Ferric maltol is effective in correcting iron deficiency anemia in patients with inflammatory bowel disease: results from a phase-3 clinical trial program

Abstract

Background: Iron deficiency anemia (IDA) is frequently seen in inflammatory bowel disease. Traditionally, oral iron supplementation is linked to extensive gastrointestinal side effects and possible disease exacerbation. This multicenter phase-3 study tested the efficacy and safety of ferric maltol, a complex of ferric (Fe) iron with maltol (3-hydroxy-2-methyl-4-pyrone), as a novel oral iron therapy for IDA.

Methods: Adult patients with quiescent or mild-to-moderate ulcerative colitis or Crohn's disease, mild-to-moderate IDA (9.5-12.0 g/dL and 9.5-13.0 g/dL in females and males, respectively), and documented failure on previous oral ferrous products received oral ferric maltol capsules (30 mg twice a day) or identical placebo for 12 weeks according to a randomized, double-blind, placebo-controlled study design. The primary efficacy endpoint was change in hemoglobin (Hb) from baseline to week 12. Safety and tolerability were assessed.

Results: Of 329 patients screened, 128 received randomized therapy (64 ferric maltol-treated and 64 placebo-treated patients) and comprised the intent-to-treat efficacy analysis: 55 ferric maltol patients (86%) and 53 placebo patients (83%) completed the trial. Significant improvements in Hb were observed with ferric maltol versus placebo at weeks 4, 8, and 12: mean (SE) 1.04 (0.11) g/dL, 1.76 (0.15) g/dL, and 2.25 (0.19) g/dL, respectively (P < 0.0001 at all time-points; analysis of covariance). Hb was normalized in two-thirds of patients by week 12. The safety profile of ferric maltol was comparable with placebo, with no impact on inflammatory bowel disease severity.

Conclusions: Ferric maltol provided rapid clinically meaningful improvements in Hb and showed a favorable safety profile, suggesting its possible use as an alternative to intravenous iron in IDA inflammatory bowel disease.

FIGURE 1

Patient disposition. *One hundred twenty-eight randomized patients were included in the main ITT FAS efficacy analysis, and the first 120 patients randomized were included in the safety analysis as predefined by statistical protocol; †Due to dose changes (n = 2) or duration of treatment (n = 1); ‡Due to timings of assessments. MCV, mean corpuscular volume.

FIGURE 2

Hb concentration from baseline to week 12 (ITT FAS). Data are mean ± SD; ***P < 0.0001 (ferric maltol versus placebo based on ANCOVA).

FIGURE 3

Responder analysis: patients achieving 1 and 2 g/dL increases, and normalization of Hb concentration between baseline and week 12 (ITT FAS). Ferric maltol versus placebo ORs were 41.8 (95% CI, 13.5–129.9) for ≥1 g/dL increases, not applicable for ≥2 g/dL increases, and 15.3 (95% CI, 5.9–39.3) for normalization.