Lengthening Adalimumab Dosing Interval in Quiescent Crohn's Disease Patients
NCT ID: NCT03172377
Last Updated: 2022-10-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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UNKNOWN
PHASE4
174 participants
INTERVENTIONAL
2017-05-03
2022-10-31
Brief Summary
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Currently, adalimumab is given every 2 weeks, by injection under the skin. The optimal time between two injections has never been investigated before. Prior research in patients with rheumatoid arthritis shows that disease remission can be maintained with longer injection-intervals. Our hypothesis is that this is the same for Crohn's disease patients. Our aim is to show non-inferiority of extending the adalimumab dosing interval, under strict disease monitoring in Crohn's disease patients in sustained (\>9 months) clinical remission, compared to standard care.
During the trial,174 patients with stable Crohn's disease will be divided into 2 groups. One group continues adalimumab injections with the same 2-week interval. And the other group will incrementally extend the interval to 4 weeks, under strict disease monitoring. If a step-down leads to recurrence of disease activity patients will return to the preceding effective dosing interval. Thus, we will investigate whether, and for whom, it is safe to extend the adalimumab injection interval.
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Detailed Description
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Adalimumab is both an effective induction and maintenance therapy for Crohn's disease (CD). Due to the risk of side effects (infections, injection reaction) and high costs, an extension of the injection interval is an attractive option. However, this strategy has not been evaluated yet in a randomized controlled trial in CD patients.
Objective
To assess non-inferiority and cost-effectiveness of disease activity guided adalimumab interval lengthening in CD patients in sustained (\>9 months) clinical remission, compared to standard dosing of every other week.
Study design
Multicenter, randomized controlled, open label non-inferiority trial, with two treatment arms.
Study population
Crohn's disease patients, in sustained clinical remission on adalimumab maintenance therapy.
Intervention
Intervention arm: The adalimumab injection interval during maintenance therapy (40 mg per 2 weeks) will be extended through a stepwise disease activity guided manner to 3 weeks and subsequently - after 24 weeks - to 4 weeks. If a step-down leads to recurrence of disease activity patients will return to the preceding effective dosing interval.
Control arm: patients will continue adalimumab maintenance treatment of 40mg per 2 weeks. Treatment decisions are made at the discretion of the treating physician.
Main study parameters/endpoints
Primary outcome: Cumulative incidence of persistent disease flares in 48 weeks of follow-up. A persistent flare is defined as two of three of the following criteria persisting for \> 8 weeks, despite dose escalation of adalimumab; FC \>250 µg/g, CRP≥10 mg/L, HBI ≥5. Non-inferiority is reached if the difference in cumulative incidence of persistent flares not exceeds the non-inferiority margin of 15%.
Secondary outcomes include cumulative incidence of transient flares, adverse events, predictors for successful dose reduction and cost-effectiveness.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Intervention group
Lengthening adalimumab dosing interval: The adalimumab injection interval during maintenance therapy (40 mg sc / 2 weeks) will be extended through a stepwise disease activity guided manner to 3 weeks and subsequently - after 24 weeks - to 4 weeks. If a step-down leads to recurrence of disease activity patients will return to the preceding effective dosing interval.
Lengthening adalimumab dosing interval
Lengthening adalimumab dosing interval from 2 weeks to 3 weeks and -later- to 4 weeks.
Control group
Standard care: patients will continue adalimumab maintenance treatment of 40mg per 2 weeks. Treatment decisions are made at the discretion of the treating physician.
No interventions assigned to this group
Interventions
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Lengthening adalimumab dosing interval
Lengthening adalimumab dosing interval from 2 weeks to 3 weeks and -later- to 4 weeks.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Sustained steroid-free clinical remission for \>9 months whilst being treated with adalimumab at a stable dose
* Adalimumab dosed at 40 mg sc every 2 weeks
* Full clinical response and disease control, all three criteria below need to be fulfilled prior to enrollment:
* Absence of active inflammatory intestinal or extra-intestinal symptoms, as judged by both patient and physician
* Fecal calprotectin (FC) \< 150 μg/g and C reactive protein (CRP) \<10 mg/L
* Harvey Bradshaw Index (HBI) \<5
Exclusion Criteria
* Concomitant corticosteroid usage
* Need for CD-related surgery
