of telemedicine on disease activity assessment and damage scores in patients with SLE. METHODS: This case-crossover study was nested within a national prospective cohort of patients with SLE in Saudi Arabia. Patients with SLE were included if they fulfilled the Systemic Lupus International Collaborating Clinics classification criteria between March 2020 and March 2021 and were assessed at three time points with 3 months between assessments, according to the standardised protocol of this cohort. Telemedicine was conducted for the first evaluation, while in-person assessments were used at the second and third visits. The primary outcome was the difference in the SLE disease activity index 2000 (SLEDAI-2K) score. The primary analysis was conducted using the repeated measure model and adjusted for potential confounders, including demographics, medications, and changes in steroid doses. Several sensitivity analyses were conducted to mitigate selection and time-varying confounders. RESULTS: A total of 92 participants were included in this study. Most patients were females (88%), with a mean (±standard deviation [SD]) age of 36 (±13) years. The mean (±SD) disease activity scores at baseline were as follows: SLEDAI-2K, 5 (±5); SLE responder index, 3.8 (±3.5); Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index, 1 (±1). The mean difference in SLEDAI-2K score was -1.641 (95% confidence interval -2.773 to -0.510, p = 0.005*) between telemedicine and follow-up visits. The results were consistent in all sensitivity analyses. CONCLUSION: We found that telemedicine assessment was associated with a much higher disease activity score than subsequent assessments, which may suggest an overestimation of disease activity and later assessment accuracy. Cautious adoption has been suggested for SLE patients with active disease.

An Examination of Infection Incidence and Management in Systemic Lupus Erythematosus Patients: A Five-Year Review from a Saudi Arabian Center.

BACKGROUND Systemic lupus erythematosus (SLE) is a chronic autoimmune condition often associated with an increased susceptibility to infections. The infections in patients with SLE, primarily involving the skin, respiratory tract, and urinary tract, can significantly complicate disease management. This study aimed to evaluate the occurrence, management, and patient outcomes associated with infections in a group of 74 SLE patients at a single center in Saudi Arabia, spanning a 5-year period. MATERIAL AND METHODS An observational, retrospective study was conducted at the King Khalid University Hospital, Riyadh, Saudi Arabia. Patient medical records from January 2016 to December 2020 were examined. All adult SLE patients (age >14 years, as per hospital policy), confirmed by SLICC criteria, and admitted due to infections (determined by quick Sequential Organ Failure Assessment or qSOFA scores) were included in the study. RESULTS Of the 74 SLE patients studied, 79.7% were administered hydroxychloroquine. A majority (83.8%) were classified as low-risk for sepsis-associated mortality based on qSOFA scores (0-1), a fact noted by 41.9% of rheumatology fellows. The sputum cultures most frequently identified were Klebsiella pneumoniae, yeast, and Haemophilus influenzae (each accounting for 33.3% of cases). Furthermore, 4.1% of patients had extended-spectrum beta-lactamases infections, and 2.7% tested positive for COVID-19. A history of sepsis was more commonly observed among non-survivors (P=0.010). CONCLUSIONS The majority of patients were classified as low-risk for sepsis-associated mortality based on qSOFA scores, with two-thirds prescribed antibiotics within 1 h. The primary causes of death were multiorgan failure and cardiac arrest.

Functional and psychosocial impact of COVID-19 pandemic on rheumatic patients' quality of life in Saudi Arabia.

PURPOSE: The COVID-19 pandemic might add to the stressors experienced by people living with rheumatic diseases. This study aimed to examine rheumatic patients' functional and psychosocial states during the pandemic and assess its impact on their quality of life. METHODS: Our time-series study included a patient-centered electronic survey, sampling adult rheumatic patients living in Saudi Arabia at different time points from March to August 2020. Patient-reported outcomes included physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles, and pain interference domains were measured using the Patient-Reported Outcomes Measurement Information System (PROMIS-29 Profile v2.1). RESULTS: A total of 1278 respondents were enrolled. Results showed significant variation in patients' experiences. Our analyses revealed that the physical well-being of rheumatic patients was significantly impacted, and such effect was persistent over time irrespective of public health measures to control the COVID-19 outbreak. CONCLUSION: Our findings consistently demonstrated the need for psychological and social consideration to improve rheumatic patients' quality of life. Nevertheless, there is still a lot to be learned about the extent of COVID-19 impact on rheumatic patients and the implications it has on long-term disease outcomes.

