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 One patient was withdrawn due to increased ulcerative colitis activity.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

AAV2 Rep68 can bind to consensus Rep-binding sites on the HSV-1 genome

Adeno-associated virus type 2 is known to inhibit replication of herpes simplex virus 1 (HSV-1). This activity has been linked to the helicase- and DNA-binding domains of the Rep68/Rep78 proteins. Here, we show that Rep68 can bind to consensus Rep-binding sites on the HSV-1 genome and that the Rep helicase activity can inhibit replication of any DNA if binding is facilitated. Therefore, we hypothesize that inhibition of HSV-1 replication involves direct binding of Rep68/Rep78 to the HSV-1 genome

Myosin IXb variants and their pivotal role in maintaining the intestinal barrier: a study in Crohn's disease

Our data suggest a link between MYO9B variants to an increased intestinal permeability in CD patients. This supports the influence of Myosin IXb on the integrity of the epithelial barrier. The role of MYO9B variants in the overall susceptibility to IBD, however, remains to be elucidated