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.

Assessment of COVID-19 Morbidity and Mortality Among Patients With Autoimmune Diseases at King Abdulaziz University Hospital.

Background The coronavirus disease 2019 (COVID-19) pandemic has raised significant concerns about the effects of the virus on patients with autoimmune diseases. Therefore, understanding the COVID-19 outcomes in this population is crucial for effective prevention and management. Objective This study aimed to investigate the association between autoimmune diseases and the severity of COVID-19 in terms of mortality and morbidity. Despite substantial advancements in pandemic-related research concerning COVID-19 and autoimmune diseases, there remain noteworthy gaps in our comprehension of this association, particularly due to limited investigations conducted in Saudi Arabia. Methods This was a retrospective record review of a tertiary center from January 2020 to January 2022. We included 120 patients, among whom 40 were diagnosed with autoimmune diseases, and 80 were age- and sex-matched controls. Afterward, we assessed their demographics, year of admission, intensive care unit (ICU) admission, health status, length of hospitalization, comorbidities, diagnosis of autoimmune diseases, and type of immunosuppressant therapy. Results Most of the included patients (mean age: 45.4 years) were females (65.8%). The ratio of non-autoimmune diseases to autoimmune diseases was 2:1, the mean length of hospitalization was 8.83 ± 8.16 days, and the median was seven days (interquartile range (IQR) = 3 to 11 days). Among them, 17.5% were admitted to the ICU and 10% died. The prevalence of autoimmune diseases was higher in women than in men (77.5%). The most common diseases were systemic lupus erythematosus (40%), rheumatoid arthritis (20%), and ankylosing spondylitis (10%). Regarding COVID-19 outcomes, ICU admissions were higher among patients with autoimmune diseases than those with non-autoimmune diseases (35% vs. 8.8%) (p<0.05). This trend was also observed in mortality, with a higher percentage of deaths among patients with autoimmune diseases (27.5% vs. 1.7%) (p<0.05). In addition, there were no significant differences between genders in terms of ICU admission, health status outcomes, or length of hospitalization among patients with autoimmune diseases (p>0.05). Notably, 25 patients were administered immunosuppressants. Of these, 18 (72%) used steroids only, while seven (28%) used both biological and steroid therapy. However, no significant associations were observed between the type of treatment used and outcomes such as ICU admission, health status at discharge, and length of hospitalization (p>0.05).  Conclusion This study suggests that individuals with autoimmune diseases have more severe COVID-19 outcomes, as shown by ICU admission and mortality rates, than patients with non-autoimmune diseases. Furthermore, we observed that the use of immunosuppressant medications among patients with autoimmune diseases showed no noticeable effect on these outcomes.

Knowledge and Awareness of Systemic Lupus Erythematosus Among the Population of Jeddah, Saudi Arabia: A Cross-Sectional Study.

Background The immune system, composed of various molecules and cells, protects humans from cancer and pathogens. A breach of tolerance, known as autoimmune disease (AD), is the root of these diseases. Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by chronic inflammation, causing tissue damage in various organ systems. The disease is influenced by hormonal, environmental, and genetic factors. The pathophysiology is unclear, and 20% to 30% of patients have a persistent illness. SLE affects young females more than males, and treatments focus on organ manifestations. Despite advancements and better diagnoses, SLE continues to contribute significantly to morbidity and early mortality. Objective This study aims to assess knowledge of SLE among the general population of Jeddah, Saudi Arabia. Methodology An online cross-sectional survey using Google Forms was conducted for Jeddah residents aged 18 and above. The survey was open for responses from August 2023 to October 2023. Results The study included 479 participants, with 19 (25%) males and 57 (75%) females diagnosed with SLE. The majority of these individuals were housewives and unemployed. The majority were married (46, 60.5%), with only 25 (32.9%) being single. Among healthy participants, there were 173 (42.9%) males and 230 (57.1%) females, with a majority being housewives and government employees (95, 23.6%). Singles accounted for 124 (30.8%), while married individuals constituted 253 (62.8%). Among the healthy population respondents, 254 (63%) lacked knowledge about SLE treatment, while 40 (52.6%) SLE patients believed that a combination of chemotherapy, malaria medication, and steroids was the best treatment. The study found that 393 (82%) of the sample had heard about SLE, and 250 (52%) believed it was not a contagious disease. More than 30 were unaware of SLE. The majority of the respondents felt they needed more awareness and health promotion about SLE, with 410 (85.77%) stating they needed more promotion. The majority of the people believed SLE was dangerous to some extent. Conclusions This study revealed the need and necessity of awareness of SLE among the general community of Jeddah. We advocate undertaking disease awareness programs and activities to increase general community knowledge and awareness of SLE in the city of Jeddah.

