Consensus-Based Overarching Principles and Recommendations on the Use of Biosimilars in the Treatment of Inflammatory Arthritis in the Gulf Region.

BACKGROUND: Though biologic agents have significantly improved the treatment of inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis), high costs, stringent regulations, strict reimbursement criteria, and existing patents have limited patient access to treatments. While being highly similar in quality, safety, and efficacy to biologic reference products, biosimilars can reduce the financial burden and prevent underutilization of medication. OBJECTIVE: The objective of this initiative was to develop an evidence-based consensus of overarching principles and recommendations aimed at standardizing the use of biosimilars in treating inflammatory arthritis in the Gulf region. METHODS: A task force of practicing rheumatologists, a clinical pharmacist, a health economist, patients, regulators, and payors from across the Gulf region developed recommendations and overarching principles based on the outputs of a systematic literature review conducted to address Patient-Intervention-Comparison-Outcome (PICO) questions specific to key challenges regarding the use of biosimilars for the treatment of inflammatory arthritis in the region. As the data before 2017 have been previously reviewed in another publication, the current review focused on data published between January 2017 and August 2022 (PROSPERO ID CRD42022364002). Consensus on each statement required a level of agreement of 70% or greater. RESULTS: Consensus was reached for five overarching principles and nine recommendations by the task force. The principles emphasize the importance of improving the awareness, understanding, and perception of biosimilars, as well as the need for regulated regional real-world data generation and protocols to make biosimilars a viable and affordable treatment option for all patients. The consensus recommendations advocate the need for shared treatment decisions between rheumatologists and patients when considering biosimilars. They further recommend that confirmation of a biosimilar's efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the reference product has been approved. Finally, there is a need for pharmacovigilance and national health policies governing the adoption and prescription of biosimilars in clinical practice across the region. CONCLUSIONS: These are the first consensus recommendations for the Gulf region based on a systematic literature review and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines, integrating clinical evidence with clinical expertise to optimize decision making for the use of biosimilars in patients with inflammatory arthritis. They were formulated based on predominantly international data because of the limited regional data and therefore can be generalized to serve as recommendations for healthcare professionals in other parts of the world.

Impact of Spondyloarthritis on Pregnancy Outcome: A Descriptive Analysis from a Specialized Center in Qatar.

Introduction: Spondyloarthritis (SpA) most commonly presents at childbearing age; thus, pregnancy is of concern. However, data on pregnancy outcomes in these patients are limited. Purpose: This study aimed to retrospectively describe pregnancy outcomes in patients with SpA from the Middle East. Patients and Methods: We reviewed the electronic health records of all pregnant women attending a specialized pregnancy and rheumatic disease clinic between 2016 and 2022. All pregnant patients diagnosed with axial spondyloarthritis (axSpA) and peripheral SpA were included. Data on adverse maternal and fetal outcomes were collected. Results: Fifty-seven eligible pregnancies were identified from hospital records: 10 pregnancies ended in early miscarriage. Forty-seven pregnancies resulted in live singleton births, 25 in patients with peripheral SpA and 22 with axSpA. Human leukocyte antigen B27 was positive in 7 (15%) patients and only in women with axSpA. Twenty-nine (64%) patients received treatment throughout pregnancy. Consistent biologic disease-modifying antirheumatic drug (bDMARD) use was high, in eight (32%) patients with peripheral SpA and in nine (41%) with axSpA. A conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) was used as treatment in 11 (50%) patients with peripheral SpA and two (8%) with axSpA. Twenty-two (53%) neonates were delivered by cesarean section, 19 (40%) by normal vaginal delivery and three (6%) by assisted delivery. Additionally, 44 (94%) deliveries were at term, and 42 (91%) neonates had a normal birth weight. Exploration of a subgroup showed no difference in reported outcomes between patients treated with bDMARD and those treated with csDMARD. Conclusion: This descriptive study reports a high rate of favorable pregnancy outcomes in patients with SpA. There was no evidence to suggest a difference in pregnancy outcomes between women with axSpA and those with peripheral SpA. This study was one of the first reports from the Middle East. Further studies with larger sample size are warranted.

Impact of Risk Factors on COVID-19 Outcomes in Unvaccinated People With Rheumatic Diseases: A Comparative Analysis of Pandemic Epochs Using the COVID-19 Global Rheumatology Alliance Registry.

