Publications by authors named "Jeffrey A Sparks"

144 Publications

Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance Vaccine Survey.

RMD Open 2021 09;7(3)

Medicine, Division of Rheumatology, University of Washington, Seattle, Washington, USA.

Background: We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine.

Methods: From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination.

Results: We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%.

Conclusion: Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.
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http://dx.doi.org/10.1136/rmdopen-2021-001814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424419PMC
September 2021

Outcome measurement instrument selection for lung physiology in systemic sclerosis associated interstitial lung disease: A systematic review using the OMERACT filter 2.1 process.

Semin Arthritis Rheum 2021 Aug 20. Epub 2021 Aug 20.

Department of Internal Medicine, Division of Rheumatology, Scleroderma Program, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:

Objective: The Outcome Measures in Rheumatology (OMERACT) is a research organization focused on improving health care outcomes for patients with autoimmune and musculoskeletal diseases. The Connective Tissue Disease-Interstitial Lung Disease (CTD-ILD) Working Group on Lung Physiology is a group within OMERACT charged with identifying outcome measures that should be implemented in studies of patients with CTD-ILD. The OMERACT Filter 2.1 is an evidence-based algorithm used to identify outcome measures that are truthful, feasible, and able to discriminate between groups of interest. Our objective was to summate evidence (published literature, key opinion leader input, patient perspectives) that would influence the CTD-ILD Working Group's vote to accept or reject the use of two measures of lung physiology, the forced vital capacity (FVC) and the diffusion capacity of carbon monoxide (DLco) for use in randomized controlled trials (RTCs) and longitudinal observational studies (LOSs) involving patients with systemic sclerosis associated ILD (SSc-ILD).

Methods: Patient Research Partners (those afflicted with SSc-ILD) and the CTD-ILD Working Group on Lung Physiology were polled to assess their opinion on the FVC and DLco in terms of feasibility; the CTD-ILD Working Group was also queried on these instruments' face and content validity. We then conducted a systematic literature review to identify articles in the SSc-ILD population that assessed the following measurement properties of FVC and DLco: (1) construct validity, (2) test-retest reliability, (3) longitudinal construct validity, (4) clinical trial discrimination/sensitivity to detect change in clinical trials, and (5) thresholds of meaning. Results were summarized in a Summary of Measurement Properties (SOMP) table for each instrument. OMERACT CTD-ILD Working Group members discussed and voted on the strength of evidence supporting these two instruments and voted to endorse, provisionally endorse, or not endorse either instrument.

Results: Forty Patient Research Partners reported these two measures are feasible (are not an unnecessary burden or represent an infeasible longitudinal assessment of their disease). A majority of the 18 CTD-ILD Working Group members voted that both the FVC and DLco are feasible and have face and content validity. The systematic literature review returned 1,447 non-duplicated articles, of which 177 met eligibility for full text review. Forty-eight studies (13 RCTs, 35 LOSs) were included in the qualitative analysis. The FVC SOMP table revealed high quality, consistent data with evidence of good performance for all five measurement properties, suggesting requisite published evidence to proceed with endorsement. The DLco SOMP table showed a lack of data to support test-retest reliability and inadequate evidence to support clinical trial discrimination. There was unanimous agreement (15 [100%]) among voting CTD-ILD Working Group members to endorse the FVC as an instrument for lung physiology in RCTs and LOSs in SSc-ILD. Based on currently available evidence, DLco did not meet the OMERACT criteria and is not recommended for use in RCTs to represent lung physiology of SSc-ILD. The OMERACT Technical Advisory Group agreed with these decisions.

Conclusion: The OMERACT Filter 2.1 was successfully applied to the domain of lung physiology in patients with SSc-ILD. The FVC was endorsed for use in RCTs and LOSs based on the Working Group's vote; DLco was not endorsed.
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http://dx.doi.org/10.1016/j.semarthrit.2021.08.001DOI Listing
August 2021

Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases.

Ann Rheum Dis 2021 Sep 6. Epub 2021 Sep 6.

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

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http://dx.doi.org/10.1136/annrheumdis-2021-221326DOI Listing
September 2021

Monitoring and management of fibrosing interstitial lung diseases: a narrative review for practicing clinicians.