Acquired low immunoglobulin levels and risk of clinically relevant infection in adult patients with systemic lupus erythematosus: a cohort study.

OBJECTIVE: Infection is a leading cause of death in the SLE population. Low immunoglobulin levels might be a potential risk for infection. We aimed to assess whether acquired low levels of any type of immunoglobulin increase the risk of clinically relevant infection in adult patients with SLE. METHODS: We compared adult SLE patients who had acquired any low immunoglobulin levels (IgA, IgM or IgG) for 2 years with patients with normal or high levels with respect to clinically relevant infection (defined as infections requiring intravenous or oral antibiotics) in a prospective cohort study. Group balance was achieved using propensity score adjustment, matching and inverse probability weighting. Primary analysis was time to event using Cox-regression modelling adjusting for potential confounders. Sensitivity analyses were conducted to examine several exposure and outcome definitions. RESULTS: Patients with hypogammaglobulinaemia had longer disease duration, more lupus nephritis history, higher proteinuria and more accumulated damage. Low IgA level was associated with increased risk of clinically relevant infection [hazard ratio (HR): 2.24, 95% CI: 1.61, 3.12] while low IgG (HR: 1.15, 95% CI: 0.84, 1.59) or low IgM (HR: 0.95, 95% CI: 0.73, 1.23) was not. Low immunoglobulin recovery in the first year was 2.5% (11), second year 8.2% (36), third year 10.1% (44) and fourth year 18.4% (80), and 60% (263) of acquired hypogammaglobulinaemia recovered over 4 years. CONCLUSION: The majority of acquired hypogammaglobulinaemia in adult patients with SLE is transient. Only low acquired IgA was associated with increased risk of infection among adult patients with SLE. Whether immunoglobulin replacement provides additional protective effect requires further investigation.

Outcomes of abdominal aortic aneurysm repair among patients with rheumatoid arthritis.

OBJECTIVE: In the present study, we compared the outcomes of elective abdominal aortic aneurysm (AAA) repair in patients with and without rheumatoid arthritis (RA) stratified by the type of surgery. METHODS: A retrospective population-based cohort study was conducted from 2003 to 2016. Linked administrative health data from Ontario, Canada were used to identify all patients aged ≥65 years who had undergone elective open or endovascular AAA repair during the study period. Patients were identified using validated procedure and billing codes and matching using propensity scores. The primary outcome was survival. The secondary outcomes were major adverse cardiovascular events (MACE)-free survival (defined as freedom from death, myocardial infarction, and stroke), reintervention, and secondary rupture. RESULTS: Of 14,816 patients undergoing elective AAA repair, a diagnosis of RA was present for 309 (2.0%). The propensity-matched cohort included 234 pairs of RA and control patients. The matched cohort was followed up for a mean ± standard deviation of 4.93 ± 3.35 years, and the median survival was 6.76 and 7.31 years for the RA and control groups, respectively. Cox regression analysis demonstrated no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. Analysis of the differences in outcomes stratified by repair approach also showed no statistically significant differences in the hazards for death, MACE, reintervention, or secondary rupture. CONCLUSIONS: We found no statistically significant differences in survival, MACE, reintervention, or secondary rupture among patients with RA undergoing elective AAA repair compared with controls. Further studies are required to evaluate the impact of comorbidities and antirheumatic medications on the outcomes of elective AAA repair.

Immunoglobulin levels in systemic lupus erythematosus: A narrative review.

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin in which interleukin (IL) 17 has been genetically and therapeutically recognised as a key player. Identification of the cellular sources and inducers of IL-17 is crucial in our understanding of the drivers of inflammation in AS. Recently, mucosal-associated invariant T (MAIT) cells have been implicated in autoimmune diseases. Their gut origin, effector phenotype and expression of multiple AS-associated genes, such as IL7R and IL23R, makes them potential contributors to the pathogenesis of AS. METHODS: Mononuclear cells from patients with AS, healthy controls (HCs) and patients with rheumatoid arthritis were isolated from blood and synovial fluid (SF). Flow cytometry was used to identify MAIT cells. Phenotype was assessed by intracellular staining for cytokines and granzyme. Function was assessed by antigen-specific stimulation using Salmonella, or antigen non-specific activation via priming with IL-7 or IL-23. RESULTS: MAIT cells were reduced in frequency in the blood of patients with AS compared with HCs, yet patients with AS had an elevated frequency IL-17A+ MAIT cells. There was an enrichment of MAIT cells in SF, which had an exaggerated IL-17 phenotype. IL-17 elevation in AS MAIT cells was dependent on priming with IL-7 but not IL-23 or antigen stimulation. The AS-associated IL7R single nucleotide polymorphism (SNP), rs11742270, had no effect on IL-7R expression or function in the experiments performed. CONCLUSIONS: This study reveals a potential role for MAIT cells in patients with AS and is the first linking IL-7 to the elevated IL-17 profile in patients through the AS-associated risk gene IL7R.

