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Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-ancestry genetic research of RA promises to improve power to detect genetic signals, fine-mapping resolution and performances of polygenic risk scores (PRS). Here, we present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P < 5 × 10 -8 ), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. Multi-ancestry fine-mapping identified putatively causal variants with biological insights (for example, LEF1). Moreover, PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries. Our study provides several insights into the etiology of RA and improves the genetic predictability of RA., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: There is limited information on the epidemiology and treatment patterns of rheumatoid arthritis (RA) across the Arab region. We aim in this study to describe the demographic characteristics, clinical profile, and treatment patterns of patients of Arab ancestry with RA., Methods: This is a cross sectional study of 895 patients with established rheumatoid arthritis enrolled from five sites (Jordan, Lebanon, Qatar, Kingdom of Saudi Arabia (KSA), and United Arab Emirates). Demographic characteristics, clinical profile, and treatment patterns are compared between the five countries., Results: The majority of our patients are women, have an average disease duration of 10 years, are married and non-smokers, with completed secondary education. We report a high (>80%) ever-use of methotrexate (MTX) and steroids among our RA population, while the ever-use of disease modifying anti-rheumatic drugs (DMARDs) and TNF-inhibitors average around 67% and 33%, respectively. There are variations in RA treatment use between the five country sites. Highest utilization of steroids is identified in Jordan and KSA (p-value < 0.001), while the highest ever-use of TNF-inhibitors is reported in KSA (p-value < 0.001)., Conclusion: Disparities in usage of RA treatments among Arab patients are noted across the five countries. National gross domestic product (GDP), as well as some other unique features in each country likely affect these. Developing treatment guidelines specific to this region could contribute in delivering standardized therapies to RA patients., Competing Interests: The authors have declared that no competing interests exist.

Clinical practice guidelines can assist rheumatologists in the proper prescription of newer treatment for rheumatoid arthritis (RA). The objective of this paper is to report on the recommendations for the management of patients with RA in the Eastern Mediterranean region. We adapted the 2015 American College of Rheumatology guidelines in two separate waves. We used the adolopment methodology, and followed the 18 steps of the "Guidelines 2.0" comprehensive checklist for guideline development. For each question, we updated the original guidelines' evidence synthesis, and we developed an Evidence Profile (EP) and an Evidence to Decision (EtD) table. In the first wave, we adoloped eight out of the 15 original questions on early RA. The strength changed for five of these recommendations from strong to conditional, due to one or more of the following factors: cost, impact on health equities, the balance of benefits, and harms and acceptability. In the second wave, we adoloped eight out of the original 44 questions on established RA. The strength changed for two of these recommendations from strong to conditional, in both cases due to cost, impact on health equities, balance of benefits and harms, and acceptability. The panel also developed a good practice recommendation. We successfully adoloped 16 recommendations for the management of early and established RA in the Eastern Mediterranean region. The process proved feasible and sensitive to contextual factors.

Recent metabolomics studies of Rheumatoid Arthritis (RA) reported few metabolites that were associated with the disease, either due to small cohort sizes or limited coverage of metabolic pathways. Our objective is to identify metabolites associated with RA and its cofounders using a new untargeted metabolomics platform. Moreover, to investigate the pathomechanism of RA by identifying correlations between RA-associated metabolites. 132 RA patients and 104 controls were analyzed for 927 metabolites. Metabolites were tested for association with RA using linear regression. OPLS-DA was used to discriminate RA patients from controls. Gaussian Graphical Models (GGMs) were used to identify correlated metabolites. 32 metabolites are identified as significantly (Bonferroni) associated with RA, including the previously reported metabolites as DHEAS, cortisol and androstenedione and extending that to a larger set of metabolites in the steroid pathway. RA classification using metabolic profiles shows a sensitivity of 91% and specificity of 88%. Steroid levels show variation among the RA patients according to the corticosteroid treatment; lowest in those taking the treatment at the time of the study, higher in those who never took the treatment, and highest in those who took it in the past. Finally, the GGM reflects metabolite relations from the steroidogenesis pathway.

