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

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. DavidsenSigne Bek Sørensen, Jacob B. Brodersen, Jens Kjeldsen, Vibeke Andersen, Torkell Ellingsen

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › Research › peer-review

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.

Original language	English
Journal	Rheumatology International
Number of pages	13
ISSN	0172-8172
DOIs	https://doi.org/10.1007/s00296-024-05744-9 https://doi.org/10.1007/s00296-024-05744-9
Publication status	E-pub ahead of print - 28 Oct 2024

Bibliographical note

Publisher Copyright:
© The Author(s) 2024.

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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Sofíudóttir, B. K., Munk, H. L., Christensen, R., Möller, S., Overgaard, S. H., Sorensen, G. L., Møllegaard, K. M., Pingel, J., Nexøe, A. B., Glerup, H., Guldmann, T., Pedersen, N., Dahlerup, J. F., Hvas, C. L., Andersen, K. W., Jawhara, M., Nielsen, O. H., Bergenheim, F. O., Bygum, A., ... Ellingsen, T. (2024). 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. Rheumatology International. https://doi.org/10.1007/s00296-024-05744-9, https://doi.org/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. / Sofíudóttir, Bjørk K.; Munk, Heidi L.; Christensen, Robin; Möller, Sören; Overgaard, Silja H.; Sorensen, Grith L.; Møllegaard, Karen M.; Pingel, Jessica; Nexøe, Anders B.; Glerup, Henning; Guldmann, Tanja; Pedersen, Natalia; Dahlerup, Jens Frederik; Hvas, Christian L.; Andersen, Karina W.; Jawhara, Mohamad; Nielsen, Ole Haagen; Bergenheim, Fredrik Olof; Bygum, Anette; Davidsen, Jesper R.; Sørensen, Signe Bek; Brodersen, Jacob B.; Kjeldsen, Jens; Andersen, Vibeke; Ellingsen, Torkell.

In: Rheumatology International, 28.10.2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Sofíudóttir, BK, Munk, HL, Christensen, R, Möller, S, Overgaard, SH, Sorensen, GL, Møllegaard, KM, Pingel, J, Nexøe, AB, Glerup, H, Guldmann, T, Pedersen, N, Dahlerup, JF, Hvas, CL, Andersen, KW, Jawhara, M, Nielsen, OH, Bergenheim, FO, Bygum, A, Davidsen, JR, Sørensen, SB, Brodersen, JB, Kjeldsen, J, Andersen, V & Ellingsen, T 2024, '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', Rheumatology International. https://doi.org/10.1007/s00296-024-05744-9, https://doi.org/10.1007/s00296-024-05744-9

Sofíudóttir BK, Munk HL, Christensen R, Möller S, Overgaard SH, Sorensen GL et al. 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. Rheumatology International. 2024 Oct 28. https://doi.org/10.1007/s00296-024-05744-9, https://doi.org/10.1007/s00296-024-05744-9

Sofíudóttir, Bjørk K. ; Munk, Heidi L. ; Christensen, Robin ; Möller, Sören ; Overgaard, Silja H. ; Sorensen, Grith L. ; Møllegaard, Karen M. ; Pingel, Jessica ; Nexøe, Anders B. ; Glerup, Henning ; Guldmann, Tanja ; Pedersen, Natalia ; Dahlerup, Jens Frederik ; Hvas, Christian L. ; Andersen, Karina W. ; Jawhara, Mohamad ; Nielsen, Ole Haagen ; Bergenheim, Fredrik Olof ; Bygum, Anette ; Davidsen, Jesper R. ; Sørensen, Signe Bek ; Brodersen, Jacob B. ; Kjeldsen, Jens ; Andersen, Vibeke ; Ellingsen, Torkell. / 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. In: Rheumatology International. 2024.

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title = "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",

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{\textquoteright}s disease, MFAP4, Psoriasis, Psoriatic arthritis, Rheumatoid arthritis, Treatment response, Ulcerative colitis",

author = "Sof{\'i}ud{\'o}ttir, {Bj{\o}rk K.} and Munk, {Heidi L.} and Robin Christensen and S{\"o}ren M{\"o}ller and Overgaard, {Silja H.} and Sorensen, {Grith L.} and M{\o}llegaard, {Karen M.} and Jessica Pingel and Nex{\o}e, {Anders B.} and Henning Glerup and Tanja Guldmann and Natalia Pedersen and Dahlerup, {Jens Frederik} and Hvas, {Christian L.} and Andersen, {Karina W.} and Mohamad Jawhara and Nielsen, {Ole Haagen} and Bergenheim, {Fredrik Olof} and Anette Bygum and Davidsen, {Jesper R.} and S{\o}rensen, {Signe Bek} and Brodersen, {Jacob B.} and Jens Kjeldsen and Vibeke Andersen and Torkell Ellingsen",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = oct,

day = "28",

doi = "10.1007/s00296-024-05744-9",

language = "English",

journal = "Rheumatology International",

issn = "0172-8172",

publisher = "Springer",

}

TY - JOUR

T1 - Microfibrillar-associated protein 4 as a predictive biomarker of treatment response in patients with chronic inflammatory diseases initiating biologics

T2 - secondary analyses based on the prospective BELIEVE cohort study

AU - Sofíudóttir, Bjørk K.

AU - Munk, Heidi L.

AU - Christensen, Robin

AU - Möller, Sören

AU - Overgaard, Silja H.

AU - Sorensen, Grith L.

AU - Møllegaard, Karen M.

AU - Pingel, Jessica

AU - Nexøe, Anders B.

AU - Glerup, Henning

AU - Guldmann, Tanja

AU - Pedersen, Natalia

AU - Dahlerup, Jens Frederik

AU - Hvas, Christian L.

AU - Andersen, Karina W.

AU - Jawhara, Mohamad

AU - Nielsen, Ole Haagen

AU - Bergenheim, Fredrik Olof

AU - Bygum, Anette

AU - Davidsen, Jesper R.

AU - Sørensen, Signe Bek

AU - Brodersen, Jacob B.

AU - Kjeldsen, Jens

AU - Andersen, Vibeke

AU - Ellingsen, Torkell

PY - 2024/10/28

Y1 - 2024/10/28

N2 - 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.

AB - 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.

KW - Axial spondyloarthritis

KW - Biologic treatment

KW - Chronic inflammatory disease

KW - Crohn’s disease

KW - MFAP4

KW - Psoriasis

KW - Psoriatic arthritis

KW - Rheumatoid arthritis

KW - Treatment response

KW - Ulcerative colitis

U2 - 10.1007/s00296-024-05744-9

DO - 10.1007/s00296-024-05744-9

M3 - Journal article

C2 - 39465398

JO - Rheumatology International

JF - Rheumatology International

SN - 0172-8172

ER -