Monitoring and management of ILD progression in RA-ILD
Regular monitoring for progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) can inform appropriate treatment decisions1,2
MONITORING FOR RA-ILD PROGRESSION WITH PFTs IS RECOMMENDED AT 3–6-MONTHLY INTERVALS, THEN EVERY 6–12 MONTHS IF STABLE1
The progressive fibrosing phenotype is defined by the presence of:5-8
Increase extent of fibrosis on HRCT
Worsening respiratory symptoms
Declining lung function
Risk factors for ILD progression in RA-ILD
Interstitial lung abnormalities occur in 20%–60% of patients with RA and have been shown to be radiographically progressive in 57% of cases over a 1.5-year period.10,15
RA-ILD patients that present progression on HRCT had significantly higher median baseline ILA/ILD involvement (p=0.001)10
UIP pattern on HRCT is a risk factor for poorer prognosis in RA-ILD, but patients with other HRCT patterns can also show progression as demonstrated in a Mayo Clinic study11
Percentage of patients that progress to FVC <50% predicted according to time since ILD diagnosis11
No difference in progression to FVC <50% was observed between patients with UIP and NSIP patterns in a Mayo Clinic study11
Estimated percentage of patients with FVC <50% according to time since diagnosis of ILD in 167 patients with RA-ILD subdivided by ILD type.
HR: 0.86; 95% CI: 0.27, 2.73.
Adapted from: Zamora-Legoff JA, et al. Arthritis Rheumatol. 2017;69:542–549.
Percentage of patients that progress to DLCO <40% predicted according to time since ILD diagnosis11
UIP pattern was more significantly associated with progression to DLCO <40% predicted vs. NSIP pattern in a Mayo Clinic study11
Estimated percentage of patients with DLCO <40% (or too ill to perform the test) according to time since diagnosis of ILD in 167 patients with RA-ILD subdivided by ILD type.
HR: 3.29; 95% CI: 1.28, 8.41.
Adapted from: Zamora-Legoff JA, et al. Arthritis Rheumatol. 2017;69:542–549.
Low baseline FVC and DLCO at RA-ILD diagnosis increase the risk of ILD progression11
Low FVC or DLCO % predicted at baseline, >10% decrease in FVC or >15% decrease in DLCO at follow-up, are all associated with progression of ILD and increased mortality in RA patients12,13
A high rate of decline in FVC and DLCO in the first 6 months increases the risk of progression to severe lung function impairment11
High baseline serum concentrations of KL-6 have been found to be associated with ILD progression in RA-ILD14*
Concentration of KL-6 (U/mL) according to the progression of RA-ILD
* As defined by progression of >10% of fibrosis on HRCT and either a FVC decline >15% or a FVC decline > 10% combined with a DLCO decline >15%
Adapted from: Avouac J, et al. PLoS One. 2020;15:e0232978.
PROGRESSION AND SEVERITY OF ILD ARE THE MAIN FACTORS TO CONSIDER WHEN MAKING TREATMENT DECISIONS FOR RA-ILD2
Treatment may be considered:17
Irrespective of whether HRCT pattern is UIP or NSIP
If ILD is clinically significant (symptoms, severity)
If ILD is progressive
A MULTIDISCIPLINARY TEAM APPROACH IS RECOMMENDED TO MAKE TREATMENT DECISIONS FOR PROGRESSIVE ILD IN RA-ILD PATIENTS2
Multidisciplinary management incorporating rheumatologists and respiratory specialists has a vital role in optimizing the care of RA-ILD patients1
What other management approaches should you consider?
Providing palliative/supportive care
- CI, confidence interval; CTD-ILD, connective tissue disease-associated interstitial lung disease; DLCO, diffusing capacity of the lung for carbon monoxide; FVC, forced vital capacity; HR, hazard ratio; HRCT, high-resolution computed tomography; IIP, idiopathic interstitial pneumonia; ILA, interstitial lung abnormality; ILD, interstitial lung disease; KL-6, Krebs von den Lungen-6; NSIP, non-specific interstitial pneumonia; PFT, pulmonary function test; RA, rheumatoid arthritis; RA-ILD, rheumatoid arthritis-associated interstitial lung disease; TLCO, transfer factor of the lung for carbon monoxide; UIP, usual interstitial pneumonia.
- Iqbal K and Kelly C. Treatment of rheumatoid arthritis-associated interstitial lung disease: a perspective review. Ther Adv Musculoskelet Dis. 2015;7(6):247–267.
- Cassone G, Manfredi A, Vacchi C, et al. Treatment of rheumatoid arthritis-associated interstitial lung disease: lights and shadows. J Clin Med. 2020;9(4):1082. doi: 10.3390/jcm9041082.
