Control Crohn Safe with episodic adalimumab monotherapy as first line treatment study.

Crohn*s disease (CD) is a chronic disease with a heterogeneous clinical
presentation, relapse rate and treatment response. Insufficient control of
mucosal inflammation results in irreversible bowel damage and complications and
at present no markers are available to predict such a complicated disease
course at diagnosis. Therefore, to prevent overtreatment of low risk patients,
step-up treatment with subsequent introduction of corticosteroids, thiopurines
maintenance and TNF-blockers if a previous category fails is standard care.
Combination treatment with thiopurines and a TNF-blocker is more effective than
monotherapy but associated with a higher risk for infectious complications.
Landmark studies convincingly showed an improved long-term outcome if the
TNF-blocker infliximab is introduced early after diagnosis. The standard
step-care approach thus prolongs steroid exposure and delays start of disease
modifying biologicals in high risks patients. Given the higher efficacy of
combination therapy with a thiopurine of infliximab and potential allergic
reactions and lower response rates after re-initiation of this chimeric
biological, temporary monotherapy with this TNF-blocker has not been studied as
first line treatment before. Adalimumab is a humanised monoclonal antibody and
subsequently, combination therapy of adalimumab + thiopurines has only a
marginal effect on anti-drug anti-body formation. Furthermore, combination
therapy with adalimumab does not enhance the clinical response. Therefore,
periodic treatment with adalimumab in combination with close monitoring after
drug-discontinuation, in newly diagnosed CD might improve outcome, reduce
drug-related side effects while still preventing overtreatment.

This study has been transitioned to CTIS with ID 2024-516002-33-01 check the CTIS register for the current data.

The aim of this study is to compare the long-term efficacy and safety of
periodic adalimumab as initial treatment in newly diagnosed CD patients
compared to standard step-care with corticosteroid/budesonide as the initial
treatment

Pragmatic randomised open label multicentre trial

24 weeks adalimumab treatment compared to standard step-care starting with
corticosteroids/budesonide. Both study groups are strictly monitored with the
validated telemedicine tool myIBDcoach and a calprotectin point of care test
during the study period.

This study compares standard care with corticosteroids as first line drug with
adalimumab as first line treatment in maintenance treatment naïve CD patients.
Outpatient clinic visits and diagnostics during the study are mainly standard
care. Strict monitoring with a colonoscopy, the telemedicine tool myIBDcoach
and calprotectin test is routine care in the participating hospitals. The first
line drug in the intervention arm of this trial is subcutaneous administered in
contrast with oral treatment with corticosteroids in the standard care arm.
Risk of subcutaneous administration with an auto-injection device is limited
and consist of mild pain or purpura after injection. There is a small risk to
hit a nerve with increased pain, or for an injectionside reactions (swelling,
pruritus and redness) all of these are local and self-limiting. There might be
discrete scarring or dimpling of the skin from a subcutaneous injection. Both
corticosteroids and adalimumab are immunosuppressive and the main adverse
effects therefore infection, however the risk for severe infectious
complications is higher for corticosteroids compared to anti-TNF monotherapy.
Anti-TNF is generally well tolerated while side effects (weight gain,
hyperglycemia, psychological complaints and development of striae) of
corticosteroid occur in up to 50% of the patients. All the patients in the
trial have a colonoscopy at week 24. Colonoscopy is an invasive uncomfortable
procedure with a time-consuming preparation. Diagnostic ileocolonoscopy without
biopsies has a 1/1000 risk for bowel perforation. In recent international
guidelines performing an endoscopy, to assess the effect of treatment and to
adjust treatment if persistent endoscopic inflammation is present is
recommended (1). Patients have a second MRI-enterography after 96 week, this is
not standard care. Participant have to drink contrast fluid as preparation for
this examination and MRI-enterography yield a small risk for allergic reactions
to intravenous administered contrast