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.

The Fidelity of Rheumatoid Arthritis Multivariate Diagnostic Biomarkers Using Discriminant Analysis and Binary Logistic Regression.

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that causes multi-articular synovitis. The illness is characterized by worsening inflammatory synovitis, which causes joint swelling and pain. Synovitis erodes articular cartilage and marginal bone, resulting in joint deterioration. This bone injury is expected to be permanent. Cytokines play a prominent role in the etiology of RA and could be useful as early diagnostic biomarkers. This research was carried out at Riyadh's King Khalid University Hospital (KKUH). Patients were enrolled from the Rheumatology unit. Seventy-eight RA patients were recruited (67 (85.9%) females and 11 (14.1%) males). Patients were selected for participation by convenience sampling. Demographic data were collected, and disease activity measurements at 28 joints were recorded using the disease activity score (DAS-28). Age- and sex-matched controls from the general population were included in the study. A panel of 27 cytokines, chemokines, and growth factors was determined in patient and control sera. Binary logistic regression (BLR) and discriminant analysis (DA) were used to analyze the data. We show that multiple cytokine biomarker profiles successfully distinguished RA patients from healthy controls. IL-17, IL-4, and RANTES were among the most predictive variables and were the only biomarkers incorporated into both BLR and DA predictive models for pooled participants (men and women). In the women-only models, the significant cytokines incorporated in the model were IL-4, IL-17, MIP-1b, and RANTES for the BLR model and IL-4, IL-1Ra, GM-CSF, IL-17, and eotaxin for the DA model. The BLR and DA men-only models contained one cytokine each, eotaxin for BLR and platelet-derived growth factor-bb (PDGF-BB) for DA. We show that BLR has a higher fidelity in identifying RA patients than DA. We also found that the use of gender-specific models marginally improves detection fidelity, indicating a possible benefit in clinical diagnosis. More research is needed to determine whether this conclusion will hold true in various and larger patient populations.

Single Nucleotide Polymorphisms Associated with Rheumatoid Arthritis in Saudi Patients.

Rheumatoid arthritis (RA) is a complex, multifactorial disorder with an autoimmune etiology. RA is highly heritable and is associated with both human leucocyte antigen (HLA) and non-HLA genes. We investigated the associations of 33 single nucleotide polymorphisms (SNPs) with RA in the Saudi population. METHODS: This study included 105 patients with RA and an equal number of age- and sex-matched controls. The patients with RA attended outpatient clinics at King Khalid University Hospital in Riyadh, Saudi Arabia. Blood samples were collected, and DNA was extracted using Qiagen kits. Primers were designed for the 33 selected SNPs using the MassEXTEND primers program, and samples were genotyped on the Sequenom MassARRAY iPLEX platform. The allele frequencies and genotypes were determined for each SNP, and the results obtained for the patients were compared to those for the controls. RESULTS: The allele and genotype frequencies of six SNPs were significantly associated with RA: rs1188934, rs10919563, rs3087243, rs1980422, rs10499194, and rs629326. The minor alleles of rs1188934, rs10919563, rs10499194, and rs629326 were protective, with odds ratios of 0.542, 0.597, 0.589, and 0.625, and p-values of 0.002, 0.023, 0.013 and 0.036, respectively. In addition, the heterozygote frequencies of two SNPs (rs6859219 and rs11586238) were significantly higher in the controls than in the patients. CONCLUSIONS: There is considerable heterogeneity in the genetics of RA in different populations, and the SNPs that are associated with RA in some populations are not in others. We studied 33 SNPs and only eight were associated with RA. The remaining SNPs showed no allelic or genotypic associations with RA.

Intranasal administration of abatacept enhances IL-35+ and IL-10+ producing Bregs in lung tissues of ovalbumin-sensitized asthmatic mice model.

BACKGROUNDS: Treating asthmatic rheumatoid arthritis patients with abatacept has been shown to associate with better control of asthma symptoms. However, the mechanism behind that is not investigated. METHODS: Ovalbumin (OVA)- sensitized BALB/c female mice were treated intranasally (IN) or intraperitoneally (IP) with abatacept 4 hrs before the OVA challenge. The effects of abatacept IN or IP on the lungs and blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and ELISA assay. RESULTS: Treating OVA- sensitized asthmatic mice model with abatacept, IN or IP, reduced lung inflammation. IN treatment with abatacept increased the frequency of IL-35 and IL-10 producing Bregs in the lung tissues to a higher level compared to IP treatment. Moreover, the frequency of lungs LAG3+ Tregs was significantly increased following treatment. This was also associated with a reduction in lung tissue and serum IL-17 levels of treated mice. CONCLUSIONS: These results suggest that abatacept by enhancing IL-35+IL-10+ Bregs and LAG3+ Tregs might reverse IL-17 induced lung inflammation during asthma.