Colchicine for cardiovascular and limb risk reduction in Medicare beneficiaries with peripheral artery disease: emulation of target trials.

Aims: Recent evidence from randomized trials demonstrates that colchicine can reduce the risk of major adverse cardiovascular events (MACE) in patients with coronary artery disease. Colchicine's effect on lower-extremity peripheral artery disease (PAD) is not known. Methods and results: To make inferences about the real-world effectiveness of colchicine in PAD, we emulated two target trials leveraging the variable prescribing practice of adding colchicine vs. a non-steroidal anti-inflammatory drug (NSAID) to urate-lowering therapy in patients with gout and PAD. Emulated Trial 1 compared colchicine initiators with NSAID initiators. Emulated Trial 2 compared long-term (indefinite) and short-term (3 months) treatment strategies after initiating colchicine. Eligible individuals were those continuously enrolled in Medicare receiving care at a multicentre academic health system between July 2007 and December 2019. The primary outcome for both trials was a 2 year composite of major adverse limb events (MALE), MACE, and all-cause mortality. Secondary outcomes included MALE and death, MACE and death, and individual components of the primary outcome. Inverse probability weighting was used to adjust for confounding. Percentile-based 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. A total of 1820 eligible patients were included; the mean age was 77 years [standard deviation (SD) 7], 32% were female, and 9% were non-White. The mean (SD) duration of colchicine and NSAID therapy was 247 (345) and 137 (237) days, respectively. In the emulation of Trial 1, the risk of the primary composite outcome of MALE, MACE, and death at 2 years was 29.9% (95% CI 27.2%, 32.3%) in the colchicine group and 31.5% (28.3%, 34.6%) in the NSAID group, with a risk difference of -1.7% (95% CI -6.5%, 3.1%) and a risk ratio of 0.95 (95% CI 0.83, 1.07). Similar findings were noted in the emulation of Trial 2, with a risk of the primary composite outcome at 2 years of 30.7% (95% CI 23.7%, 38.1%) in the long-term colchicine group and 33.4% (95% CI 29.4%, 37.7%) in the short-term group, with a risk difference of -2.7% (95% CI -10.3%, 5.4%) and risk ratio of 0.92 (95% CI 0.70, 1.16). Conclusion: In a real-world sample of patients with PAD and gout, estimates of the effect of colchicine were consistent across two analyses and provided no conclusive evidence that colchicine decreased the risk of adverse cardiovascular or limb events and death. The cardiovascular and limb benefits of colchicine in older, comorbid populations with PAD and advanced systematic atherosclerosis remain uncertain.

Saudi National Clinical Practice Guidelines for Management of Adult Systemic Lupus Erythematosus.

OBJECTIVE: To provide evidence-based clinical practice recommendations for managing Systemic Lupus Erythematosus (SLE) in Saudi Arabia. METHODS: This EULAR-adapted national guideline in which a multidisciplinary task force utilized the modified Delphi method to develop 31 clinical key questions. A systematic literature review was conducted to update the evidence since the EULAR publication. After reaching a consensus agreement, two rounds of voting and group discussion were conducted to generate consolidated recommendations/statements. RESULTS: A significant number of patients in Saudi Arabia experience delays in accessing rheumatologists, highlighting the significance of timely referral to SLE specialists or rheumatologists to ensure accurate diagnosis and prompt treatment. The primary goal of Glucocorticoid (GC) therapy in SLE patients is to establish disease control with a minimum dose and duration. Steroid-sparing agent utilization facilitates steroid-sparing goals. Hydroxychloroquine is recommended for all SLE patients, though physicians must carefully monitor toxicity and prioritize regular medication adherence assessment. SLE management during pregnancy starts from preconception time by assessing disease activity, major organ involvement, hypercoagulability status, and concomitant diseases that may negatively impact maternal and fetal outcomes. Multidisciplinary care with close monitoring may optimize both maternal and fetal outcomes. For patients with antiphospholipid antibodies, low-dose aspirin prophylaxis is recommended. Also, Long-term anticoagulant medications are fundamental to prevent secondary antiphospholipid syndrome due to high thrombosis recurrence. CONCLUSION: This Saudi National Clinical Practice guidelines for SLE management provide evidence-based recommendations and guidance for healthcare providers in Saudi Arabia who are managing patients with SLE. These guidelines will help to standardize healthcare service, improve provider education, and perhaps lead to better treatment outcomes for SLE patients.