Exploring factors influencing patient activation in Saudi rheumatoid arthritis patients: A Nationwide Cross-Sectional Survey-Results from the COPARA study.

OBJECTIVES: To evaluate patient activation in rheumatoid arthritis (RA) patients using patient activation measure 13 (PAM-13) on a national level in Saudi Arabia. METHOD: A national survey was administered across multiple centers in Saudi Arabia. Patient activation was assessed using the PAM-13. The Compliance Questionnaire for Rheumatology (CQR) and the RA Impact of Disease (RAID) tool were also administered. The data from the survey were analyzed, and the results were stratified based on activation level. All factors affecting patient activation were explored and reported. RESULTS: A total of 1241 participants were included. Most of the patients were females (85%), the mean age was 47 (±14), and most patients lived in the central region (47%). The mean (±standard deviation) patient activation score was 578.7 (±13.0). Patient activation was affected by multiple factors: demographic characteristics, such as education, with a beta value of 1.11 (95% confidence interval [CI] 0.64 ̶1.58, p < .001). Higher CQR scores were associated with higher activation levels, with a beta value of 2.61 (95% CI 0.80 ̶4.44, p = .005), and higher RAID scores were associated with lower activation levels, with a beta value of 3.13 (95% CI 1.36 ̶4.91, p = .001). CONCLUSIONS: Patient activation was affected by several demographic characteristics and the impact of RA. A higher activation may improve compliance. Future longitudinal studies are required to confirm these findings and should explore the underlying mechanism of these effects.

Exploring Impact of Multidisciplinary Care on Patient Activation in Saudi Rheumatoid Arthritis Patients: A Cross-Sectional Survey-Extended Results from the COPARA National Project.

Introduction: Multidisciplinary setting in healthcare provide positive patient outcomes. Objective: To evaluate the impact of specialized rheumatology clinics (multidisciplinary settings) on the activation and engagement of rheumatoid arthritis (RA) patients. Material and Methods: This cross-sectional survey assessed patient activation using the patient activation measure-13. Participants attending Specialized Rheumatology Clinics (SRC multidisciplinary clinics) were compared with age- and sex-matched patients attending Standard of Care (SOC). The study was observational in nature, assessing several demographic and therapeutic options and their relation to the clinical setting and patient activation. Results: This study included 117 SRC matched RA patients with 117 SOC. The majority of the included patients were female (n=211, 90.2%), >40 years of age (n=177, 75.6%), and had intermediate-to-high education (n=147, 62.8%). Patients in the SRC were also more likely to have activation levels 3 and 4 with an odds ratio of 3.194 (95% confidence interval [CI] 1.835-5.562, p<0.001). In addition, SRC participants were more likely to be in levels 3 and 4 activation, even after adjustment for confounding variables, with an adjusted odds ratio of 2.401 (95% CI 1.121-4.758, p=0.012) and 2.175 (95% CI 1.127-4.196, p=0.020), respectively. Conclusion: Establishing SRC for RA patients seems to have a positive impact on patient activation and engagement and adds to the previously explored benefits of multidisciplinary care in chronic disease management.

Immunoprofiling of cytokines, chemokines, and growth factors in female patients with systemic lupus erythematosus- a pilot study.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease affecting different organ systems. This study aimed to determine the concentrations of 30 different human cytokines, chemokines, and growth factors in human plasma to understand the role of these markers in the pathogenicity of SLE using Luminex Multiple Analyte Profiling (xMAP) technology. Plasma samples were obtained from patients with SLE (n = 28), osteoarthritis (OA) (n = 9), and healthy individuals (n = 12) were obtained. High levels of TNF, IL-6, IFN-γ, INF-α, IL-4, IL-5, IL-13, IL-8, IP-10, MIG, MCP-1, MIP-1ß, GM-CSF, G-CSF, EGF, VEGF, IL-12, IL-1RA, and IL-10 was detected in SLE patients compared with the OA and healthy control groups. xMAP analysis has been used to address the differential regulation of clinical heterogeneity and immunological phenotypes in SLE patients. In addition, complete disease phenotyping information along with cytokine immune profiles would be useful for developing personalized treatments for patients with SLE.

Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials.

INTRODUCTION: The Routine Assessment of Patient Index Data 3 (RAPID3) is a patient-reported outcome tool recommended for the assessment of disease activity in patients with rheumatoid arthritis (RA) in clinical practice. This analysis evaluated the long-term effect of upadacitinib vs. comparators on RAPID3 scores in patients with RA in the phase 3 SELECT clinical trial program. METHODS: This post hoc analysis included data from five randomized controlled trials (RCTs) in patients receiving upadacitinib 15 mg or 30 mg once daily (QD) as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). The proportions of patients reporting RAPID3 remission (scores ≤ 3) were assessed at week 60. Correlations between absolute scores for RAPID3 and Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI), and 28-joint Disease Activity Score with C-reactive protein (DAS28[CRP]) at week 60 were assessed using Spearman correlation coefficients. RESULTS: A total of 3117 patients were included from the SELECT-NEXT, -BEYOND, -MONOTHERAPY, -COMPARE, and -EARLY trials. By week 60, 32-52% of methotrexate-naïve and csDMARD inadequate responder (IR) patients treated with either upadacitinib 15 mg QD or upadacitinib 30 mg QD reported RAPID3 scores consistent with remission. The proportions were slightly lower in the biologic DMARD-IR SELECT-BEYOND population (19-28%). RAPID3 scores highly correlated (Spearman correlation values ≥ 0.58) with CDAI, SDAI, and DAS28(CRP) scores through week 60 (all p < 0.001). CONCLUSIONS: Upadacitinib, as monotherapy or in combination with csDMARDs, was associated with patient-reported remission assessed by RAPID3 over 60 weeks across the SELECT RCTs in patients with RA. TRIAL REGISTRATION: SELECT-BEYOND (NCT02706847); SELECT-NEXT (NCT02675426); SELECT-MONOTHERAPY (NCT02706951); SELECT-EARLY (NCT02706873); SELECT-COMPARE (NCT02629159).

Rheumatoid arthritis (RA) is a disease that causes inflammation of the joints. Doctors have several ways of assessing how bad a patient's disease is, and these often use a combination of signs and symptoms to develop a 'score'. One method is called RAPID3, which is a score based on an overall assessment of the disease by the patient, the level of pain, and the amount of physical disability. An advantage of RAPID3 is that it is quick and easy to use, and since it uses only patient-reported symptoms, it can be measured easily via telemedicine, without the need for an in-person consultation. In this study, we decided to look into the effect of upadacitinib, a drug used for the treatment of RA, on RAPID3 score in patients with RA. We also investigated whether RAPID3 correlates with other ways of measuring RA severity, including scores that use physician-measured factors such as number of affected joints, as this can help show whether RAPID3 is a valid and useful tool. We found that upadacitinib led to long-term improvements in RAPID3 score, and that results were the same in different studies and patient groups, including patients who had not responded well to other treatments. We also found that RAPID3 correlated well with other measures, i.e., improvements in RAPID3 happened in parallel with improvements in other scores. Overall, these results suggest that RAPID3 can be a useful tool in patients with RA.

Exploring Factors Influencing Medication Compliance in Saudi Rheumatoid Arthritis Patients: A Nationwide Cross-Sectional Survey - Results from the COPARA Study.