OBJECTIVE: Approximately one third of individuals worldwide have not received a COVID-19 vaccine. Although studies have investigated risk factors linked to severe COVID-19 among unvaccinated people with rheumatic diseases (RDs), we know less about whether these factors changed as the pandemic progressed. We aimed to identify risk factors associated with severe COVID-19 in unvaccinated individuals in different pandemic epochs corresponding to major variants of concern. METHODS: Patients with RDs and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance Registry between March 2020 and June 2022. An ordinal logistic regression model (not hospitalized, hospitalized, and death) was used with date of COVID-19 diagnosis, age, sex, race and/or ethnicity, comorbidities, RD activity, medications, and the human development index (HDI) as covariates. The main analysis included all unvaccinated patients across COVID-19 pandemic epochs; subanalyses stratified patients according to RD types. RESULTS: Among 19,256 unvaccinated people with RDs and COVID-19, those who were older, male, had more comorbidities, used glucocorticoids, had higher disease activity, or lived in lower HDI regions had worse outcomes across epochs. For those with rheumatoid arthritis, sulfasalazine and B-cell-depleting therapy were associated with worse outcomes, and tumor necrosis factor inhibitors were associated with improved outcomes. In those with connective tissue disease or vasculitis, B-cell-depleting therapy was associated with worse outcomes. CONCLUSION: Risk factors for severe COVID-19 outcomes were similar throughout pandemic epochs in unvaccinated people with RDs. Ongoing efforts, including vaccination, are needed to reduce COVID-19 severity in this population, particularly in those with medical and social vulnerabilities identified in this study.

Obstetric outcomes in women with rheumatic disease and COVID-19 in the context of vaccination status.

OBJECTIVE: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy. METHODS: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy. Descriptive differences between groups were tested using the chi-squared or Fisher's exact test. RESULTS: There were 73 pregnancies in 73 women with RMD and COVID-19. Overall, 24.7% (18) of pregnancies were ongoing, while of the 55 completed pregnancies, 90.9% (50) of pregnancies resulted in livebirths. At the time of COVID-19 diagnosis, 60.3% (n = 44) of women were unvaccinated, 4.1% (n = 3) had received one vaccine dose while 35.6% (n = 26) had two or more doses. Although 83.6% (n = 61) of women required no treatment for COVID-19, 20.5% (n = 15) required hospital admission. COVID-19 resulted in delivery in 6.8% (n = 3) of unvaccinated women and 3.8% (n = 1) of fully vaccinated women. There was a greater number of preterm births (PTB) in unvaccinated women compared with fully vaccinated 29.5% (n = 13) vs 18.2% (n = 2). CONCLUSIONS: In this descriptive study, unvaccinated pregnant women with RMD and COVID-19 had a greater number of PTB compared with those fully vaccinated against COVID-19. Additionally, the need for COVID-19 pharmacological treatment was uncommon in pregnant women with RMD regardless of vaccination status. These results support active promotion of COVID-19 vaccination in women with RMD who are pregnant or planning a pregnancy.

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study.

Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 µg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities. Funding: American College of Rheumatology and European Alliance of Associations for Rheumatology.

Rate of secondary HLH and performance of H-score in patients with severe COVID-19.

