Clinical trial NCT04731831: Characterization of Immunogenicity of TNF Inhibitors in Arthritis Patients With Poorer Treatment Response.
Official title: Characterization of Immunogenicity of Tumor Necrosis Factor Inhibitors in Arthritis Patients With Poorer Treatment Response Due to Gender, Obesity and Smoking Status.
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Arthritis, Rheumatoid
Arthritis, Psoriatic
Spondylitis, Ankylosing
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2021-02-01
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients at department of Rheumatology in Aalborg Universityhospital, Denmark. Other sites in Jutland, Denmark may be inkluded later.

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.

Eligibility criteria: 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:

-

Primary outcomes:
measure: Treatment response
timeFrame: 12 months
Secondary outcomes:
measure: Immunogenesity
timeFrame: 12 months
measure: Drug koncentration
timeFrame: 12 months
measure: Concentration of markers of inflammation
timeFrame: 12 months
measure: Concentration of autoantibodies
timeFrame: Day 1
measure: HLA-type
timeFrame: Day 1
Other outcomes:
Locations:
city: Aalborg
country: Denmark
facility: Department of rheumatology
Study officials:
affiliation: Department of Clinical Medicine, Aalborg University and Aalborg University Hospital
name: Lene Dreyer, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
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