Ther Adv Respir Dis 2021 Jan-Dec;15:17534666211039771

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Close monitoring of patients with fibrosing interstitial lung diseases (ILDs) is important to enable prompt identification and management of progressive disease. Monitoring should involve regular assessment of physiology (including pulmonary function tests), symptoms, and, when appropriate, high-resolution computed tomography. The management of patients with fibrosing ILDs requires a multidisciplinary approach and should be individualized based on factors such as disease severity, evidence of progression, risk factors for progression, comorbidities, and the preferences of the patient. In this narrative review, we discuss how patients with fibrosing ILDs can be effectively monitored and managed in clinical practice.
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http://dx.doi.org/10.1177/17534666211039771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422822PMC
September 2021

Prevalence and risk factors of bronchiectasis in rheumatoid arthritis: A systematic review and meta-analysis.

Semin Arthritis Rheum 2021 Aug 20;51(5):1067-1080. Epub 2021 Aug 20.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, 60 Fenwood Road, 6016U, Boston, MA 02115, United States; Harvard Medical School, Boston, MA, United States. Electronic address:

Objectives: We performed a systematic review and meta-analysis for the prevalence and risk factors of rheumatoid arthritis-related bronchiectasis (RA-BR).

Methods: We queried PubMed and EMBASE databases to identify published literature related to prevalence and risk factors for RA-BR among patients with RA. Data extraction included study design, country, year, method of RA-BR detection, RA characteristics, numerator of RA-BR cases and denominator of patients with RA, and associations with RA-BR presence. We performed a meta-analysis using random or fixed effects models to estimate the prevalence of RA-BR among RA.

Results: Out of a total of 253 studies, we identified 41 total studies that reported on prevalence (n = 34), risk factors (n = 5), or both (n = 2). The included studies had heterogeneous methods to identify RA-BR. Among the 36 studies reporting prevalence, 608 RA-BR cases were identified from a total of 8569 patients with RA. In the meta-analysis, the pooled overall prevalence of RA-BR among RA was 18.7% (95%CI 13.7-24.3%) using random effects and 3.8% (95%CI 3.3-4.2%) using fixed effects. Among studies that used high-resolution chest computed tomography (HRCT) imaging, the prevalence of RA-BR was 22.6% (95%CI 16.8-29.0%) using random effects. When only considering retrospective studies (n = 12), the pooled prevalence of RA-BR among RA was 15.5% (95%CI 7.5-25.5%); among prospective studies (n = 24), the pooled prevalence was 20.7% (95% CI 14.7-27.4%). Risk factors for RA-BR included older age, longer RA duration, genetics (CFTR and HLA), and undetectable circulating mannose binding lectin (MBL) as a biomarker.

Conclusion: In this systematic review and meta-analysis, the prevalence of RA-BR was nearly 20% among studies with HRCT imaging, suggesting that bronchiectasis may be a common extra-articular feature of RA. Relatively few factors have been associated with RA-BR. Future studies should standardize methods to identify RA-BR cases and investigate the natural history and clinical course given the relatively high prevalence among RA.
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http://dx.doi.org/10.1016/j.semarthrit.2021.08.005DOI Listing
August 2021

Assessing improved risk prediction of rheumatoid arthritis by environmental, genetic, and metabolomic factors.

Semin Arthritis Rheum 2021 Jul 10;51(5):1016-1022. Epub 2021 Jul 10.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Objective: We sought to improve seropositive rheumatoid arthritis (RA) risk prediction using a novel weighted genetic risk score (wGRS) and preclinical plasma metabolites associated with RA risk. Predictive performance was compared to previously validated models including RA-associated environmental factors.

Methods: This nested case-control study matched incident seropositive RA cases (meeting ACR 1987 or EULAR/ACR 2010 criteria) in the Nurses' Health Studies (NHS) to two controls on age, blood collection features, and post-menopausal hormone use at pre-RA blood draw. Environmental variables were measured at the questionnaire cycle preceding blood draw. Four models were generated and internally validated using a bootstrapped optimism estimate: (a) base with environmental factors (E), (b) environmental, genetic and gene-environment interaction factors (E + G + GEI), c) environmental and metabolic factors (E + M), and d) all factors (E + G + GEI + M). A fifth model including all factors and interaction terms was fit using ridge regression and cross-validation. Models were compared using area under the receiver operating characteristic curve (AUC).