Objective: Genetic factors underlying susceptibility to rheumatoid arthritis (RA) in Arab populations are largely unknown. This genome-wide association study (GWAS) was undertaken to explore the generalizability of previously reported RA loci to Arab subjects and to discover new Arab-specific genetic loci., Methods: The Genetics of Rheumatoid Arthritis in Some Arab States Study was designed to examine the genetics and clinical features of RA patients from Jordan, the Kingdom of Saudi Arabia, Lebanon, Qatar, and the United Arab Emirates. In total, >7 million single-nucleotide polymorphisms (SNPs) were tested for association with RA overall and with seropositive or seronegative RA in 511 RA cases and 352 healthy controls. In addition, replication of 15 signals was attempted in 283 RA cases and 221 healthy controls. A genetic risk score of 68 known RA SNPs was also examined in this study population., Results: Three loci (HLA region, intergenic 5q13, and 17p13 at SMTNL2/GGT6) reached genome-wide significance in the analyses of association with RA and with seropositive RA, and for all 3 loci, evidence of independent replication was demonstrated. Consistent with the findings in European and East Asian populations, the association of RA with HLA-DRB1 amino acid position 11 conferred the strongest effect (P = 4.8 × 10 -16 ), and a weighted genetic risk score of previously associated RA loci was found to be associated with RA (P = 3.41 × 10 -5 ) and with seropositive RA (P = 1.48 × 10 -6 ) in this population. In addition, 2 novel associations specific to Arab populations were found at the 5q13 and 17p13 loci., Conclusion: This first RA GWAS in Arab populations confirms that established HLA-region and known RA risk alleles contribute strongly to the risk and severity of disease in some Arab groups, suggesting that the genetic architecture of RA is similar across ethnic groups. Moreover, this study identified 2 novel RA risk loci in Arabs, offering further population-specific insights into the pathophysiology of RA., (© 2017, American College of Rheumatology.)

Objective This study assessed the mode of application (oral, intravenous or subcutaneous (SC)) currently employed in the treatment of rheumatoid arthritis (RA) in patients from Qatar in comparison with patients' individual preferences for the mode of application of their treatment. Methods This study included 294 RA patients visiting three clinics at the main referral hospital in Qatar who were interviewed using a standard questionnaire to determine their preference of mode of application for their disease-modifying antirheumatic drug (DMARD) treatment in relation to their currently employed mode of application. Results The majority of patients were female (76%), and 93% of male patients and 61% of female patients in the study clinics were of a nationality other than Qatari. The highest patient preference recorded was for an oral therapy (69%), compared with injection (23%) and intravenous (8%) therapy. In total, 85% of patients expressed a preference to remain on oral therapy compared with 63% and 58% of intravenous and SC injection patients indicating a preference to remain on their current method of administration. Conclusions This high preference for oral therapies highlights the considerable need for incorporation of new oral targeted synthetic DMARD therapies into clinical practice within the region.

Background: We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy., Methods: Patients with early active disease who had not previously received methotrexate or biologic therapy received 50 mg of etanercept plus methotrexate weekly for 52 weeks (open-label phase). We then randomly assigned patients who had qualifying responses at weeks 39 and 52 to receive 25 mg of etanercept plus methotrexate (combination-therapy group), methotrexate alone, or placebo for 39 weeks (double-blind phase). Patients who had qualifying responses at week 39 of the double-blind phase had all treatment withdrawn at that time and were followed to week 65 (treatment-withdrawal phase). The primary end point was the proportion of patients with sustained remission in the double-blind phase., Results: Of 306 patients enrolled, 193 underwent randomization in the double-blind phase; 131 qualified for the treatment-withdrawal phase. More patients in the combination-therapy group than in the methotrexate-alone group or the placebo group met the criterion for the primary end point (40 of 63 [63%] vs. 26 of 65 [40%] and 15 of 65 [23%], respectively; P=0.009 for combination therapy vs. methotrexate alone; P<0.001 for combination therapy vs. placebo). At 65 weeks, 28 patients (44%) who had received combination therapy, 19 (29%) who had received methotrexate alone, and 15 (23%) who had received placebo were in remission (P=0.10 for combination therapy vs. methotrexate alone; P=0.02 for combination therapy vs. placebo; P=0.55 for methotrexate alone vs. placebo). No significant between-group differences were observed in radiographic progression of disease. Serious adverse events were reported in 3 patients (5%) in the combination-therapy group, 2 (3%) in the methotrexate-alone group, and 2 (3%) in the placebo group., Conclusions: In patients with early rheumatoid arthritis who had a remission while receiving full-dose etanercept-plus-methotrexate therapy, continuing combination therapy at a reduced dose resulted in better disease control than switching to methotrexate alone or placebo, but no significant difference was observed in radiographic progression. (Funded by Pfizer; ClinicalTrials.gov number, NCT00913458.).

