Publications by authors named "Zachary S Wallace"

78 Publications

COVID-19 severity in asthma patients: a multi-center matched cohort study.

J Asthma 2021 Mar 2:1-14. Epub 2021 Mar 2.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA.

Objective: The evidence pertaining to the effects of asthma on Coronavirus disease 2019 outcomes has been unclear. To improve our understanding of the clinically important association of asthma and Coronavirus disease 2019.

Methods: A matched cohort study was performed using data from the Mass General Brigham Health Care System (Boston, MA). Adult (age ≥18 years) patients with confirmed Coronavirus disease 2019 and without chronic obstructive pulmonary disease, cystic fibrosis, or interstitial lung disease between March 4, 2020 and July 2, 2020 were analyzed. Up to five non-asthma comparators were matched to each asthma patient based on age (within 5 years), sex, and date of positive test (within 7 days). The primary outcomes were hospitalization, mechanical ventilation, and death, using multivariable Cox-proportional hazards models accounting for competing risk of death, when appropriate. Patients were followed for these outcomes from diagnosis of Coronavirus disease 2019 until July 2, 2020.

Results: Among 562 asthma patients, 199 (21%) were hospitalized, 15 (3%) received mechanical ventilation, and 7 (1%) died. Among the 2686 matched comparators, 487 (18%) were hospitalized, 107 (4%) received mechanical ventilation, and 69 (3%) died. The adjusted Hazard Ratios among asthma patients were 0.99 (95% Confidence Internal 0.80, 1.22) for hospitalization, 0.69 (95% Confidence Internal 0.36, 1.29) for mechanical ventilation, and 0.30 (95% Confidence Internal 0.11, 0.80) for death.

Conclusions: In this matched cohort study from a large Boston-based healthcare system, asthma was associated with comparable risk of hospitalization and mechanical ventilation but a lower risk of mortality.
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http://dx.doi.org/10.1080/02770903.2020.1857396DOI Listing
March 2021

Congruent microbiome signatures in fibrosis-prone autoimmune diseases: IgG4-related disease and systemic sclerosis.

Genome Med 2021 Feb 28;13(1):35. Epub 2021 Feb 28.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Background: Immunoglobulin G4-related disease (IgG4-RD) and systemic sclerosis (SSc) are rare autoimmune diseases characterized by the presence of CD4+ cytotoxic T cells in the blood as well as inflammation and fibrosis in various organs, but they have no established etiologies. Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors.

Methods: The gut microbiomes from IgG4-RD and SSc patients as well as healthy individuals with no recent antibiotic treatment were studied by metagenomic sequencing of stool DNA. De novo assembly-based taxonomic and functional characterization, followed by association and accessory gene set enrichment analysis, were applied to describe microbiome changes associated with both diseases.

Results: Microbiomes of IgG4-RD and SSc patients distinctly separated from those of healthy controls: numerous opportunistic pathogenic Clostridium and typically oral Streptococcus species were significantly overabundant, while Alistipes, Bacteroides, and butyrate-producing species were depleted in the two diseases compared to healthy controls. Accessory gene content analysis in these species revealed an enrichment of Th17-activating Eggerthella lenta strains in IgG4-RD and SSc and a preferential colonization of a homocysteine-producing strain of Clostridium bolteae in SSc. Overabundance of the classical mevalonate pathway, hydroxyproline dehydratase, and fibronectin-binding protein in disease microbiomes reflects potential functional differences in host immune recognition and extracellular matrix utilization associated with fibrosis. Strikingly, the majority of species that were differentially abundant in IgG4-RD and SSc compared to controls showed the same directionality in both diseases. Compared with multiple sclerosis and rheumatoid arthritis, the gut microbiomes of IgG4-RD and SSc showed similar signatures; in contrast, the most differentially abundant taxa were not the facultative anaerobes consistently identified in inflammatory bowel diseases, suggesting the microbial signatures of IgG4-RD and SSc do not result from mucosal inflammation and decreased anaerobism.

Conclusions: These results provide an initial characterization of gut microbiome ecology in fibrosis-prone IgG4-RD and SSc and reveal microbial functions that offer insights into the pathophysiology of these rare diseases.
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http://dx.doi.org/10.1186/s13073-021-00853-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919092PMC
February 2021

COVID-19 and rheumatoid arthritis.

Curr Opin Rheumatol 2021 Feb 22. Epub 2021 Feb 22.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital Clinical Epidemiology Program, Mongan Institute, Department of Medicine, Massachusetts General Hospital Harvard Medical School, Boston, Massachusetts, USA.

Purpose Of Review: The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. Patients with rheumatoid arthritis (RA) face unique challenges during the pandemic, including concerns regarding infection risk, drug shortages, limited access to care, social isolation, and mental health. This review will examine the multifaceted impacts of the COVID-19 pandemic on patients living with RA.

Recent Findings: In patients with RA, risk factors for severe COVID-19 outcomes include older age and comorbidities, similar to those in the general population. Glucocorticoids, but not other classes of disease-modifying antirheumatic drugs (DMARDs), appear to be associated with a higher risk of severe COVID-19 outcomes. RA patients have been affected by changes in access to care, telemedicine, drug shortages, anxiety, and social isolation, which may contribute to disease flares.

Summary: Glucocorticoids, but not other DMARDs, are associated with a higher risk of severe COVID-19 outcomes in RA patients. Further studies are needed to explore the impact of specific DMARDs on COVID-19 outcomes, understand the broader implications of the COVID-19 pandemic on RA disease activity, and optimize the use of telemedicine in RA management.
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http://dx.doi.org/10.1097/BOR.0000000000000786DOI Listing
February 2021

ANCA-Associated Vasculitis Management in the United States: Data from the Rheumatology Informatics System for Effectiveness (RISE) Registry.

