Rationale: Iron deficiency anemia is the most common systemic manifestation of Inflammatory Bowel Diseases (IBD)-Crohn's disease and ulcerative colitis. Iron deficiency with or without anemia poses a diagnostic and therapeutic challenge due to chronic gastrointestinal blood loss and the inflammatory nature of IBD. Oral iron supplementation in active disease states is controversial. Hepcidin levels can be considered as the sum effect of all regulatory processes. Studies suggested that iron stores and hypoxia reduce hepcidin levels even in an inflammatory state. This is also reflected by a study which demonstrated low levels of hepcidin in patients with ferritin levels under 30μg/ml, regardless of disease activity or type. Furthermore, studies show that immunosuppressive medication decrease the level of hepcidin. This raises the question: is oral iron a viable alternative for patients under immunosuppressive treatment for active IBD? Objective: The hypothesis is that patients with mild to moderate IBD activity on immunosuppressive medication, show the same level of Hb increase after 12 weeks after either oral or iv iron supplementation, while the price of oral iron supplementation is significantly lower.

Study design: multicenter, prospective randomized non-inferiority study. Study population: Patients with inflammatory bowel disease on immunosuppressive medication with iron deficiency anemia, with increased inflammation parameters, but without an elevated ferritin (<100 μg/L).

Intervention: 152 patients will be randomized to a treatment group with either low dose oral iron or iv iron supplementation.

Main study endpoints: Normalization of Hb concentration (> 7.3 mmol/L (females) or > 8.0 mmol/L (males)) from baseline to week 12 in both oral and iv iron supplementation group.

Patients will receive either oral or intravenous iron therapy. Both therapies will be given according to existing guidelines. Participation to this trial will not increase the frequency of regular follow-up visits for patients. Blood for study measurements will be drawn simultaneously as blood for standard care tests. In addition, three questionnaires will be sent out regarding the patient's quality of life, disease activity, and productivity impairment. Iron therapy and biomaterial acquisition do not increase patients' risk because patients would have to undergo the same tests for standard IBD-care and receive iron therapy outside of the study. The study will be directly beneficial to participating patients because patients will undergo treatment for iron deficiency. The findings might help to develop guidelines for personalized iron therapy in the IBD population.

Inclusion Criteria:

• Established IBD diagnosis (Crohn's disease, ulcerative colitis, IBD-unclassified)
• Adults (≥18 years of age)
• Any single Hb level between 6,2 - 7,3 mmol/L (females) 6,2 - 8,0 mmol/L (males)
• Any single ferritin <100 μg/L and transferrin saturation <20% within 4 weeks of study inclusion
• CRP > 5 mg/L and / or fecal calprotectin > 150 within 4 weeks of randomization
• Patients on immunosuppressive medication (thiopurine, methotrexate, biologicals, JAK inhibitor) for at least 8 weeks or if prednisone, for at least 2 weeks
• Mild to moderate disease according to the treating physician; a Physician Global Assessment (PGA) score of 1 or 2
• Documented informed consent

Exclusion Criteria:

• Anemia due to reasons other than iron deficiency or chronic disease (e.g. hemoglobinopathy).
• Severe disease with a PGA score of 3
• IBD patients with a location of IBD at other places than ileum and / or colon (according to treating physician)
• Patients who are prescribed PPI
• Earlier significant side effect of oral iron or iv iron
• Folic acid deficiency (<2.5 μg/ml)
• Vitamin B12 deficiency (<150 mg/l)
• Patients can proceed with their regular diet, but during the study they cannot take supplements that contain iron. For example, commercial vitamins with iron or a well-known iron supplement Floradix®. Intake of said supplements must be stopped at the moment of inclusion.
• Documented history of bariatric surgery or gastric/duodenal resections due to benign or malignant pathologies
• Documented major operation (e.g., laparotomy) less than six weeks before inclusion
• Documented history of liver cirrhosis, heart failure, hemoglobinopathies, autoimmune hemolytic anemia, myelodysplastic syndrome, or chronic obstructive pulmonary disease (COPD)
• Documented history of recent treatment for a malignancy (excluding dermatological malignancies such as basal cell carcinoma or squamous cell carcinoma). Patients can be included if the treatment for malignancy has been finalized ≥6 months before the inclusion date.
• End-stage renal disease (impaired renal function, defined as eGFR <30 ml/min/1.73m2)
• Documented pregnancy or breastfeeding at the time of inclusion