Journal Article

POS0043 COMPLEMENT IN RADIOGRAPHIC AXSPA – BIOMARKERS OF RADIOGRAPHIC PROGRESSION? POST HOC ANALYSIS FROM CONSUL, A LONGITUDINAL MULTI-CENTER RANDOMIZED CONTROLLED TRIAL COHORT OF AXSPA-PATIENTS WITH A HIGH RISK OF STRUCTURAL PROGRESSION INITIATING TREATMENT WITH TNF-I

Sieper, J., Listing, J., Protopopov, M., Troldborg, A., Loft, A. G., Torgutalp, M., Proft, F., Thiel, S., Rios Rodriguez, V., Muche, B., Mistegaard, C. E., Poddubnyy, D.

2023

Overview

BackgroundThe biological processes involved in the development of structural changes associated with radiographic axial spondyloarthritis (r-axSpA) remain largely unraveled. Still, high disease activity, elevated C-reactive protein (CRP), and existing syndesmophytes are associated with radiographic progression. The complement system is an inflammation-generating part of the innate immune system. Animal models have shown inhibition of complement activation to diminish structural changes associated with axSpA [1].ObjectivesThis project aimed to investigate complement activation and serum levels of complement proteins and their correlations with radiographic spinal progression over a two years follow-up period in a longitudinal cohort of axSpA patients with active r-axSpA, and high risk of radiographic progression, recruited from the randomized controlled trial CONSUL.MethodsAll patients had active r-axSpA and risk factors for radiographic spinal progression (BASDAI ≥4, and elevated CRP and/ or ≥1 syndesmophyte(s)). Serum samples were collected at baseline (n = 96) and after 108 weeks (n = 89) of TNF-I therapy and analyzed by immunoassays for complement lectin pathway proteins (L-ficolin, M-ficolin, H-ficolin, CL-L1, MBL, MASP-1, MASP-2, MASP-3, and MAp44) and the complement activation product C3dg. X-rays were performed at baseline and after 108 weeks and read blinded for clinical data and chronology by three independent expert readers. New bone formation was defined as the growth of syndesmophyte(s) and/or new syndesmophyte(s) determined by 3-reader-agreement.ResultsPatient characteristics are shown in Table 1. In total, 19 patients developed new bone formation at week 108. Baseline serum levels of MASP-1, MASP-2, and C3dg were elevated in patients with new bone formation, whereas baseline serum levels of MASP-3 were decreased (all p<0.05). Baseline MASP-1, MASP-3, and C3dg predicted the development of new bone formation in a univariate logistic regression analysis, whereas CRP did not. Baseline MASP-1, MASP-3, and C3dg remained significant in a multivariate logistic regression analysis. L-ficolin and C3dg levels at week 108 were elevated in patients with new bone formation, and the serum levels at week 108 predicted development of new bone formation in a univariate logistic regression analysis. In a multivariate regression analysis, C3dg remained significant (p<0.05).ConclusionIn this study, complement activation measured by C3dg and serum levels of MASP-1 and MASP-3, prior to TNF-I therapy, predicted development of new bone formation at week 108. Furthermore, elevated levels of C3dg and L-ficolin at week 108 were associated with new bone formation. These findings support the involvement of complement activation in new bone formation in r-axSpA.Reference[1]Yang C et al. Sci Rep. 2016.Table 1.Baseline demographics of the investigated patient population from the CONSUL RCT (n = 96)Age, median (IQR)37 (31-45)Male, n (%)70 (73)HLA-B27 positive, n (%)80 (83)Previous bDMARD treatment, n (%)21 (22)Symptom duration in years, median (IQR)12 (6.0-20)Smoking, n (%)36 (38)mSASSS, median (IQR)5.0 (0.3-18)Syndesmophytes, median (IQR)1.8 (0-6.3)Presence of ≥1 syndesmophyte(s)δ, n (%)47 (49)CRP, median (IQR)9.2 (3.2-19)Elevated CRP (>5 mg/L), n (%)64 (67)ASDAS-CRP, median (IQR)3.6 (3.1-4.1)BASDAI, median (IQR)6.2 (5.2-6.8)δDetermined by 3 expert readers blinded for clinical data.Figure 1.a) Baseline MASP-1, MASP-2, MASP-3, and C3dg levels according to development of new bone formation at week 108. b) L-ficolin and C3dg levels at week 108 according to development of new bone formation at week 108. New bone formation: growth of syndesmophytes and/or new syndesmophytes determined by 3-reader-agreement. p-values indicate comparisons between groups by t-test. Bars indicate median and IQR (MASP-1, MASP-2, MASP-3, C3dg), and mean and sd (L-ficolin).Acknowledgements:NIL.Disclosure of InterestsClara Elbæk Mistegaard: None declared, Anne Troldborg: None declared, Anne Gitte Loft Speakers bureau: AbbVie, MSD, Novartis, Pfizer, UCB, Consultant of: AbbVie, MSD, Novartis, Pfizer, UCB, Grant/research support from: Novartis, Steffen Thiel: None declared, Burkhard Muche: None declared, Valeria Rios Rodriguez: None declared, Murat Torgutalp: None declared, Mikhail Protopopov: None declared, Joachim Listing: None declared, Joachim Sieper: None declared, Denis Poddubnyy: None declared, Fabian Proft Speakers bureau: AMGEN, AbbVie, BMS, Celgene, Janssen, MSD, Novartis, Pfizer, Roche, UCB, Consultant of: Novartis, Grant/research support from: Novartis, Lilly, UCB.

• Publisher: BMJ Publishing Group Ltd and European League Against Rheumatism,Elsevier Limited
• Subject: Animal models / bDMARD / Bone growth / C-reactive protein / Clinical trials / Complement activation / Immune system / Inflammatory diseases / Innate immunity / M-ficolin / MASP-1 protein / MASP-2 protein / Medical treatment / Osteogenesis / Patients / Regression analysis / Rheumatic diseases / Risk factors / Scientific Abstracts / Serum levels / Spondyloarthritis