Results: 150 pre-RA cases and 455 matched controls were included. The E model yielded an optimism-corrected AUC of 0.622. The E + M model did not show improvement over the E model (corrected AUC 0.620). Including genetic factors increased prediction, producing corrected AUCs of 0.677 in the E + G + GEI model and 0.674 in the E + G + GEI + M model. Similarly, the performance of the cross-validated ridge regression model yielded an AUC of 0.657.

Conclusion: Addition of wGRS and gene-environment interaction improved seropositive RA risk prediction models. Preclinical metabolite levels did not significantly contribute to prediction.
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http://dx.doi.org/10.1016/j.semarthrit.2021.07.006DOI Listing
July 2021

Passive Smoking Throughout the Life Course and the Risk of Incident Rheumatoid Arthritis in Adulthood Among Women.

Arthritis Rheumatol 2021 Aug 18. Epub 2021 Aug 18.

Division of Rheumatology, Inflammation, and Immunity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States.

Objective: To investigate passive smoking throughout the life course and the risk of rheumatoid arthritis (RA), while accounting for personal smoking.

Methods: We analyzed the Nurses' Health Study II prospective cohort, using information collected via biennial questionnaires. We assessed the influence of (1) maternal smoking during pregnancy (in utero exposure), (2) childhood parental smoking, and (3) years lived with smokers since age 18. Incident RA and serostatus was determined by medical record review. Using the marginal structural model framework, we estimated the controlled direct effect of each passive smoking exposure on adult incident RA risk by serologic phenotype, controlling for early-life and time-updated adult factors including personal smoking.

Results: Among 90,923 women, we identified 532 incident RA cases (66% seropositive) during 27.7 years (median) of follow-up. Maternal smoking during pregnancy was associated with RA after confounding adjustment (HR 1.25 [95% CI 1.03, 1.52]), but not after accounting for subsequent smoking exposures. Childhood parental smoking was associated with seropositive RA after adjusting for confounders (HR 1.41 [95% CI 1.08, 1.83]). In the controlled direct effect analyses, childhood parental smoking was associated with seropositive RA (HR 1.75 [95% CI 1.03, 2.98]) after controlling for adult personal smoking, which was accentuated among ever smokers (HR 2.18 [95% CI 1.23, 3.88]). There was no significant association of adult passive smoking with RA (20+ years lived smoker: HR 1.30 [95% CI 0.97, 1.74] vs. none).

Conclusion: We found a potential direct influence of childhood parental smoking on adult-onset incident seropositive RA even after controlling for adult personal smoking.
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http://dx.doi.org/10.1002/art.41939DOI Listing
August 2021

No association between recent antibiotic use and risk of rheumatoid arthritis: results from two prospective cohort studies.

Expert Opin Drug Saf 2021 Aug 25:1-6. Epub 2021 Aug 25.

Pharmacy Department, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China.

Background: Retrospective research partly characterizes the link between antibiotic use and rheumatoid arthritis (RA) development. This prospective cohort study may help reassess the association.

Research Design And Methods: We included 133,125 participants from the Nurses' Health Study (NHS) and NHS II databases. Three groups were established: nonuse, short-term use (1-14 days), and middle- to long-term use (≥15 days) to explore the link. Cox regression model was chosen to evaluate the hazard ratios (HRs) for RA.

Results: Short-term antibiotic use was not associated with the subsequent risk of RA (adjusted HR = 0.88, 95% Confidence Interval [CI] 0.38-1.38) compared to the no antibiotic use group in the multivariable adjusted model. The age-stratified model showed no sufficient evidence of increased risk in participants with middle- to long-term antibiotic use (HR = 1.32, 95% CI 0.89-1.98). The effect further attenuated to null after controlling for confounding factors (adjusted HR = 1.06, 95% CI 0.42-1.71).

Conclusions: We found no evidence of an association between antibiotic use and RA risk. Our findings may reduce potential concerns about increased RA risk among antibiotic users.
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http://dx.doi.org/10.1080/14740338.2021.1970134DOI Listing
August 2021

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

medRxiv 2021 Aug 9. Epub 2021 Aug 9.

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: 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. 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. 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.
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http://dx.doi.org/10.1101/2021.08.05.21261643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8366799PMC
August 2021

Predictors of rheumatic immune-related adverse events and de novo inflammatory arthritis after immune checkpoint inhibitor treatment for cancer.

Arthritis Rheumatol 2021 Aug 16. Epub 2021 Aug 16.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.

Objective: To identify predictors of rheumatic immune-related adverse events (rheum-irAEs) after immune checkpoint inhibitor (ICI) treatment for cancer.