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.

Perception of Biosimilar Biologics and Non-Medical Prescription Switching among Rheumatologists: A Saudi Society for Rheumatology Initiative.

BACKGROUND: The aim of this study was to evaluate rheumatologists' perceptions of biosimilar biologics and Non-Medical Switching (NMS). METHODS: A cross-sectional survey was conducted among registered members of the Saudi Society for Rheumatology. The questionnaire focused on biosimilars and NMS. Logistic regression was performed to ascertain the effect of demographics and practice characteristics on the use of biosimilars and NMS. RESULTS: Out of 249 SSR members, 143 completed the survey, generating a response rate of 57.4%. Of those (59.44%) were men with a mean (±SD) age and years of practice of 42.3 ± 9.13 and 10.3 ± 8.9, respectively. Rheumatologists managing adult patients (81.82%) and Ministry of Health practice (43.36 %) were the majority of respondents. Previous experience in prescribing a biosimilar was reported by 43 (30.07%) participants, with a higher probability among women (p = 0.015). A total of 26 (18.18%) participants had performed NMS on eligible patients. Adequate knowledge on biosimilars was reported by 69 (48.25%) participants. The adequacy of evidence to grant biosimilar approval for the studied indication and extrapolation to treat other conditions was reported by 88 (61.5%) and 69 (48.3%), respectively. The concept of totality-of-the-evidence was well understood by 37.1%. Biosimilars had been previously used by 43 (30.07) participants in their practice. NMS had been attempted by 26 (18.18), while 86 (60.1%) participants believed that NMS might harm patients. CONCLUSION: There is a clear knowledge gap about the biosimilar approval process among adult and pediatric rheumatologists who took part in the survey. In addition, a large number of participants reported having negative opinions about NMS. There is a need to organize SSR-led educational activities, and develop national guidelines regarding biosimilars and NMS.

Venom of the desert black snake Walterinnesia aegyptia enhances anti-tumor immunity via its beneficial modulatory effects on pro- and anti-tumorigenic inflammatory mediators in cultured colon cancer cells.

The role of inflammation in colon cancer is understood as a well-accepted factor that has the tendency to release multiple pro- and anti-tumorigenic inflammatory mediators. Inflammation-induced increased expression of anti-tumorigenic inflammatory mediators and decreased expression of pro-tumorigenic inflammatory mediators encourage beneficial inflammatory effects in terms of powerful anti-tumor immunity. The present study aims to screen the beneficial inflammatory effects of Walterinnesia aegyptia venom via determining its modulatory tendency on the expression of 40 pro- and anti-tumorigenic inflammatory mediators (cytokines/growth factors/chemokines) in LoVo human colon cancer cell line. LoVo-cells were treated with varying doses of crude venom of W. aegyptia. Cell viability was checked utilizing flow cytometry, and IC50 of venom was determined. Venom-induced inflammatory effects were evaluated on the expression of 40 different inflammatory mediators (12 anti-tumorigenic cytokines, 11 pro-tumorigenic cytokines, 7 pro-tumorigenic growth factors, 9 pro-tumorigenic chemokines and 1 anti-tumorigenic chemokine) in treated LoVo-cells [utilizing enzyme-linked immunosorbent assay (ELISA)] and compared with controls. Treatment of venom induced significant cytotoxic effects on inflamed LoVo-cells. IC50 treatment of venom caused significant modulations on the expression of 22 inflammatory mediators in treated LoVo-cells. The beneficial modulatory effects of venom were screened via its capability to significantly increase the expression of five powerful anti-tumorigenic mediators (IL-9, IL-12p40, IL-15, IL-1RA and Fractalkine) and decrease the expression of four major pro-tumorigenic mediators (IL-1ß, VEGF, MCP-1 and MCP-3). Walterinnesia aegyptia venom-induced beneficial modulations on the expression of nine crucial pro/anti-tumorigenic inflammatory mediators can be effectively used to enhance powerful anti-tumor immunity against colon cancer.

