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; Heidi L Munk; Robin Christensen; Sören Möller; Silja H Overgaard; Grith L Sorensen; Karen M Møllegaard; Jessica Pingel; Anders B Nexøe; Henning Glerup; Tanja Guldmann; Natalia Pedersen; Jens Frederik Dahlerup; Christian L Hvas; Karina W Andersen; Mohamad Jawhara; Ole Haagen Nielsen; Fredrik Olof Bergenheim; Anette Bygum; Jesper R Davidsen; Signe Bek Sørensen; Jacob B Brodersen; Jens Kjeldsen; Vibeke Andersen; Torkell Ellingsen

doi:10.1007/s00296-024-05744-9

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

Rheumatol Int. 2024 Oct 28. doi: 10.1007/s00296-024-05744-9. Online ahead of print.

Authors

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 Sorensen¹³, Karen M Møllegaard^{11

12}, Jessica Pingel^{11

12}, Anders B Nexøe^{13

14}, Henning Glerup¹⁵, Tanja Guldmann¹⁵, Natalia Pedersen¹⁶, Jens Frederik Dahlerup¹⁷, Christian L Hvas¹⁷, Karina W Andersen^{12

18}, Mohamad Jawhara¹⁸, Ole Haagen Nielsen¹⁹, Fredrik Olof Bergenheim²⁰, Anette Bygum¹⁰, 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

¹ Department of Rheumatology, Odense University Hospital, Odense, Denmark. [email protected].
² Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark. [email protected].
³ Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark. [email protected].
⁴ Department of Rheumatology, Odense University Hospital, Odense, Denmark.
⁵ Center for Rheumatology and Spine Diseases, Rigshospitalet, Glostrup, Denmark.
⁶ Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense University Hospital, Odense, Denmark.
⁷ Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
⁸ Cochrane Denmark & Centre for Evidence-Based Medicine Odense (CEBMO), Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
⁹ OPEN - Open Patient Data Explorative Network, Odense University Hospital, Odense, Denmark.
¹⁰ Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
¹¹ Internal Medicine Research, Unit University Hospital of Southern Denmark, Aabenraa, Denmark.
¹² Department of Regional Health Research, University of Southern, Odense, Denmark.
¹³ Department of Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
¹⁴ Department of Medical Gastroenterology, Odense University Hospital, Odense, Denmark.
¹⁵ University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark.
¹⁶ Department of Gastroenterology, Slagelse Hospital, Slagelse, Denmark.
¹⁷ Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
¹⁸ Department of Surgery, University Hospital of Southern Denmark, Aabenraa, Denmark.
¹⁹ Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
²⁰ The Abdominal Center, Medical Section, Bispebjerg and Frederiksberg University Hospital, Copenhagen, Denmark.
²¹ Department of Respiratory Medicine, Odense University Hospital, Odense, Denmark.
²² Department of Gastroenterology, Esbjerg and Grindsted Hospital - University Hospital of Southern Denmark, Esbjerg, Denmark.
²³ Research Unit of Medical Gastroenterology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

PMID: 39465398
DOI: 10.1007/s00296-024-05744-9

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.