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Predictive Significance of Serum Interferon‐Inducible Protein Score for Response to Treatment in Systemic Sclerosis–Related Interstitial Lung Disease
Author(s) -
Assassi Shervin,
Li Ning,
Volkmann Elizabeth R.,
Mayes Maureen D.,
Rünger Dennis,
Ying Jun,
Roth Michael D.,
Hinchcliff Monique,
Khanna Dinesh,
Frech Tracy,
Clements Philip J.,
Furst Daniel E.,
Goldin Jonathan,
Bernstein Elana J.,
Castelino Flavia V.,
Domsic Robyn T.,
Gordon Jessica K.,
Hant Faye N.,
Shah Ami A.,
Shanmugam Victoria K.,
Steen Virginia D.,
Elashoff Robert M.,
Tashkin Donald P.
Publication year - 2021
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.41627
Subject(s) - medicine , interstitial lung disease , gastroenterology , immunosuppression , scleroderma (fungus) , c reactive protein , immunology , mycophenolic acid , lung , transplantation , inflammation , inoculation
Objective Response to immunosuppression is highly variable in systemic sclerosis (SSc)–related interstitial lung disease (ILD). This study was undertaken to determine whether a composite serum interferon (IFN)–inducible protein score exhibits predictive significance for the response to immunosuppression in SSc‐ILD. Methods Serum samples collected in the Scleroderma Lung Study II, a randomized controlled trial of mycophenolate mofetil (MMF) versus cyclophosphamide (CYC), were examined. Results were validated in an independent observational cohort receiving active treatment. A composite score of 6 IFN‐inducible proteins IFNγ‐inducible 10‐kd protein, monokine induced by IFNγ, monocyte chemotactic protein 2, β 2 ‐microglobulin, tumor necrosis factor receptor type II, and macrophage inflammatory protein 3β) was calculated, and its predictive significance for longitudinal forced vital capacity percent predicted measurements was evaluated. Results Higher baseline IFN‐inducible protein score predicted better response over 3 to 12 months in the MMF arm (point estimate = 0.41, P = 0.001) and CYC arm (point estimate = 0.91, P = 0.009). In contrast, higher baseline C‐reactive protein (CRP) levels were predictive of a worse ILD course in both treatment arms. The predictive significance of the IFN‐inducible protein score and CRP levels remained after adjustment for baseline demographic and clinical predictors. During the second year of treatment, in which patients in the CYC arm were switched to placebo, a higher IFN‐inducible protein score at 12 months showed a trend toward predicting a worse ILD course (point estimate = −0.61, P = 0.068), while it remained predictive of better response to active immunosuppression in the MMF arm (point estimate = 0.28, P = 0.029). The predictive significance of baseline IFN‐inducible protein score was replicated in the independent cohort (r s = 0.43, P = 0.028). Conclusion A higher IFN‐inducible protein score in SSc‐ILD is predictive of better response to immunosuppression and could potentially be used to identify patients who may derive the most benefit from MMF or CYC.