Hussein Halabi

Challenges and opportunities in the early diagnosis and optimal management of rheumatoid arthritis in Africa and the Middle East

Early diagnosis and early initiation of disease‐modifying antirheumatic drug (DMARD) therapy slow the progression of joint damage and decrease the morbidity and mortality associated with rheumatoid arthritis (RA). According to the European League Against Rheumatism (EULAR) guidelines, treatment should be initiated with methotrexate and addition of biological DMARDs such as tumour necrosis factor (TNF) inhibitors should be considered for RA patients who respond insufficiently to methotrexate and/or other synthetic DMARDs and have poor prognostic factors. Africa and the Middle East is a large geographical region with varying treatment practices and standards of care in RA. Existing data show that patients with RA in the region are often diagnosed late, present with active disease and often do not receive DMARDs early in the course of the disease. In this review, we discuss the value of early diagnosis and remission‐targeted treatment for limiting joint damage and improving disease outcomes in RA, and the challenges in adopting these strategies in Africa and the Middle East. In addition, we propose an action plan to improve the overall long‐term outlook for RA patients in the region.

Rheumatoid arthritis in the Middle East and Africa: are we any closer to optimising its management?

A recent editorial considered the management of rheumatoid arthritis (RA) in the Middle East and Africa [1]. Following review of the limited available evidence in the literature specifically that is from this region, it was suggested that management of RA is suboptimal for a variety of reasons [1]. The editorial authors met to determine whether the European League Against Rheumatism (EULAR) consensus recommendations published in 2010 [2] were applicable and appropriate for implementation in the MENA region and South Africa [1]. The group made recommendations on next steps to improve the management of RA in this region, including collection of epidemiological data to elucidate better the prevalence, severity and burden of RA in this region; educational initiatives to raise awareness of the disease and dispel misconceptions among health care professionals (HCPs) and patients; development of regional guidelines to increase implementation of an evidence-based approach and improve outcomes; and facilitation of access to treatments in line with the recommendations [1]. In addition, locally relevant issues not commonly seen in Europe such as high rates of hepatitis B and C, tuberculosis (TB) and parasitic infections as well as access and monitoring difficulties should be considered.

The practical value of biologics registries in Africa and Middle East: challenges and opportunities.

Biologics, including tumor necrosis factor (TNF) inhibitors, are increasingly used for the treatment of inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis. The efficacy of these drugs has been demonstrated in randomized controlled trials (RCTs). However, these studies are conducted in controlled environments, and the results may not necessarily reflect clinical outcomes in daily clinical practice. In Europe and other western countries, numerous biologics registries that enroll and monitor patients receiving biologics have been established. These registries follow patients irrespective of whether they continue with the initial biologic drug. Thus, real-life efficacy data from these registries can be used to assess the long-term safety of biologics through longitudinal studies. In Africa and Middle East (AFME), such registries currently exist only in Morocco and South Africa. In light of the increasing availability of biologics and scarcity of long-term safety data of these agents in the AFME population, there is a need to establish biologics registries in other countries across the region. This review discusses the value of biologics registries versus RCTs as well as safety and efficacy data from observational studies presented as lessons from well-established biologics registries. In addition, the rationale for establishing such registries in the AFME region is also presented.

A Multinational Arab Genome-Wide Association Study Identifies New Genetic Associations for Rheumatoid Arthritis.

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.

Large Scale Metabolic Profiling identifies Novel Steroids linked to Rheumatoid Arthritis

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.

Recommendations for the management of rheumatoid arthritis in the Eastern Mediterranean region: an adolopment of the 2015 American College of Rheumatology guidelines

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.

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

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.

