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Multicenter Study
. 2024 Dec;44(12):2935-2947.
doi: 10.1007/s00296-024-05744-9. Epub 2024 Oct 28.

Microfibrillar-associated protein 4 as a predictive biomarker of treatment response in patients with chronic inflammatory diseases initiating biologics: secondary analyses based on the prospective BELIEVE cohort study

Bjørk K Sofíudóttir  1   2   3 , Heidi L Munk  4   5 , Robin Christensen  6   7   8 , Sören Möller  9   10 , Silja H Overgaard  7   11   12 , Grith L Sorensen  13 , Karen M Møllegaard  11   12 , Jessica Pingel  11   12 , Anders B Nexøe  13   14 , Henning Glerup  15 , Tanja Guldmann  15 , Natalia Pedersen  16 , Jens Frederik Dahlerup  17 , Christian L Hvas  17 , Karina W Andersen  12   18 , Mohamad Jawhara  18 , Ole Haagen Nielsen  19 , Fredrik Olof Bergenheim  20 , Anette Bygum  10 , Jesper R Davidsen  10   21 , Signe Bek Sørensen  11   12   13 , Jacob B Brodersen  12   22 , Jens Kjeldsen  14   23 , Vibeke Andersen  11   12   13 , Torkell Ellingsen  4   6   10
Affiliations
Multicenter Study

Microfibrillar-associated protein 4 as a predictive biomarker of treatment response in patients with chronic inflammatory diseases initiating biologics: secondary analyses based on the prospective BELIEVE cohort study

Bjørk K Sofíudóttir et al. Rheumatol Int. 2024 Dec.

Abstract

Background: Currently, there are no reliable biomarkers for predicting treatment response in chronic inflammatory diseases (CIDs).

Objective: To determine whether serum microfibrillar-associated protein 4 (MFAP4) levels can predict the treatment response to biological therapy in patients with CIDs.

Methods: The BELIEVE study was originally designed as a prospective, multi-center cohort study of 233 patients with either rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, Crohn's disease, or ulcerative colitis, initiating treatment with a biologic agent (or switching to another). Clinical assessment and blood sample collection were performed at baseline and 14-16 weeks after treatment initiation. The primary analyses included participants with available blood samples at baseline; missing data were handled as non-responders. The patients were stratified into the upper tertile of serum MFAP4 (High MFAP4) versus a combined category of middle and lower tertiles (Other MFAP4). The primary outcome was the proportion of patients with clinical response to biologic therapy after 14-16 weeks.

Results: 211 patients were included in the primary analysis population. The mean age was 43.7 (SD: 14.8) years, and 120 (59%) were female. Positive treatment response was observed in 41 (59%) and 69 (49%) for High MFAP4 and Other MFAP4, respectively. When adjusting for pre-specified variables (CID, age, sex, smoking status, and BMI), the adjusted OR was 2.28 (95% CI: 1.07 to 4.85) for a positive treatment outcome in the High MFAP4 group.

Conclusion: A high MFAP4 status before initiating biological treatment is associated with a positive clinical response, when adjusting for confounding factors.

Keywords: Axial spondyloarthritis; Biologic treatment; Chronic inflammatory disease; Crohn’s disease; MFAP4; Psoriasis; Psoriatic arthritis; Rheumatoid arthritis; Treatment response; Ulcerative colitis.

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Conflict of interest statement

Declarations. Disclaimer: This study is part of a PhD thesis, and some of the main findings of this study have been presented in the PhD thesis. The thesis can be accessed here: Bjork.K.Sofiudottir_rsyd.dk.pdf_reduced.pdf (sdu.dk). Competing interests: The authors report no conflict of interest in relation to this study. BKS reports a congress-fee grant from Boehringer-Ingelheim, and JRD reports that he received teaching fees, congress-fee grants, and research grant from Boehringer-Ingelheim for another study.

Figures

Fig. 1
Fig. 1
Flow Diagram. RA; Rheumatoid arthritis, PsA; Psoriatic arthritis, AxSPA; Axial Spondyloarthritis, PSO; Psoriasis, CD; Crohn’s disease, UC; Ulcerative Colitis, MFAP4; Microfibrillar-associated protein 4, ITT; Intention to treat. *MFAP4 levels are divided into tertiles; “High sMFAP4” is the upper tertile and “Other sMFAP4” is the medium and lower tertile
Fig. 2
Fig. 2
Forest plot; Effect of MFAP4 profile on treatment response. Values are presented as responder/all and % Explanation: CID = Chronic Inflammatory Disease, OR = Odds ratio, CI = Confidence interval, High MFAP4 =  the upper 33.3% of the study sample based on serum MFAP4 measurements, Other MFAP4 = the lower 66.7% of the study sample based on serum MFAP4 measurements
Fig. 3
Fig. 3
Receiver operator curve (ROC) for levels of MFAP4 in predicting treatment response in all CIDs. (A) is not adjusted (Crude), (B) is CID adjusted, and (C) is the fully adjusted model
See this image and copyright information in PMC

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