BACKGROUND: Severe COVID-19 is thought to be caused by immune overdrive and cytokine storm. One of the cytokine storm syndromes frequently induced by infections is secondary hemophagocytic lymphohistiocytosis (HLH) which can be assessed using H-score. In this study, we aimed to evaluate the rate of patients with COVID-19 who meet HLH criteria based on H-score and the association of H-score with poor outcomes. METHODS: In a prospective cohort study of 19 patients with COVID-19 requiring ICU stay from March to May, 2020, we collected demographic and clinical data that focused on H-score's variables and COVID-19 outcomes. H-score ≥ 169 was used to determine the percentage of patients who met the HLH criteria. Mann-Whitney, Kruskal-Wallis, and Spearman rho tests and multiple regression analyses were carried out to evaluate the associated factors. The optimal H-score cut-off to predict poor COVID-19 outcome (need for intubation ± ECMO) was determined using receiver operating characteristic (ROC) analysis. RESULTS: In 669 patients with severe COVID-19 with a mean ± SD age of 50.3 ± 12.8 years, which comprised 95% men; 66% required intubation, 4% ECMO, and 16% died. Only 2% had an H-score ≥ 169. Patients with poor outcomes had a higher mean (SD) H-score than those without; intubation (96.0 [50.0] vs 75.0 [35.0], p < 0.01), ECMO (113.0 [25.0] vs 93.0 [50.0], p < 0.01) and death (98.0 [62.0] vs 93.0 [48.0], p < 0.01). Factors associated with H-score were diabetes (ß coeff = - 10.4, p < 0.01), abdominal pain (ß coeff = 19.1, p < 0.01), duration of COVID-19 symptoms (ß coeff = - 0.7, p = 0.049), and days before ICU admission (ß coeff = - 1.2, p = 0.01). H-score showed a fair ability to discriminate COVID-19 outcomes (AUC 0.61, 95% CI 0.54-0.67). An H-score of 85 was the optimal cut-off with a sensitivity 69% and 1-specificity 53%. CONCLUSION: Despite its association with severity in COVID-19, H-score's ability to predict poor outcomes was only fair, indicating differences in the cytokine storm faced in COVID-19 compared with that during secondary HLH.

Development of a Prediction Model for COVID-19 Acute Respiratory Distress Syndrome in Patients With Rheumatic Diseases: Results From the Global Rheumatology Alliance Registry.

OBJECTIVE: Some patients with rheumatic diseases might be at higher risk for coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). We aimed to develop a prediction model for COVID-19 ARDS in this population and to create a simple risk score calculator for use in clinical settings. METHODS: Data were derived from the COVID-19 Global Rheumatology Alliance Registry from March 24, 2020, to May 12, 2021. Seven machine learning classifiers were trained on ARDS outcomes using 83 variables obtained at COVID-19 diagnosis. Predictive performance was assessed in a US test set and was validated in patients from four countries with independent registries using area under the curve (AUC), accuracy, sensitivity, and specificity. A simple risk score calculator was developed using a regression model incorporating the most influential predictors from the best performing classifier. RESULTS: The study included 8633 patients from 74 countries, of whom 523 (6%) had ARDS. Gradient boosting had the highest mean AUC (0.78; 95% confidence interval [CI]: 0.67-0.88) and was considered the top performing classifier. Ten predictors were identified as key risk factors and were included in a regression model. The regression model that predicted ARDS with 71% (95% CI: 61%-83%) sensitivity in the test set, and with sensitivities ranging from 61% to 80% in countries with independent registries, was used to develop the risk score calculator. CONCLUSION: We were able to predict ARDS with good sensitivity using information readily available at COVID-19 diagnosis. The proposed risk score calculator has the potential to guide risk stratification for treatments, such as monoclonal antibodies, that have potential to reduce COVID-19 disease progression.

Humoral Response of Patients With Autoimmune Rheumatic Disease to BNT162b2 Vaccine: A Retrospective Comparative Study.

Objective The effectiveness and safety of SARS-CoV-2 vaccines in patients with autoimmune rheumatic diseases (ARDs) treated with immunomodulators remain uncertain. Therefore, this study aimed to evaluate whether the humoral immune response to the BNT162b2 vaccine differs between patients without and with ARDs treated with immunomodulators. Methods We retrospectively reviewed 3208 electronic medical records from the database of the Hamad Medical Corporation (HMC) outpatient rheumatology clinics to capture patients with ARDs and control patients without autoimmune inflammatory diseases. All patients who were SARS-CoV-2 infection-naïve, had received two doses of BNT162b2 vaccination, and had been serologically tested using Elecsys® anti-SARS-CoV-2 S immunoassays (Roche Holdings AG, Basel, Switzerland), were included in the analysis. Patients with ARD were classified into six subgroups according to the received ARD immunomodulators: methotrexate monotherapy (MTXM), a combination of conventional synthetic disease-modifying antirheumatic drugs (Cs-DMARDs), tumor necrosis factor inhibitor (TNF-i), rituximab, interleukin-6 inhibitor (IL6-i), and Janus kinase inhibitor (JAK-i). Samples with an anti-SARS-CoV-2 S titer of <0.8 and <132 binding antibody unit (BAU)/mL were defined as negative and poor seroconversion, respectively. The overall mean of anti-SARS-CoV-2 S titer and its level at <0.8 and <132 were compared between the six subgroups of patients with ARD and the controls by performing an unpaired t-test and Chi-squared or Fisher's exact test as appropriate. Results The mean (SD) age of 110 patients with ARDs and 20 controls was 47.1 (12) and 59.3 (8.9) years (P < 0.001), respectively, and women predominated both groups (60% vs. 75%, P = 0.20). The most frequently prescribed Cs-DMARDs was methotrexate in 50 (45.5%) patients, followed by TNF-i in 46 (41.8%), rituximab in 20 (18.2%), JAK-i in 12 (10.9%), and IL6-i in 7 (6.4%) patients. The mean (SD) anti-SARS-CoV-2 S antibody titer of only the rituximab subgroup significantly differed from the controls (P = 0.012). Conclusion The most prevalent ARD immunomodulators (Cs-DMARDs, TNF-i, JAK-i, and IL6-i) were associated with comparable seroconversion rates to the BNT162b2 vaccine. In comparison, rituximab was significantly associated with decreased immunogenicity.