J Rheumatol 2021 Feb 1. Epub 2021 Feb 1.

Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital and Harvard Medical School; University of Alabama at Birmingham, Birmingham AL. Funding Sources: This work was funded by NIH/NIAMS [K23 AR073334 and L30 AR070520 to ZSW] and the Rheumatology Research Foundation [Scientist Development Award to ZSW]. Address correspondence to Zachary S. Wallace, MD, MSc, Clinical Epidemiology Program, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, 100 Cambridge Street, 16th Floor, E-mail:

Objective: ANCA-associated vasculitis (AAV) management has evolved substantially over the last two decades. We sought to characterize AAV treatment patterns in the United States.

Methods: We identified AAV patients in the Rheumatology Informatics System for Effectiveness (RISE) registry who had at least two rheumatology clinician visits between January 1st, 2015 and December 31st, 2017. Demographics, medications, laboratory test results, and billing codes were extracted from the medical record. Demographic and prescription trends were assessed overall and across US regions.

Results: We identified 1,462 AAV patients, 259 (18%) with new or relapsing AAV. The majority were classified as having granulomatosis with polyangiitis (GPA, 75%). The mean age was 59.8 years and 59% were female. The majority of patients were in the South (45%) followed by the Mid-West (32%), West (12%), and Northeast (8%). Patients had a median of 3 visits and follow-up of 579 days. The most commonly prescribed medications during the study period were glucocorticoids (86%) followed by rituximab (45%), methotrexate (33%), azathioprine (32%) and mycophenolate mofetil (18%); cyclophosphamide was rarely used (97, 7%). At the most recent visits in RISE, 47% of patients were on glucocorticoids. Prescription trends were similar across regions.

Conclusion: This is the first study to evaluate the demographics and management of AAV by rheumatologists outside of major referral centers. Management strategies vary widely but cyclophosphamide is rarely used. These observations can be used to inform future research priorities. Additional studies are needed to characterize AAV severity in RISE and patient and provider treatment preferences.
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http://dx.doi.org/10.3899/jrheum.201330DOI Listing
February 2021

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

Ann Rheum Dis 2021 Jan 27. Epub 2021 Jan 27.

National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre, University College London Hospitals National Health Service (NHS) Trust, London, UK

Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases.

Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category.

Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death.

Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.
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http://dx.doi.org/10.1136/annrheumdis-2020-219498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843211PMC
January 2021

SARS-CoV-2 antibody response after COVID-19 in patients with rheumatic disease.

Ann Rheum Dis 2021 Jan 12. Epub 2021 Jan 12.

Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA

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http://dx.doi.org/10.1136/annrheumdis-2020-219808DOI Listing
January 2021

Temporal trends in severe COVID-19 outcomes in patients with rheumatic disease: a cohort study.

Lancet Rheumatol 2021 Feb 24;3(2):e131-e137. Epub 2020 Dec 24.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA.

Background: As the COVID-19 pandemic continues worldwide, severe COVID-19 outcomes remain a major concern for patients with rheumatic and musculoskeletal diseases. We aimed to investigate temporal trends in COVID-19 outcomes in patients with rheumatic and musculoskeletal diseases over the course of the pandemic.

Methods: Using a large, multicentre, electronic health record network (TriNetX), we did a comparative cohort study of patients with rheumatic and musculoskeletal diseases who were diagnosed with COVID-19 (by International Classification of Diseases, Tenth Revision code or positive PCR test) during the first 90 days of the pandemic (early cohort) compared with the second 90 days of the pandemic (late cohort), matched (1:1) for demographics, comorbidities, laboratory results, glucocorticoid use, and previous hospitalisations using an exposure score method. Outcomes were assessed within 30 days of COVID-19 diagnosis, including hospitalisation, intensive care unit admission, invasive mechanical ventilation, renal failure, and death. We did a subgroup analysis among patients with rheumatic and musculoskeletal diseases who were hospitalised with COVID-19.

Findings: We identified 8540 patients with rheumatic and musculoskeletal diseases who were diagnosed with COVID-19 during the 6-month study period, including 2811 in the early cohort and 5729 in the late cohort. In the exposure score matched analysis, the risk of hospitalisation was lower in the late cohort than in the early cohort (874 [32·4%] of 2701 patients 1227 [45·4%] of 2701 patients; relative risk [RR] 0·71, 95% CI 0·67-0·76). The risks of intensive care unit admission (214 [7·9%] 385 [14·3%]; RR 0·56, 95% CI 0·47-0·65), mechanical ventilation (96 [3·6%] 247 [9·1%]; 0·39, 0·31-0·49), acute kidney injury (372 [13·8%] 560 [20·7%]; 0·66, 0·59-0·75), renal replacement therapy (17 [0·6%] 32 [1·2%]; 0·53, 0·30-0·96), and death (122 [4·5%] 252 [9·3%]; 0·48, 0·39-0·60) were lower in the late cohort compared with the early cohort. Among the hospitalised subgroup, the risk of the composite outcome of intensive care unit admission, mechanical ventilation, and death was lower in the late cohort than in the early cohort (334 [30·7%] of 1089 patients 450 [41·3%] of 1089 patients; RR 0·74, 95% CI 0·67-0·83).

Interpretation: The risks of severe COVID-19 outcomes have improved over time in patients with rheumatic and musculoskeletal disease but remain substantial. These findings might reflect ascertainment of milder cases in the later cohort and improvements in treatment and supportive care.

