To evaluate whether a faecal calprotectin guided strategy of anti-TNF dosing interval lengthening is non-inferior in maintaining remission in patients with IBD compared with an unchanged dosing interval.
ID
Source
Brief title
Condition
- Gastrointestinal inflammatory conditions
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The cumulative incidence of out-of-range FC results at 48 weeks follow-up.
Secondary outcome
(1) time to get out-of-range FC results
(2) cumulative incidence of anti-TNF-associated respiratory infections and
dermatological adverse effects at 48 weeks follow-up
(3) evolution of FC and anti-TNF trough levels in the first 16 weeks after
reverting to previous dosing interval
(4) proportion of patients developing loss-of-response in the first 16 weeks
after reverting to the previous dosing interval
(5) identification of predictors of successful de-escalation.
Background summary
Treatment outcomes of patients with inflammatory bowel disease (IBD) have
improved enormously during the past decade due to the use of anti-tumour
necrosis factor (anti-TNF) therapy. As a result, 67 to 91% of paediatric
patients and 66% of adult patients is still in sustained remission two years
after the initiation of anti-TNF therapy. Prolonged use of anti-TNFs comes with
disadvantages such as dose dependent susceptibility to infections and
dermatological adverse effects. Preliminary, mostly uncontrolled studies
suggest that dose reduction by dosing interval lengthening is a realistic
option in a relevant proportion of patients with IBD, provided that intensive
follow-up is applied.
Study objective
To evaluate whether a faecal calprotectin guided strategy of anti-TNF dosing
interval lengthening is non-inferior in maintaining remission in patients with
IBD compared with an unchanged dosing interval.
Study design
International, multi-centre, prospective, partially randomised
patient-preference trial.
Intervention
In patients treated with adalimumab, the dosing interval will be lengthened
from 2 to 3 weeks. In patients treated with infliximab, the dosing interval
will be lengthened from 8 to 12 weeks. FC rapid tests will be performed every 4
weeks and rapid tests for anti-TNF trough levels will be performed every 12
weeks.
Study burden and risks
Patients with reduced anti-TNF exposure may have a higher risk of out-of-range
FC results and, on the other hand, may benefit from fewer hospital visits or
injections and possibly a decrease in adverse effects of anti-TNF therapy.
Tight monitoring of FC levels (i.e. 4 weekly) will allow institution of
re-escalation before the patient manifests clinical signs of relapse. This
study could not be conducted without the participation of minors, who typically
have a short disease duration and therefore have a window of opportunity to
de-escalate anti-TNF therapy.
Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Aged 12-25 years
- Diagnosed with luminal Crohn*s disease or ulcerative colitis
- Treated with either 8-weekly infliximab or 2-weekly adalimumab
- Current anti-TNF agent as first ever anti-TNF agent or prior anti-TNF agent
discontinued for reason other than primary non-response or secondary
loss-of-response
- No previous attempts to lengthen the dosing interval
- Three consecutive faecal calprotectin (FC) results in the target range (i.e.
<250 µg/g for CD patients; <150 µg/g for UC patients) in the previous 6 months
or
NL73966.042.20 / FREE-study (v3.6)
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confirmed endoscopic remission within 2 months before study entry (i.e. simple
endoscopic score for Crohn*s disease (SES-CD) <3 points; ulcerative colitis
endoscopic index of severity (UCEIS) <=1 point or Mayo endoscopic subscore <=1
point)
- Absence of symptoms associated with active IBD (judged by the local IBD-team)
- Written informed consent granted
Exclusion criteria
- Perianal fistula
- Presence of ileostomy or ileoanal pouch
- Any inflammatory comorbidity, such as rheumatoid arthritis
- Current treatment with corticosteroids (prednisone or budesonide)
- Current pregnancy
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 | EUCTR2020-001811-26-NL |
| CCMO | NL73966.042.20 |