1. To determine the proportion of patients developing anti-drug antibodies (ADA) detectable with an antigen binding test (ABT, radioimmunoassay) in patients experiencing inefficacy of their first TNF inhibitor treatment (phase 1).2. To study…
ID
Source
Brief title
Condition
- Joint disorders
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Phase 1:
Amongst patients that perceive inefficacy of their first TNF inhibitor, the
percentage of patients that test positive for anti-drug antibodies, detectable
with a radioimmunoassay.
Phase 2:
Efficacy:
- RA: minimal disease activity (DAS28 < 2.6)
- AS: ASDAS, inactive disease (>1.3)
- PsA: minimal disease activity**
- Pso: PASI 75
**MDA is defined as a score of at least 5 out of 7 from the following outcome
measures: TJC (0-68) *1, SJC (0-66) *1, PASI *3, patient pain VAS *15 (scale
0-100), patient global disease activity VAS *15 (scale 0-100); HAQ score *0.5,
and tender entheseal points *1(using Leeds Enthesitis Index, LEI).
Immunogenicity: the percentage of patients that test positive for anti-drug
antibodies, detectable with a radioimmunoassay
Secondary outcome
Phase 2:
Efficacy:
- RA: SDAI remission. Effect on HaQ.
- AS: ASDAS, minimal disease activity (<2.1); BASDAI50 response.
- PsA: ACR 20, 50, 70. Effect on HaQ.
- Pso: PASI 50, PASI 90. Effect on DLQI.
Background summary
Presently there are five TNF inhibitors approved for clinical use in rheumatoid
arthritis, psoriatic arthritis, ankylosing spondylitis and psoriasis, i.e.
infliximab, adalimumab, etanercept, golimumab and certolizumab pegol.
Potentially, all biologicals can induce an unwanted immune response, which is
associated with diminished serum drug levels and a diminished treatment
response. The incidence of anti-drug antibodies (ADA) is dependent on the
therapeutic itself e.g. dosing scheme/route of administration, and other
factors like study population, use of concomitant medication and assay
techniques used to measure these antibodies. It is known that the presence or
absence of ADA has implications for response to a second TNF inhibitor.
Since low or absent serum drug levels are associated with lack or loss of
clinical response, therapeutic drug monitoring (TDM) would be an important
tool in clinical decision making in patients with inflammatory diseases.
Study objective
1. To determine the proportion of patients developing anti-drug antibodies
(ADA) detectable with an antigen binding test (ABT, radioimmunoassay) in
patients experiencing inefficacy of their first TNF inhibitor treatment (phase
1).
2. To study response to a subsequent TNF inhibitor treatment after patients
experienced inefficacy of a first TNF inhibitor (phase 2).
3. To investigate the predictive value of ADA and drug levels for response to
subsequent TNF inhibitor treatment (phase 1 and 2).
Study design
Prospective observational multicenter European cohort study in RA, PsA, AS and
PsO patients.
Trough serum samples (for drug level and anti-drug antibody testing 1st TNF
inhibitor) and clinical data will be obtained from patients with inflammatory
diseases (RA, AS, PsA and Pso) failing to respond to their first TNF inhibitor
as judged by the treating rheumatologist or dermatologist (baseline, phase 1).
Treatment failure is defined as inefficacy of the drug (primary or secondary),
patients with other reasons of treatment failure, such as side effects, will
not be included in this study.
Patients in whom treatment is switched to a second TNF-inhibitor enter phase 2
of this study. In this phase, at 3-4 months a second trough sample (for drug
level and anti-drug antibody testing 2nd TNF inhibitor) and clinical data, and
at 6 months clinical data will be collected.
Study burden and risks
The additional burden consists of an extra blood sample taken at moments that
this would already have been done in view of routine patient care.
Dr. Jan van Breemenstraat 2
Amsterdam 1056 AB
NL
Dr. Jan van Breemenstraat 2
Amsterdam 1056 AB
NL
Listed location countries
Age
Inclusion criteria
Phase 1:
- patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS) or psoriasis (Pso) treated with a first TNF inhibitor (adalimumab, infliximab, etanercept, golimumab or certolizumab pegol) in daily clinical practice across different European countries.
- TNF inhibitor treatment has been initiated and continued until failure at dose and interval according to label (adalimumab 40 mg every other week (eow); etanercept 50 mg once weekly or 25 mg twice weekly; golimumab 50 mg once monthly; certolizumab pegol 200 mg eow; infliximab 3 mg/kg per 8 weeks (RA), infliximab 5 mg/kg per 6-8 weeks (AS), infliximab 5 mg/kg per 8 weeks (PsA or Pso).
- Inefficacy of first TNF inhibitor (both 'primary' and 'secondary' failure) resulting in switch of therapy.
- planned treatment with a second TNF inhibitor.
- written informed consent.;Phase 2:
- participation in phase 1.
- first TNF inhibitor treatment is switched to second TNF inhibitor treatment (at labeled dose).
Exclusion criteria
Phase 1:
- current TNF inhibitor treatment is not the first TNF inhibitor ever used for this patient.
- first TNF inhibitor treatment switched due to other reasons than inefficacy (e.g. side effects).
- serum sample not taken at trough (=prior to the next infusion/injection with the TNF inhibitor for patients on drug).;Phase 2:
- treatment is switched to other treatment than TNF inhibitor.
- serum sample not taken at trough (prior to the next infusion/injection with the TNF inhibitor).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL51186.048.14 |