High-Dosed Intravenous Iron Replacement Therapy for Iron Deficiency Anemia Does Not Hinder Drug-Induced Amelioration of Disease Activity in IBD Patients

Abstract

BACKGROUND: Iron deficiency and iron deficiency anemia (IDA) are common complications in IBD patients, and can seriously affect quality of life, hospitalization rates, and time lost from work. In IBD patients, anemia is caused by chronic blood loss and/or impaired iron intake and absorption. International guidelines recommend intravenous iron supplementation in IBD patients with moderate-severe anemia or intolerance to oral iron. While oral supplements are convenient and relatively inexpensive, they fail to compensate continuous iron loss due to inadequate intestinal absorption in the presence of inflammation. Oral iron intake is associated with gastrointestinal side-effects including abdominal pain and nausea. Moreover, mounting evidence from animal and human studies shows that non-absorbed iron enhances mucosal inflammation. Intravenous iron has been demonstrated to be safe, effective and well tolerated in correction of IDA and maintenance of iron stores in patients with IBD. Intravenous ferric carboxymaltose (FCM; Ferinject® 50mg ferric iron(III)/mL suspension) can be administered in single 15-minute infusions of up to 1,000mg per week. Here, we assess the effect of high-dosed intravenous FCM on inflammatory activity in IBD patients. METHODS: A prospective non-interventional post-marketing study was performed in 101 centers in Germany to assess efficacy, tolerability, and convenience of Ferinject® in clinical practice. Alongside primary outcomes including response rates and adverse events, changes in clinical disease indices (CDAI/CAI), changes in CRP values, and self-reported disease-related symptoms (fatigue, concentration lack, headache, paleness of mucous membranes, hair loss, (exertional) dyspnoea, sleeping disorders, restless legs syndrome) rated on a severity scale of 1 to 4, were analyzed. Patients were additionally analyzed in subgroups according to baseline CRP levels (<5mg/L, >5mg/L, 5-10mg/L, >10mg/L). RESULTS: Intravenous FCM was administered to 224 subjects (127 CD; 97 UC). Mean total iron dose over ca. 12 weeks was 1,139mg (range: 100mg-4,800mg). 76.7% of doses were between 500mg and 2,000mg. Concomitant drugs included aminosalicylates (89 patients/46.1%), corticosteroids (84/43.5%), immunosuppressants (36/18.7%), biologics (36/19%), antibiotics (8/4.1%) and antidiarrheics (11/5.7%). Although patients (n=97) with elevated CD or UC activity indices (CDAI ≥150; CAI ≥5) presented with lower mean Hb values at baseline compared to those with normal activity indices, mean Hb levels at end of study (EOS) were similar. Subjects with higher activity indices presented with higher mean CRP values at baseline (6.1mg/L) compared to those with normal activity indices (3.6mg/L). CRP levels decreased significantly during the observation period, falling from 6.4mg/L to 3.5mg/L in mean (median 1.9 -1.0mg/L), indicating a general reduction in inflammatory activity, which was independent of baseline Hb levels. Change in CRP levels was statistically significant in subgroups of patients with high disease activity, CD and UC patients treated with a total dose of 500-1000mg iron, and patients who completed therapy. Amelioration of inflammatory activity as indicated by lower CRP levels was confirmed by reduced mean clinical disease activity indices (CDAI/CAI). Patients in both CRP subgroups showed increases in Hb, s-ferritin and TSAT, but reduced CRP levels and fewer symptoms. CONCLUSION(S): High-dosed FCM therapy does not appear to inhibit drug-induced amelioration of inflammatory activity in patients with IBD.