Association Between Race/Ethnicity and COVID-19 Outcomes in Systemic Lupus Erythematosus Patients From the United States: Data From the COVID-19 Global Rheumatology Alliance.

OBJECTIVE: To determine the association between race/ethnicity and COVID-19 outcomes in individuals with systemic lupus erythematosus (SLE). METHODS: Individuals with SLE from the US with data entered into the COVID-19 Global Rheumatology Alliance registry between March 24, 2020 and August 27, 2021 were included. Variables included age, sex, race, and ethnicity (White, Black, Hispanic, other), comorbidities, disease activity, pandemic time period, glucocorticoid dose, antimalarials, and immunosuppressive drug use. The ordinal outcome categories were: not hospitalized, hospitalized with no oxygenation, hospitalized with any ventilation or oxygenation, and death. We constructed ordinal logistic regression models evaluating the relationship between race/ethnicity and COVID-19 severity, adjusting for possible confounders. RESULTS: We included 523 patients; 473 (90.4%) were female and the mean ± SD age was 46.6 ± 14.0 years. A total of 358 patients (74.6%) were not hospitalized; 40 patients (8.3%) were hospitalized without oxygen, 64 patients (13.3%) were hospitalized with any oxygenation, and 18 (3.8%) died. In a multivariable model, Black (odds ratio [OR] 2.73 [95% confidence interval (95% CI) 1.36-5.53]) and Hispanic (OR 2.76 [95% CI 1.34-5.69]) individuals had higher odds of more severe outcomes than White individuals. CONCLUSION: Black and Hispanic individuals with SLE experienced more severe COVID-19 outcomes, which is consistent with findings in the US general population. These results likely reflect socioeconomic and health disparities and suggest that more aggressive efforts are needed to prevent and treat infection in this population.

Assessing the Severity of COVID-19 Lung Injury in Rheumatic Diseases Versus the General Population Using Deep Learning-Derived Chest Radiograph Scores.

OBJECTIVE: COVID-19 patients with rheumatic disease have a higher risk of mechanical ventilation than the general population. The present study was undertaken to assess lung involvement using a validated deep learning algorithm that extracts a quantitative measure of radiographic lung disease severity. METHODS: We performed a comparative cohort study of rheumatic disease patients with COVID-19 and ≥1 chest radiograph within ±2 weeks of COVID-19 diagnosis and matched comparators. We used unadjusted and adjusted (for age, Charlson comorbidity index, and interstitial lung disease) quantile regression to compare the maximum pulmonary x-ray severity (PXS) score at the 10th to 90th percentiles between groups. We evaluated the association of severe PXS score (>9) with mechanical ventilation and death using Cox regression. RESULTS: We identified 70 patients with rheumatic disease and 463 general population comparators. Maximum PXS scores were similar in the rheumatic disease patients and comparators at the 10th to 60th percentiles but significantly higher among rheumatic disease patients at the 70th to 90th percentiles (90th percentile score of 10.2 versus 9.2; adjusted P = 0.03). Rheumatic disease patients were more likely to have a PXS score of >9 (20% versus 11%; P = 0.02), indicating severe pulmonary disease. Rheumatic disease patients with PXS scores >9 versus ≤9 had higher risk of mechanical ventilation (hazard ratio [HR] 24.1 [95% confidence interval (95% CI) 6.7, 86.9]) and death (HR 8.2 [95% CI 0.7, 90.4]). CONCLUSION: Rheumatic disease patients with COVID-19 had more severe radiographic lung involvement than comparators. Higher PXS scores were associated with mechanical ventilation and will be important for future studies leveraging big data to assess COVID-19 outcomes in rheumatic disease patients.

Factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To investigate factors associated with severe COVID-19 in people with idiopathic inflammatory myopathy (IIM). METHODS: Demographic data, clinical characteristics and COVID-19 outcome severity of adults with IIM were obtained from the COVID-19 Global Rheumatology Alliance physician-reported registry. A 3-point ordinal COVID-19 severity scale was defined: (1) no hospitalisation, (2) hospitalisation (and no death) and (3) death. ORs were estimated using multivariable ordinal logistic regression. Sensitivity analyses were performed using a 4-point ordinal scale: (1) no hospitalisation, (2) hospitalisation with no oxygen (and no death), (3) hospitalisation with oxygen/ventilation (and no death) and 4) death. RESULTS: Of 348 patients, 48% were not hospitalised, 39% were hospitalised (and did not die) and 13% died. Older age (OR=1.59/decade, 95% CI 1.31 to 1.91), high disease activity (OR=3.50, 95% CI 1.25 to 9.83; vs remission), ≥2 comorbidities (OR=2.63, 95% CI 1.39 to 4.98; vs none), prednisolone-equivalent dose >7.5 mg/day (OR=2.40, 95% CI 1.09 to 5.28; vs no intake) and exposure to rituximab (OR=2.71, 95% CI 1.28 to 5.72; vs conventional synthetic disease-modifying antirheumatic drugs only) were independently associated with severe COVID-19. In addition to these variables, in the sensitivity analyses, male sex (OR range: 1.65-1.83; vs female) was also significantly associated with severe outcomes, while COVID-19 diagnosis after 1 October 2020 (OR range: 0.51-0.59; vs on/before 15 June 2020) was significantly associated with less severe outcomes, but these associations were not significant in the main model (OR=1.57, 95% CI 0.95 to 2.59; and OR=0.61, 95% CI 0.37 to 1.00; respectively). CONCLUSIONS: This is the first large registry data on outcomes of COVID-19 in people with IIM. Older age, male sex, higher comorbidity burden, high disease activity, prednisolone-equivalent dose >7.5 mg/day and rituximab exposure were associated with severe COVID-19. These findings will enable risk stratification and inform management decisions for patients with IIM.

DMARD disruption, rheumatic disease flare, and prolonged COVID-19 symptom duration after acute COVID-19 among patients with rheumatic disease: A prospective study.

OBJECTIVE: To describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). METHODS: We surveyed people with pre-existing SARDs who had confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression. RESULTS: We analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6±2.9 vs. 7.6±2.3, p<0.001). Median time to COVID-19 symptom resolution was 25 days (IQR 11, 160). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. CONCLUSION: DMARD disruption, SARD flare, and prolonged COVID-19 symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.

The Ultrasound-guided Anteromedial Joint Line Approach: A Targeted Corticosteroid Injection Technique for Patients With Medial Knee Pain.

BACKGROUND: Medial knee pain is a common complaint in the adult population. When conservative measures fail, intraarticular knee corticosteroid injections are often offered through the superolateral approach into the suprapatellar recess to provide short-term relief. However, some patients fail to respond and require alternative approaches. The anteromedial joint line (AMJL) approach, which targets the medial compartment, may be more effective when pain-generating pathologies such as synovitis are located in the medial compartment. To date, there have been no dedicated studies evaluating ultrasound-guided (USg) corticosteroid injections through the AMJL approach to reduce medial knee pain. OBJECTIVES: The current study aims to assess the clinical characteristics, ultrasound findings, and clinical outcomes for patients with medial knee pain who received USg corticosteroid injections via the AMJL approach. STUDY DESIGN: Retrospective study. SETTING: This study took place at one academic musculoskeletal ultrasound clinic at an urban tertiary care center. METHODS: Sixty-five patients (76 knees; 11 patients with bilateral injections) with medial knee pain who had received USg-AMJL corticosteroid injections from January 2016 through  March 2020 were reviewed for inclusion. Baseline demographic information and clinical characteristics from one year prior to 6 months following USg-AMJL injection were analyzed for each patient. Responders were defined as those who reported pain relief, decreased usage of analgesic medications, or increased physical activity. Nonresponders  were defined as those not meeting any of the responder endpoints. RESULTS: Within one year prior to receiving a USg-AMJL injection, 51.3% (39/76 knees) had attempted superolateral knee injections without relief. Immediately following a USg-AMJL injection, 98.7% (75/76) experienced symptomatic relief. Follow-up visits took place on average at 11 weeks postinjection with 92.3% (60/65 patients) responding positively. In comparison to the responder group, the nonresponder group had a significantly older mean age (P = 0.009), lower mean body mass index (P = 0.007), and higher burden of morbidities as measured by the Charlson Comorbidity Index (P = 0.044). One patient reported a steroid flare within one week of injection. The most common diagnoses contributing to medial knee pain for these patients were osteoarthritis, medial meniscal injury, crystal arthropathy, and medial collateral ligament injury, which were supported by point-of-care ultrasound findings. LIMITATIONS: This study was limited by its sample size and retrospective observational design. CONCLUSIONS: USg AMJL injection is a safe and effective procedure for targeting medial knee pain, particularly in the settings of obesity and prior failed superolateral and suprapatellar knee injections. Further investigation is required to assess long-term clinical outcomes of this injection approach.

