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Pre-treatment calprotectin (MRP8/14) provides no added value to testing CRP alone in terms of predicting response to TNF inhibitors in rheumatoid arthritis in a post hoc analysis

Lookup NU author(s): Professor John IsaacsORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.Objectives: The inflammatory protein calprotectin (MRP8/14) has been identified as a promising biomarker of treatment response in rheumatoid arthritis (RA). Our aim was to test MRP8/14 as a biomarker of response to tumour necrosis factor (TNF)-inhibitors in the largest RA cohort to date and to compare with C-reactive protein (CRP). Methods: Serum MRP8/14 was measured in 470 patients with RA about to commence treatment with adalimumab (n=196) or etanercept (n=274). Additionally, MRP8/14 was measured in the 3-month sera of 179 adalimumab-treated patients. Response was determined using European League against Rheumatism (EULAR) response criteria calculated using the traditional 4-component (4C) DAS28-CRP and alternate validated versions using 3-component (3C) and 2-component (2C), clinical disease activity index (CDAI) improvement criteria and change in individual outcome measures. Logistic/linear regression models were fitted for response outcome. Results: In the 3C and 2C models, patients with RA were 1.92 (CI: 1.04 to 3.54) and 2.03 (CI: 1.09 to 3.78) times more likely to be classified as EULAR responders if they had high (75th quartile) pre-treatment levels of MRP8/14 compared with low (25th quartile). No significant associations were observed for the 4C model. When only using CRP as a predictor, in the 3C and 2C analyses, patients above the 75th quartile were 3.79 (CI: 1.81 to 7.93) and 3.58 (CI: 1.74 to 7.35) times more likely to be EULAR responders and addition of MRP8/14 did not significantly improve model fit (p values=0.62 and 0.80, respectively). No significant associations were observed in the 4C analysis. Exclusion of CRP from the outcome measure (CDAI) did not result in any significant associations with MRP8/14 (OR 1.00 (CI: 0.99 to 1.01), suggesting that the associations were due to the correlation with CRP and that there is no additional utility of MRP8/14 beyond use of CRP in patients with RA starting TNFi therapy. Conclusion: Beyond correlation with CRP, we found no evidence to suggest that MRP8/14 explains additional variability in response to TNFi in patients with RA over and above CRP alone.

Publication metadata

Author(s): Smith SL, Alexander S, Nair N, Viatte S, Eyre S, Hyrich KL, Morgan AW, Wilson AG, Isaacs JD, Plant D, Barton A

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2023

Volume: 82

Issue: 5

Pages: 611-620

Print publication date: 01/05/2023

Online publication date: 21/02/2023

Acceptance date: 12/01/2023

Date deposited: 04/05/2023

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

Publisher: BMJ Publishing Group


DOI: 10.1136/ard-2022-222519

PubMed id: 36810200


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