Characteristics and Obstetric Outcomes in Women With Autoimmune Rheumatic Disease During the COVID-19 Pandemic in Qatar.

OBJECTIVE: Pregnant women with autoimmune rheumatic diseases are considered to have a high risk of obstetric complications with the emergence of the Coronavirus disease (COVID-19) pandemic. Therefore, we aimed to assess the impact of COVID-19 on this high-risk group. METHODS: This cross-sectional cohort study (March to December 2020) was conducted at the largest tertiary center in Qatar (Hamad Medical Corporation). Eighty consecutive patients following up at the center during pregnancy were surveyed through telephonic interviews. Data on COVID-19 and pregnancy outcomes were extracted from electronic hospital records. RESULTS: Eighty pregnant women with autoimmune rheumatic diseases were included. Among them, 17 (21.3%) (95% confidence interval [CI]: 12.9-31.8%) were diagnosed with COVID-19, five were hospitalized, and only one required intensive care unit admission. The proportion of adverse obstetric outcomes in the cohort was 29.5% (n = 23; 95% CI: 19.7-40.9%). Prematurity (n = 14; 19.4%) and caesarean section (n = 30; 41.1%) were the most prevalent adverse events. There was no statistical difference in adverse pregnancy outcomes between women with and without COVID-19. CONCLUSION: COVID-19 did not affect pregnancy outcomes in women with autoimmune rheumatic diseases.

SARS-CoV-2 breakthrough infections among vaccinated individuals with rheumatic disease: results from the COVID-19 Global Rheumatology Alliance provider registry.

OBJECTIVE: While COVID-19 vaccination prevents severe infections, poor immunogenicity in immunocompromised people threatens vaccine effectiveness. We analysed the clinical characteristics of patients with rheumatic disease who developed breakthrough COVID-19 after vaccination against SARS-CoV-2. METHODS: We included people partially or fully vaccinated against SARS-CoV-2 who developed COVID-19 between 5 January and 30 September 2021 and were reported to the Global Rheumatology Alliance registry. Breakthrough infections were defined as occurring ≥14 days after completion of the vaccination series, specifically 14 days after the second dose in a two-dose series or 14 days after a single-dose vaccine. We analysed patients' demographic and clinical characteristics and COVID-19 symptoms and outcomes. RESULTS: SARS-CoV-2 infection was reported in 197 partially or fully vaccinated people with rheumatic disease (mean age 54 years, 77% female, 56% white). The majority (n=140/197, 71%) received messenger RNA vaccines. Among the fully vaccinated (n=87), infection occurred a mean of 112 (±60) days after the second vaccine dose. Among those fully vaccinated and hospitalised (n=22, age range 36-83 years), nine had used B cell-depleting therapy (BCDT), with six as monotherapy, at the time of vaccination. Three were on mycophenolate. The majority (n=14/22, 64%) were not taking systemic glucocorticoids. Eight patients had pre-existing lung disease and five patients died. CONCLUSION: More than half of fully vaccinated individuals with breakthrough infections requiring hospitalisation were on BCDT or mycophenolate. Further risk mitigation strategies are likely needed to protect this selected high-risk population.