DMARD disruption, disease flare, and prolonged symptom duration after acute COVID-19 among participants with rheumatic disease: A prospective study.

OBJECTIVE: To describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs). METHODS: We surveyed patients with SARDs after confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression. RESULTS: We analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6±2.9 vs. 7.6±2.3, p<0.001). Median time to COVID-19 symptom resolution was 14 days (IQR 9,29). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms. CONCLUSION: DMARD disruption, SARD flare, and prolonged symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.

Secular Trends in the Pharmacologic Treatment of Osteoporosis and Malignancy-Related Bone Disease from 2009 to 2020.

BACKGROUND: New bone-directed therapies, including denosumab, abaloparatide, and romosozumab, emerged during the past decade, and recent trends in use of these therapies are unknown. OBJECTIVE: To examine temporal trends in bone-directed therapies. DESIGN: An open cohort study in a US commercial insurance database, January 2009 to March 2020. PARTICIPANTS/INTERVENTIONS: All-users of bone-directed therapies age >50 years, users with osteoporosis, users with malignancies, and patients with recent (within 180 days) fractures at key osteoporotic sites. MAIN MEASURES: The percentage of each cohort with prescription dispensing or medication administration claims for each bone-directed therapy during each quarter of the study period. KEY RESULTS: We analyzed 15.48 million prescription dispensings or medication administration claims from 1.46 million unique individuals (89% women, mean age 69 years). Among all users of bone-directed therapies, alendronate, and zoledronic acid use increased modestly (49 to 63% and 2 to 4%, respectively, during the study period). In contrast, denosumab use increased rapidly after approval in 2010, overtaking use of all other medications except alendronate by 2017 and reaching 16% of users by March 2020. Similar trends were seen in cohorts of osteoporosis, malignancy, and recent fractures. Importantly, use of any bone-directed therapy after fractures was low and declined from 15 to 8%. CONCLUSIONS: Rates of denosumab use outpaced growth of all other bone-directed therapies over the past decade. Treatment rates after osteoporotic fractures were low and declined over time, highlighting major failings in osteoporosis treatment in the US.

Systemic bevacizumab to facilitate anticoagulation in antiphospholipid syndrome and bleeding gastrointestinal angiodysplasia.

Bleeding gastrointestinal angiodysplasia may occur in patients with vasculitis and can be challenging to treat. We describe the novel use of bevacizumab therapy to treat bleeding gastrointestinal angiodysplasia and severe anemia in a patient with eosinophilic granulomatosis with angiitis complicated by antiphospholipid antibody syndrome requiring indefinite warfarin therapy. Studies confirmed multiple bleeding jejunal angiodysplasias unamenable to endoscopic intervention, and the patient required ongoing support with iron infusions and blood transfusions to maintain a minimally acceptable hemoglobin. Given the severe anemia, need for continued, indefinite antiplatelet and anticoagulation therapy, and failure of standard treatment approaches, the patient was initiated on systemic bevacizumab therapy, on the basis of prior documented success of bevacizumab to manage gastrointestinal telangiectasias in patients with hereditary hemorrhagic telangiectasia. Bevacizumab was highly effective, with rapid resolution of bleeding, normalization of hemoglobin, liberation from hematologic support and no adverse events, including no thromboembolic events. Vascular endothelial growth factor (VEGF-A) rose paradoxically after initiation of bevacizumab and normalized after its discontinuation. Given these findings, use of systemic bevacizumab to manage bleeding angiodysplasia in patients with acquired vascular disorders merits further study.

Increased Risk of COVID-19 in Patients With Rheumatoid Arthritis: A General Population-Based Cohort Study.

