Characterization of Immunogenicity of TNF Inhibitors in Arthritis Patients With Poorer Treatment Response.
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|ClinicalTrials.gov Identifier: NCT04731831|
Recruitment Status : Recruiting
First Posted : February 1, 2021
Last Update Posted : February 1, 2021
|Condition or disease|
|Arthritis, Rheumatoid Arthritis, Psoriatic Spondylitis, Ankylosing|
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 Type :||Observational|
|Estimated Enrollment :||120 participants|
|Official Title:||Characterization of Immunogenicity of Tumor Necrosis Factor Inhibitors in Arthritis Patients With Poorer Treatment Response Due to Gender, Obesity and Smoking Status.|
|Actual Study Start Date :||August 1, 2020|
|Estimated Primary Completion Date :||August 2023|
|Estimated Study Completion Date :||June 30, 2024|
Patient with arthritis starting infliximab or adalimumab
Patients with Rheumatoid Artritis, Psoriatic Arthritis, Anchylosing Spondylitis starting treament with infliximab or adalimumab
- Treatment response [ Time Frame: 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)
- Immunogenesity [ Time Frame: 12 months ]Antibodies directed against infliximab or adalimumab. Concentration of anti-drug-antibodies
- Drug koncentration [ Time Frame: 12 months ]Plasma koncentration of infliximab or adalimumab
- Concentration of markers of inflammation [ Time Frame: 12 months ]C-reactive protein (CRP), IL1, .
- Concentration of autoantibodies [ Time Frame: Day 1 ]ANA, ACPA, IgM-RF
- HLA-type [ Time Frame: Day 1 ]Genomic determination of Human Leucocyte antigens
Biospecimen Retention: Samples With DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04731831
|Contact: Karen B Lauridsen, MD||0045 firstname.lastname@example.org|
|Department of rheumatology||Recruiting|
|Aalborg, Denmark, 8000|
|Principal Investigator:||Lene Dreyer, MD, Prof.||Department of Clinical Medicine, Aalborg University and Aalborg University Hospital|