Primary objective: to evaluate the disease activity after dose reduction, aiming adalimumab concentration of 2 mg/L or 5 mg/L, in rheumatoid arthritis patients responding to adalimumab.Secondary objectives: to evaluate whether reducing adalimumab…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study endpoint is the difference in mean time weighted DAS28-CRP
between week 0 and 24.
Secondary outcome
Difference in mean time weighted DAS28-CRP between study groups after 12 weeks
Direct medical costs (medication, non-scheduled visits due flares, cost TDM
testing) over 24 weeks
Agreement between algorithm predicted and measured adalimumab concentrations at
week 24.
Number of flares and dose-interval shortenings after 24 weeks.
Background summary
Several prior studies have shown that dose reduction or discontinuation of
tumor necrosis factor (TNF)-inhibitors, like adalimumab, is possible in
substantial number of patients with a rheumatic disease without an increase in
disease activity. Prior studies showed that patients with concentrations higher
than 5 mg/L are overexposed to adalimumab and can safely reduce the dose. In
the first phase of treatment, an adalimumab concentration of 5mg/L is needed to
achieve adequate clinical response. However to control disease activity after
28 weeks, lower concentration than 5 mg/L are probably sufficient. Recent
published data suggest that concentrations of 0.1-0.5 mg/L are enough to
control TNF blockade in this state. Yet, a study which investigates the lowest
effective drug serum concentration is missing so far. We hypothesize that serum
adalimumab concentration of 2 mg/L is sufficient to control disease activity.
Study objective
Primary objective: to evaluate the disease activity after dose reduction,
aiming adalimumab concentration of 2 mg/L or 5 mg/L, in rheumatoid arthritis
patients responding to adalimumab.
Secondary objectives: to evaluate whether reducing adalimumab dose aiming a
concentration of 2 mg/L is superior in costs savings compared to dose tapering
aiming adalimumab concentration of 5 mg/L; to evaluate the algorithm used to
achieve target concentration of 2 mg/L or 5 mg/L; to study the difference in
cumulative incidence of flares between the two study groups
Study design
single blinded randomized, non-inferiority, trial
Intervention
Patients are randomly assigned to dose reduction aiming a drug level of
respectively 2 mg/L or 5 mg/L
Study burden and risks
We hypothesize that dose reduction aiming a drug level of 2 mg/L is possible
with disease activity remaining stable, however, an increased disease activity
risk cannot be excluded.
dr jan van breemenstraat 2
Amsterdam 1056 AB
NL
dr jan van breemenstraat 2
Amsterdam 1056 AB
NL
Listed location countries
Age
Inclusion criteria
Rheumatoid arthritis patient, according to ACR 1987/2010 criteria;
Treated for at least 28 weeks with adalimumab
Adalimumab trough concentration >5mg/L
Who has agreed to participate (written informed consent);
Age 16 years or older.
Exclusion criteria
Scheduled surgery during the follow-up of the study or other pre-planned
reasons for treatment discontinuation
Life expectancy shorter than follow-up period of the study;
No other disease that might flare if adalimumab is tapered like psoriasis,
inflammatory bowel disease
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2019-001793-28-NL |
| CCMO | NL69883.029.19 |