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at an increased risk of acquiring infections owing to immunologic dysfunction and use of potent immunomodulatory medications; however, few data are available on their risk of COVID-19. We estimated the rate of COVID-19 among RA participants and compared it with that of the general population. METHODS: Using the Health Improvement Network, we identified RA patients before February 2020 and followed them to September 2020. We calculated the rate of COVID-19 among participants with RA and compared it with that of the general population using a Cox proportional hazards model, adjusting for potential confounders using overlap weighting of exposure score. We repeated the same analysis among participants with osteoarthritis, a nonautoimmune rheumatic disease, as a negative control exposure. RESULTS: We identified 225 cases of suspected and confirmed COVID-19 among 17,268 RA patients, and 14,234 cases among 1,616,600 participants in the general population (1.4 versus 0.9/1,000 person-months), with the adjusted hazard ratio (HRadj ) being 1.19 (95% confidence interval [95% CI] 1.04-1.36). Confirmed COVID-19 cases developed in 46 RA participants and in 2,249 in the general population (0.3 versus 0.1/1,000 person-months), with the HRadj being 1.42 (95% CI 1.01-1.95). No statistically significant difference was observed for suspected and confirmed (HR 1.00 [95% CI 0.93-1.07]) or confirmed (HR 1.08 [95% CI 0.92-1.27]) COVID-19 rates between participants with osteoarthritis and the general population. CONCLUSION: RA, but not osteoarthritis, was associated with an increased risk of COVID-19. Our findings provide timely evidence to support recommendations that booster vaccines and priority access to anti-SARS-CoV-2 monoclonal antibody treatments should be encouraged for RA patients.

Coronavirus Disease 2019 Outcomes Among Recipients of Anti-CD20 Monoclonal Antibodies for Immune-Mediated Diseases: A Comparative Cohort Study.

OBJECTIVE: Patients with immune-mediated diseases treated with anti-CD20 monoclonal antibodies may have worse coronavirus disease 2019 (COVID-19) outcomes due to impaired humoral immunity, but differences compared with the general population are unknown. METHODS: We identified patients with immune-mediated diseases who received anti-CD20 monoclonal antibodies within 1 year prior to the index date of polymerase chain reaction-confirmed COVID-19 between January 31, 2020, and January 31, 2021. General population comparators with COVID-19 were matched up 5:1 by age, sex, and polymerase chain reaction date. Unadjusted and multivariable adjusted (for age, race, body mass index, and Charlson Comorbidity Index) hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in recipients of anti-CD20 monoclonal antibodies versus comparators were estimated by using Cox regression. RESULTS: We identified 114 cases patients COVID-19 who had received anti-CD20 monoclonal antibodies for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). Patients treated with anti-CD20 monoclonal antibodies had higher mortality (adjusted HR 2.16; 95% CI: 1.03-4.54) than matched comparators. Risks of hospitalization (adjusted HR 0.88; 95% CI: 0.62-1.26) and mechanical ventilation use (adjusted HR 0.82; 95% CI: 0.36-1.87) were similar. Similar trends were seen in analyses according to type of indication (eg, rheumatic or neurologic disease) and duration of anti-CD20 monoclonal antibody use (<1 or ≥1 year) and after patients with interstitial lung disease, those with cancer, and those on glucocorticoids prior to COVID-19 diagnosis were excluded. CONCLUSION: Patients who received anti-CD20 monoclonal antibodies for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in recipients of anti-CD20 monoclonal antibodies during the ongoing pandemic.

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.

Rituximab for interstitial pneumonia with autoimmune features at two medical centres.

OBJECTIVES: Many patients with interstitial lung disease (ILD) have autoimmune manifestations but do not meet criteria for a systemic rheumatic disease. A subset meets criteria for interstitial pneumonia with autoimmune features (IPAF) and have ILD requiring therapy. We conducted a multicentre observational study to examine the use of rituximab (RTX) in IPAF. METHODS: Patients from Mass General Brigham (MGB) and University of Chicago Medicine (UCM) were included if they were ≥18 years old, met the 2015 classification criteria for IPAF and were treated with RTX. Clinical improvement was defined as improvement in four out of four domains at 1 year after RTX initiation: documented clinician global assessment; oxygen requirement; need for respiratory-related hospitalization; and survival. RESULTS: At MGB, 36 IPAF patients (mean age 61 years, 44% female) were treated with RTX. At 1 year, 18 (50%) were clinically improved, 12 (33%) were stable, and 6 (17%) died from progressive respiratory failure. At UCM, 14 IPAF patients (mean age 53 years, 71% female) were treated with RTX. At 1 year, eight (57%) were improved, two (14%) were stable, three (21%) died from progressive respiratory failure, and one (7%) was lost to follow-up. Two patients experienced minor infusion reactions, and two patients discontinued therapy owing to adverse events (infections). CONCLUSION: In patients with IPAF treated with RTX at two medical centres, the majority (40 [80%]) demonstrated improvement/stability at 1 year. These findings call for prospective studies, including randomized clinical trials, to determine the risks, benefits and cost effectiveness of RTX in IPAF.