Epidemiology of hip fracture in Qatar and development of a country specific FRAX model.

Hip fracture data were retrieved from electronical medical records for the years 2017-2019 in the State of Qatar and used to create a FRAX® model to facilitate fracture risk assessment. Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi, and Kuwait but fracture probabilities varied due to differences in mortality. OBJECTIVE: This paper describes the epidemiology of osteoporotic fractures in the State of Qatar that was used to develop the country-specific fracture prediction FRAX® tool. METHODS: Hip fracture data were retrieved from electronic medical records for the years 2017-2019 in the State of Qatar. The age and sex specific incidence of hip fracture in Qatari residents and national mortality rates were used to create a FRAX® model. Fracture probabilities were compared with those from neighboring countries having FRAX models. RESULTS: Hip fracture rates were comparable with estimates from Saudi Arabia, Abu Dhabi and Kuwait. In contrast, probabilities of a major osteoporotic fracture or hip fracture were lower in Qatar than in Kuwait but higher than those in Abu Dhabi and Saudi Arabia due to differences in mortality. CONCLUSION: The FRAX model should enhance accuracy of determining fracture probability among the Qatari population and help guide decisions about treatment.

Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance.

AIM: To determine characteristics associated with more severe outcomes in a global registry of people with systemic lupus erythematosus (SLE) and COVID-19. METHODS: People with SLE and COVID-19 reported in the COVID-19 Global Rheumatology Alliance registry from March 2020 to June 2021 were included. The ordinal outcome was defined as: (1) not hospitalised, (2) hospitalised with no oxygenation, (3) hospitalised with any ventilation or oxygenation and (4) death. A multivariable ordinal logistic regression model was constructed to assess the relationship between COVID-19 severity and demographic characteristics, comorbidities, medications and disease activity. RESULTS: A total of 1606 people with SLE were included. In the multivariable model, older age (OR 1.03, 95% CI 1.02 to 1.04), male sex (1.50, 1.01 to 2.23), prednisone dose (1-5 mg/day 1.86, 1.20 to 2.66, 6-9 mg/day 2.47, 1.24 to 4.86 and ≥10 mg/day 1.95, 1.27 to 2.99), no current treatment (1.80, 1.17 to 2.75), comorbidities (eg, kidney disease 3.51, 2.42 to 5.09, cardiovascular disease/hypertension 1.69, 1.25 to 2.29) and moderate or high SLE disease activity (vs remission; 1.61, 1.02 to 2.54 and 3.94, 2.11 to 7.34, respectively) were associated with more severe outcomes. In age-adjusted and sex-adjusted models, mycophenolate, rituximab and cyclophosphamide were associated with worse outcomes compared with hydroxychloroquine; outcomes were more favourable with methotrexate and belimumab. CONCLUSIONS: More severe COVID-19 outcomes in individuals with SLE are largely driven by demographic factors, comorbidities and untreated or active SLE. Patients using glucocorticoids also experienced more severe outcomes.

Telehealth in rheumatology: the 2021 Arab League of Rheumatology Best Practice Guidelines.

To develop Best Practice Guidelines (BPG) for the use of Telehealth in Rheumatology in the Arab region, to identify the main barriers and facilitators of telehealth, and to provide rheumatologists with a practical toolkit for the implementation of telehealth. Guidelines were drafted by a core steering committee from the Arab League of Associations for Rheumatology (ArLAR) after performing a literature search. A multidisciplinary task force (TF), including 18 rheumatologists, 2 patients, and 2 regulators from 15 Arab countries, assessed the BPG using 3 rounds of anonymous online voting by modified Delphi process. The statements were included in the final BPG without further voting if ≥ 80% of TF members indicated high agreement. The voting on barriers and facilitators was performed through one voting round. The toolkit was developed based on available literature and discussions during the Delphi rounds. Four General Principles and twelve Statements were formulated. A teleconsultation was specifically defined for the purpose of these guidelines. The concept of choice in telehealth was highlighted, emphasizing patient confidentiality, medical information security, rheumatologist's clinical judgment, and local jurisdictional regulations. The top barrier for telehealth was the concern about the quality of care. The toolkit emphasized technical aspects of teleconsultation and proposed a triage system. The ArLAR BPG provide rheumatologists with a series of strategies about the most reliable, productive, and rational approaches to apply telehealth.