Funding: None.
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http://dx.doi.org/10.1016/S2665-9913(20)30422-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758725PMC
February 2021

Topic modeling to characterize the natural history of ANCA-Associated vasculitis from clinical notes: A proof of concept study.

Semin Arthritis Rheum 2021 Feb 24;51(1):150-157. Epub 2020 Dec 24.

Harvard Medical School, Boston, MA, United States; Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, United States; Clinical Epidemiology Program, Mongan Institute, Massachusetts General Hospital, Boston, MA, United States. Electronic address:

Objectives: Clinical notes from electronic health records (EHR) are important to characterize the natural history, comorbidities, and complications of ANCA-associated vasculitis (AAV) because these details may not be captured by claims and structured data. However, labor-intensive chart review is often required to extract information from notes. We hypothesized that machine learning can automatically discover clinically-relevant themes across longitudinal notes to study AAV.

Methods: This retrospective study included prevalent PR3- or MPO-ANCA+ AAV cases managed within the Mass General Brigham integrated health care system with providers' notes available between March 1, 1990 and August 23, 2018. We generated clinically-relevant topics mentioned in notes using latent Dirichlet allocation-based topic modeling and conducted trend analyses of those topics over the 2 years prior to and 5 years after the initiation of AAV-specific treatment.

Results: The study cohort included 660 patients with AAV. We generated 90 topics using 113,048 available notes. Topics were related to the AAV diagnosis, treatment, symptoms and manifestations (e.g., glomerulonephritis), and complications (e.g., end-stage renal disease, infection). AAV-related symptoms and psychiatric symptoms were mentioned months before treatment initiation. Topics related to pulmonary and renal diseases, diabetes, and infections were common during the disease course but followed distinct temporal patterns.

Conclusions: Automated topic modeling can be used to discover clinically-relevant themes and temporal patterns related to the diagnosis, treatment, comorbidities, and complications of AAV from EHR notes. Future research might compare the temporal patterns in a non-AAV cohort and leverage clinical notes to identify possible AAV cases prospectively.
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http://dx.doi.org/10.1016/j.semarthrit.2020.10.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902471PMC
February 2021

Lifetime Allergy Symptoms in IgG4-Related Disease: A Case-Control Study.

Arthritis Care Res (Hoboken) 2020 Dec 20. Epub 2020 Dec 20.

Harvard Medical School, Massachusetts General Hospital in Boston, Boston, MA, USA.

Objective: The etiology of IgG4-related disease (IgG4-RD) is unknown and there has been controversy over the significance of allergic conditions in IgG4-RD. We examined the prevalence of lifetime allergy symptoms in IgG4-RD and the association between these and IgG4-RD.

Methods: We identified IgG4-RD patients and non-IgG4-RD controls without autoimmune conditions seen at a single center. IgG4-RD patients were classified using the ACR/EULAR classification criteria. Allergy symptoms were ascertained by questionnaire. We assessed the association of IgG4-RD features with allergy symptoms. We compared the proportion of cases and controls with allergy symptoms using conditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) after matching cases and controls 1:1 by age and sex.

Results: Lifetime allergy symptoms were reported by 165 (71%) of 231 IgG4-RD cases. Aero-allergen symptoms were most commonly reported (135, 58%) followed by skin allergy symptoms (97, 42%) and food allergy symptoms (47, 20%). IgG4-RD cases with a history of allergy symptoms were more likely to have head and neck involvement (OR 2.0 [95% CI: 1.1-3.6]) and peripheral eosinophilia (OR 3.3 [95% CI: 1.2-9.0]) than those without allergy symptoms. The prevalence of any allergy symptoms was similar between cases and controls (OR 0.7 [95% CI: 0.4-1.1]); this remained consistent after stratifying by head and neck involvement.

Conclusion: Lifetime allergy symptoms are common in IgG4-RD but are not reported more often in IgG4-RD compared to non-IgG4-RD patients without autoimmune conditions. These findings suggest that allergies are not uniquely associated with the pathogenesis or presentation of IgG4-RD.
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http://dx.doi.org/10.1002/acr.24545DOI Listing
December 2020

COVID-19 Outcomes in Patients with Systemic Autoimmune Rheumatic Diseases (SARDs) Compared to the General Population: A US Multi-Center Comparative Cohort Study.

Arthritis Rheumatol 2020 Dec 10. Epub 2020 Dec 10.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital & Harvard Medical School, Boston, MA, USA.

Objective: Patients living with systemic autoimmune rheumatic diseases (SARDs) continue to be concerned about risks of severe COVID-19 outcomes.

Methods: Using a large multi-center electronic health record network, we conducted a comparative cohort study of patients with SARDs diagnosed with COVID-19 (identified by diagnostic code or positive molecular test) versus non-SARD comparators with COVID-19, matched by age, sex, race/ethnicity, and body mass index (primary model) and comorbidities and health care utilization (extended model). Thirty-day outcomes were assessed, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation, acute renal failure requiring renal replacement therapy (ARF), ischemic stroke, venous thromboembolism (VTE), and death.

Results: We initially identified 2,379 SARD patients with COVID-19 (mean age 58 years, 79% female) and 142,750 comparators (mean age 47 years, 54% female). In the primary matched model (2,379 SARD patients and 2,379 matched non-SARD comparators with COVID-19), SARD patients had significantly higher risks of hospitalization (RR 1.14, 95% CI: 1.03 to 1.26), ICU admission (RR 1.32, 95% CI: 1.03 to 1.68), ARF (RR 1.81, 95% CI: 1.07 to 3.07), and VTE (RR 1.74, 95% CI: 1.23 to 2.45) versus comparators but did not have significantly higher risks of mechanical ventilation or death. In the extended model, all risks were largely attenuated except risk of VTE (RR 1.60, 95% CI: 1.14 to 2.25).

