ACR CONVERGENCE 2020—Moderated by Bill St.Clair, MD, MACR, an ACR past president and a professor of medicine and immunology at Duke University Medical Center, Durham, N.C., an abstract session on Friday, Nov. 6, focused on the diagnosis, manifestations and outcomes of rheumatoid arthritis (RA), with a focus on interstitial lung disease.
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RA with ILD
Jeffrey Sparks, MD, MSc, an assistant professor of medicine at Brigham and Women’s Hospital, Boston, presented the results of two studies: “Prevalence, Incidence, and Cause-Specific Mortality of Rheumatoid Arthritis-Associated Interstitial Lung Disease Among Older Patients with Rheumatoid Arthritis: A Nationwide Cohort Study” (abstract 0489) and “Fine Specificity Anti-Citrullinated Protein Antibodies as Biomarkers for Prediction of Incident Rheumatoid Arthritis-Associated Interstitial Lung Disease” (abstract 0490).1,2
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is one of the most serious extra-articular RA manifestations, and its prevalence may be increasing. According to Dr. Sparks, “RA-ILD is associated with a median overall survival of only three to eight years.” Thus, Dr. Sparks and his colleagues investigated the prevalence, incidence and cause-specific mortality of RA-ILD using a recently validated claims-based algorithm in a retrospective cohort study using U.S. claims data from Medicare (2008–17).
The researchers concluded that RA-ILD was present or developed in nearly 5% of “older” patients with RA (Note: The abstract did not define older; however, the study population comprised Medicare patients, so the patients were 65 or older.) RA-ILD was associated with excess total mortality that was not explained by measured factors. They confirmed the association of male sex and smoking with incident RA-ILD. They further noted that biologic disease-modifying anti-rheumatic drug (DMARD) use and glucocorticoid use were associated with incident RA-ILD. Patients with RA-ILD had a strongly associated increased risk of respiratory mortality than patients with RA without ILD.
In the second study presentation, Dr. Sparks said the researchers investigated fine specificity anti-citrullinated protein antibodies (ACPA) and the subsequent risk of RA-ILD. They were able to identify several fine specificity ACPA associated with subsequent risk of RA-ILD that may inform pathogenesis. In particular, their study showed that “autoimmunity to a specific citrullinated epitope of filaggrin was associated with RA-ILD across all isotypes investigated and is potentially a novel predictive biomarker for RA-ILD. … These results suggest that fine specificity ACPA biomarkers may have utility in RA-ILD prediction.”
RA & Pulmonary Function
Lauren Prisco, BA, the clinical research coordinator at Brigham and Women’s Hospital, presented the results of a study on the relationship between RA and pulmonary function (abstract 0491).3
In a cross-sectional study, these researchers investigated the relationship of RA with type and severity of pulmonary function test (PFT) abnormalities in comparison to the general population, accounting for smoking. Two acceptable measurements were obtained from all individuals: % predicted values of FEV1 and FVC (calculated on the basis of age, sex, race and height).
RA cases were identified by self-report and current DMARD use, as previously published in the UK Biobank. They compared RA cases with general population controls in the UK Biobank who denied having RA or another systemic rheumatic disease. Outcomes were continuous PFT results, type of PFT abnormality (i.e., restrictive pattern [% predicted FVC<80], obstructive pattern [FEV1/FVC <0.7] or either abnormality), and level of severity (i.e., mild, moderate or severe) according to standard clinical PFT cutpoints from population prediction equations. Covariates included age, sex, smoking status and pack-years. The researchers used linear regression to compare RA cases with controls for continuous PFT results. They used logistic regression to estimate adjusted odds ratios for type and severity of PFT abnormality, comparing RA cases with controls.
The bottom line: RA patients were more likely than general population controls to have restrictive (36% increased risk) or obstructive pattern (28% increased risk) abnormalities on PFTs obtained for research purposes. In addition to restriction, said Ms. Prisco, obstructive lung diseases may be a pulmonary manifestation of RA not explained by smoking.
Characterized by damage to the lining of the intestine, leaky gut leads to increased intestinal permeability. According to researcher Carolin Brandl of the Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany, the purpose of this study was to test whether a leaky gut occurs before the onset of human RA and experimental arthritis, and to seek for evidence that immune cells from the gut migrate to the joints (abstract 0492).4
The data in this study show that intestinal barrier dysfunction does precede the onset of RA and allows the trafficking of immune cells from the gut to the joints. Targeting intestinal tight junction function may, therefore, provide a way to prevent the onset of RA.
Can a Computer Score Joint Space in Hand Radiographs?
The final presentation in this abstract session took a turn away from RA complications. Yun-Ju Huang, MD, of the Chang Gung Memorial Hospital, Taoyuan City, Taiwan (Republic of China), discussed the results of a study intended to assess the performance of a deep-learning model for detecting and scoring joint space automatically in comparison to physician performance (abstract 0493).5
Assessment of joint space is a fundamental radiographic task to diagnose RA and to assess disease severity and progression. The clinical assessment of joint space is a visual task, and the current scoring systems, such as the modified Sharp’s score, generally follow the semiquantitative grading. Inter- and intra-observer variation impede the development of computer-aided detection and diagnosis software to help physicians.
The researchers collected 1,397 conventional hand radiographs from 450 RA patients (309 training radiographs and 141 validation radiographs) whose diagnoses were based on the 2010 ACR/EULAR classification criteria for RA. Three rheumatologists assessed the joint space independently according to the van der Heijde-modified Sharp scoring method. The consensus was the ground truth for training data.
The researchers then trained a model to detect joints automatically using the Deep Adaptive Graph.
The short answer to the question is, yes, deep learning models are useful to detect specific joint area and score the joint space with performance comparable with rheumatologists.
The data presented in this session exceeded the scope of this article. We encourage readers to review the abstracts for details.
Keri Losavio is the editor of The Rheumatologist.
- Sparks J, Jin Y, Cho S, et al. Prevalence, incidence, and cause-specific mortality of rheumatoid arthritis-associated interstitial lung disease among older patients with rheumatoid arthritis: A nationwide cohort study [abstract]. Arthritis Rheumatol. 2020 Oct;72(suppl 10).
- Kronzer V, Huang W, Dellaripa P, et al. Fine specificity anti-citrullinated protein antibodies as biomarkers for prediction of incident rheumatoid arthritis-associated interstitial lung disease [abstract]. Arthritis Rheumatol. 2020 Oct;72(suppl 10).
- Prisco L, Moll M, Wang J, et al. Relationship between rheumatoid arthritis and pulmonary function in the UK Biobank [abstract]. Arthritis Rheumatol. 2020 Oct;72(suppl 10).
- Tajik N, Frech M, Brandl C, et al. Microbiota-induced intestinal barrier dysfunction initiates the shuttling of immune cells from the gut to the joints [abstract]. Arthritis Rheumatol. 2020 Oct;72(suppl 10).
- Huang Y, Kuo C, Wang F, et al. Automatic joint space assessment in hand radiographs with deep learning among patients with rheumatoid arthritis [abstract]. Arthritis Rheumatol. 2020 Oct;72(suppl 10).