Salmonella-Related Septic Arthritis in an Immunocompetent Adult: A Case Report.

Salmonella is a well-known cause of foodborne illness, commonly resulting in gastroenteritis, bacteremia, and focal infections. Salmonella septic arthritis is a rare entity with cases mostly prevalent in patients with sickle cell disease, immunocompromised state, and advanced age. Here, we present a case of Salmonella septic arthritis in a previously healthy young gentleman with no risk factors who presented with fever, skin rash, abdominal pain, and left hip pain. Initial laboratory findings showed high inflammatory markers and negative blood culture. MRI of the left hip joint showed effusion and features of inflammatory changes. The diagnosis was confirmed by joint aspirate culture growing Salmonella B. Furthermore, he underwent joint arthrotomy; pus was drained and treated with an antibiotic. Subsequently, the patient responded to treatment with marked clinical recovery.

COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020, the COVID-19 Global Rheumatology Alliance has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included rheumatoid arthritis (n = 9), systemic lupus erythematosus (n = 9), psoriatic arthritis/other inflammatory arthritides (n = 8), and antiphospholipid syndrome (n = 6). Most had a term birth (16/22), with 3 preterm births, 1 termination, and 1 miscarriage; 1 woman had yet to deliver at the time of report. One-quarter (n = 10/39) of pregnant women were hospitalized following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalized); no patients died. The majority did not receive specific medication treatment for their COVID-19 (n = 32/39, 82%), and 7 patients received some combination of antimalarials, colchicine, anti-interleukin 1ß, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favorable outcomes. These data have limitations due to the small size and methodology; however, they provide cautious optimism for pregnancy outcomes for women with rheumatic disease particularly in comparison to the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19.

Subclinical Corneal Nerve Fiber Damage and Immune Cell Activation in Systemic Lupus Erythematosus: A Corneal Confocal Microscopy Study.

Purpose: The purpose of this study was to evaluate the utility of corneal confocal microscopy (CCM) in identifying small nerve fiber damage and immune cell activation in patients with systemic lupus erythematosus (SLE). Methods: This cross-sectional comparative study included 39 consecutive patients with SLE and 30 healthy control participants. Central corneal sensitivity was assessed using a Cochet-Bonnet contact corneal esthesiometer and a laser scanning CCM (Heidelberg, Germany) was used to quantify corneal nerve fiber density (CNFD), nerve branch density (CNBD), nerve fiber length (CNFL), and Langerhans cell (LC) density. Results: Age was comparable among patients with SLE (33.7 ± 12.7) and controls (35.0 ± 13.7 years, P = 0.670) and the median duration of disease was 3.0 years (2.0-10.0 years). CNBD (P = 0.003) and CNFL (P = 0.019) were lower and mature LC density (P = 0.002) was higher, but corneal sensitivity (P = 0.178) and CNFD (P = 0.198) were comparable in patients with SLE compared with controls. The SELENA-SLEDAI score correlated with CNFD (ρ = -0.319, P = 0.048) and CNFL (ρ = -0.373, P = 0.019), and the total and immature LC densities correlated with CNBD (ρ = -0.319. P = 0.048, and ρ = -0.328, P = 0.041, respectively). Immature LC density was higher (P = 0.025), but corneal sensitivity and nerve fiber parameters were comparable between patients with (33%) and without neuropsychiatric symptoms and SLE. Conclusions: Corneal confocal microscopy identifies distal corneal nerve fiber loss and increased immune cell density in patients with SLE and corneal nerve loss was associated with disease activity. Translational Relevance: Corneal confocal microscopy may enable the detection of subclinical corneal nerve loss and immune cell activation in SLE.

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study.

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31-1·57]), were male compared with female (1·38 [1·05-1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23-1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50-3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49-3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology.

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.

Importance: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. Objective: To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. Design, Setting, and Participants: This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age ≥18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. Exposures: Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. Main Outcomes and Measures: The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. Results: A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. Conclusions and Relevance: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.

Associations of baseline use of biologic or targeted synthetic DMARDs with COVID-19 severity in rheumatoid arthritis: Results from the COVID-19 Global Rheumatology Alliance physician registry.