Conclusions: SARD patients with COVID-19 may be at higher risk of hospitalization, ICU admission, ARF, and VTE versus matched comparators. These risks may be largely mediated by comorbidities, except for risk of VTE.
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http://dx.doi.org/10.1002/art.41619DOI Listing
December 2020

Coronavirus disease 2019 outcomes among patients with rheumatic diseases 6 months into the pandemic.

Ann Rheum Dis 2020 Nov 30. Epub 2020 Nov 30.

Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA

Objective: In earlier studies, patients with rheumatic and musculoskeletal disease (RMD) who got infected with COVID-19 had a higher risk of mechanical ventilation than comparators. We sought to determine COVID-19 outcomes among patients with RMD 6 months into the pandemic.

Methods: We conducted a cohort study at Mass General Brigham in Boston, Massachusetts, of patients with RMD matched to up to five comparators by age, sex and COVID-19 diagnosis date (between 30 January 2020 and 16 July 2020) and followed until last encounter or 18 August 2020. COVID-19 outcomes were compared using Cox regression. Risk of mechanical ventilation was compared in an early versus a recent cohort of patients with RMD.

Results: We identified 143 patients with RMD and with COVID-19 (mean age 60 years; 76% female individuals) and 688 comparators (mean age 59 years; 76% female individuals). There were no significantly higher adjusted risks of hospitalisation (HR: 0.87, 95% CI: 0.68-1.11), intensive care unit admission (HR: 1.27, 95% CI: 0.86-1.86), or mortality (HR: 1.02, 95% CI: 0.53-1.95) in patients with RMD versus comparators. There was a trend towards a higher risk of mechanical ventilation in the RMD cohort versus comparators, although not statistically significant (adjusted HR: 1.51, 95% CI: 0.93-2.44). There was a trend towards improvement in mechanical ventilation risk in the recent versus early RMD cohort (10% vs 19%, adjusted HR: 0.44, 95% CI: 0.17-1.12).

Conclusions: Patients with RMD and comparators had similar risks of poor COVID-19 outcomes after adjusting for race, smoking and comorbidities. The higher risk of mechanical ventilation in the early RMD cohort was no longer detected in a recent cohort, suggesting improved management over time.
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http://dx.doi.org/10.1136/annrheumdis-2020-219279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705424PMC
November 2020

Prolonged Increases in Public-Payer Spending and Prices After Unapproved Drug Initiative Approval of Colchicine.

JAMA Intern Med 2021 Feb;181(2):284-287

Clinical Epidemiology Program,Division of Rheumatology, Allergy, and Immunology,Massachusetts General Hospital, Harvard Medical School, Boston.

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http://dx.doi.org/10.1001/jamainternmed.2020.5017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851728PMC
February 2021

Management of primary vasculitides with biologic and novel small molecule medications.

Curr Opin Rheumatol 2021 Jan;33(1):8-14

Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital.

Purpose Of Review: Vasculitides can affect small, medium and/or large vessels, leading to end-organ damage, decreased quality of life and death. Glucocorticoids remain the backbone of treatment for systemic vasculitis but are associated with numerous toxicities. In recent years, the efficacy of glucocorticoid-sparing biologic and novel small molecule therapies has been demonstrated.

Recent Findings: In giant cell arteritis, tocilizumab was superior to glucocorticoid monotherapy in maintenance remission and cumulative glucocorticoid exposure and is now approved for the treatment of giant cell arteritis. In addition to the previously demonstrated efficacy of rituximab for remission induction in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, recent trials have also demonstrated its superiority for remission maintenance compared to alternative approaches. Mepolizumab is superior to standard of care alone with regard to remission rates and glucocorticoid-sparing effect in refractory eosinophilic granulomatosis with polyangiitis. Avacopan has shown significant promise in ANCA-associated vasculitis as part of a glucocorticoid-free induction regimen in a recently completed phase 3 trial. Use of biologics in rarer vasculitides remains guided by reports from small case series.

Summary: Biologics and other novel therapies have an increasingly important role in the management of systemic vasculitis. Additional studies are needed to define their optimal use and to guide their use in more rare forms of vasculitis.
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http://dx.doi.org/10.1097/BOR.0000000000000756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813157PMC
January 2021

Association of Race and Ethnicity With COVID-19 Outcomes in Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance Physician Registry.

Arthritis Rheumatol 2021 03 2;73(3):374-380. Epub 2021 Feb 2.

University of California, San Francisco.

Objective: Racial/ethnic minorities experience more severe outcomes of coronavirus disease 2019 (COVID-19) in the general US population. This study was undertaken to examine the association between race/ethnicity and COVID-19 hospitalization, ventilation status, and mortality in people with rheumatic disease.

Methods: US patients with rheumatic disease and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance physician registry between March 24, 2020 and August 26, 2020 were included. Race/ethnicity was defined as White, African American, Latinx, Asian, or other/mixed race. Outcome measures included hospitalization, requirement for ventilatory support, and death. Multivariable regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for age, sex, smoking status, rheumatic disease diagnosis, comorbidities, medication use prior to infection, and rheumatic disease activity.

Results: A total of 1,324 patients were included, of whom 36% were hospitalized and 6% died; 26% of hospitalized patients required mechanical ventilation. In multivariable models, African American patients (OR 2.74 [95% CI 1.90-3.95]), Latinx patients (OR 1.71 [95% CI 1.18-2.49]), and Asian patients (OR 2.69 [95% CI 1.16-6.24]) had higher odds of hospitalization compared to White patients. Latinx patients also had 3-fold increased odds of requiring ventilatory support (OR 3.25 [95% CI 1.75-6.05]). No differences in mortality based on race/ethnicity were found, though power to detect associations may have been limited.

