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.

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.

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.

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.

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.