Characterisation of incident interstitial lung disease in late systemic sclerosis.

Objective: Interstitial lung disease (ILD) is a common and potentially lethal complication of systemic sclerosis (SSc). Screening by HRCT is recommended in all patients with risk factors, including early disease. Little is known on late presentations of ILD. This study aimed to characterize the incidence, risk factors and outcomes of late-onset SSc-ILD.

Methods: Subjects enrolled in the Canadian Scleroderma Research Group (CSRG) cohort from 2004 to 2020 without prevalent ILD were included. Incidence and risk factors for ILD (on HRCT) were compared according to disease duration above (late) and below (earlier) 7 years from first non-Raynaud manifestation. Risk of ILD progression was compared using Kaplan-Meier and multivariable Cox models.

Results: Overall, 199/969 (21%) patients developed incident ILD over a median of 2.4 [1.2, 4.3] years. The incidence rate in late SSc (3.7/100 person-years) was lower than in earlier SSc (relative risk 0.68, 95%CI:0.51-0.92). Risk factors for incident ILD included male sex, diffuse subtype, myositis, anti-topoisomerase I autoantibodies and higher C-reactive protein levels. Patients with late-onset ILD were also less frequently White and more frequently had arthritis and anti-RNA-polymerase III autoantibodies. Lung disease severity was similar between late- and earlier-onset SSc-ILD (FVC 88% and 87%, DLCO 64% and 62%, respectively). Progression rates were also similar between late- and earlier-onset SSc-ILD (log-rank p=0.8, hazard ratio 1.11, 95% CI: 0.58-2.10).

Conclusion: ILD can present in late SSc. Risk factors and progression rates overlapped with earlier-onset SSc-ILD. Surveillance for ILD should continue in longstanding SSc. Frequency and modality of monitoring remain to be defined.