Conclusion: Similar to findings in the general US population, racial/ethnic minorities with rheumatic disease and COVID-19 had increased odds of hospitalization and ventilatory support. These results illustrate significant health disparities related to COVID-19 in people with rheumatic diseases. The rheumatology community should proactively address the needs of patients currently experiencing inequitable health outcomes during the pandemic.
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http://dx.doi.org/10.1002/art.41567DOI Listing
March 2021

Challenges, collaboration, and innovation in rheumatology education during the COVID-19 pandemic: leveraging new ways to teach.

Clin Rheumatol 2020 Dec 16;39(12):3535-3541. Epub 2020 Oct 16.

Department of Medicine, Division of Rheumatology, Allergy, and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.

The novel coronavirus disease (COVID-19) pandemic has significantly impacted the field of rheumatology, in both the delivery of clinical care and didactic education for our trainees. These changes have generated significant strain for program directors and clinical educators who have had to leverage technology and develop new systems to ensure continued trainee education and assessment. We aim to outline the impacts on formal education programs presented by these unprecedented disruptions, describe the development and deployment of online teaching, reflect on the challenges and opportunities for technology-enabled learning and use of social media for education, and give some international perspectives on impacts on postgraduate rheumatology training outside the USA. With the rapid dissolution of barriers in place during the pre-COVID-19 era, we have the opportunity to assess the efficacy of new methods of care and further integrate technology into teaching and assessment. We propose that a hybrid in-person and technology-enabled learning approach, so-called blended learning, is likely to remain the most desirable future model for supporting trainee learning.
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http://dx.doi.org/10.1007/s10067-020-05449-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567647PMC
December 2020

Prostate and pancreas involvement are linked in IgG4-related disease.

Semin Arthritis Rheum 2020 12 15;50(6):1245-1251. Epub 2020 Sep 15.

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard, Cambridge, MA, United States; Rheumatology Unit, Clinical Epidemiology Unit, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, MA, United States; Harvard Medical School, Boston, MA, United States. Electronic address:

Objective: Prostate involvement by IgG4-related disease (IgG4-RD) is a rarely described organ manifestation and knowledge regarding its frequency and clinical features is limited.

Methods: From a single-center cohort, 168 male patients were examined who satisfied the 2019 ACR/EULAR classification criteria or 2012 consensus histopathologic criteria for IgG4-RD.

Results: Prostate involvement were identified in 25 (15%) of these cases. The majority of patients with IgG4-RD involving the prostate gland (80%) were symptomatic at presentation with incomplete voiding (64%), urinary frequency (52%), and urinary hesitancy (48%) being the most common complaints. The radiologic presentation of prostate disease is most often a focal abnormality suggesting inflammation rather than a mass lesion. While most patients with IgG4-related prostate disease (89%) experienced recurrence after or during glucocorticoid tapering, patients treated with B cell targeted therapy in this series experienced clinical improvement and were tapered off of glucocorticoids. Additionally, patients with IgG4-RD involving the pancreas (p = < 0.001) were more likely to have prostate involvement than were those with other types of organ involvement.

Conclusion: This report provides the first comprehensive clinical description of IgG4-RD involving the prostate gland and links this manifestation with pancreatic involvement.
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http://dx.doi.org/10.1016/j.semarthrit.2020.09.002DOI Listing
December 2020

Acute respiratory viral adverse events during use of antirheumatic disease therapies: A scoping review.

Semin Arthritis Rheum 2020 10 22;50(5):1191-1201. Epub 2020 Jul 22.

Division of Rheumatology, Department of Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA. Electronic address:

Introduction: COVID-19 is an acute respiratory viral infection that threatens people worldwide, including people with rheumatic disease, although it remains unclear to what extent various antirheumatic disease therapies increase susceptibility to complications of viral respiratory infections.

Objective: The present study undertakes a scoping review of available evidence regarding the frequency and severity of acute respiratory viral adverse events related to antirheumatic disease therapies.

Methods: Online databases were used to identify, since database inception, studies reporting primary data on acute respiratory viral infections in patients utilizing antirheumatic disease therapies. Independent reviewer pairs charted data from eligible studies using a standardized data abstraction tool.

Results: A total of 180 studies were eligible for qualitative analysis. While acknowledging that the extant literature has a lack of specificity in reporting of acute viral infections or complications thereof, the data suggest that use of glucocorticoids, JAK inhibitors (especially high-dose), TNF inhibitors, and anti-IL-17 agents may be associated with an increased frequency of respiratory viral events. Available data suggest no increased frequency or risk of respiratory viral events with NSAIDs, hydroxychloroquine, sulfasalazine, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide, or apremilast. One large cohort study demonstrated an association with leflunomide use and increased risk of acute viral respiratory events compared to non-use.

Conclusion: This scoping review identified that some medication classes may confer increased risk of acute respiratory viral infections. However, definitive data are lacking and future studies should address this knowledge gap.
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http://dx.doi.org/10.1016/j.semarthrit.2020.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832282PMC
October 2020

Incidence, Clinical Features, and Outcomes of Late-Onset Neutropenia From Rituximab for Autoimmune Disease.

Arthritis Rheumatol 2021 02 29;73(2):347-354. Epub 2020 Dec 29.

Massachusetts General Hospital, Boston.