Purpose: Compliance is essential to achieve treatment goals in rheumatoid arthritis (RA) patients. The current study evaluated compliance and related factors in a large and diverse population. Patients and Methods: Patients with RA who received active treatment were invited to participate in an online survey. The Arabic versions of the 5-Item Compliance Questionnaire for Rheumatology (ACQR-5) and the RA Impact of Disease (RAID) were used to measure compliance and disability, respectively. The patients were sub-grouped based on background disease-modifying anti-rheumatic drugs (DMARDs). Variables associated with high compliance were selected for the logistic regression analysis. Results: A total of 1241 patients completed the survey and were included in the final analysis. Of those, 1055 (85%) were females with a mean (±SD) age and disease duration of 47.14 ± 13.71 and 8.77 ± 7.43 years, respectively. The mean RAID was 4.4±2.58, with 980 (79%) having an unacceptable level state. Patients with an unacceptable RAID level had a lower compliance rate (78.8% vs 85.8%, p = 0.001). Demographics associated with high compliance were female sex and increased age, with reported odds ratios of 1.018 (95% CI: 1.007-1.028) and 1.464 (95% CI: 1.016-2.108), respectively. Compliance was similar between patients on Janus kinase inhibitors or biological DMARDs (88.14% vs 80.83%, p = 0.17), between monotherapy, double therapy, or triple therapy recipients (80% vs 82.23% vs 81.32%, p = 0.665), and between patients receiving injectable and oral therapy (77.32% vs 81.14%, p = 0.246). Conclusion: A high compliance level was observed in this population, with patient demographics influencing compliance rather than the medication type or route of administration. Interventional studies should focus on the of high-risk patients identified in this study.

Implications of SARS-CoV-2 infection on the clinical, hematological, and inflammatory parameters in COVID-19 patients: A retrospective cross-sectional study.

BACKGROUND: The current coronavirus pandemic (COVID-19) was caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2). COVID-19 is characterized by atypical pneumonia, mild colds, and more severe illnesses, such as severe acute respiratory distress, thrombosis, organ failure, and various secondary bacterial and fungal infections. Notably, the severity of COVID-19 in different age groups is not well known, and the validity of clinical laboratory data remains unclear. METHODS: In this retrospective cross-sectional study, we examined differential regulation of clinical, hematologic, and inflammatory biomarkers in COVID-19 patients. We divided 104 COVID-19 patients into five different groups according to age (0-17, 18-45, 46-65, 66-79, and >80 years). Baseline data (sex, comorbidities, intensive care admission, and medications), hematologic markers, liver, and renal function tests, coagulation, and inflammatory markers were examined in these groups. Receiver operator characteristic (ROC) analysis was used to determine the optimal threshold for predicting COVID-19 biological markers. RESULTS: We found that the highest percentage (45%) of COVID-19 patients was in the age group of 46-65 years. The hematologic parameters (WBC, HB, and PLT) were normal between the patient groups. The area under the curve in ROC analysis showed significant differences in the levels of creatine, GGT, BUN, CRP, D-dimer, ferritin, AST, and procalcitonin between the patients of age groups 46-65 and 66-79 years. Renal biomarkers were significantly high in most patients, regardless of age. In contrast, the liver biomarkers, did not differ significantly between patient groups. CONCLUSION: The main finding of our study is that laboratory parameters such as GGT, creatinine, BUN, CRP, procalcitonin, ferritin and D-dimer were differentially regulated in COVID -19 patients of different age groups. Importantly, these laboratory parameters may help as clinical predictors to assess the severity of the disease in the population. We conclude here that age is an important factor influencing COVID-19 severity.

Circulating extracellular vesicles and rheumatoid arthritis: a proteomic analysis.

Circulating extracellular vesicles (EVs) are membrane-bound nanoparticles secreted by most cells for intracellular communication and transportation of biomolecules. EVs carry proteins, lipids, nucleic acids, and receptors that are involved in human physiology and pathology. EV cargo is variable and highly related to the type and state of the cellular origin. Three subtypes of EVs have been identified: exosomes, microvesicles, and apoptotic bodies. Exosomes are the smallest and the most well-studied class of EVs that regulate different biological processes and participate in several diseases, such as cancers and autoimmune diseases. Proteomic analysis of exosomes succeeded in profiling numerous types of proteins involved in disease development and prognosis. In rheumatoid arthritis (RA), exosomes revealed a potential function in joint inflammation. These EVs possess a unique function, as they can transfer specific autoantigens and mediators between distant cells. Current proteomic data demonstrated that exosomes could provide beneficial effects against autoimmunity and exert an immunosuppressive action, particularly in RA. Based on these observations, effective therapeutic strategies have been developed for arthritis and other inflammatory disorders.