Prevalence of major adverse cardiovascular events among Saudi patients with systemic lupus erythematosus compared with the general population: updates from the national SLE and PURE cohorts.

OBJECTIVE: This study examined the prevalence of major adverse cardiovascular events (MACE) among Saudi patients with SLE and the general population and considered factors associated with such outcomes were taken into consideration. METHODS: This is a cohort study evaluating the period prevalence of MACE from 2020 to 2023. The study used two datasets, namely the Saudi national prospective cohort for SLE patients and the Prospective Urban-Rural Epidemiology Study Saudi subcohort (PURE-Saudi) for the general population. Participants in both studies were monitored using a standardised protocol. MACE was defined as myocardial infarction (MI), stroke or angina. The analysis was adjusted for demographics, traditional cardiovascular risk factors and SLE diagnosis through logistic regression models. RESULTS: The PURE and national SLE cohorts comprised 488 and 746 patients, respectively. Patients with SLE from the SLE cohort were younger (40.7±12.5 vs 49.5±8.6 years) and predominantly female (90.6% vs 41.6%). The prevalence of traditional risk factors was greater in the PURE cohort compared with the SLE cohort. These factors included dyslipidaemia (28.9% vs 49.4%), obesity (63% vs 85%) and diabetes (7.8% vs 27.2%), but not hypertension (19.3% vs 18.8%). MACE (defined as MI or stroke or venous thromboembolism or heart failure) occurred more frequently in patients with SLE (4.3% vs 1.6%, p=0.004). Older age and lupus diagnosis were independently associated with MACE after adjusting for conventional risk factors. The odds of MACE were significantly related to age and lupus diagnosis (p=0.00 and p=0.00, respectively), but not cardiovascular disease (CVD) risk factors (p=0.83). CONCLUSION: Patients with SLE have a significantly higher risk of developing MACE than the general population. This risk is not well explained by traditional risk factors, which may explain the failure of CVD risk scores to stratify patients with SLE adequately. Further studies are needed to understand CVD risk's pathogenesis in SLE and mitigate it.

Ocular Manifestations in Juvenile Behçet's Disease: A Registry-Based Analysis from the AIDA Network.

INTRODUCTION: This study aims to characterize ocular manifestations of juvenile Behçet's disease (jBD). METHODS: This was a registry-based observational prospective study. All subjects with jBD from the Autoinflammatory Diseases Alliance (AIDA) Network BD Registry showing ocular manifestations before 18 years were enrolled. RESULTS: We included 27 of 1000 subjects enrolled in the registry (66.7% male patients, 45 affected eyes). The median (interquartile range [IQR]) age at ocular involvement was 14.2 (4.7) years. Uveitis affected 91.1% of eyes (anterior 11.1%, posterior 40.0%, panuveitis 40.0%), retinal vasculitis 37.8% and other manifestations 19.8%. Later onset (p = 0.01) and male predominance (p = 0.04) characterized posterior involvement. Ocular complications occurred in 51.1% of eyes. Patients with complications had earlier onset (p < 0.01), more relapses (p = 0.02) and more prolonged steroidal treatment (p = 0.02). The mean (standard deviation [SD]) central macular thickness (CMT) at the enrolment and last visit was 302.2 (58.4) and 293.3 (78.2) µm, respectively. Fluorescein angiography was pathological in 63.2% of procedures, with a mean (SD) Angiography Scoring for Uveitis Working Group (ASUWOG) of 17.9 (15.5). At the last visit, ocular damage according to the BD Overall Damage Index (BODI) was documented in 73.3% of eyes. The final mean (SD) best corrected visual acuity (BCVA) logMAR was 0.17 (0.47) and blindness (BCVA logMAR < 1.00 or central visual field ≤ 10°) occurred in 15.6% of eyes. At multivariate regression analysis, human leukocyte antigen (HLA)-B51 + independently predicted a + 0.35 change in the final BCVA logMAR (p = 0.01), while a higher BCVA logMAR at the first assessment (odds ratio [OR] 5.80; p = 0.02) independently predicted blindness. CONCLUSIONS: The results of this study may be leveraged to guide clinical practice and future research on this rare sight-threatening condition.

