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Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.

Publication ,  Journal Article
Wampler Muskardin, T; Vashisht, P; Dorschner, JM; Jensen, MA; Chrabot, BS; Kern, M; Curtis, JR; Danila, MI; Cofield, SS; Shadick, N; Furie, R ...
Published in: Ann Rheum Dis
October 2016

OBJECTIVE: Studies suggest that circulating type I interferon (IFN) may predict response to biological agents in rheumatoid arthritis (RA). Prediction of response prior to initiating therapy would represent a major advancement. METHODS: We studied sera from a test set of 32 patients with RA from the Auto-immune Biomarkers Collaborative Network Consortium and a validation set of 92 patients with RA from the Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository registry. The test set included those with good response or no response to tumour necrosis factor (TNF) inhibitors at 14 weeks by European League Against Rheumatism criteria. The validation set included subjects with good, moderate or no response at 12 weeks. Total serum type I IFN activity, IFN-α and IFN-β activity were measured using a functional reporter cell assay. RESULTS: In the test set, an increased ratio of IFN-β to IFN-α (IFN-β/α activity ratio) in pretreatment serum associated with lack of response to TNF inhibition (p=0.013). Anti-cyclic citrullinated peptide antibody titre and class of TNF inhibitor did not influence this relationship. A receiver-operator curve supported a ratio of 1.3 as the optimal cut-off. In the validation set, subjects with an IFN-β/α activity ratio >1.3 were significantly more likely to have non-response than good response (OR=6.67, p=0.018). The test had 77% specificity and 45% sensitivity for prediction of non-response compared with moderate or good response. Meta-analysis of test and validation sets confirmed strong predictive capacity of IFN-β/α activity ratio (p=0.005). CONCLUSIONS: Increased pretreatment serum IFN-β/α ratio strongly associated with non-response to TNF inhibition. This study supports further investigation of serum type I IFN in predicting outcome of TNF inhibition in RA.

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Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

October 2016

Volume

75

Issue

10

Start / End Page

1757 / 1762

Location

England

Related Subject Headings

  • Young Adult
  • Tumor Necrosis Factor-alpha
  • Treatment Outcome
  • Sensitivity and Specificity
  • Registries
  • Prognosis
  • Predictive Value of Tests
  • Middle Aged
  • Male
  • Interferon-beta
 

Citation

APA
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Wampler Muskardin, T., Vashisht, P., Dorschner, J. M., Jensen, M. A., Chrabot, B. S., Kern, M., … Niewold, T. B. (2016). Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis. Ann Rheum Dis, 75(10), 1757–1762. https://doi.org/10.1136/annrheumdis-2015-208001
Wampler Muskardin, Theresa, Priyanka Vashisht, Jessica M. Dorschner, Mark A. Jensen, Beverly S. Chrabot, Marlena Kern, Jeffrey R. Curtis, et al. “Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.Ann Rheum Dis 75, no. 10 (October 2016): 1757–62. https://doi.org/10.1136/annrheumdis-2015-208001.
Wampler Muskardin T, Vashisht P, Dorschner JM, Jensen MA, Chrabot BS, Kern M, et al. Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis. Ann Rheum Dis. 2016 Oct;75(10):1757–62.
Wampler Muskardin, Theresa, et al. “Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis.Ann Rheum Dis, vol. 75, no. 10, Oct. 2016, pp. 1757–62. Pubmed, doi:10.1136/annrheumdis-2015-208001.
Wampler Muskardin T, Vashisht P, Dorschner JM, Jensen MA, Chrabot BS, Kern M, Curtis JR, Danila MI, Cofield SS, Shadick N, Nigrovic PA, St Clair EW, Bingham CO, Furie R, Robinson W, Genovese M, Striebich CC, O’Dell JR, Thiele GM, Moreland LW, Levesque M, Bridges SL, Gregersen PK, Niewold TB. Increased pretreatment serum IFN-β/α ratio predicts non-response to tumour necrosis factor α inhibition in rheumatoid arthritis. Ann Rheum Dis. 2016 Oct;75(10):1757–1762.

Published In

Ann Rheum Dis

DOI

EISSN

1468-2060

Publication Date

October 2016

Volume

75

Issue

10

Start / End Page

1757 / 1762

Location

England

Related Subject Headings

  • Young Adult
  • Tumor Necrosis Factor-alpha
  • Treatment Outcome
  • Sensitivity and Specificity
  • Registries
  • Prognosis
  • Predictive Value of Tests
  • Middle Aged
  • Male
  • Interferon-beta