Management of neuropathic pain in patients with diabetic peripheral neuropathy and low back pain in Saudi Arabia: Evidence and gaps.

We report existing evidence and gaps in neuropathic pain management in Saudi Arabia, the prevalence and patient management stages in diabetic peripheral neuropathy (DPN) and low back pain (LBP) with a neuropathic component. A semi-systematic approach was adopted to identify data on neuropathic pain. A structured search was conducted through MEDLINE, Embase, and BIOSIS databases to identify articles published in English between January 2010 and December 2019. Unstructured search was conducted through various sources including Google Scholar and Saudi Arabia's Ministry of Health website. Studies including populations ≥18 years and neuropathic pain were included; data gaps were supplemented with anecdotal data from local experts. Weighted or simple means were calculated for overall data; synthesized evidence was represented as an evidence gap map. Of 37 articles retrieved from structured search, none were eligible for final analyses. Thirteen articles from unstructured search and two anecdotal data sources were included for final analyses. The majority of articles included were of cross-sectional design (n = 10) in diabetes patients. The mean (range; number of articles) DPN prevalence was estimated as 33.6% (5.6%-65.3%; n = 8). Data on DPN patient management stages were limited; synthesized evidence indicated that 37.2% (0.41%-80.0%; n = 3) of patients had DPN awareness, 17.8% (n = 1) underwent screening, 22.4% (18.4%-65.3%; n = 2) had DPN diagnosis, and 45.1% (0.0%-62.7%; n = 2) received treatment for pain management. Data on LBP with neuropathic component were scarce (prevalence, 41.0% [n = 1]; diagnosis, 54.7% [n = 1]). Data are limited, so more studies are needed to accurately estimate the prevalence and stages of patient management for neuropathic pain in the country.

Association Between Hypocomplementemia (C3 and C4) and MRI Findings in Different Neuropsychiatric Lupus Syndromes in a Tertiary Hospital.

Objective The aim of this study was to describe the magnetic resonance imaging (MRI) findings and correlate them with the complements level. Methodology This is a retrospective chart review study involving 187 lupus patients attending the rheumatology clinic during the period between 2010 and 2020. Out of the 187 patients, only 49 patients were diagnosed to have neuropsychiatric lupus manifestation and underwent MRI study. Results We included 49 neuropsychiatric systemic lupus erythematosus patients with a mean age of 35.33 years; most of them were Saudi (51%), with disease duration between -six and nine years (40.8%). In regard to MRI brain findings, 51% had abnormal findings, most commonly white matter changes in 42.9% followed by contrast enhancement in 36.7% and mild volume loss in 16.3%. Regarding the complement level, 21 (42.9%) patients had a low C3 level and 35 (71.4%) had a low C4 level. Lastly, following the main objective, C3 and C4 do not have a statistically significant relationship with white matter lesion given the sample of this data (p = 0.589 and p = 0.657, respectively). Conclusion MRI provides a significant clinical information to evaluate neuropsychiatric lupus manifestations. These clinical data can be correlated with immunological findings, which can help in the early diagnosis and management of this disease.

Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia?

BACKGROUND: The prevalence of sarcopenia with osteoporosis results in a higher risk of falling and fractures. It was noted that patients who had completed their planned 5-year denosumab therapy course as treatment for these conditions started to sustain falls. PURPOSE: To assess (a) whether denosumab has a unique dual effect on both bone and muscle in comparison to other anti-resorptive agents and (b) its effectiveness in the follow-up period post-treatment completion compared to other anti-resorptive agents. METHOD: One hundred thirty-five patients diagnosed to have postmenopausal/senile osteoporosis and who were prescribed denosumab were compared to a control group of 272 patients stratified into 2 subgroups - 136 prescribed alendronate and 136 prescribed zoledronate. All patients were assessed for: BMD (DXA), falls risk (FRAS), fracture risk (FRAX), and sarcopenia measures. All were re-assessed after 5 years of denosumab/alendronate therapy and 3 years of zoledronate and 1 year after stopping the osteoporosis therapy. RESULTS: No significant baseline demographic differences between the 3 groups. On completion of the 5-year denosumab therapy, there was significant decrease in falls risk (P = 0.001) and significant improvements in all sarcopenia measures (P = 0.01). One-year post-discontinuation of denosumab, a significant worsening of both falls risk and sarcopenia measures (P = 0.01) noticed. CONCLUSION: Denosumab displayed positive impact and significant improvements in BMD and sarcopenia measures. It also enhanced multidirectional agility as depicted by Timed Up and Go (TUG). Collectively, this would explain the reduction of falls risk which got worse on stopping the medication. Key points • The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'. • Bone and muscle closely interact with each other not only anatomically, but also at the chemical and metabolic levels. • Denosumab displayed positive impact and significant improvements in all sarcopenia measures, and enhanced multidirectional agility with consequent reduction in falls risk. • Denosumab can be considered as a first osteoporosis therapeutic option in this group of patients presenting with osteosarcopenia manifestations.