Objective: Late-onset neutropenia (LON) is an underrecognized complication of rituximab treatment. We undertook this study to describe its incidence, risk factors, clinical features, management, and recurrence.

Methods: We conducted a single-center retrospective cohort study of 738 adult patients with autoimmune disease who were treated with rituximab to induce continuous B cell depletion. The primary outcome measure was LON, defined as an unexplained absolute neutrophil count of <1,000 cells/µl during B cell depletion. Secondary outcome measures included incidental diagnosis, fever, sepsis, filgrastim use, and recurrent LON. We assessed predictors of LON using Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.

Results: We identified 107 episodes of LON in 71 patients. The cumulative incidence at 1 year of B cell depletion therapy was 6.6% (95% CI 5.0-8.7). The incidence rate during the first year was higher compared to thereafter (7.2 cases per 100 person-years [95% CI 5.4-9.6] versus 1.5 cases per 100 person-years [95% CI 1.0-2.3]). Systemic lupus erythematosus and combination therapy with cyclophosphamide were each independently associated with an increased risk of LON (adjusted HR 2.96 [95% CI 1.10-8.01] and 1.98 [95% CI 1.06-3.71], respectively). LON was not observed in minimal change disease or focal segmental glomerulosclerosis. The majority of episodes (59.4%) were asymptomatic. Fever and sepsis complicated 31.3% and 8.5% of episodes, respectively. Most patients (69%) were treated with filgrastim. Rituximab rechallenge occurred in 87% of patients, of whom 21% developed recurrent LON.

Conclusion: LON is common and often incidental. Most cases are reversible and respond well to filgrastim. However, LON can be associated with serious infections and thus warrants vigilant monitoring.
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http://dx.doi.org/10.1002/art.41501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902364PMC
February 2021

The COVID-19 Global Rheumatology Alliance: evaluating the rapid design and implementation of an international registry against best practice.

Rheumatology (Oxford) 2021 01;60(1):353-358

Department of Medicine and Department of Pathology and Molecular Medicine, University of Otago, Wellington, New Zealand.

Objectives: As the coronavirus disease 2019 pandemic developed there was a paucity of data relevant to people living with rheumatic disease. This led to the development of a global, online registry to meet these information needs. This manuscript provides a detailed description of the coronavirus disease 2019 Global Rheumatology Alliance registry development, governance structure, and data collection, and insights into new ways of rapidly establishing global research collaborations to meet urgent research needs.

Methods: We use previously published recommendations for best practices for registry implementation and describe the development of the Global Rheumatology Alliance registry in terms of these steps. We identify how and why these steps were adapted or modified. In Phase 1 of registry development, the purpose of the registry and key stakeholders were identified on online platforms, Twitter and Slack. Phase 2 consisted of protocol and data collection form development, team building and the implementation of governance and policies.

Results: All key steps of the registry development best practices framework were met, though with the need for adaptation in some areas. Outputs of the registry, two months after initial conception, are also described.

Conclusion: The Global Rheumatology Alliance registry will provide highly useful, timely data to inform clinical care and identify further research priorities for people with rheumatic disease with coronavirus disease 2019. The formation of an international team, easily able to function in online environments and resulting in rapid deployment of a registry is a model that can be adapted for other disease states and future global collaborations.
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http://dx.doi.org/10.1093/rheumatology/keaa483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454885PMC
January 2021

SARS CoV-2 infection among patients using immunomodulatory therapies.

Ann Rheum Dis 2021 02 5;80(2):269-271. Epub 2020 Aug 5.

Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

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http://dx.doi.org/10.1136/annrheumdis-2020-218580DOI Listing
February 2021

Antirheumatic Disease Therapies for the Treatment of COVID-19: A Systematic Review and Meta-Analysis.

Arthritis Rheumatol 2021 01 19;73(1):36-47. Epub 2020 Nov 19.

Mayo Clinic, Rochester, Minnesota, United States.

Objective: Antirheumatic disease therapies have been used to treat coronavirus disease 2019 (COVID-19) and its complications. We conducted a systematic review and meta-analysis to describe the current evidence.

Methods: A search of published and preprint databases in all languages was performed. Included studies described ≥1 relevant clinical outcome for ≥5 patients who were infected with severe acute respiratory syndrome coronavirus 2 and were treated with antirheumatic disease therapy between January 1, 2019 and May 29, 2020. Pairs of reviewers screened articles, extracted data, and assessed risk of bias. A meta-analysis of effect sizes using random-effects models was performed when possible.

Results: The search identified 3,935 articles, of which 45 were included (4 randomized controlled trials, 29 cohort studies, and 12 case series). All studies evaluated hospitalized patients, and 29 of the 45 studies had been published in a peer-reviewed journal. In a meta-analysis of 3 cohort studies with a low risk of bias, hydroxychloroquine use was not significantly associated with mortality (pooled hazard ratio [HR] 1.41 [95% confidence interval (95% CI) 0.83, 2.42]). In a meta-analysis of 2 cohort studies with some concerns/higher risk of bias, anakinra use was associated with lower mortality (pooled HR 0.25 [95% CI 0.12, 0.52]). Evidence was inconclusive with regard to other antirheumatic disease therapies, and the majority of other studies had a high risk of bias.

Conclusion: In this systematic review and meta-analysis, hydroxychloroquine use was not associated with benefit or harm regarding COVID-19 mortality. The evidence supporting the effect of other antirheumatic disease therapies in COVID-19 is currently inconclusive.
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http://dx.doi.org/10.1002/art.41469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435536PMC
January 2021

The use of tocilizumab and tofacitinib in patients with resolved hepatitis B infection: a case series.

Ann Rheum Dis 2021 02 30;80(2):274-276. Epub 2020 Jul 30.