Adverse Effects of Selected Markers on the Metabolic and Endocrine Profiles of Obese Women With and Without PCOS.

The aim of the present study, is to investigate the influence of obesity, with and without polycystic ovarian syndrome (PCOS), on the levels of kisspeptin, vitamin D (Vit D), and vascular endothelial growth factor (VEGF) and to explore the relationship between these parameters and endocrine and metabolic variables. The study group included 126 obese Saudi females. Of these 63 were suffering from PCOS while the rest were normo-ovulatory obese women (non-PCOS obese). In the obese PCOS, VEGF was almost four times as high as in the non-PCOS obese, while kisspeptin and Vit D did not differ. A highly significant elevation was recorded in the waist/hip (WHR), cholesterol, LDL-C, fasting glucose, LH, LH/FSH ratio, estradiol (E2), and testosterone, while hip circumference, leptin, progesterone, and sex hormone binding globulin (SHBG) were lower in the obese PCOS subjects. BMI, HDL-C, ghrelin, insulin, and FSH levels did not differ significantly between the two groups. The obese PCOS had the same level of insulin resistance as the non-PCOS group, as judged by QUICK Index. Correlation studies showed a significant negative correlation between kisspeptin and glucose and LH levels, and a positive correlation with LH/FSH ratio in obese PCOS while in the non-PCOS obese, the kisspeptin correlated positively with glucose, and there was no correlation with LH or LH/FSH. VEGF negatively correlated with FSH and positively with LH/FSH ratio in the non-PCOS obese but this was lost in the obese PCOS. PCOS had no effect on the correlation between Vit D and all studied parameters. Multiple regression analysis showed triglyceride as predictor variable for kisspeptin as a dependent variable, while, leptin is a predictor variable for VEGF as a dependent variable. ROC studies showed the highest sensitivity and specificity for VEGF (AOC=1.00), followed by LH/FSH ratio (AOC=0.979). In conclusion, our study shows that PCOS results in significant elevation of VEGF in obese females, while kisspeptin and Vit D levels are not affected. It also leads to elevation in several of the lipid and hormonal abnormalities in the obese females. In addition, PCOS influences relationship between Kisspeptin and VEGF and some parameters such as glucose, LH or FSH and LH/FSH ratio in obese females, but does not affect Vit D relationship with other parameter.

Abatacept enhances blood regulatory B cells of rheumatoid arthritis patients to a level that associates with disease remittance.

Abatacept, an inhibitor of CD28 mediated T-cell activation, has been shown to be effective in controlling inflammation during rheumatoid arthritis (RA). However, its effects on immune regulatory B and T cells (Bregs and Tregs) has not been fully explored. Thirty-one RA patients treated with abatacept for ≥ 6 months along with 31 RA patients treated with other modalities as well as 30 healthy controls were recruited. Of these 62 RA patient, 49 (79%) were females with a mean age of 54 ± 12 years and disease duration of 10 ± 6 years. The blood levels of Tregs and Bregs and their production of immunosuppressive cytokines, were determined using FACS analysis and Luminex Multiplex assay. Treatment with abatacept significantly enhanced the blood level of IL-35+ IL-10+ Bregs (P = 0.0007). Their levels were higher in the blood of remitted patients (DAS28-CRP < 2.6) compared to the unremitted ones (P = 0.0173), 6 months following abatacept treatment initiation. Moreover, abatacept treatment significantly enhanced the blood levels of LAG3+ conventional and unconventional Tregs of RA patients. This increase in the blood levels of Bregs and Tregs was accompanied with an elevated serum level of IL-35 and IFN-ß in abatacept-treated patients. Therefore, Abatacept efficiency to achieve remittance in RA could be attributed, in part, to its ability to enhance immune regulatory cells, especially IL-135+ IL-10+ Bregs.

Prevalence of fibromyalgia in physicians in training: a cross-sectional study.