Decoding the Role of Sphingosine-1-Phosphate in Asthma and Other Respiratory System Diseases Using Next Generation Knowledge Discovery Platforms Coupled With Luminex Multiple Analyte Profiling Technology.

Sphingosine-1-phosphate (S1P) is a pleiotropic sphingolipid derived by the phosphorylation of sphingosine either by sphingosine kinase 1 (SPHK1) or SPHK2. Importantly, S1P acts through five different types of G-protein coupled S1P receptors (S1PRs) in immune cells to elicit inflammation and other immunological processes by enhancing the production of various cytokines, chemokines, and growth factors. The airway inflammation in asthma and other respiratory diseases is augmented by the activation of immune cells and the induction of T-helper cell type 2 (Th2)-associated cytokines and chemokines. Therefore, studying the S1P mediated signaling in airway inflammation is crucial to formulate effective treatment and management strategies for asthma and other respiratory diseases. The central aim of this study is to characterize the molecular targets induced through the S1P/S1PR axis and dissect the therapeutic importance of this key axis in asthma, airway inflammation, and other related respiratory diseases. To achieve this, we have adopted both high throughput next-generation knowledge discovery platforms such as SwissTargetPrediction, WebGestalt, Open Targets Platform, and Ingenuity Pathway Analysis (Qiagen, United States) to delineate the molecular targets of S1P and further validated the upstream regulators of S1P signaling using cutting edge multiple analyte profiling (xMAP) technology (Luminex Corporation, United States) to define the importance of S1P signaling in asthma and other respiratory diseases in humans.

Prevalence of obstructive sleep apnea in patients with rheumatoid arthritis.

STUDY OBJECTIVES: Although previous studies suggested an increased prevalence of obstructive sleep apnea (OSA) among patients with rheumatoid arthritis (RA), no existing large prospective study has addressed this association using objective measures. This study aims to assess the prevalence of OSA using polysomnography (PSG) in patients with RA and its relationship with RA activity. METHODS: Patients with RA who presented at the rheumatology clinic at a university hospital from 2017 to 2018 were eligible. In the first stage, data from the Disease Activity Score 28, Berlin questionnaire, and Epworth Sleepiness Scale were obtained, along with personal data and a comprehensive medical history. The second stage involved a case-control study confirming OSA with PSG. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 events/h, whereas patients with an AHI ≥ 15 events/h were categorized as having moderate-severe OSA. RESULTS: In total, 199 patients with RA were recruited, 110 patients (55%) underwent PSG, and 5 were excluded. The mean age was 48.93 ± 12.7 years, and the mean body mass index was 31.70 ± 9.74 kg/m²; 94% were female. In total, 67 participants (33.2%) were at high risk for OSA (36 [55.4%] underwent PSG), whereas 132 (66.8%) were at low risk (69 [51.5%] underwent PSG). The estimated prevalence of OSA (AHI ≥ 5 events/h) in the whole population was 58.1%, whereas the prevalence of moderate-to-severe OSA (AHI ≥ 15) was 22.9%. CONCLUSIONS: This prospective PSG-based study demonstrated that OSA is more common in patients with RA than in the general population, but there appears to be no relationship with disease activity.

Frequency of sleep disorders in patients with rheumatoid arthritis.