Rheumatology Unit, Massachusetts General Hospital, Boston, Massachusetts, USA

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http://dx.doi.org/10.1136/annrheumdis-2020-218289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855328PMC
February 2021

Conducting research in a pandemic: The power of social media.

Eur J Rheumatol 2020 Aug 21;7(Suppl 2):S85-S88. Epub 2020 Jul 21.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.

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http://dx.doi.org/10.5152/eurjrheum.2020.2066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431333PMC
August 2020

Response to: 'Incidence of severe COVID-19 in a Spanish cohort of 1037 patients with rheumatic diseases treated with biologics and JAK-inhibitors' by Jovani .

Ann Rheum Dis 2020 Jun 25. Epub 2020 Jun 25.

Rheumatology Unit, Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, MA, USA

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http://dx.doi.org/10.1136/annrheumdis-2020-218179DOI Listing
June 2020

CD4 and CD8 cytotoxic T lymphocytes may induce mesenchymal cell apoptosis in IgG-related disease.

J Allergy Clin Immunol 2021 Jan 30;147(1):368-382. Epub 2020 May 30.

Ragon Institute of MGH, MIT, and Harvard, Cambridge, Mass. Electronic address:

Background: IgG-related disease (IgG-RD) is an immune-mediated fibrotic disorder that has been linked to CD4 cytotoxic T lymphocytes (CD4CTLs). The effector phenotype of CD4CTLs and the relevance of both CD8 cytotoxic T lymphocytes (CD8CTLs) and apoptotic cell death remain undefined in IgG-RD.

Objective: We sought to define CD4CTL heterogeneity, characterize the CD8CTL response in the blood and in lesions, and determine whether enhanced apoptosis may contribute to the pathogenesis of IgG-RD.

Methods: Blood analyses were undertaken using flow cytometry, cell sorting, transcriptomic analyses at the population and single-cell levels, and next-generation sequencing for the TCR repertoire. Tissues were interrogated using multicolor immunofluorescence. Results were correlated with clinical data.

Results: We establish that among circulating CD4CTLs in IgG-RD, CD27CD28CD57 cells are the dominant effector subset, exhibit marked clonal expansion, and differentially express genes relevant to cytotoxicity, activation, and enhanced metabolism. We also observed prominent infiltration of granzyme A-expressing CD8CTLs in disease tissues and clonal expansion in the blood of effector/memory CD8 T cells with an activated and cytotoxic phenotype. Tissue studies revealed an abundance of cells undergoing apoptotic cell death disproportionately involving nonimmune, nonendothelial cells of mesenchymal origin. Apoptotic cells showed significant upregulation of HLA-DR.

Conclusions: CD4CTLs and CD8CTLs may induce apoptotic cell death in tissues of patients with IgG-RD with preferential targeting of nonendothelial, nonimmune cells of mesenchymal origin.
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http://dx.doi.org/10.1016/j.jaci.2020.05.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704943PMC
January 2021

Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry.

Ann Rheum Dis 2020 07 29;79(7):859-866. Epub 2020 May 29.

Faculty of Medicine, The University of Queensland, Herston, Queensland, Australia

Objectives: COVID-19 outcomes in people with rheumatic diseases remain poorly understood. The aim was to examine demographic and clinical factors associated with COVID-19 hospitalisation status in people with rheumatic disease.

Methods: Case series of individuals with rheumatic disease and COVID-19 from the COVID-19 Global Rheumatology Alliance registry: 24 March 2020 to 20 April 2020. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Age, sex, smoking status, rheumatic disease diagnosis, comorbidities and rheumatic disease medications taken immediately prior to infection were analysed.

Results: A total of 600 cases from 40 countries were included. Nearly half of the cases were hospitalised (277, 46%) and 55 (9%) died. In multivariable-adjusted models, prednisone dose ≥10 mg/day was associated with higher odds of hospitalisation (OR 2.05, 95% CI 1.06 to 3.96). Use of conventional disease-modifying antirheumatic drug (DMARD) alone or in combination with biologics/Janus Kinase inhibitors was not associated with hospitalisation (OR 1.23, 95% CI 0.70 to 2.17 and OR 0.74, 95% CI 0.37 to 1.46, respectively). Non-steroidal anti-inflammatory drug (NSAID) use was not associated with hospitalisation status (OR 0.64, 95% CI 0.39 to 1.06). Tumour necrosis factor inhibitor (anti-TNF) use was associated with a reduced odds of hospitalisation (OR 0.40, 95% CI 0.19 to 0.81), while no association with antimalarial use (OR 0.94, 95% CI 0.57 to 1.57) was observed.

Conclusions: We found that glucocorticoid exposure of ≥10 mg/day is associated with a higher odds of hospitalisation and anti-TNF with a decreased odds of hospitalisation in patients with rheumatic disease. Neither exposure to DMARDs nor NSAIDs were associated with increased odds of hospitalisation.
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http://dx.doi.org/10.1136/annrheumdis-2020-217871DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299648PMC
July 2020

Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: a comparative cohort study from a US 'hot spot'.

Ann Rheum Dis 2020 09 26;79(9):1156-1162. Epub 2020 May 26.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts, USA

Objective: To investigate differences in manifestations and outcomes of coronavirus disease 2019 (COVID-19) infection between those with and without rheumatic disease.

Methods: We conducted a comparative cohort study of patients with rheumatic disease and COVID-19 (confirmed by severe acute respiratory syndrome coronavirus 2 PCR), compared in a 1:2 ratio with matched comparators on age, sex and date of COVID-19 diagnosis, between 1 March and 8 April 2020, at Partners HealthCare System in the greater Boston, Massachusetts area. We examined differences in demographics, clinical features and outcomes of COVID-19 infection. The main outcomes were hospitalisation, intensive care admission, mechanical ventilation and mortality.

