The MIRACLE trial is for patients who have been newly diagnosed with moderate to severe ulcerative colitis in the last 12 months and who have not responded adequately to treatment with mesalazine and prednisolone alone. The standard drug therapy for ulcerative colitis begins with mesalazine (+cortisone) and, if the response is insufficient, continues with azathioprine (+cortisone). Only in the next step are biologics (biotechnologically produced protein substances such as antibodies) such as mirikizumab used as needed. Recent studies have now shown that earlier treatment with mirikizumab without prior treatment with azathioprine may be more effective in the long term, and there are indications that this may result in fewer side effects. This study aims to investigate whether direct, early treatment with mirikizumab is more effective than the usual initiation of standard therapy with azathioprine, whereby these patients can then switch to mirikizumab at predetermined times during the course of the study from week 24 onwards if they have a defined disease activity despite the previous azathioprine treatment. The study consists of an initial treatment period of 12 weeks (induction therapy) and a maintenance therapy period of 40 weeks. Patients in the mirikizumab arm receive 12 doses of mirikizumab. This includes initially 300 mg intravenously every 4 weeks at the trial site, followed by 200 mg subcutaneously via two subcutaneous injections of 100 mg each, administered independently at home. In the azathioprine arm patients receive daily administration of azathioprine tablets in combination with a steroid. Assignment to one of the two treatment options is randomised with equal probability for each of the treatment options.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
300
Patients in the mirikizumab arm will receive an initial 300 mg dose every 4 weeks intravenously for three doses during the 12-week induction period.After completing induction, patients will switch to maintenance therapy with 200 mg mirikizumab subcutaneously.
Patients in the azathioprine arm will receive oral azathioprine at a dose of 2.0-2.5 mg/kg body weight daily in combination with an initial daily dose of 40-60 mg glucocorticoids, which may be tapered as clinically appropriate.
University Hospital Schleswig-Holstein
Kiel, Germany
RECRUITINGcomprehensive disease control
The proportion of patients achieving comprehensive disease control at Week 52, defined as: Steroid-free clinical remission (modified Mayo score remission \[ES ≤1, SF ≤1, RB=0\] and no glucocorticoid use for at least 12 weeks prior to week 52) achieved without surgery, and Biochemical remission (CRP \<0.5 mg/dl and Fcal \<250 μg/g stool), and Endoscopic improvement (eMayo=0-1), and Histologic remission (RHI ≤3, with subscores of 0 for lamina propria neutrophils and of 0 for neutrophils in epithelium), and Normalization of IBD-related QoL (sIBDQ ≥60 points).
Time frame: Week 52
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