Methods: We performed a case-control study to predict rheum-irAEs at Mass General Brigham and Dana-Farber Cancer Institute (2011-2020). We screened for rheum-irAEs by reviewing patients evaluated by rheumatology or prescribed non-glucocorticoid immunomodulators (IM) after ICI (baseline). Medical review confirmed the presence of rheum-irAEs and indication for IM. Controls lacked rheum-irAEs (had no glucocorticoid use, rheumatology evaluation, IM use, and survived 6 months after baseline). We used logistic regression to estimate odds ratios (ORs) of the baseline predictors of rheum-irAEs.

Results: We identified 8,028 ICI recipients (mean age 65.5 years, 43.1% female, and 31.8% with lung cancer). After ICI, 404 (5.0%) were evaluated by rheumatology and 475 (5.9%) received an IM to treat any irAE. There were 226 (2.8%) confirmed rheum-irAE cases and 118 (1.5%) had de novo inflammatory arthritis. Rheumatic diseases (either pre-existing or rheum-irAEs) were a leading indication for IM use (27.9%). Baseline predictors of rheum-irAEs included melanoma (multivariable OR 4.06, 2.54-6.51) and genitourinary cancer (OR 2.22, 1.39-3.54; ref=lung cancer), combination ICI (OR 2.35, 1.48-3.74; ref=PD-1 inhibitor monotherapy), autoimmune disease (OR 2.04, 1.45-2.85), and recent glucocorticoid use (OR 2.13, 1.51-2.98; ref=no use) compared to 2,312 controls without rheum-irAEs. Predictors of de novo inflammatory arthritis were similar.

Conclusion: We identified novel predictors of rheum-irAEs that included melanoma, genitourinary cancer, pre-existing autoimmune disease, combination ICI, and glucocorticoid use. The proportion of cancer patients experiencing rheum-irAEs may be even higher than we report since we used stringent criteria to identify cases. These findings may identify cancer patients at risk of developing rheum-irAEs and de novo inflammatory arthritis and inform pathogenesis.
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http://dx.doi.org/10.1002/art.41949DOI Listing
August 2021

Towards clinical significance of the promoter variant and risk of rheumatoid arthritis-associated interstitial lung disease.

Authors:
Jeffrey A Sparks

Ann Rheum Dis 2021 Aug 3. Epub 2021 Aug 3.

Department of Medicine, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA

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http://dx.doi.org/10.1136/annrheumdis-2021-220856DOI Listing
August 2021

Immediate effect of the COVID-19 pandemic on patient health, health-care use, and behaviours: results from an international survey of people with rheumatic diseases.

Lancet Rheumatol 2021 Jul 22. Epub 2021 Jul 22.

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

Background: The impact and consequences of the COVID-19 pandemic on people with rheumatic disease are unclear. We developed the COVID-19 Global Rheumatology Alliance Patient Experience Survey to assess the effects of the COVID-19 pandemic on people with rheumatic disease worldwide.

Methods: Survey questions were developed by key stakeholder groups and disseminated worldwide through social media, websites, and patient support organisations. Questions included demographics, rheumatic disease diagnosis, COVID-19 diagnosis, adoption of protective behaviours to mitigate COVID-19 exposure, medication access and changes, health-care access and communication with rheumatologists, and changes in employment or schooling. Adults age 18 years and older with inflammatory or autoimmune rheumatic diseases were eligible for inclusion. We included participants with and without a COVID-19 diagnosis. We excluded participants reporting only non-inflammatory rheumatic diseases such as fibromyalgia or osteoarthritis.

Findings: 12 117 responses to the survey were received between April 3 and May 8, 2020, and of these, 10 407 respondents had included appropriate age data. We included complete responses from 9300 adults with rheumatic disease (mean age 46·1 years; 8375 [90·1%] women, 893 [9·6%] men, and 32 [0·3%] participants who identified as non-binary). 6273 (67·5%) of respondents identified as White, 1565 (16·8%) as Latin American, 198 (2·1%) as Black, 190 (2·0%) as Asian, and 42 (0·5%) as Native American or Aboriginal or First Nation. The most common rheumatic disease diagnoses included rheumatoid arthritis (3636 [39·1%] of 9300), systemic lupus erythematosus (2882 [31·0%]), and Sjögren's syndrome (1290 [13·9%]). Most respondents (6921 [82·0%] of 8441) continued their antirheumatic medications as prescribed. Almost all (9266 [99·7%] of 9297) respondents adopted protective behaviours to limit SARS-CoV-2 exposure. A change in employment status occurred in 2524 (27·1%) of 9300) of respondents, with a 13·6% decrease in the number in full-time employment (from 4066 to 3514).

