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

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 lg/L (baseline) to 26.0 lg/L (Week 12) in ferric maltol-treated patients, and to 57.4 lg/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 One patient was withdrawn due to increased ulcerative colitis activity.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

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

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

Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management.

Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases. Early pregnancy is a contraindication to iron infusions, while old age and serious co-morbidity may worsen the impact of acute reactions if they occur. Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff

A Randomised, Double-blind, Placebo-controlled Trial ofTrichuris suisova in Active Crohn’s disease

Background and Aims: To investigate the efficacy and safety of three different dosages of embryonated, viable eggs of Trichuris suis [TSO] versus placebo for induction of remission in mildly-to-moderately active ileocolonic, uncomplicated Crohn's disease [CD]. Methods: Adults with active CD [n = 252] randomly received six fortnightly doses of 250, 2500, or 7500 TSO/15 ml suspension/day [TSO 250, TSO 2500, TSO 7500], or 15 ml placebo solution/day, in a double-blind fashion, with 4 weeks' follow-up. Primary endpoint was the rate of clinical remission [Crohn's Disease Activity Index [CDAI] < 150] at end of treatment, ie at Week 12 or withdrawal. Secondary endpoints included the course of clinical remission, rate of clinical response, change in CDAI, change in markers of inflammation, mucosal healing, and Physician's Global Assessment. Results: Clinical remission at Week 12 occurred in 38.5%, 35.2%, and 47.2% of TSO 250, TSO 2500, and TSO 7500 patients, respectively, and in 42.9% of placebo recipients. TSO induced a dose-dependent immunological response. There was no response regarding laboratory markers of inflammation. Other secondary efficacy variables also showed no advantage of TSO over placebo for treatment of active CD. Administration of TSO did not result in any serious adverse drug reaction. Review of non-serious suspected adverse drug reactions following TSO did not reveal any safety concerns. Conclusions: Administration of 250-7500 TSO fortnightly over 12 weeks was safe and showed a dose-dependent immunological response, but no TSO dose showed a clinically relevant effect over placebo for induction of clinical remission or response in mildly-to-moderately active, ileocolonic CD