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.

COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort Study.

OBJECTIVE: Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown. METHODS: We identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression. RESULTS: We identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or ≥1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis. CONCLUSIONS: Patients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic. KEY MESSAGES: What is already known about this subject?: Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes than those treated with other immunomodulatory medications, but differences compared to the general population are unknown.What does this study add?: CD20 inhibitor-treated cases had over two-fold higher risk of mortality than matched general population comparators, although risks of hospitalization and mechanical ventilation were similar.How might this impact on clinical practice or future developments?: There is an urgent need for risk mitigation strategies, such as SARS-CoV-2 monoclonal antibodies or booster vaccinations, for patients with immune-mediated diseases treated with CD20 inhibitors during the ongoing COVID-19 pandemic.

Laboratory trends, hyperinflammation, and clinical outcomes for patients with a systemic rheumatic disease admitted to hospital for COVID-19: a retrospective, comparative cohort study.

BACKGROUND: COVID-19 can induce a hyperinflammatory state, which might lead to poor clinical outcomes. We aimed to assess whether patients with a systemic rheumatic disease might be at increased risk for hyperinflammation and respiratory failure from COVID-19. METHODS: We did a retrospective, comparative cohort study of patients aged 18 years or older admitted to hospital with PCR-confirmed COVID-19 at Mass General Brigham (Boston, USA). We identified patients by a search of electronic health records and matched patients with a systemic rheumatic disease 1:5 to comparators. We compared individual laboratory results by case status and extracted laboratory results and COVID-19 outcomes for each participant. We calculated the COVID-19-associated hyperinflammation score (cHIS), a composite of six domains (a score of ≥2 indicating hyperinflammation) and used logistic regression to estimate odds ratios (ORs) for COVID-19 outcomes by hyperinflammation and case status. FINDINGS: We identified 57 patients with a systemic rheumatic disease and 232 matched comparators who were admitted to hospital with COVID-19 between Jan 30 and July 7, 2020; 38 (67%) patients with a rheumatic disease were female compared with 158 (68%) matched comparators. Patients with a systemic rheumatic disease had higher peak median neutrophil-to-lymphocyte ratio (9·6 [IQR 6·4-22·2] vs 7·8 [4·5-16·5]; p=0·021), lactate dehydrogenase concentration (421 U/L [297-528] vs 345 U/L [254-479]; p=0·044), creatinine concentration (1·2 mg/dL [0·9-2·0] vs 1·0 mg/dL [0·8-1·4], p=0·014), and blood urea nitrogen concentration (31 mg/dL [15-61] vs 23 mg/dL [13-37]; p=0·033) than comparators, but median C-reactive protein concentration (149·4 mg/L [76·4-275·3] vs 116·3 mg/L [58·8-225·9]; p=0·11) was not significantly different. Patients with a systemic rheumatic disease had higher peak median cHIS than comparators (3 [1-5] vs 2 [1-4]; p=0·013). All patients with a peak cHIS of 2 or more had higher odds of admission to intensive care (OR 3·45 [95% CI 1·98-5·99]), mechanical ventilation (66·20 [8·98-487·80]), and in-hospital mortality (16·37 [4·75-56·38]) than patients with a peak cHIS of less than 2. In adjusted analyses, patients with a rheumatic disease had higher odds of admission to intensive care (2·08 [1·09-3·96]) and mechanical ventilation (2·60 [1·32-5·12]) than comparators, but not in-hospital mortality (1.78 [0·79-4·02]). Among patients who were discharged from hospital, risk of rehospitalisation (1·08 [0·37-3·16]) and mortality within 60 days (1·20 [0·58-2·47]) was similar in patients and comparators. INTERPRETATION: Patients with a systemic rheumatic disease who were admitted to hospital for COVID-19 had increased risk for hyperinflammation, kidney injury, admission to intensive care, and mechanical ventilation compared with matched comparators. However, among patients who survived, post-discharge outcomes were not significantly different. The cHIS identified patients with hyperinflammation, which was strongly associated with poor COVID-19 outcomes in both patients with a rheumatic disease and comparators. Clinicians should be aware that patients with systemic rheumatic diseases and COVID-19 could be susceptible to hyperinflammation and poor hospital outcomes. FUNDING: None.