Interpretation: People with rheumatic disease maintained therapy and followed public health advice to mitigate the risks of COVID-19. Substantial employment status changes occurred, with potential implications for health-care access, medication affordability, mental health, and rheumatic disease activity.

Funding: American College of Rheumatology.
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http://dx.doi.org/10.1016/S2665-9913(21)00175-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298011PMC
July 2021

A Combination of Healthy Lifestyle Behaviors Reduces Risk of Incident Systemic Lupus Erythematosus.

Arthritis Rheumatol 2021 Jul 27. Epub 2021 Jul 27.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Objective: While the association between individual factors related to lifestyle and the risk of SLE has been previously evaluated, it is unclear how the combination of these factors might affect the risk of incident SLE. We prospectively evaluated whether a combination of healthy lifestyle factors is associated with lower risk of incident SLE and its subtypes (dsDNA positive and negative).

Methods: We included 185,962 women with 203 incident SLE cases (96 anti-dsDNA positive,107 anti-dsDNA negative) during 4,649,477 person-years of follow-up from the Nurses' Health Study (NHS) and NHSII cohorts. The Healthy Lifestyle Index Score (HLIS) was calculated at baseline and approximately every 2 years in follow-up using five factors: alcohol consumption, body mass index, smoking, diet, and exercise. A time-varying Cox hazards regression model estimated the adjusted hazard ratios (HR) for SLE risk. The partial population attributable risk (PAR%) of SLE development was calculated.

Results: A higher HLIS was associated with a lower risk of SLE overall (HR 0.81 [95%CI 0.71-0.94]) and dsDNA positive SLE (HR 0.78 [95%CI 0.63-0.95]). Women with four or more healthy factors had the lowest SLE risk overall (HR 0.42 [95%CI 0.25-0.70]) and dsDNA positive SLE (HR 0.35 [95%CI 0.17-0.75]) compared to women with less than or equal to one healthy behavior. The PAR% for SLE from adhering to four or more healthy behaviors was 47.7% [95%CI 23.1-66.6].

Conclusion: Nearly half of SLE risk, a disease where significant evidence of genetic involvement has been established, might be reduced with adherence to modifiable healthy lifestyle behaviors.
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http://dx.doi.org/10.1002/art.41935DOI Listing
July 2021

Long-term Weight Changes and Risk of Rheumatoid Arthritis Among Women in a Prospective Cohort: A Marginal Structural Model Approach.

Rheumatology (Oxford) 2021 Jul 10. Epub 2021 Jul 10.

Division of Rheumatology, Inflammation, and Immunity, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115.

Objective: To examine the association of long-term weight change with rheumatoid arthritis (RA) risk in a large prospective cohort study.

Methods: The Nurses' Health Study (NHS) II started in 1989 (baseline); after exclusions, we studied 108,505 women 25-42 years old without RA. Incident RA was reported by participant and confirmed by medical record review. Body weight was reported biennially through 2015. We investigated two time-varying exposures: weight changes from baseline and from age 18; change was divided into 5 categories. We used a marginal structural model (MSM) approach to account for time-varying weight change and covariates.

Results: Over 2,583,266 person-years, with a median follow-up time of 25.3 years, 541 women developed RA. Compared to women with stable weight from baseline, weight change was significantly associated with increased RA risk [weight gain 2-<10 kg: RR = 1.98 (95% CI 1.38, 2.85); 10-<20 kg: RR = 3.28 (95% CI 2.20, 4.89); ≥20 kg: RR = 3.81 (95% CI 2.39, 6.07); and weight loss >2 kg: RR = 2.05 (95% CI 1.28, 3.28)]. Weight gain of 10 kg or more from age 18 compared with stable weight was also associated with increased RA risk [10-< 20 kg: RR = 2.12 (95% CI 1.37, 3.27), ≥20 kg: RR = 2.31 (95% CI 1.50, 3.56)]. Consistent findings were observed for seropositive and seronegative RA.

