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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Characterization of Immunogenicity of Tumor Necrosis Factor Inhibitors in Arthritis Patients With Poorer Treatment Response Due to Gender, Obesity and Smoking Status.

Conditions
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Arthritis, Rheumatoid, Arthritis, Psoriatic, Spondylitis, Ankylosing

Participation Criteria
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Eligibility Criteria
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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: -

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient with arthritis starting infliximab or adalimumab<br>Patients with Rheumatoid Artritis, Psoriatic Arthritis, Anchylosing Spondylitis starting treament with infliximab or adalimumab | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment response | 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) | 12 months | 

Secondary Outcome Measures

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