Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs

De Moel EC, Rech J, Mahler M, Roth J, Vogl T, Schouffoer A, Goekoop RJ, Huizinga TW, Allaart CF, Toes RE, Schett G, Van Der Woude D (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Arthritis Research & Therapy BioMed Central

Book Volume: 21

Article Number: 268

Journal Issue: 1

DOI: 10.1186/s13075-019-2064-y

Abstract

Objective: To investigate whether calprotectin (S100A8/A9 or MRP8/14), an inflammatory complex released by monocytes, could indicate residual subclinical inflammation in rheumatoid arthritis (RA) patients who are in stable remission on disease-modifying anti-rheumatic drugs (DMARDs) and serve as a marker for disease flare after DMARD tapering. Methods: We used data from two trials. Patients from the IMPROVED study had early (< 2 years) RA, and when they achieved disease activity score remission (DAS44 < 1.6), they stopped methotrexate to attempt drug-free remission. Patients from the RETRO study had established RA in stable remission (DAS28 < 2.6) and either tapered by 50% or stopped (biological or conventional) DMARDs. Circulating calprotectin at the tapering time point was determined by ELISA, and its predictive value for flare (loss of remission) within 12 months of DMARD tapering/stopping was determined. Results: In both IMPROVED (n = 104) and RETRO (n = 57), patients that flared within 12 months had higher calprotectin at the moment of DMARD tapering/stopping. Twofold higher calprotectin at the moment of DMARD tapering/stopping was associated with an increased risk (odds ratio) of flare of 1.07 (95% CI 0.98-1.18, p = 0.14) in the IMPROVED and 3.62 (95% CI 1.76-7.46, p < 0.001) in the RETRO. Correcting for clinical predictors of flare (DAS at study inclusion, anti-CCP2 positivity, gender) did not change these estimates. The area under the receiver operating curve of calprotectin levels for predicting flare within 12 months was 0.63 (95% CIs 0.51-0.76) in the IMPROVED study and 0.80 (95% CIs 0.69 to 0.92) in the RETRO study. Conclusion: Circulating calprotectin levels in RA patients in remission on DMARDs are higher in patients that will flare upon DMARD tapering/stopping. Since the differences between the cohorts precluded definitive conclusions, more research is needed to determine whether calprotectin has prognostic value in predicting flare after attempting drug tapering in RA. Trial registration: IMPROVED, ISRCTN11916566. RETRO, 2009-015740-42.

Authors with CRIS profile

Hans Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

Leiden University Medical Center NL Netherlands (NL) Werfen S.A. ES Spain (ES) Westfälische Wilhelms-Universität (WWU) Münster DE Germany (DE) HagaZiekenhuis NL Netherlands (NL)

How to cite

APA:

De Moel, E.C., Rech, J., Mahler, M., Roth, J., Vogl, T., Schouffoer, A.,... Van Der Woude, D. (2019). Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs. Arthritis Research & Therapy, 21(1). https://doi.org/10.1186/s13075-019-2064-y

MLA:

De Moel, Emma C., et al. "Circulating calprotectin (S100A8/A9) is higher in rheumatoid arthritis patients that relapse within 12 months of tapering anti-rheumatic drugs." Arthritis Research & Therapy 21.1 (2019).

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