Conclusion: Long-term weight gain was strongly associated with increased RA risk in women, with weight gain of ≥ 20 kg associated with more than a three-fold increased RA risk. Maintenance of healthy weight may be a strategy to prevent or delay RA.
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http://dx.doi.org/10.1093/rheumatology/keab535DOI Listing
July 2021

Coronavirus disease 2019: update on coronavirus disease 2019 outcomes and vaccine efficacy in patients with immune-mediated inflammatory disease.

Curr Opin Rheumatol 2021 09;33(5):412-418

University of Queensland School of Clinical Medicine, Faculty of Medicine.

Purpose Of Review: Although the literature to date on COVID-19 outcomes in those with immune-mediated inflammatory disease has been largely reassuring there remain many unanswered questions. These include the impact of specific medications on outcomes and the antibody response after COVID-19 vaccination.

Recent Findings: We summarized the current literature related to COVID-19 outcomes in immune-mediated inflammatory diseases in rheumatology, gastroenterology, dermatology, and neurology. Overall, we found either no difference or modest differences in risk for severe COVID-19 for people with immune-mediated diseases compared with the general population. When considering disease-specific factors, glucocorticoid use and underlying immune-mediated disease activity were generally associated with worse outcomes. Specific medications varied in associations: tumor necrosis factor inhibitors generally had lower odds for severe COVID-19 outcomes, whereas rituximab use generally had higher odds for severe outcomes. We also detailed the recent reports of antibody response to COVID-19 vaccination in people with immune-mediated inflammatory diseases.

Summary: Investigations of immune-mediated inflammatory diseases across several organ systems have offered important insight into the COVID-19 disease course. Overall, these studies have provided reassurance to patients and clinicians while also identifying groups who may be at higher risk for poor outcomes.
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http://dx.doi.org/10.1097/BOR.0000000000000812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8373387PMC
September 2021

Clinical application of personalized rheumatoid arthritis risk information: Translational epidemiology leading to precision medicine.

Authors:
Jeffrey A Sparks

Expert Rev Precis Med Drug Dev 2021 14;6(3):147-149. Epub 2020 Dec 14.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, 75 Francis Street, Boston, MA, USA.

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http://dx.doi.org/10.1080/23808993.2021.1857237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192070PMC
December 2020

2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

Arthritis Care Res (Hoboken) 2021 07 8;73(7):924-939. Epub 2021 Jun 8.

Weill Cornell Medicine, New York, New York.

Objective: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.

Methods: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.

Results: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).

Conclusion: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.
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http://dx.doi.org/10.1002/acr.24596DOI Listing
July 2021

2021 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.

Arthritis Rheumatol 2021 07 8;73(7):1108-1123. Epub 2021 Jun 8.

Weill Cornell Medicine, New York, New York, United States.

Objective: To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.

Methods: We developed clinically relevant population, intervention, comparator, and outcomes (PICO) questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.

Results: The guideline addresses treatment with disease-modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high-risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).

Conclusion: This clinical practice guideline is intended to serve as a tool to support clinician and patient decision-making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision-making process based on patients' values, goals, preferences, and comorbidities.
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http://dx.doi.org/10.1002/art.41752DOI Listing
July 2021

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

Lancet Rheumatol 2021 Sep 28;3(9):e638-e647. Epub 2021 May 28.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.

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] 7·8 [4·5-16·5]; p=0·021), lactate dehydrogenase concentration (421 U/L [297-528] 345 U/L [254-479]; p=0·044), creatinine concentration (1·2 mg/dL [0·9-2·0] 1·0 mg/dL [0·8-1·4], p=0·014), and blood urea nitrogen concentration (31 mg/dL [15-61] 23 mg/dL [13-37]; p=0·033) than comparators, but median C-reactive protein concentration (149·4 mg/L [76·4-275·3] 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] 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.
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http://dx.doi.org/10.1016/S2665-9913(21)00140-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163294PMC
September 2021

Multimorbidity Accrual After Incident Rheumatoid Arthritis: A Wolf at the Door.

Authors:
Jeffrey A Sparks

J Rheumatol 2021 Jun 1. Epub 2021 Jun 1.

