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AB0810 PERFORMANCE OF CIRCULATING BIOMARKERS FOR PREDICTING PROGRESSION OF INTERSTITIAL LUNG DISEASE IN PATIENTS WITH SYSTEMIC SCLEROSIS

Yomono, K. ; Kuwana, M.

Annals of the rheumatic diseases, 2023-06, Vol.82 (Suppl 1), p.1618-1618 [Periódico revisado por pares]

London: BMJ Publishing Group LTD

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  • Título:
    AB0810 PERFORMANCE OF CIRCULATING BIOMARKERS FOR PREDICTING PROGRESSION OF INTERSTITIAL LUNG DISEASE IN PATIENTS WITH SYSTEMIC SCLEROSIS
  • Autor: Yomono, K. ; Kuwana, M.
  • Assuntos: Biomarkers ; C-reactive protein ; Clinical trials ; Erythrocyte sedimentation rate ; Fibrosis ; Inflammation ; Lung diseases ; Risk factors ; Scleroderma ; Systemic sclerosis
  • É parte de: Annals of the rheumatic diseases, 2023-06, Vol.82 (Suppl 1), p.1618-1618
  • Descrição: Background In patients with systemic sclerosis (SSc), progression of interstitial lung disease (ILD) is associated with an increased risk of mortality. Since the course of SSc-ILD is variable, it is critical to predict progression of ILD in clinical practice as well as in designing clinical trials. Risk factors for ILD progression include short SSc duration, male, elevated inflammatory markers and Krebs von den Lungen-6 (KL-6), and progression of skin thickness in diffuse cutaneous SSc (dcSSc). Objectives To investigate if inflammatory markers and KL-6 at baseline are useful to efficiently capture patients who subsequently experience ILD progression in patients with dcSSc or SSc-ILD using a single-center cohort. Methods Patients with dcSSc or SSc-ILD were selected from the prospective SSc registry. C-reactive protein (CRP) ≥6 mg/L and erythrocyte sedimentation rate (ESR) ≥28 mm/hour were used as inflammatory markers [1], and a cutoff level of KL-6 was provisionally set at 1,000 U/ml. ILD progression was defined as the first event developing progressive fibrosing ILD (PF-ILD) [2] or progressive pulmonary fibrosis (PPF) [3]. Receiver operating characteristic curve (ROC) analysis was used to determine the sensitivity, specificity, and area under the curve (AUC) values of individual biomarkers and their combinations for predicting ILD progression. Cumulative rates free from ILD progression were assessed using Kaplan-Meier analysis and were compared using log-rank test. Results We enrolled 109 patients with dcSSc and 136 patients with SSc-ILD. The median disease duration at baseline was 15 and 17.5 months for dcSSc and SSc-ILD, respectively, and 87 patients with SSc-ILD (64%) had dcSSc. During median of 37 months of follow-up of dcSSc patients, 27 (25%) and 22 (20%) developed PF-ILD and PPF, respectively; and during median of 44.5 months of follow-up of SSc-ILD patients, 43 (31%) and 36 (26%) developed PF-ILD and PPF, respectively. As shown in Table, specificity of CRP, ESR and KL-6 for predicting ILD progression was favorable (73.6-88%), but sensitivity of CRP and ESR was low (9.1-16%). KL-6 provided better sensitivity (29.2-45.2%). The combination of CRP/KL-6 showed the AUC value (0.57-0.60), with sensitivity of 38.1-52.4% amd specificity of 69.1-77.8%. Kaplan-Meier analysis found that ILD progression occurred more frequently in patients with increased KL-6 than in those without irrespective of definition of ILD progression (P = 0.0001-0.03). The same trend was observed when combination of CRP/KL-6 was used (P = 0.001-0.14). Conclusion Increased KL-6 at baseline is the best biomarker for predicting ILD progression in patients with dcSSc or SSc-ILD. When KL-6 was combined with CRP, sensitivity was increased by maintaining acceptable specificity, proposing use of this combination as inclusion criteria for enriching an “at risk” patients in clinical trials for dcSSc or SSc-ILD. References [1]Khanna D, et al. Lancet Respir Med 2020; 8: 963 [2]Flaherty KR, et al. N Engl J Med. 2019; 381: 1718 [3]Raghu G, et al. Am J Respir Crit Care Med. 2022; 205: e18. Table : CRP, ESR, KL-6 and their combinations for predicting ILD progression dcSSc SSc-ILD PF-ILD PPF PF-ILD PPF AUC Sensitivity Specificity AUC Sensitivity Specificity AUC Sensitivity Specificity AUC Sensitivity Specificity CRP 0.52 16.0 88.0 0.48 9.1 86.0 0.51 14.0 87.9 0.49 11.1 86.7 ESR 0.47 13.6 80.3 0.45 10.5 79.7 0.44 14.7 73.6 0.44 14.3 74.4 KL-6 0.58 29.2 86.4 0.57 28.6 85.7 0.64 45.2 82.8 0.61 42.9 79.8 CRP or ESR 0.49 22.7 76.1 0.45 15.8 62.4 0.46 25.7 66.7 0.45 24.1 66.7 CRP or KL-6 0.60 41.7 77.8 0.57 38.1 76.2 0.62 52.4 72.4 0.59 48.6 69.1 ESR or KL-6 0.51 31.8 70.0 0.51 31.6 69.9 0.57 52.5 60.8 0.55 51.5 59.3 CRP or ESR or KL-6 0.53 40.9 65.7 0.51 36.8 64.4 0.56 57.5 54.1 0.53 54.5 51.9 Acknowledgements: NIL. Disclosure of Interests Keina Yomono: None declared, Masataka Kuwana Speakers bureau: Abbvie, Asahi-Kasei, Astellas, Boehringer-Ingelheim, Chugai, Eisai, MBL, Mochida, Nippon Shinyaku, Ono Pharmaceuticals, Tanabe-Mitsubishi, Consultant of: Astra Zeneka, Boehringer-Ingelheim, Chugai, Corbus, GSK, Horizon, Tanabe-Mitsubishi, Grant/research support from: Boehringer-Ingelheim.
  • Editor: London: BMJ Publishing Group LTD
  • Idioma: Inglês
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