Purpose: To determine the prevalence of common sleep problems among patients with rheumatoid arthritis (RA) and their relationship with the disease activity and quality of life. Patients and methods: The study sample consisted of 101 patients who attended a rheumatology clinic at a university hospital between October 2015 and May 2016. All subjects were clinically examined and interviewed by physicians using a questionnaire. The collected information included sociodemographic characteristics, the patients' medical histories, the Disease Activity Score (DAS28), the Berlin questionnaire to assess the risk of obstructive sleep apnea (OSA), the Epworth Sleepiness Scale to assess excessive daytime sleepiness (EDS), the Athens Insomnia Scale to assess insomnia, the International RLS Study Group score to diagnose restless legs syndrome (RLS), and the Health Assessment Questionnaire (HAQ) to assess the quality of life. Results: The mean age of the participants was 48.7±14.6 years, and 95% of the participants were females. Approximately 60% of the participants were in the remission/low category of disease activity, and the average DAS28 score was 3.3±0.8 years. The prevalence rates of insomnia, EDS, sleep disturbance, risk of OSA, and RLS were 63%, 20%, 20%, 37%, and 63%, respectively. Furthermore, the distribution of sleep disorders was not affected by the disease activity. The association between the HAQ and sleep disorders among the RA patients was not significant. Conclusion: Sleep disorders are common among RA patients and may require further attention by treating clinicians; nevertheless, these disorders are not associated with disease activity and do not affect the quality of life.

Rapid immunoprofiling of cytokines, chemokines and growth factors in patients with active rheumatoid arthritis using Luminex Multiple Analyte Profiling technology for precision medicine.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of unknown etiology, characterised by symmetric erosive synovitis, leading inevitably to the destruction of cartilage and bone as well as bursa and tendon sheaths of joints. Our aim of this study was to decipher the differential expression of cytokines, chemokines and growth factors in the plasma of RA patients with active disease, using magnetic bead-based Luminex Multiple Analyte Profiling (xMAP) technology, for precision medicine. METHODS: We obtained plasma samples from RA patients (n=25) from the Rheumatology Clinic at the King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA) after written informed consent for their inclusion in this study. Besides, we have used the plasma samples from inflammatory osteoarthritis (OA) patients (n=10) and healthy volunteers (n=10) for comparison analyses. Plasma samples were examined using the Human Cytokine Magnetic 30-plex panel (Novex®), Invitrogen, USA) and analysed by MAGPIX® instrument (Luminex Corporation, USA). RESULTS: Though several pro-inflammatory cytokines, chemokines and growth factors present in the 30plex magnetic bead panel were not significantly (p>0.05) increased in the plasma of RA patients, the levels of plasma Th1 associated proinflammatory cytokines TNFα, and IL-6 and Th2 associated cytokines such as IL-4, IL-5 and IL-13 were significantly (p<0.05) upregulated compared to OA and normal controls. The proinflammatory IL-12 as well as anti-inflammatory IL-10 and IL-1RA were significantly (p<0.05) upregulated in the plasma of RA patients compared to normal controls. Also, the chemokines such as IP-10, RANTES and IL-8 as well as growth factors such as EGF, and VEGF were significantly (p<0.05) increased in RA. CONCLUSIONS: The MAGPIX data showed that the cytokines, chemokines and growth factors were differentially regulated systemically in patients with active RA compared to OA and normal controls. Hence, the Luminex xMAP technology-based multiplex immunoassays offer clues to formulate effective therapeutic strategies for RA patients with active disease irrespective of their treatment regimen and duration of treatment and, thus, an indispensable tool in precision medicine.

Associations of Vitamin D Levels and Vitamin D Receptor Genotypes with Patient-Reported Outcome/Disease Activity in Patients with Rheumatoid Arthritis.