The Systemic Score May Identify Life-Threatening Evolution in Still Disease: Data from the GIRRCS AOSD-Study Group and the AIDA Network Still Disease Registry.

OBJECTIVE: We aimed to evaluate the clinical usefulness of the systemic score in the prediction of life-threatening evolution in Still disease. We also aimed to assess the clinical relevance of each component of the systemic score in predicting life-threatening evolution and to derive patient subsets accordingly. METHODS: A multicenter, observational, prospective study was designed including patients included in the Gruppo Italiano Di Ricerca in Reumatologia Clinica e Sperimentale Adult-Onset Still Disease Study Group and the Autoinflammatory Disease Alliance Network Still Disease Registry. Patients were assessed to see if the variables to derive the systemic score were available. The life-threatening evolution was defined as mortality, whatever the clinical course, and/or macrophage activation syndrome, a secondary hemophagocytic lymphohistiocytosis associated with a poor prognosis. RESULTS: A total of 597 patients with Still disease were assessed (mean ± SD age 36.6 ± 17.3 years; male 44.4%). The systemic score, assessed as a continuous variable, significantly predicted the life-threatening evolution (odds ratio [OR] 1.24; 95% confidence interval [CI] 1.07-1.42; P = 0.004). A systemic score ≥7 also significantly predicted the likelihood of a patient experiencing life-threatening evolution (OR 3.36; 95% CI 1.81-6.25; P < 0.001). Assessing the clinical relevance of each component of the systemic score, liver involvement (OR 1.68; 95% CI 1.48-2.67; P = 0.031) and lung disease (OR 2.12; 95% CI 1.14-4.49; P = 0.042) both significantly predicted life-threatening evolution. The clinical characteristics of patients with liver involvement and lung disease were derived, highlighting their relevance in multiorgan disease manifestations. CONCLUSION: The clinical utility of the systemic score was shown in identifying Still disease at a higher risk of life-threatening evolution in a large cohort. Furthermore, the clinical relevance of liver involvement and lung disease was highlighted.

IL-22 contributes to TGF-ß1-mediated epithelial-mesenchymal transition in asthmatic bronchial epithelial cells.

BACKGROUND: Allergic asthma is characterized by airway inflammation in response to antigen exposure, leading to airway remodeling and lung dysfunction. Epithelial-mesenchymal transition (EMT) may play a role in airway remodeling through the acquisition of a mesenchymal phenotype in airway epithelial cells. TGF-ß1 is known to promote EMT; however, other cytokines expressed in severe asthma with extensive remodeling, such as IL-22, may also contribute to this process. In this study, we evaluated the contribution of IL-22 to EMT in primary bronchial epithelial cells from healthy and asthmatic subjects. METHODS: Primary bronchial epithelial cells were isolated from healthy subjects, mild asthmatics and severe asthmatics (n=5 patients per group). The mRNA and protein expression of epithelial and mesenchymal cell markers and EMT-associated transcription factors was evaluated following stimulation with TGF-ß1, IL-22 and TGF-ß1+IL-22. RESULTS: Primary bronchial epithelial cells stimulated with TGF-ß1 underwent EMT, demonstrated by decreased expression of epithelial markers (E-cadherin and MUC5AC) and increased expression of mesenchymal markers (N-cadherin and vimentin) and EMT-associated transcription factors. IL-22 alone had no effect on epithelial or mesenchymal gene expression. However, IL-22+TGF-ß1 promoted the expression of some EMT transcription factors (Snail1 and Zeb1) and led to a more profound cadherin shift, but only in cells obtained from severe asthmatics. CONCLUSION: The impact of IL-22 on airway epithelial cells depends on the cytokine milieu and the clinical phenotype of the patient. Further studies are required to determine the molecular mechanism of IL-22 and TGF-ß1 cooperativity in driving EMT in primary human bronchial epithelial cells.

CYP2D6 genetic polymorphisms in Saudi systemic lupus erythematosus patients: A cross-sectional study.