This work was not funded. Dr. Sparks is supported by the National Institutes of Health (grant numbers R03 AR075886, K23 AR069688, and L30 AR066953), the Rheumatology Research Foundation K Supplement Award, and the Brigham Research Institute. 1J.A. Sparks, MD, MMSc, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA. JAS has consulted for Bristol Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer, unrelated to this work. Address correspondence to Dr. J.A. Sparks, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, 60 Fenwood Road, #6016U, Boston, MA 02115, USA. Email:

Rheumatoid arthritis (RA) has long been recognized to have serious extraarticular manifestations such as interstitial lung disease (ILD). Consequences of immunosuppressive medications used to treat RA include serious infections, liver toxicity, and osteoporosis leading to fracture..
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http://dx.doi.org/10.3899/jrheum.210224DOI Listing
June 2021

Challenges and Opportunities of Targeted Behavioral Interventions for Groups at Risk for Developing Rheumatoid Arthritis.

Healthcare (Basel) 2021 May 28;9(6). Epub 2021 May 28.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, 60 Fenwood Road, Boston, MA 02115, USA.

: Rheumatoid arthritis (RA) is a serious autoimmune disease which causes painful, swollen joints and can impact quality of life and increase morbidity and mortality. There are several preclinical stages of RA that correspond to at-risk groups that include: genetic risk, risk from behaviors, elevation of RA-related autoantibodies, and early clinical disease manifestations such as undifferentiated arthritis. Early interventions are crucial to slowing progression to and potentially preventing RA onset. Modification of behaviors among at-risk individuals may decrease RA risk. There are several challenges and opportunities in implementing preventative behavioral interventions, which may vary within different at-risk groups. : We performed a narrative review of the literature, including meta-analyses focused on RA risk-related behaviors as well as publications investigating the potential efficacy of behavioral modifications on RA risk. : There are multiple behavioral risk factors associated with RA, including smoking, obesity, low physical activity, low quality diet, and poor dental hygiene, which may contribute to progression to clinical RA. Meta-analyses have been performed for smoking, excess body weight, and physical activity. Likelihood of adopting behavioral modifications may increase as RA risk increases. : Clinicians may be able to tailor preventative approaches to various RA at-risk groups to help reduce RA risk, but further research is needed. A better understanding of the relationship of behaviors with RA risk and optimized approaches to implementing behavioral changes may allow for clinicians to tailor their preventative approaches for at-risk individuals.
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http://dx.doi.org/10.3390/healthcare9060641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226912PMC
May 2021

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.

Ann Rheum Dis 2021 09 28;80(9):1137-1146. Epub 2021 May 28.

Rheumatology Department, Hamad Medical Corporation, Doha, Qatar.

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.
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http://dx.doi.org/10.1136/annrheumdis-2021-220418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172266PMC
September 2021

Relationship between rheumatoid arthritis and pulmonary function measures on spirometry in the UK Biobank.

Arthritis Rheumatol 2021 May 13. Epub 2021 May 13.

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.

Objective: We investigated the independent relationship of rheumatoid arthritis (RA) with type and severity of pulmonary patterns on spirometry compared to general population controls.

Methods: This cross-sectional study investigated the association of RA and pulmonary function measures on spirometry among subjects who had spirometry performed for research purposes in the UK Biobank. RA cases were identified by self-report and current DMARD/glucocorticoid use. General population controls denied RA. Outcomes included continuous % predicted forced expiratory volume in 1 second (FEV ) and forced vital capacity (FVC), type of spirometric pattern (restrictive or obstructive), and severity. We used multivariable regression to estimate the effects of RA cases versus controls, adjusting for age, sex, body mass index (BMI), and smoking status/pack-years.

Results: Among 350,776 analyzed subjects with spirometry performed (mean age 56.3 years, 55.8% female, and 45.5% ever smokers), we identified 2,008 cases of treated RA. In multivariable analyses, RA was associated with lower % predicted FEV (β -2.93, 95%CI -3.63,-2.24), % predicted FVC (β -2.08, 95%CI -2.72,-1.45), and FEV /FVC (β -0.008, 95%CI -0.010,-0.005) than controls. RA was associated with restrictive (OR 1.36, 95%CI 1.21,1.52) and obstructive (OR 1.21, 95%CI 1.07,1.37) patterns independent of confounders. RA had the strongest associations for severe restrictive and obstructive patterns.

Conclusion: RA was associated with increased odds of restrictive and obstructive patterns, and this relationship was not explained by confounders including smoking. In addition to restrictive lung disease, clinicians should also be aware that airflow obstruction may be a pulmonary manifestation of RA.
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http://dx.doi.org/10.1002/art.41791DOI Listing
May 2021

Incident systemic rheumatic disease following COVID-19.

