The primary objective is to evaluate whether a switching strategy using adalimumab concentration (TDM) is superior to usual care in rheumatoid arthritis patients failing adalimumab treatment with regard to response rates. The secondary objectives…
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
after 24 weeks.
Secondary outcome
• percentage of patients with good or moderate response according the EULAR
response criteria after 12 and 24 weeks of treatment
• percentage of patients with minimal disease activity (DAS28-CRP<2.9) after 24
weeks
• percentage of non-responders to the subsequent biological after 24 weeks
• number of flares after 24 weeks
• numbers and severity of adverse events
• use of co-medication/rescue medication use
Background summary
A potential application of therapeutic drug monitoring is to predict efficacy
after switch to another biological in the case of inefficacy of the previous
biological in rheumatoid artritis patients. It has been shown that when
antidrug antibodies against a TNF blocker are detected (resulting in lower drug
serum concentrations) in patients failing a TNF blocker, a normal response to a
next TNF blocker can be anticipated. However, when clinical response is
unsatisfactory and no antidrug antibodies against the first TNF blocker are
detected (generally drug levels are adequate in this case), this predicts a
lower response to a next TNF blocker. This means drug resistant failure in the
former, compared to class resistant failure in latter category of patients. The
current RA treatment strategy after failure of the first TNF-inhibitor is to
start either a second TNF blocker or a non-TNF blocker. However, by channelling
patients with sufficient adalimumab concentration, to a non-TNF class
biological will provide higher chance of disease control. Patients with very
low or undetectable drug levels have an equal high chance of disease control
with a drug of the same class (i.e. another TNF blocker).
Study objective
The primary objective is to evaluate whether a switching strategy using
adalimumab concentration (TDM) is superior to usual care in rheumatoid
arthritis patients failing adalimumab treatment with regard to response rates.
The secondary objectives are to evaluate the response rate after 12 weeks of
treatment in both arms; to evaluate percentage of patients reaching minimal
disease activity (DAS28-CRP<2.9) in both arms; to compare percentages of EULAR
non-responders to the subsequent biological; to compare the number and severity
of adverse events in both arms; to compare the use of co-medication/rescue
medication use
Study design
Blinded randomized multi-centre trail
Intervention
Patients are randomly assigned to usual care or *drug concentration* guided
switch. When randomized to the usual care group, patients are switched to TNFi
(etanercept, infliximab, golimumab or certolizumab pegol) or a non-TNFi
(abatacept, rituximab, tocilizumab, sarilumab, baricitinib, filgotinib,
upadacitinib or tofacitinib), based on a secondary randomization schedule. When
randomized to a non-TNFi, the treating rheumatologist will choose the specific
TNFi or non-TNFi. In the *drug concentration guided* group, in patients with a
concentration <1.0 mg/L adalimumab is switched to TNFi and in patients with a
concentration >= 1.0 adalimumab is switched to a non-TNF-inhibitor (the same
drugs and dosing as in usual care group).
Study burden and risks
Using serum drug levels may facilitate decision making regarding the subsequent
biological. Patients assigned to usual care group will not benefit from the
aforementioned possible advantage. In addition, patients have to visit the
outpatient clinic more often. Other burdens and risks seem not to be present.
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;
Failed treatment with adalimumab (defined as DAS28-CRP >2,9) and not treated
with a subsequent biological DMARD (bDMARD) or target synthetic DMARD (tsDMARD)
Who has agreed to participate (written informed consent);
Age 18 years or older.
Received adalimumab for at least 10 weeks in standard dosing (40mg
subcutaneously every other week, either in monotherapy or combined with
methotrexate or leflunomide)
Stop adalimumab due to inefficacy, either alone or combined with side effects
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 possibility to safely receive an TNF-inhibitor or a non-TNF-inhibitor '
Treatment with another TNF inhibitor prior to adalimumab
Treatment with all non-TNFi options (abatacept, rituximab, sarilumab,
tocilizumab, baricitinib, filgotinib, upadacitinib or tofacitinib) prior to
adalimumab
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 | EUCTR2019-001754-25-NL |
| CCMO | NL69841.091.19 |
| Other | NL8210 |