BACKGROUND: The aim of this study is to evaluate the prevalence of vitamin-D insufficiency and vitamin-D receptor (VDR) polymorphisms in rheumatoid arthritis (RA) patients and its association with disease activity and patient reported outcomes (PROs). METHODS: Eighty-two individuals were included in a cross-sectional study (41 RA patients, 41 controls). Prior to assessment, each patient completed a PRO questionnaire. Serum vitamin-D levels and genotyping for VDR were assessed. Vitamin-D deficient patients received vitamin-D supplementation. Re-assessment of disease activity (DAS28) was performed after 9-months. RESULTS: Low vitamin-D levels were more frequent in RA patients (p < 0.01). A negative, but insignificant, association with DAS-28 score was identified; whereas, there was a significant negative association with the PROs (p < 0.01). Vitamin-D supplementation was associated with significant improvement in the patients' scores for pain, fatigue, global assessment, physical disability, and quality of life. In contrast to the control group, the frequency of the recessive TaqI and FokI genotypes was higher in RA patients. CONCLUSIONS: In RA patients, serum vitamin-D level was significantly and inversely associated with both PROs and disease activity. The TaqI and FokI fragment length polymorphisms of VDR significantly contributed to the risk of RA. Having a significant positive impact on patient reported outcomes, vitamin-D supplementation may have a role in RA management.

Association of Paraoxonase 1 Polymorphism and Serum 25-Hydroxyvitamin D with the Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.

BACKGROUND: Patients with rheumatoid arthritis (RA) have significantly increased cardiovascular (CV) morbidity and mortality that are not accounted for by traditional risk factors alone. Paraoxonase 1 (PON1) and 25-hydroxyvitamin D have been shown to be involved in the pathogenesis of CV diseases. Objective: This study aimed to investigate PON1 gene polymorphism and serum 25-hydroxyvitamin D concentrations in RA patients, and to determine their association with CV risk in RA. METHODS: Serum samples from 46 RA patients and 45 healthy controls were tested for PON1 R192Q genotypes and serum vitamin D concentrations. The cardiovascular risks were assessed by Q-risk. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease activity status were also assessed. RESULTS: PON1 polymorphism and low serum 25-hydroxyvitamin D were significantly associated with increased CV risk (p < 0.05). Compared to patients with either the PON1 QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased CV risk on multivariate analysis, controlling for traditional CV risk factors, C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (p < 0.05). CONCLUSIONS: There was a relationship of the genetic determinants of paraoxonase 1 (PON1 192) and serum 25-hydroxyvitamin D to CV risk in RA patients. Paired measurement of paraoxonase 1 genotype and serum 25-hydroxyvitamin D can be used as biomarkers of CV risk in RA patients.

Optimizing therapy in inflammatory arthritis: prediction of relapse after tapering or stopping treatment for rheumatoid arthritis patients achieving clinical and radiological remission.

This study aims to assess clinical, lab/immunological or imaging (joint ultrasonography) markers able to predict disease relapse in RA patients in sustained remission when tapering or stopping their treatment. One hundred fifty-seven RA patients in clinical remission (DAS-28 <2.6 for >6 months), receiving treatment with sDMARDs and bDMARD therapy, were randomly allocated into any of five groups: Group 1: continue full dose DMARDs and taper biologic therapy by 50 % (31 patients); Group 2: taper both DMARDs and biologic therapy dose by 50 % (32 patients); Group 3: taper DMARDs by 50 % and stop biologic therapy (31 patients); Group 4: stop both DMARDs and biologic therapy (31 patients); Group 5: continue medications without change (31 patients). Forty joints were assessed ultrasonographically (DAS-28 joints + ankles + metatarsophalangeal joints) and prospectively monitored for 12 months. The primary endpoint was sustained remission for 12 months. Patients were considered as having a relapse when the DAS-28 score was >3.2 and anti-rheumatic treatment was escalated. The frequency of relapse was 41.9 % in Group 1, 59.3 % in Group 2, 67.7 % in Group 3, 77.4 % in Group 4 and 6.5 % in Group 5. Relapse rates were significantly higher in patients whose ultrasound scores raised within 3 months of stopping their medications (P < 0.001 for both GS and PD scores). Cox regression identified ACPA positivity (at baseline) and progression of functional disability (at 2 months) as predictors for relapse. Tapering therapy is feasible in RA patients. Tailored dynamic approach is advised. Joint ultrasonographic assessment, ACPA positivity and worsening functional disability predicted relapse within a short term after discontinuation of the treatment. RA patients whose DAS-28 score was <2 were more likely to remain in remission.