OBJECTIVE: To investigate baseline use of biologic or targeted synthetic (b/ts) disease-modifying antirheumatic drugs (DMARDs) and COVID-19 outcomes in rheumatoid arthritis (RA). METHODS: We analysed the COVID-19 Global Rheumatology Alliance physician registry (from 24 March 2020 to 12 April 2021). We investigated b/tsDMARD use for RA at the clinical onset of COVID-19 (baseline): abatacept (ABA), rituximab (RTX), Janus kinase inhibitors (JAKi), interleukin 6 inhibitors (IL-6i) or tumour necrosis factor inhibitors (TNFi, reference group). The ordinal COVID-19 severity outcome was (1) no hospitalisation, (2) hospitalisation without oxygen, (3) hospitalisation with oxygen/ventilation or (4) death. We used ordinal logistic regression to estimate the OR (odds of being one level higher on the ordinal outcome) for each drug class compared with TNFi, adjusting for potential baseline confounders. RESULTS: Of 2869 people with RA (mean age 56.7 years, 80.8% female) on b/tsDMARD at the onset of COVID-19, there were 237 on ABA, 364 on RTX, 317 on IL-6i, 563 on JAKi and 1388 on TNFi. Overall, 613 (21%) were hospitalised and 157 (5.5%) died. RTX (OR 4.15, 95% CI 3.16 to 5.44) and JAKi (OR 2.06, 95% CI 1.60 to 2.65) were each associated with worse COVID-19 severity compared with TNFi. There were no associations between ABA or IL6i and COVID-19 severity. CONCLUSIONS: People with RA treated with RTX or JAKi had worse COVID-19 severity than those on TNFi. The strong association of RTX and JAKi use with poor COVID-19 outcomes highlights prioritisation of risk mitigation strategies for these people.

Epidemiology of musculoskeletal complaints and diseases in Qatar: A cross-sectional study.

BACKGROUND: Musculoskeletal (MSK) conditions are considered a significant public health problem on account of their high prevalence in communities worldwide and their pervasive impact. Knowledge of the epidemiology of MSK symptoms and diseases is lacking in Qatar. Obtaining this information will guide local health policymakers in the future strategic planning of the health budget. OBJECTIVE: To estimate the prevalence rate of MSK disorders in the Qatari population above 15 years of age using the Community Oriented Program for the Control of Rheumatic Disease (COPCORD) survey. METHODS: This cross-sectional study targeted 1000 Qatari participants, including 500 males and 500 females. A door-to-door survey was conducted using the Arabic version of the COPCORD questionnaire with the help of research assistants. Participants with positive surveys were asked to visit Hamad General Hospital Rheumatology outpatient clinics for clinical evaluation by a rheumatologist. When necessary, laboratory testing and X-rays were conducted to confirm any MSK diagnosis. RESULTS: A total of 1239 (males, 50.8%) Qatari individuals randomly selected from the different municipalities of Qatar completed the COPCORD survey. Among the participants, 563 (45.4%) screened positive for MSK pain. Knee pain (24.5%) and back pain (23.3%) were the most common sites of pain, and both conditions showed no gender predominance (p = 0.073 and 0.108, respectively). Shoulder, wrist, hand, hip, and neck pain were significantly predominant in females (p < 0.001 for all). A total of 237 MSK disorders were diagnosed in 196 (15.8%) participants, including 181 degenerative joint diseases, 52 soft-tissue rheumatism conditions, and 4 autoimmune inflammatory disorders. Among degenerative joint diseases, knee osteoarthritis (6.4%) was the most common. Among soft-tissue rheumatic conditions, muscular lower back pain (1.9%), myofascial neck pain (0.64%), generalized body pain (0.32%), and shoulder tendinitis (0.7%) were the most common diseases. The autoimmune inflammatory disorders identified included rheumatoid arthritis (n = 2), connective tissue disease (n = 1), and inflammatory bowel disease-associated arthritis (n = 1). CONCLUSION: The overall prevalence rate of MSK disorders in this small cross-sectional cohort of Qatari individuals was 15.8%. Knee pain (24.5%) and knee osteoarthritis (6.4%) were the most common MSK complaints and diagnosis in the studied Qatari population. This study guides future efforts directed toward the prevention and management of MSK diseases. Further studies with a larger sample size are needed to verify the findings.