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Rheumatoid arthritis disease activity predicting incident clinically-apparent RA-associated interstitial lung disease: A prospective cohort study


Sparks JA1,2, He X1, Huang J1, Fletcher EA3, Zaccardelli A1, Friedlander HM1, Gill RR2,4, Hatabu H2,5, Nishino M2,5,6, Murphy DJ7, Iannaccone CK2, Mahmoud TG2, Frits ML2, Lu B1,2, Rosas IO2,3, Dellaripa PF1,2, Weinblatt ME1,2, Karlson EW1,2, Shadick NA1,2, Doyle TJ2,3. Arthritis Rheumatol. 2019 Apr 5. doi: 10.1002/art.40904. [Epub ahead of print]

Author Information

1 Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA.

2 Harvard Medical School, Boston, MA.

3 Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA.

4 Department of Radiology, Beth-Israel Deaconess Medical Center, Boston, MA.

5 Department of Radiology, Brigham and Women's Hospital, Boston, MA.

6 Department of Radiology, Dana-Farber Cancer Institute, Boston, MA.

7 Department of Radiology, St Vincent's University Hospital, Dublin, Ireland.



To evaluate rheumatoid arthritis (RA) disease activity and risk for RA-associated interstitial lung disease (RA-ILD).


We investigated disease activity and RA-ILD risk using the Brigham RA Sequential Study (BRASS, 2003-2016). All subjects had RA according to accepted criteria. Disease activity scores using 28 joints (DAS28) and covariate data were measured prospectively at annual study visits. RA-ILD was determined by research review of images from clinically-indicated chest computed tomography scans. We analyzed subjects without RA-ILD at baseline. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for RA-ILD by time-updated DAS28 categories, adjusting for known RA-ILD risk factors (age, sex, smoking, RA duration, and serologic status). We performed alternative analyses not censoring after missing DAS28 and adjusting for methotrexate/glucocorticoids/bone erosions/rheumatoid nodules.


Among 1,419 participants, mean age was 55.8 years (SD 14.2) and 68.6% were seropositive. We identified 85 incident RA-ILD cases during mean 8.9 years (SD 4.2) of follow-up/subject. Moderate/high disease activity had multivariable HR of 2.22 (95%CI 1.28-3.82) for RA-ILD compared to remission/low. Risk for RA-ILD increased across disease activity categories; multivariable HRs(95%CIs) were: 1.00(reference) for remission, 1.41(0.61-3.28) for low, 2.08(1.06-4.05) for moderate, and 3.48(1.64-7.38) for high (p trend=0.001). For every unit increase in DAS28, RA-ILD risk increased by 35% (95%CI 14-60%). Results were similar in analyses including follow-up after missing DAS28 and adjusting for methotrexate, glucocorticoids, bone erosions, or rheumatoidnodules.


Active RA was associated with increased risk for developing RA-ILD. These results suggest that decreasing systemic inflammation may alter the natural history of RA-ILD development.