Results: We identified 52 rheumatic disease patients with COVID-19 (mean age, 63 years; 69% female) and matched these to 104 non-rheumatic disease comparators. The majority (39, 75%) of patients with rheumatic disease were on immunosuppressive medications. Patients with and without rheumatic disease had similar symptoms and laboratory findings. A similar proportion of patients with and without rheumatic disease were hospitalised (23 (44%) vs 42 (40%)), p=0.50) but those with rheumatic disease required intensive care admission and mechanical ventilation more often (11 (48%) vs 7 (18%), multivariable OR 3.11 (95% CI 1.07 to 9.05)). Mortality was similar between the two groups (3 (6%) vs 4 (4%), p=0.69).

Conclusions: Patients with rheumatic disease and COVID-19 infection were more likely to require mechanical ventilation but had similar clinical features and hospitalisation rates as those without rheumatic disease. These findings have important implications for patients with rheumatic disease but require further validation.
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http://dx.doi.org/10.1136/annrheumdis-2020-217888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456555PMC
September 2020

Increasing Operational Capacity and Reducing Costs of Rituximab Administration: A Costing Analysis.

ACR Open Rheumatol 2020 May 21;2(5):261-268. Epub 2020 Apr 21.

Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Objective: Originator intravenous rituximab is an important rheumatology treatment but is costly, and administration requires several hours. Because biosimilar rituximab may cost less and subcutaneous rituximab requires a shorter visit, both may reduce costs and increase treatment capacity (infusions per year).

Methods: We implemented time-driven activity-based costing (TDABC), a method to assess costs and opportunities to increase capacity, throughout the care pathway for 26 patients receiving a total of 30 rituximab infusions. Using the TDABC estimates, we created a base case, which included provider time, salaries, infusion rates and times, and drug formulation, to simulate an induction cycle (two infusions). We varied these parameters in sensitivity analyses and assessed the impact of infusion rates and formulation (biosimilar vs. subcutaneous) on capacity before and after assuming a fixed budget.

Results: The base-case cost was $19 452; more than 90% was due to drug cost. In sensitivity analyses, varying projected biosimilar cost led to the greatest cost savings ($8,988 per cycle). Faster infusion rates and subcutaneous rituximab increased annual capacity (300% and 800%, respectively). With a fixed budget, subcutaneous rituximab led to a relative increase in capacity over biosimilar rituximab except when biosimilar cost savings relative to originator rituximab exceeded 40%; faster biosimilar infusion rates did not meaningfully affect these findings.

Conclusion: Using TDABC, we demonstrate that rituximab cost is the primary driver of treatment cost, but capacity is largely driven by treatment time. Subcutaneous rituximab leads to higher capacity than biosimilar rituximab across a range of plausible costs; its use in rheumatology should be studied.
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http://dx.doi.org/10.1002/acr2.11133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231514PMC
May 2020

Association of Cigarette Smoking With Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

JAMA Intern Med 2020 06;180(6):870-876

Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston.

Importance: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a systemic small vessel vasculitis characterized by circulating ANCAs targeting proteinase 3 (PR3) or myeloperoxidase (MPO) and associated with excess morbidity and mortality. Myeloperoxidase-ANCA-positive AAV and PR3-ANCA-positive AAV are increasingly recognized to have differences in genetic risk, pathogenesis, and response to treatment. Risk factors for AAV, including cigarette smoking, are poorly understood.

Objective: To examine the association between cigarette smoking and AAV.

Design, Setting, And Participants: This case-control study included a consecutive inception cohort of 484 patients with AAV diagnosed from 2002 to 2017 compared with a cohort of sex-, race-, and age-matched controls. Eleven cases were excluded owing to discordant smoking information in the electronic health record. Controls were randomly selected from participants recruited to the Partners HealthCare Biobank between its inception in 2010 and 2018 and who completed a smoking questionnaire and were not diagnosed with AAV (n = 30 536).

Exposures: Smoking status (current, former, never) and pack-years of cigarette smoking were determined from review of the electronic medical record and smoking questionnaires.

Main Outcomes And Measures: Patients with AAV were individually matched with 3 randomly-selected controls based on sex, race, and age (within 2 years difference). Conditional logistic regression was performed to examine the association between cigarette smoking and AAV using odds ratios (OR) and 95% confidence intervals (CIs).

Results: Overall, 473 cases were matched with 1419 controls (mean [SD] age, 59 [16] years; 281 women [59%], 396 white [84%]). Patients with AAV were more likely to be former (OR, 1.6; 95% CI, 1.3-2.0) or current smokers (OR, 2.7; 95% CI, 1.8-4.1); there was a dose-response relationship according to pack-years of exposure (P < .001). These associations were especially strong among participants with MPO-ANCA-positive disease (former smokers: OR, 1.7; 95% CI, 1.3-2.3; current smokers: OR, 3.5; 95% CI, 2.1-6.1) but not in participants with PR3-ANCA-positive AAV (former smokers: OR, 1.3; 95% CI, 0.9-2.0; current smokers: OR, 1.7; 95% CI, 0.8-3.5). After stratifying by selected demographics and disease manifestations, these associations remained strong.

Conclusions And Relevance: Cigarette smoking was associated with AAV, especially MPO-ANCA-positive AAV. Further studies are needed to investigate a potential pathogenic mechanism.
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http://dx.doi.org/10.1001/jamainternmed.2020.0675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154954PMC
June 2020