Biological therapy in arthritis patients with hepatitis B or C infection: a multicenter retrospective case series

Objective Reactivation of viral hepatitis B (HBV) and C (HCV) has been reported in various case reports of patients with arthritis on biological therapy. The objective of this study was to describe the clinical characteristics and outcomes of arthritis patients with HBV or HCV treated with biological therapy. Material and Methods This is a retrospective case series including all patients above 13 years of age with arthritis patients from four centers in Saudi Arabia with concurrent chronic viral hepatitis infection (HBV or HCV) who received biological agents in the rheumatology clinics during their course of their disease from duration of the disease onset until last outpatient visit up to November 2015. Demographic information, full details about the hepatitis status of each patient, rheumatic disease diagnosis and different therapies used were reviewed. Results We identified 10 cases each with HBV and HCV on biological therapy. The mean age in the HBV group was 51 (34-85) years and 80% were females. Eight patients had rheumatoid arthritis (RA), one patient had RA/systemic lupus erythematosus, and one had human immunodeficiency virus related-arthritis. Seven were chronic inactive HBsAg carriers and three had chronic active HBV. Nine HBV patients received prophylactic antiviral therapy. Two cases with chronic HBV had reactivation with no elevation of the transaminases.The mean age in the HCV group was 54 (23-79) years and all were female RA patients. Three had detectable hepatitis C virus-ribonuecleic acid (HCV-RNA) before the start of biological therapy. Nine HCV patients received antiviral treatment and seven had a sustained virologic response (SVR) before start of biological treatment. Three patients had detectable HCV-RNA during the course of biological therapy. One of the three was a non-responder and two were relapsers. One of the patients with HCV relapse was started on sofosbuvir plus ribavirin and achieved SVR on follow-up. Conclusion We report the successful use of biological therapy in arthritis patients with hepatitis B infection with antiviral therapy with no detoriation of their viral status. Due to the lack of sufficient prospective studies demonstrating the rate of HCV flare on biological therapy, caution should be exercised and careful monitoring with liver enzymes and viral load is mandated in vulnerable HCV RNA patients. Treatment should be individualized by the rheumatologist in collaboration with the hepatologist to minimize complications.

SAT0103 Variations in the Prescription Patterns of Physicians for Patients with RA across Several Arab States

Background Variations exist in the prescription of non-biologic and biologic DMARDS for patients with Rheumatoid Arthritis (RA).Low and middle income countries use Methotrexate (MTX) and Biologics less frequently compared to high-income countries.These variations are attributed to provider and patient preferences, practice settings, and countrys GDP1. Objectives To examine the prevalence of prescription of MTX & Anti-TNF drugs for RA treatment in some Arab States. Methods The Genetics of Rheumatoid Arthritis in some Arab States (GRAAS) is a multinational study designed to study the genetics & clinical characteristics of Arab RA patients from Jordan, Kingdom of Saudi Arabia (KSA),Lebanon, Qatar and the United Arab Emirates (UAE).Inclusion criteria are age≥18, Arab ancestry & diagnosis of RA based on ACR criteria.Data collected includes demographics,ancestry, disease duration, comorbidities,and the use of DMARDS.To assess prescribing patterns,we analyzed the prevalence of ever use of MTX and available anti-TNF (Infliximab,Etanercept and Adalimumab)in each of the countries.Because of difference in countries per Capita GDP,the countries were divided into two regions:Levant (Jordan and Lebanon) and Gulf (KSA and Qatar).Analysis using mean, standard deviation,t test,frequency and Chi square were used as appropriate.Adjusted analysis was done using logistic regression. Results 470 patients were included in the study.Mean age is 49±13.0 years.Female to male ratio is 5:1.Mean disease duration is 10.2±8.74 years. 52.3% of the patients were positive for both ACPA and RF. Patients from the Gulf were more likely to be seropositivethan patients from the Levant (57% vs 44% p=0.009) and significantly less likely to be seroengative (14%vs. 28% p<0.01).Methotrexate was the most commonly prescribed DMARD (87.0%). Anti-TNF drugs were prescribed in 31.2%. Patients from the Levant were less likely to receive MTX and anti-TNF as compared to patients from the Gulf (Table).After adjusting for age, gender, seropositivity&disease duration, patients from the Gulf are more likely to have received any anti-TNF (OR=3.78). Frequency of prescription of methotrexate and anti-TNF drugs across sites Differences in prescription across regions Medication Jordan KSA Lebanon Qatar Levant Gulf p N=130 N=96 N=80 N=162 N=210 N=258 Methotrexate 76.2% 97.9% 86.6% 89.5% 80.2% 92.6% <0.001 At least one anti-TNF 11.5% 51.0% 23.8% 38.9% 16.2% 43.4% <0.001 Conclusions Patterns of prescription of MTX & Anti-TNF for RA patients vary among Arab countries.Countries in the Gulf have prescription frequency for MTX similar to rates from developed countries, but high frequency of prescription of Anti-TNF in excess of what is reported from the developed countries. In depth analysis of patients level of disease activity,physician practice patterns and site,& health insurance type is needed to understand these variations. References Putrik et al.,Inequities in access to biologic and synthetic DMARDs across 46 European countries, Ann Rheum Dis.2014 Jan;73(1). Acknowledgements The study is funded by QNRF, NPRP#4-344-3-105. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4354