Lancet Rheumatol 2021 Jun 6;3(6):e402-e404. Epub 2021 Apr 6.

Department of Medicine, Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA 02115, USA.

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http://dx.doi.org/10.1016/S2665-9913(21)00106-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023691PMC
June 2021

Reply.

Arthritis Rheumatol 2021 09 3;73(9):1767-1768. Epub 2021 Aug 3.

Mayo Clinic, Rochester, MN.

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http://dx.doi.org/10.1002/art.41745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251029PMC
September 2021

Circulating blood metabolite trajectories and risk of rheumatoid arthritis among military personnel in the Department of Defense Biorepository.

Ann Rheum Dis 2021 Mar 22. Epub 2021 Mar 22.

Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Objectives: We sought to identify metabolic changes potentially related to rheumatoid arthritis (RA) pathogenesis occurring in the blood prior to its diagnosis.

Methods: In a US military biorepository, serum samples collected at two timepoints prior to a diagnosis of RA were identified. These were matched to controls who did not develop RA by subject age, race and time between sample collections and RA diagnosis time to stored serum samples. Relative abundances of 380 metabolites were measured using liquid chromatography-tandem mass spectrometry. We determined whether pre-RA case versus control status predicted metabolite concentration differences and differences over time (trajectories) using linear mixed models, assessing for interactions between time, pre-RA status and metabolite concentrations. We separately examined pre-RA and pre-seropositive RA cases versus matched controls and adjusted for smoking. Multiple comparison adjustment set the false discovery rate to 0.05.

Results: 291 pre-RA cases (80.8% pre seropositive RA) were matched to 292 controls, all with two serum samples (2.7±1.6 years; 1.0±0.9 years before RA/matched date). 52.0% were women; 52.8% were White, 26.8% Black and 20.4% other race. Mean age was 31.2 (±8.1) years at earliest blood draw. Fourteen metabolites had statistically significant trajectory differences among pre-RA subjects versus controls, including sex steroids, amino acid/lipid metabolism and xenobiotics. Results were similar when limited to pre seropositive RA and after adjusting for smoking.

Conclusions: In this military case-control study, metabolite concentration trajectory differences in pre-RA cases versus controls implicated steroidogenesis, lipid/amino acid metabolism and xenobiotics in RA pathogenesis. Metabolites may have potential as biomarkers and/or therapeutic targets preceding RA diagnosis.
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http://dx.doi.org/10.1136/annrheumdis-2020-219682DOI Listing
March 2021

Response to: 'Correspondence on 'SARS-CoV-2 antibody response after COVID-19 in patients with rheumatic disease'' by Shanoj .

Ann Rheum Dis 2021 Mar 10. Epub 2021 Mar 10.

Division of Rheumatology, Allergy, and Immunology, Harvard Medical School, Boston, Massachusetts, USA

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http://dx.doi.org/10.1136/annrheumdis-2021-220166DOI Listing
March 2021

Interstitial lung disease throughout the rheumatoid arthritis disease course.

Curr Opin Rheumatol 2021 05;33(3):284-291

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital.

Purpose Of Review: To summarize the current understanding of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) throughout the rheumatoid arthritis (RA) disease course from preclinical to established disease.

Recent Findings: ILD is a serious extra-articular manifestation of RA. Multiple studies have demonstrated a high prevalence of both subclinical and clinical ILD throughout the RA disease course. Investigations of patients without RA have demonstrated an association between RA-related autoantibodies like anticitrullinated protein antibodies (ACPA) and interstitial abnormalities on lung imaging. A significant proportion of RA-ILD patients develop ILD prior to articular manifestations, suggesting that the lung plays a central role in RA development, perhaps through ACPA production. RA-ILD also occurs in early RA, when exuberant autoantibody production and systemic inflammation may propagate pulmonary disease activity. In patients with established RA, a high burden of subclinical and clinical ILD results in significant morbidity, mortality, and healthcare expenditure. Multiple epidemiologic and genetic risk factors, as well as serum biomarkers, have been associated with RA-ILD.

Summary: Subclinical and clinical ILD occur frequently in preclinical, early, and established RA and may play a key role in RA-related autoantibody production and disease progression. Further studies are needed to better understand the risk factors, prognosis, and potential therapies for RA-ILD.
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http://dx.doi.org/10.1097/BOR.0000000000000787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268047PMC
May 2021
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