* Actively draining peri-anal fistula
* Pregnancy or lactation
* Other significant medical conditions that might interfere with this study (such as current/recent malignancy, immunodeficiency syndromes and psychiatric illness)
* Impossibility to measure outcomes, e.g. planned relocation, language issues, short life expectancy
18 Years
ALL
No
Sponsors
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Erasmus Medical Center
OTHER
Radboud University Medical Center
OTHER
Responsible Party
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Principal Investigators
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Dr. Hoentjen, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Radboud University Medical Center
Prof. dr. van der Woude, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
Erasmus Medical Center
Locations
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Radboudumc University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands
Jeroen Bosch Ziekenhuis
's-Hertogenbosch, North Brabant, Netherlands
Amphia Ziekenhuis
Breda, North Brabant, Netherlands
Bernhoven
Uden, North Brabant, Netherlands
VU Medisch Centrum
Amsterdam, North Holland, Netherlands
Albert Schweitzer Ziekenhuis
Dordrecht, South Holland, Netherlands
Franciscus Gasthuis & Vlietland
Rotterdam, South Holland, Netherlands
Erasmus Medical Center
Rotterdam, South Holland, Netherlands
Ikazia Ziekenhuis
Rotterdam, South Holland, Netherlands
Flevoziekenhuis
Almere Stad, , Netherlands
AmsterdamUMC - location AMC
Amsterdam, , Netherlands
Onze Lieve Vrouwe Gasthuis (OLVG)
Amsterdam, , Netherlands
Reinier de Graaf
Delft, , Netherlands
Maxima Medisch Centrum
Eindhoven, , Netherlands
Medisch Spectrum Twente
Enschede, , Netherlands
Zuyderland ziekenhuis
Geleen, , Netherlands
Spaarne Gasthuis
Haarlem, , Netherlands
Leids Universitair Medisch Centrum
Leiden, , Netherlands
Maastricht UMC+
Maastricht, , Netherlands
Canisius Wilhelmina Ziekenhuis
Nijmegen, , Netherlands
Elisabeth-TweeSteden Ziekenhuis
Tilburg, , Netherlands
UMC Utrecht
Utrecht, , Netherlands
Countries
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References
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van Linschoten RCA, Jansen FM, Pauwels RWM, Smits LJT, Atsma F, Kievit W, de Jong DJ, de Vries AC, Boekema PJ, West RL, Bodelier AGL, Gisbertz IAM, Wolfhagen FHJ, Romkens TEH, Lutgens MWMD, van Bodegraven AA, Oldenburg B, Pierik MJ, Russel MGVM, de Boer NK, Mallant-Hent RC, Ter Borg PCJ, van der Meulen-de Jong AE, Jansen JM, Jansen SV, Tan ACITL, van der Woude CJ, Hoentjen F; LADI study group, the Dutch Initiative on Crohn, Colitis (ICC). A Prediction Model for Successful Increase of Adalimumab Dose Intervals in Patients with Crohn's Disease: Secondary Analysis of the Pragmatic Open-Label Randomised Controlled Non-inferiority LADI Trial. Dig Dis Sci. 2024 Jun;69(6):2165-2174. doi: 10.1007/s10620-024-08410-z. Epub 2024 Apr 9.
Jansen FM, van Linschoten RCA, Kievit W, Smits LJT, Pauwels RWM, de Jong DJ, de Vries AC, Boekema PJ, West RL, Bodelier AGL, Gisbertz IAM, Wolfhagen FHJ, Romkens TEH, Lutgens MWMD, van Bodegraven AA, Oldenburg B, Pierik MJ, Russel MGVM, de Boer NK, Mallant-Hent RC, Ter Borg PCJ, van der Meulen-de Jong AE, Jansen JM, Jansen SV, Tan ACITL, Hoentjen F, van der Woude CJ; LADI study group. Cost-Effectiveness Analysis of Increased Adalimumab Dose Intervals in Crohn's Disease Patients in Stable Remission: The Randomized Controlled LADI Trial. J Crohns Colitis. 2023 Nov 24;17(11):1771-1780. doi: 10.1093/ecco-jcc/jjad101.
van Linschoten RCA, Jansen FM, Pauwels RWM, Smits LJT, Atsma F, Kievit W, de Jong DJ, de Vries AC, Boekema PJ, West RL, Bodelier AGL, Gisbertz IAM, Wolfhagen FHJ, Romkens TEH, Lutgens MWMD, van Bodegraven AA, Oldenburg B, Pierik MJ, Russel MGVM, de Boer NK, Mallant-Hent RC, Ter Borg PCJ, van der Meulen-de Jong AE, Jansen JM, Jansen SV, Tan ACITL, van der Woude CJ, Hoentjen F; LADI study group and the Dutch Initiative on Crohn and Colitis. Increased versus conventional adalimumab dose interval for patients with Crohn's disease in stable remission (LADI): a pragmatic, open-label, non-inferiority, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023 Apr;8(4):343-355. doi: 10.1016/S2468-1253(22)00434-4. Epub 2023 Jan 31.
Smits LJT, Pauwels RWM, Kievit W, de Jong DJ, de Vries AC, Hoentjen F, van der Woude CJ; LADI study group. Lengthening adalimumab dosing interval in quiescent Crohn's disease patients: protocol for the pragmatic randomised non-inferiority LADI study. BMJ Open. 2020 May 26;10(5):e035326. doi: 10.1136/bmjopen-2019-035326.
Related Links
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Dutch organisation for healthcare research and innovation (ZonMW)
Other Identifiers
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848015002
Identifier Type: OTHER_GRANT
Identifier Source: secondary_id
2016-003321-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
NL58948.091.16
Identifier Type: -
Identifier Source: org_study_id
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