Characterization of Immunogenicity of TNF Inhibitors in Arthritis Patients With Poorer Treatment Response.

Recruiting

• Conditions: Arthritis, Rheumatoid; Arthritis, Psoriatic; Spondylitis, Ankylosing

• Registration Number: NCT04731831
• Lead Sponsor: Aalborg University Hospital

Brief Summary

The aim of the study is to explore whether the influence of gender, tobacco smoking and obesity on treatment response in tumor necrosis factor inhibitors (TNFIs) can be explained by high degree of inflammation, human leucocyte antigen (HLA) type, autoantibodies, TNF and TNFI concentration and presence of ADA.

Detailed Description

Tumor necrosis factor inhibitors (TNFIs) have been uses with success since 1999 in Denmark in treatment of various inflammatory diseases, eg. rheumatoid arthritis (RA), Chrohn's disease, psoriasis, psoriatic arthritis (PsA) and ankylosing spondylitis (AS).

TNFIs block a central cytokine in the inflammatory process, tumor necrosis factor (TNF).

Because the drugs are large proteins, they are prone to trigger an immune response and elicit anti-drug antibodies(ADA).

Epidemiologic studies have revealed that groups of patients (women, tobacco smokers, obese patients) with inflammatory rheumatic diseases have a lower response to TNFIs. The reasons for this are not fully elucidated. The hypothesis is that immunogenicity and changed pharmacokinetic of TNFI are causes of the inferior response.

The investigators will carry out a prospective clinical studies of 120 arthritis patients (RA, PsA and AS) initiating treatment with adalimumab or infliximab. The patients will be followed for 12 months and will be registered in DANBIO as normal praxis. Blood samples will be collected at baseline, 2, 4 and 12 months or at termination of the treatment.

Genotypes, autoantibodies, inflammation markers, TNFI and ADA will be measured.

The aim of the study is to explore:

A: If differences between men and women with respect to different markers of inflammation, human leucocyte antigen (HLA), autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among women.

B: If differences between smokers and non-smokers with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment among patients with arthritis who smoke tobacco.

C: If differences between obese and normal weight patients with respect to different markers of inflammation, HLA, autoantibodies, TNFI concentration and presence of ADAs can explain the lower response and adherence to the treatment.

The study will contribute with new knowledge, which hopefully can make the treatment more personalized and efficient.

Study Timeline

• Study Start: 2020-08-01
• Study First Submitted: 2020-12-19
• Study First Submitted QC: 2021-01-28
• Study First Posted: 2021-02-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-27
• Last Update Posted: 2024-06-28
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Patients > 18 years
• Diagnosed with RA, PsA or AS.
• Starting treatment with infliximab or adalimumab.
• Co- treatment with csDMARD or glucocorticoid is acceptable.
• No new bDMARD is initiated at the time of sampling.

Exclusion Criteria

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Treatment response	12 months	Changes in disease activity score according to the diagnose. A reduction in the disease activity score indicates a good treatment response.; * Disease Activity Score 28 joints with C-reactive protein (DAS28-CRP); * Disease Activity in Psoriasis Arthritis (DAPSA); * Ankylosing Spondylitis Activity Score (ASDAS); * Bath Ankylosing Spondylitis Disease Activity Index (BASDAI); * Bath Ankylosin Spondylitis Functional Index (BASFI)

Secondary Outcome Measures

Name	Time	Method
Concentration of autoantibodies	Day 1	ANA, ACPA, IgM-RF
Immunogenesity	12 months	Antibodies directed against infliximab or adalimumab. Concentration of anti-drug-antibodies
Drug koncentration	12 months	Plasma koncentration of infliximab or adalimumab
Concentration of markers of inflammation	12 months	C-reactive protein (CRP), IL1, .
HLA-type	Day 1	Genomic determination of Human Leucocyte antigens

Trial Locations

Locations (1)

Department of rheumatology; 🇩🇰 Aalborg, Denmark