AB0139 Genome-Wide Analysis of Population Structure in A Multi-National Arab Rheumatoid Arthritis Case-Control Study

Background Genetic and ancestral risk factors underlying Rheumatoid Arthritis (RA) susceptibility in Arab populations are largely unknown.Elucidating these factors provide insights for the practice of precision medicine in Arab populations. Objectives 1)Examine population structure in Arab RA cases/controls,2)test for association of ancestral principal components with RA risk,and 3)test if inbreeding,relatedness and markers of RA severity differ between individuals from the Gulf (G) vs.the Levant (L). Methods The study Genetics of Rheumatoid Arthritis in some Arab States examines the genetics & clinical features of Arab RA patients from Jordan,KSA,Lebanon, Qatar & the UAE.To date,604 cases & 444 controls enrolled.In a pilot of a GWAS targeted for 500 cases/controls,DNA from 163 subjects from Jordan,Qatar & the UAE was genotyped using the Illumina Human Core Exome Array.PC analysis was performed in Eigenstrat.Identity-by-state clustering,pair-wise identity-by-descent and the inbreeding coefficient based on observed vs.expected homozygous genotypes were calculated using Plink.T-tests were done to assess difference in inbreeding & relatedness between cases of G and L ancestry.Association between 10 PC of ancestry & RA status & between self-reported ancestry & seropositivity were assessed using logistic regression adjusting for age and gender. Results After quality control,genotype data were available for 93 cases and 59 controls for 539,346 SNPs.PC analysis including reference panels from the HapMap2 populations revealed proximity to the CEU European population,with most G and L subjects in a line from the European to the Yoruban African population & greater heterogeneity observed in G samples.Pair-wise identity by state distance-based clustering identified one primary Arab population group comprising all individuals.PC3, the principal component that clearly separated subjects from the Levant from those from the Gulf, was associated with RA (p=0.038),suggesting that subjects with G ancestry captured by this PC might be at greater RA risk. The Arab population showed more inbreeding than outbred populations,but no significant difference in the inbreeding coefficient was found between L and G populations. While overall,the study population was not highly related, cases from the Levant showed greater inter-relatedness than cases from the Gulf (p=0.011).After adjusting for age and gender, more patients with G ancestry compared to L ancestry reported either ACPA or RF positivity (p=0.021). Conclusions An Arab RA case-control sample with Gulf and Levant sub-components clusters as one population proximal to European populations and exhibits subtle population structure.The sub-population of G ancestry is more genetically diverse than the L sub-population, and may contain genetic variation that contributes to increased risk of RA, and seropositivity.Imminent GWAS should clarify if risk alleles for RA in European populations contribute to disease risk and/or severity in some Arab groups. Acknowledgements The study is funded by QNRF, NPRP#4-344-3-105 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.4891