OBJECTIVES: To determine the prevalence of selected single nucleotide polymorphisms (rs1080985, rs28624811, rs1065852, rs28371725, and rs1135840) in cytochrome P450 2D6 (CYP2D6) gene among Saudi systemic lupus erythematosus (SLE) patients and to investigate the association between the genetic variants and clinical features of SLE. METHODS: This cross-sectional study was carried out on adult Saudi patients at King Khalid University Hospital, Riyadh, Saudi Arabia. Patients with confirmed SLE based on the 2012 Systemic Lupus International Collaborating Clinics classification criteria were included in the study. Peripheral blood was collected for genomic deoxyribonucleic acid extraction and TaqMan® technologies were used for target genotyping. For statistical analysis, differences in genotype frequencies were determined using the Chi-square test, and the association between the variant genotypes and SLE features was evaluated using logistical regression models. RESULTS: There were 107 participants included in this study. Overall, the most predominant (23.4%) recessive genotype was AA in rs28624811, and the least prevalent (1.9%) recessive genotype was TT in rs28371725. Moreover, the variant rs1080985 genotypes (GC or CC) were significantly associated with the presence of serositis manifestation (OR=3.15, p=0.03), even after adjusting for age and gender. However, the dominant rs28624811 genotype (GG) was associated with renal involvement (OR=2.56, p=0.03). CONCLUSION: Systemic lupus erythematosus patients carrying CYP2D6 variants might be considered at risk for certain manifestations of SLE. Further studies are needed to investigate the implication of these genetic variations in clinical outcomes and drug response.

Cost Consequence Analysis of Belimumab versus Standard of Care for the Management of Systemic Lupus Erythematosus in Saudi Arabia: A Retrospective Cohort Study.

BACKGROUND: Belimumab use for the management of systemic lupus erythematosus (SLE) has been limited, in part due to its high acquisition cost relative to the standard of care (SoC) and the uncertainties about its cost-effectiveness. Therefore, the aim of this study was to compare the cost and effectiveness of belimumab versus the SoC alone for the management of SLE using real-world data from the perspective of public healthcare payers in Saudi Arabia. METHODS: Data were retrieved from a national prospective cohort of SLE, Saudi Arabia. Adult SLE patients (≥18 yrs.) treated with belimumab plus the SoC or the SoC alone for at least six months were recruited. The effectiveness was measured using the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Unit costs for health services and prescription drugs were retrieved from the Saudi ministry of health. Nonparametric bootstrapping with inverse probability weighting was conducted to generate the 95% confidence limits for the cost and effectiveness. RESULTS: A total of 15 patients on belimumab plus the SoC and 41 patients on the SoC alone met the inclusion criteria and were included in the analysis. The majority of patients were females (91.07%) with a mean age of 38 years. The mean difference in cost and SLEDAI-2K score reduction between belimumab versus the SoC were USD 5303.16 [95% CI: USD 2735.61-USD 7802.52] and 3.378 [95% CI: 1.769-6.831], respectively. Belimumab demonstrated better effectiveness but higher cost in 96% of the bootstrap cost-effectiveness distributions. CONCLUSION: Future studies should use more robust research designs and a larger sample size to confirm the findings of this study.

Early Cytokine Signatures of Hospitalized Mild and Severe COVID-19 Patients: A Prospective Observational Study.

Background: The severe manifestation of coronavirus disease 2019 (COVID-19) is known to be mediated by several cytokines and chemokines. The study aimed to compare the early cytokine profile of mild and severe COVID-19 patients to that with COVID-19-like symptoms and tested negative for Severe Acute Respiratory Syndrome Coronavirus-2 in the Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR) test. Methods: This was a prospective, observational study on COVID-19 patients admitted to King Khalid University Hospital, King Saud University Medical City from June to November 2020. Clinical and biochemical data were collected from hospital charts. Blood samples were collected at the time of hospital admission to measure cytokines. A Cytokine and Growth Factor High-Sensitivity Array was used to quantitatively measure cytokines. Results: The study included 202 RT-PCR-positive individuals and 61 RT-PCR-negative individuals. C-Reactive protein (CRP) and Interleukin-10 (IL-10) levels were found significantly elevated in the RT-PCR positive group compared to the RT-PCR negative group (p=0.001). Patients with severe COVID-19 had significantly longer median hospital stays than those with mild COVID-19 cases (7 vs 6 days). They also had higher CRP and Vascular Endothelial Growth Factor (VEGF) levels and lower Interleukin-4 (IL-4) levels compared to the mild cases. CRP, interleukin-6, IL-10, VEGF, and Monocyte Chemoattractant Protein-1 (MCP-1) levels were significantly elevated in men and IL-10 was significantly higher and interleukin-8 was significantly lower in women compared to negative controls. Elevated Interferon-É£ (IFN-γ) and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital. Conclusion: CRP and IL-10 levels were elevated in the RT-PCR positive group. People with severe COVID-19 had higher CRP and VEGF levels and lower IL-4 levels. Elevated IFN-γ and IL-10 levels were seen in mild COVID-19 cases and elevated level of MCP-1 was seen in severe COVID-19 cases when categorized according to the length of stay in the hospital.