- Olson AL, Hartmann N, Padmaja P, et al. Estimation of the Prevalence of Progressive Fibrosing Interstitial Lung Diseases: Systematic Literature Review and Data from a Physician Survey. Adv Ther. 2020; https://doi.org/10.1007/s12325-020-01578-6.
- Wijsenbeek M, Kreuter M, Olson A, et al. Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management. Curr Med Res Opin. 2019;35(11):2015–2024.
- Flaherty KR, Brown KK, Wells AU, et al. Design of the PF-ILD trial: a doubleblind, randomised, placebo-controlled phase III trial of nintedanib in patients with progressive fibrosing interstitial lung disease. BMJ Open Respir Res. 2017;4(1):e000212. doi: 10.1136/bmjresp-2017-000212.
- Cottin V, Hirani NA, Hotchkin DL, et al. Presentation, diagnosis and clinical course of the spectrum of progressive fibrosing interstitial lung diseases. Eur Respir Rev. 2018;27(150):180076. doi: 10.1183/16000617.0076-2018.
- Cottin V, Wollin L, Fischer A, et al. Fibrosing interstitial lung diseases: knowns and unknowns. Eur Respir Rev. 2019;28(151):180100. doi: 10.1183/16000617.0100-2018.
- Kolb M and Vašáková M. The natural history of progressive fibrosing interstitial lung diseases. Respir Res. 2019;20(1):57. doi: 10.1186/s12931-019-1022-1.
- Dawson JK, Fewins HE, Desmond J, et al. Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis. Ann Rheum Dis. 2002;61:517–521.
- Kawano-Dourado L, Doyle TJ, Bonfiglioli K, et al. Baseline characteristics and progression of a spectrum of interstitial lung abnormalities and disease in rheumatoid arthritis. Chest. 2020:S0012-3692(20)31412-4. doi: 10.1016/j.chest.2020.04.061.
- Zamora-Legoff JA, Krause ML, Crowson CS, et al. Progressive decline of lung function in rheumatoid arthritis associated interstitial lung disease. Arthritis Rheumatol. 2017;69(3):542–549.
- Esposito AJ, Chu SG, Madan R, et al. Thoracic manifestations of rheumatoid arthritis. Clin Chest Med. 2019;40(3):545–560.
- Solomon JJ, Chung JH, Cosgrove GP, et al. Predictors of mortality in rheumatoid arthritis-associated interstitial lung disease. Eur Respir J. 2016;47(2):588–596.
- Avouac J, Cauvet A, Steelandt A, et al. Improving risk-stratification of rheumatoid arthritis patients for interstitial lung disease. PLoS One. 2020;15(5):e0232978. doi:10.1371/journal.pone.0232978.
- Gochuico BR, Avila NA, Chow CK, et al. Progressive preclinical interstitial lung disease in rheumatoid arthritis. Arch Intern Med. 2008;168(2):159–166.
- Assayag D, Lee JS, King Jr TE. Rheumatoid arthritis associated interstitial lung disease: a review. Medicina (B Aires). 2014;74(2):158–165.
- Lake F and Proudman S. Rheumatoid arthritis and lung disease: from mechanisms to a practical approach. Semin Respir Crit Care Med. 2014;35(2):222–238.
- Wallace B, Vummidi D, Khanna D. Management of connective tissue diseases associated interstitial lung disease: a review of the published literature. Curr Opin Rheumatol. 2016;28(3):236–245.
- Chowaniec M, Skoczyńska M, Sokolik R, Wiland P. Interstitial lung disease in systemic sclerosis: challenges in early diagnosis and management. Reumatologia. 2018;56(4):249–254.
- Cottin V, Brown KK. Interstitial lung disease associated with systemic sclerosis (SSc–ILD). Respir Res. 2019a;20(1):13.
- Wijsenbeek M, Cottin V. Spectrum of Fibrotic Lung Diseases. N Engl J Med. 2020;383:958–968.
- Ryerson CJ, Cayou C, Topp F, et al. Pulmonary rehabilitation improves long-term outcomes in interstitial lung disease: a prospective cohort study. Respir Med. 2014;108(1):203-210.
- Kreuter M, Bendstrup E, Russell A, et al. Palliative care in interstitial lung disease: living well. Lancet Respir Med. 2017;5(12):968-980.
- Maher TM, Wuyts W. Management of Fibrosing Interstitial Lung Diseases. Adv Ther. 2019;doi:10.1007/s12325-019-00992-9. [Epub ahead of print].
- Sgalla G, Cerri S, Ferrari R, et al. Mindfulness-based stress reduction in patients with interstitial lung diseases: a pilot, single-centre observational study on safety and efficacy. BMJ Open Respir Res. 2015;2(1):e000065.