Dataset Information

Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study.

ABSTRACT:

Background

The complement system is involved in pathogenesis of cardiovascular disease, and might play a role in accelerated atherogenesis in spondylarthropathies (SpA). Hence, we examined complement activation in SpA, and its relationship to antirheumatic treatment, inflammatory and cardiovascular markers.

Methods

From PSARA, a prospective observational study, we examined 51 SpA patients (31 psoriatic arthritis (PsA), and 20 ankylosing spondylitis (AS)), starting tumor necrosis factor (TNF) inhibitor alone (n = 25), combined with methotrexate (MTX) (n = 10), or MTX monotherapy (n = 16). Complement activation was determined by the soluble terminal complement complex (sC5b-9), inflammation by erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and endothelial function by finger plethysmography (Endopat) at baseline, after 6 weeks and 6 months of treatment.

Results

SpA patients had sC5b-9 levels at (PsA) or above (AS) the upper limit of the estimated reference range. Median sC5b-9 levels decreased significantly from baseline to 6 weeks, with no significant difference between the AS and PsA group. Notably, a significant reduction in sC5b-9 was observed after administration of TNF inhibitor ± MTX, whereas no significant changes were observed in patients treated with MTX alone. Between 6 weeks and 6 months, sC5b-9 remained stable across all subgroups. Reduction in sC5b-9 was independently related to decreased ESR and CRP, and to increased high density cholesterol and total cholesterol. Reduction in sC5b-9 from baseline to 6 weeks was associated with improved EF in age and gender adjusted analyses.

Conclusion

TNF-inhibition, but not MTX monotherapy, led to rapid and sustained reduction of complement activation in SpA. Thus, the observed decrease in cardiovascular morbidity in patients treated with TNF-inhibitors might be partly due to its beneficial effect on complement.

Trial registration

Clinical Trials (NCT00902005), retrospectively registered on the 14th of May 2009.

SUBMITTER: Hokstad I

PROVIDER: S-EPMC6650069 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study.

Hokstad Ingrid I Deyab Gia G Wang Fagerland Morten M Lyberg Torstein T Hjeltnes Gunnbjørg G Førre Øystein Ø Agewall Stefan S Mollnes Tom Eirik TE Hollan Ivana I

PloS one 20190723 7

<h4>Background</h4>The complement system is involved in pathogenesis of cardiovascular disease, and might play a role in accelerated atherogenesis in spondylarthropathies (SpA). Hence, we examined complement activation in SpA, and its relationship to antirheumatic treatment, inflammatory and cardiovascular markers.<h4>Methods</h4>From PSARA, a prospective observational study, we examined 51 SpA patients (31 psoriatic arthritis (PsA), and 20 ankylosing spondylitis (AS)), starting tumor necrosis f ...[more]

PMID: 31335881

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Project description:Objective: This prospective observational study investigated the efficacy of tumor necrosis factor inhibitors (TNFis) on disease activity, physical functionality, and mobility in patients with ankylosing spondylitis (AS) in a real-world setting. Methods: The Chinese Ankylosing Spondylitis Prospective Imaging Cohort (CASPIC) is an ongoing cohort study. Patients with AS were included to one of two groups: the TNFi user group included those who received TNFi at any time point; the non-TNFi user group included those who did not receive TNFi. Disease activity, physical functionality, and mobility were assessed by AS Disease Activity Scores (ASDAS), Bath AS Functional Index (BASFI), and Bath AS Metrology Index (BASMI), respectively. Results: A total of 804 patients with AS (241 TNFi users and 563 non-TNFi users) were recruited. For TNFi users, 83% received an etanercept biosimilar and 17.0% received adalimumab. Seventy-three TNFi users (30.3%) discontinued TNFis during the follow-up period; the mean duration of TNFi treatment was 6.9 ± 3.2 months. Reductions in ASDAS were significantly greater in TNFi users than in nonusers at 3, 6, and 12 months (differences in ASDAS reduction were 0.61, 0.56, and 0.46 units, respectively, all P < 0.05). Similarly, the improvement in BASFI was significantly greater in users than in nonusers at 3, 6, and 12 months (differences in BASFI improvement: 0.31, 0.75, and 0.74 units, respectively, all P < 0.05). BASMI increased in nonusers at 6 and 12 months (0.27, P = 0.47; 0.66, P < 0.001, respectively), but did not change in users (-0.16 and -0.13, respectively, both P > 0.05). At 12 months, changes in BASMI were significantly greater in nonusers than in users (-0.60, P = 0.47). Conclusion: TNFis are effective against disease activity and improve the physical functionality of patients with AS, even in those who taper or discontinue TNFis. Thus, TNFis may retard the progression of spinal mobility dysfunction in AS patients. TNF may maintain spinal mobility as indicated by the BASMI.

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Dataset Information

Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study.

Background

Methods

Results

Conclusion

Trial registration

Publications

Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study.

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