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

Julie

MONITORING FOR RA-ILD PROGRESSION WITH PFTs IS RECOMMENDED AT 3–6-MONTHLY INTERVALS, THEN EVERY 6–12 MONTHS IF STABLE1

It is estimated that 40% of patients with RA—ILD develop a progressive fibrosing phenotype3,4

The progressive fibrosing phenotype is defined by the presence of:5-8
Increase extent of fibrosis on HRCT

Increase extent of fibrosis on HRCT
Worsening respiratory symptoms

Worsening respiratory symptoms
Declining lung function

Declining lung function

Risk factors for ILD progression in RA-ILD
HRCT

  • Extent of interstitial lung abnormalities (ILAs)9,10

  • UIP pattern11
PFTs

  • Lower baseline FVC or DLCO11,12

  • >10% decrease in FVC or >15% decrease in DLCO at follow-up12,13

  • TLCO <54% predicted9
Serological biomarkers

  • High baseline concentration of KL-614

 

HRCT

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

Find out how to use HRCT in clinical practice

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

Graph showing the percentage of patients progressing since ILD diagnosis to FVC lower than 50 percentage

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

Graph showing the percentage of patients progressing since ILD diagnosis to DLco lower than 40 percentage

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. 

 

PFTs

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

 

SEROLOGY

High baseline serum concentrations of KL-6 have been found to be associated with ILD progression in RA-ILD14*
The link between serum concentrations of KL-6 and ILD progression in RA-ILD

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.

In patients with asymptomatic RA-ILD, a clinical, functional and radiologic follow-up of the lung is mandatory to identify those with progressive disease2

Tight follow-up, to monitor for ILD progression, is recommended in RA-ILD patients using periodic assessment of respiratory symptoms, PFTs, DLCO and HRCT2,16

 

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

Irrespective of whether HRCT pattern is UIP or NSIP
If ILD is clinically significant (symptoms, severity)

If ILD is clinically significant (symptoms, severity)
If ILD is progressive

If ILD is progressive

Treatment for RA-ILD should be escalated when ILD progresses.18 If the RA-ILD patient fails to respond to first-line treatment or deteriorates, different treatment options could be considered.17

 

 

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
A multidisciplinary team including a range of specialists should be involved in ILD diagnosis

Learn how to proactively collaborate to optimise ILD care through a multidisciplinary team approach

 

 

What other management approaches should you consider?
Footnotes
  • 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.

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  9. 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.

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  11. 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.

  12. Esposito AJ, Chu SG, Madan R, et al. Thoracic manifestations of rheumatoid arthritis. Clin Chest Med. 2019;40(3):545–560.

  13. 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.

  14. 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.

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  19. 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.

  20. Cottin V, Brown KK. Interstitial lung disease associated with systemic sclerosis (SSc–ILD). Respir Res. 2019a;20(1):13.

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  22. 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.

  23. Kreuter M, Bendstrup E, Russell A, et al. Palliative care in interstitial lung disease: living well. Lancet Respir Med. 2017;5(12):968-980. 

  24. Maher TM, Wuyts W. Management of Fibrosing Interstitial Lung Diseases. Adv Ther. 2019;doi:10.1007/s12325-019-00992-9. [Epub ahead of print].

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