Objective: To describe the clinical characteristics, serologic, radiological and clinical disease activity, and modality of therapy in patients with rheumatoid arthritis (RA) at tertiary outpatient care in Qatar., Methods: The study design was cross-sectional where 100 consecutive cases who met 1987 American College of Rheumatology criteria for diagnosis of RA were enrolled in this study. Demographic data (sex, nationality and age) numbers of swollen and tender joints, X-rays and current medications were collected during outpatients visits to Hamad General Hospital. Disease Activity Score of 28 joints (DAS28) and Health Assessment Questionnaires (HAQ) scores were calculated. All patients with RA who were seen as rheumatology outpatients were invited to participate in the study., Results: One hundred patients were seen and examined during their follow-up at the outpatient clinic; data were collected and analyzed. Females represented 67% of all patients, 6% had more than six swollen joints, 9% had more than six tender joints. DAS28 and erythrocyte sedimentation rate (DAS28) calculation revealed 49% of patients were in remission (DAS28 < 2.6), 15% had low disease activity (DAS28 2.6-3.2) and 36% had DAS28 > 3.2.Mean HAQ score was 1.02. Rheumatoid factor (RF) was positive in 63%, while anti-cyclic citrullinated protein antibody (anti-CCP) was positive in 71%, and 49% were positive for both. Radiography of hands and feet during the previous year was done in 65% of patients: 11% of them had erosions. Sixty-six percent were on one synthetic disease-modifying anti-rheumatic drug (DMARD) and 27% where on more than one synthetic DMARD and 7% where on no DMRD. Glucocorticoids were used in 51% and 29% were on biologics., Conclusion: Sixty-four percent of rheumatoid arthritis patients in Qatar were in remission or had low disease activity while the remaining 36% had active disease and among these patients 29% were on biologics., (© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Multiple studies of patients in Western countries with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have indicated increased risk for active tuberculosis (TB) and other infections among these individuals. It has also been consistently reported that patients receiving tumor necrosis factor (TNF) inhibitors for these conditions have higher rates of active TB and other infections than RA or AS patients not receiving these medications. These issues have been studied less extensively in the Asia and Africa-Middle East regions, and information from these regions is important because of higher rates of TB in the general population. This paper reviews studies of RA and AS patients from Asia, Africa, and the Middle East who received TNF inhibitors. A literature search was conducted using http://www.ncbi.nlm.nih.gov/pubmed to collect and report these data. The years included in the PubMed literature search ranged from January 2000 to October 2011. Additionally, information from the China Hospital Knowledge Database was used to report data from Chinese patients with RA and AS treated with TNF inhibitors. Results from these studies indicate that the risk for active TB and other infections in AS and RA patients from Asia, Africa, and the Middle East are increased in patients receiving TNF inhibitors and that the risk is higher among those treated with monoclonal antibodies versus soluble TNF receptor.

It is well known that rheumatoid arthritis improves in the majority of patients during pregnancy and that aggravation of disease symptoms occurs within the first 6 months postpartum. We report a female patient who had 4 postpartum episodes of transient polyarthritis typical of rheumatoid arthritis with positive serum rheumatoid factor and anti-CCP antibodies. All bouts resolved within 4 to 10 weeks after onset without any symptoms in between the episodes.