The prevalence of fibromyalgia (FM) in physicians in training (PIT) in Saudi Arabia is unknown. The aim of this study is to evaluate the prevalence of FM in PIT using different screening tools and factors associated with its development. We also aimed at evaluating the level of agreement and correlation between screening tools. This was a cross-sectional study conducted in a single academic institution. PIT were invited to fill three questionnaires: Fibromyalgia Rapid Screening tool (FirST), Fibromyalgia Survey Questionnaire (FSQ), and London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ). A total of 182 PIT completed the questionnaire. They were predominantly males (57.1%), single (56.0%), and at resident level (86.7%). The median age was 28 (interquartile range = 4). The average number of house-calls/month was 3.2 (SD = 2.3). The prevalence of FM using the FirST, FSQ, and LFESSQ was 6.0%, 8.2%, and 11.6%, respectively. Six (3.3%) fulfilled the three criteria concurrently. After adjusting for different variables using the FSQ, PIT with family history of FM had 23.6 times the odds for testing positive (95% CI = 3.12, 178.37), and every extra house-call/month was associated with a 50% increase in the odds for testing positive for FM (95% CI = 1.00, 2.25). Percent agreement between tools was high (all > 86%). Results for kappa coefficient showed moderate agreement between FSQ scores and each of FirST and LFESSQ. There was poor agreement between FirST and LFESSQ. FM is prevalent among PIT. There is a high percent agreement and poor to moderate correlation between the screening tools used.

Prevalence of HLA-B27 in the general population and in patients with axial spondyloarthritis in Saudi Arabia.

The prevalence of HLA-B27 in the general population and in axial spondyloarthritis (axSpA) patients in Saudi Arabia is unknown. The aim of this study was to evaluate the prevalence of HLA-B27 in these two populations and describe the delay in diagnosis of axSpA patients. The prevalence of HLA-B27 in the general population was evaluated using cord blood and healthy organ transplant donor databases. Data from patients with axSpA were collected retrospectively from five centers. Ankylosing spondylitis (AS) was diagnosed based on a positive X-ray, as evaluated by two independent readers. Patients with inflammatory bowel disease and psoriasis were excluded. A total of 134 axSpA patients were included, of whom 107 (79.9%) had AS, and most (67.2%) were males. HLA-B27 was positive in 60.4, 69, and 25.9% of patients with axSpA, AS, and non-radiographic axSpA (nr-axSpA), respectively. The median and interquartile range (IQR) ages at symptom onset and disease diagnosis were 26 (20-33) and 30 (25-38) years, respectively. The median delay to diagnosis was 3 (1-6) years. There was a negative correlation between the time of onset of symptoms and the delay in diagnosis (r = -0.587). Male gender and HLA-B27 positivity were associated with a younger age at symptom onset/diagnosis (p < 0.05). HLA-B27 was positive in 82/3332 (2.5%) and 27/1164 (2.3%) individuals in the cord blood and healthy organ transplant donor databases, respectively. The prevalence of HLA-B27 is lower in the general Saudi population and in axSpA patients compared to Caucasians, thus, limiting its utility as a diagnostic criterion.

Survey on management strategies of rheumatoid arthritis in Saudi Arabia: a Saudi Society for Rheumatology Initiative.

AIM: Currently there are no national recommendation guidelines for the management of rheumatoid arthritis (RA) in Saudi Arabia, which has led to a lack of standard of care. The aim of this study is to explore RA management strategies in practicing rheumatologists in Saudi Arabia. METHODS: A 38 questions survey was designed using an electronic website. The survey was distributed through the official email of the Saudi Society for Rheumatology. Rheumatologists with at least 1 year of experience were included. Descriptive analysis was used to report demographics and participants' answers. Chi-square and Fischer's exact test were used to evaluate the relation between the characteristics of participants and their answers. RESULTS: Out of 120 registered practicing adult rheumatologists, 54 (45%) completed the survey. The majority were male 31 (57.4%) and Saudis 36 (66.7%). Forty-two participants (77.8%) use clinical outcome measures in daily clinical practice to guide treatment decisions with the majority using the Disease Activity Score of 28 joints (61.1%). Quality of life measures were used by 22 (40.7%) participants with statistically significant male predominance (P = 0.043). Time consumption was the most important cause for not using any outcome measures. Thirteen (24.1%) and 17 (31.5%) participants do not use parenteral methotrexate and leflunomide, respectively, because of unavailability in the hospital formulary. Nine (16.7%) and 38 (70.37%) participants do not see a role for tofacitinib and biosimilars, respectively, in the management of RA. CONCLUSION: This survey has highlighted many areas of improvement in the practice of rheumatologists in Saudi Arabia and should be the focus of future educational activities.