Ferric maltol therapy for iron deficiency anaemia in patients with inflammatory bowel disease: long-term extension data from a Phase 3 study

Abstract

Background: Ferric maltol was effective and well-tolerated in iron deficiency anaemia patients with inflammatory bowel disease during a 12-week placebo-controlled trial.

Aim: To perform a Phase 3 extension study evaluating long-term efficacy and safety with ferric maltol in inflammatory bowel disease patients in whom oral ferrous therapies had failed to correct iron deficiency anaemia.

Methods: After 12 weeks of randomised, double-blind treatment, patients with iron deficiency anaemia and mild-to-moderate ulcerative colitis or Crohn's disease received open-label ferric maltol 30 mg b.d. for 52 weeks.

Results: 111 patients completed randomised treatment and 97 entered the open-label ferric maltol extension. In patients randomised to ferric maltol ('continued'; n = 50), mean ± s.d. haemoglobin increased by 3.07 ± 1.46 g/dL between baseline and Week 64. In patients randomised to placebo ('switch'; n = 47), haemoglobin increased by 2.19 ± 1.61 g/dL. Normal haemoglobin was achieved in high proportions of both continued and switch patients (89% and 83% at Week 64, respectively). Serum ferritin increased from 8.9 μg/L (baseline) to 26.0 μg/L (Week 12) in ferric maltol-treated patients, and to 57.4 μg/L amongst all patients at Week 64. In total, 80% of patients reported ≥1 adverse event by Week 64. Adverse events considered related to ferric maltol were recorded in 27/111 (24%) patients: 8/18 discontinuations due to adverse events were treatment-related. One patient was withdrawn due to increased ulcerative colitis activity.

Conclusions: Normal haemoglobin was observed in ≥80% of patients from weeks 20-64 of long-term ferric maltol treatment, with concomitant increases in iron storage parameters. Ferric maltol was well-tolerated throughout this 64-week study.

Figure 1

Patient disposition. *Ten Austrian patients (four initially randomised to ferric maltol and six to placebo) who completed double‐blind treatment did not have the option of entering the extended phase of the study due to lack of Austrian IEC approval of the study protocol; ^†one patient randomised to ferric maltol discontinued during open‐label treatment but had no recorded reason for withdrawal at the end of study; ^‡one patient was recorded as withdrawn from extension treatment due to study termination by the sponsor.

Figure 2

Absolute haemoglobin concentrations in continued patients and switch patients over time (N = 128). Data points are means + s.d. RCT, randomised controlled trial; OLE, open‐label extension.

Figure 3

Cumulative proportions of patients with normal haemoglobin by number of weeks on active treatment with ferric maltol (full analysis set; N = 128). *Cumulative proportion includes all patients from both continued switch group who had normal haemoglobin levels at each time point according to number of weeks on active treatment (i.e., ferric maltol therapy). 6.3% of patients who had haemoglobin values ≥9.5 g/dL and <12.0 g/dL for females and ≥9.5 g/dL and <13.0 g/dL for males at screening had normal values at initiation of randomised treatment.

Figure 4

Absolute serum ferritin concentration (a) and transferrin saturation (b) in all ferric maltol‐treated patients during randomised and extension treatment (full analysis set; N = 128), including both continued and switch patients; data points are means + s.d. Note: grey box in panel (a) represents lower limits of normal in women and men: 15 μg/L and 30 μg/L, respectively; horizontal dashed line at 30 μg/L in denotes the study inclusion criterion for ‘iron deficiency’; grey box in panel (b) represents lower limits of normal in women and men: 12% and 15%, respectively.