Prevalence of fatigue functional and social impairment among patients with rheumatic diseases compared to patients without: A cross-sectional comparison.

Rheumatic diseases (RD) are chronic diseases that significantly affect the lives of patients. Assessing health outcomes through a patient-reported outcome measurement information system (PROMIS) is essential for RD management. Moreover, these tend to be less favorable among individuals than among the rest of the population. This study aimed to compare PROMIS between RD patients and other patients. This cross sectional study was conducted in the year 2021. Information about patients with RD was obtained from the RD registry at King Saud University Medical City. Patients without RD were recruited from family medicine clinics. Patients were contacted electronically through WhatsApp© to complete the PROMIS surveys. We compared the individual PROMIS scores between the 2 groups using linear regression, adjusting for sex, nationality, marital status, education level, employment, family history of RD, income, and chronic comorbidities. There were 1024 individuals (512 with RD and 512 without RD). The most common RD was systemic lupus erythematosus (51.6%), followed by rheumatoid arthritis (44.3%). Individuals with RD reported significantly higher PROMIS T-scores for pain [ß = 6.2; 95% confidence interval (CI) = 4.76, 7.71] and fatigue (ß = 2.9; 95% CI = 1.37, 4.38) compared to those without RD. Moreover, RD individuals reported lower physical functioning (ß = -5.4; 95% CI = -6.50, -4.24) and social interaction (ß = -4.5; 95% CI = -5.73, -3.20). Patients with RD in Saudi Arabia, particularly those with systemic lupus erythematosus and rheumatoid arthritis, have significantly greater impairment in physical functioning and social interaction and report higher levels of fatigue and pain. Addressing and ameliorating these negative outcomes is necessary to improve quality of life.

Axial spondyloarthritis in patients with recurrent fever attacks: data from the AIDA network registry for undifferentiated autoInflammatory diseases (USAIDs).

Beckground: Despite the recent advances in the field of autoinflammatory diseases, most patients with recurrent fever episodes do not have any defined diagnosis. The present study aims at describing a cohort of patients suffering from apparently unexplained recurrent fever, in whom non-radiographic axial spondylarthritis (SpA) represented the unique diagnosis identified after a complete clinical and radiologic assessment. Materials and methods: Patients' data were obtained from the international registry on Undifferentiated Systemic AutoInflammatory Diseases (USAIDs) developed by the AutoInflammatory Disease Alliance (AIDA) network. Results: A total of 54 patients with recurrent fever episodes were also affected by non-radiographic axial SpA according to the international classification criteria. SpA was diagnosed after the start of fever episodes in all cases; the mean age at the diagnosis of axial SpA was 39.9 ± 14.8 years with a diagnostic delay of 9.3 years. The highest body temperature reached during flares was 42°C, with a mean temperature of 38.8 ± 1.1°C. The most frequent manifestations associated to fever were: arthralgia in 33 (61.1%) cases, myalgia in 24 (44.4%) cases, arthritis in 22 (40.7%) cases, headache in 15 (27.8%) cases, diarrhea in 14 (25.9%) cases, abdominal pain in 13 (24.1%) cases, and skin rash in 12 (22.1%) cases. Twenty-four (44.4%) patients have taken daily or on-demand non-steroidal anti-inflammatory drugs (NSAIDs) and 31 (57.4%) patients have been treated with daily or on demand oral glucocorticoids. Colchicine was used in 28 (51.8%) patients, while other conventional disease modifying anti-rheumatic drugs (cDMARDs) were employed in 28 (51.8%) patients. Forty (74.1%) patients underwent anti-tumor necrosis factor (TNF) agents and 11 (20.4%) were treated with interleukin (IL)-1 inhibitors. The response to TNF inhibitors on recurrent fever episodes appeared more effective than that observed with anti-IL-1 agents; colchicine and other cDMARDs were more useful when combined with biotechnological agents. Conclusion: Signs and symptoms referring to axial SpA should be inquired in patients with apparently unexplained recurrent fever episodes. The specific treatment for axial SpA may lead to a remarkable improvement in the severity and/or frequency of fever episodes in patients with unexplained fevers and concomitant axial SpA.

Efficacy and Safety of Adalimumab in Pediatric Non-infectious Non-anterior Uveitis: Real-life Experience From the International AIDA Network Uveitis Registry.

INTRODUCTION: Scientific evidence of the effectiveness of the tumor necrosis factor inhibitor adalimumab (ADA) in pediatric patients with non-infectious non-anterior uveitis is still limited. The aim of this study is to investigate the therapeutic role of ADA in a cohort of pediatric patients with non-anterior uveitis. METHODS: This is an international multicenter study analyzing real-life data referred to pediatric patients treated with ADA for intermediate uveitis/pars planitis, posterior uveitis and panuveitis. Data were drawn from the AutoInflammatory Disease Alliance (AIDA) registry for patients with uveitis. RESULTS: Twenty-one patients (36 affected eyes) were enrolled, and all patients benefited from ADA administration. In detail, 11 patients (19 affected eyes) did not experience further ocular inflammation after ADA introduction; 10 cases (17 affected eyes) showed a significant clinical improvement consisting of a decrease in severity and/or frequency of ocular relapses. The number of ocular flares dropped from 3.91 to 1.1 events/patient/year after ADA introduction (p = 0.0009); macular edema and retinal vasculitis were respectively observed in 18 eyes and 20 eyes at the start of ADA and in 4 eyes and 2 eyes at the last assessment. The mean daily glucocorticoid dosage significantly decreased from 26.8 ± 16.8 mg/day at the start of ADA to 6.25 ± 6.35 mg/day at the last assessment (p = 0.002). Intermediate uveitis/pars planitis (p = 0.01) and posterior uveitis (p = 0.03) were more frequently observed in patients with full response to ADA; panuveitis (p = 0.001) was significantly more frequent among patients continuing to experience uveitic flares. This could be related to a higher use of systemic glucocorticoids (p = 0.002) and conventional immunosuppressants (p = 0.007) at the start of ADA when treating intermediate uveitis/pars planitis. Regarding the safety profile, only one adverse event was reported during ADA treatment, consisting of the development of generalized adenopathy. CONCLUSIONS: ADA proved to have an effective therapeutic role in all pediatric patients with non-anterior uveitis enrolled in the study. An overall glucocorticoid-sparing effect was observed despite the severity of cases enrolled. A more aggressive treatment of panuveitis and posterior uveitis at start of ADA could increase the likelihood of full response to therapy.

The administration of methotrexate in patients with Still's disease, "real-life" findings from AIDA Network Still Disease Registry.

OBJECTIVES: To describe clinical characteristics of patients with Still's disease treated with methotrexate (MTX) and to assess drug effectiveness evaluating change in disease activity, reduction of inflammatory markers, and glucocorticoid (GC)-sparing effect. METHODS: Patients with Still's disease treated with MTX were assessed among those included in AIDA Network Still Disease Registry. RESULTS: In this registry, 171 patients with Still's disease were treated with MTX (males 43.3%, age 37.1 ± 16.0 years). They were mainly characterised by joint features and fever without a prominent multiorgan involvement. MTX was administered with GCs in 68.4% of patients, with other conventional synthetic DMARDs in 6.4%, and with biologic DMARDs in 25.1%. A significant reduction of the modified systemic score was observed, and 38.6% patients were codified as being in clinical remission at the end of follow-up. The concomitant administration of a biologic DMARD resulted a predictor of the clinical remission. Furthermore, a reduction of inflammatory markers and ferritin levels was observed following the administration of MTX. Additionally, a marked reduction of the dosage of concomitant GCs was identified, while 36.7% discontinued such drugs. Male gender appeared as a predictor of GC discontinuation. MTX was discontinued in 12.3% of patients because of adverse effects, and in 12.3% for lack of efficacy. CONCLUSIONS: Clinical characteristics of patients with Still's disease treated with MTX were described, mainly joint features and fever without a prominent multiorgan involvement. The clinical usefulness of MTX was reported in reducing the disease activity, decreasing the inflammatory markers, and as GC-sparing agent.