Intravenous iron: an update.

Iron deficiency is the most common nutritional deficiency worldwide, with significant adverse health consequences in the presence or absence of anaemia. Total dose intravenous iron replacement is recommended for replacement of iron in patients with severe iron deficiency, especially in the presence of anaemia, intolerance or inefficacy following oral iron, or states of inflammation where upregulation of hepcidin may impair gastrointestinal absorption of iron. Currently, available intravenous iron formulations have been demonstrated to have an excellent overall safety profile, but potential adverse effects, including skin staining, infusion-related reactions and hypophosphataemia, have been described. Knowledge of differences in administration and safety profiles of currently available iron formulations will allow appropriate prescription, counselling, as well as recognition and management of adverse events in patients requiring intravenous iron.

Administration of intravenous iron through a home-based infusion strategy is safe and has high patient acceptance.

BACKGROUND AND AIMS: To evaluate the safety and patient experience of a hospital-initiated home-based iron infusion service in patients with iron deficiency with or without anaemia. METHODS: Retrospective cohort study, including adult patients who received intravenous iron through a Hospital in The Home service in a single tertiary centre between August 2020 and 2021. A chart review was conducted for documented adverse events (AEs). A telephone survey assessed patient acceptance with three questions on a 5-point Likert scale: (i) How do you perceive the experience of having your infusion given in the home? (ii) Would you like to have the infusion in the same location if you require one in the future? and (iii) Do you feel safe having your infusion at home? OUTCOME MEASURES: Percentage of patients experiencing AEs and patient acceptance of a home-based iron infusion strategy. RESULTS: One hundred ninety-seven patients were included (181 ferric carboxymaltose and 16 ferric derisomaltose). Six (3%) patients (2 of 181 patients who received ferric carboxymaltose compared with 4 of 16 patients who received ferric derisomaltose, P < 0.001, Fisher's exact) experienced AEs, mostly headache and pruritus. Most patients who participated in the telephone survey had a positive experience (57/58 (98%)), felt safe (57/58 (98%)) and preferred future infusions to occur at home (52/58 (90%)). CONCLUSION: A home-based iron infusion strategy was safe and well accepted by patients. Larger studies evaluating the safety profile of different iron formulations in the home setting are required.

Development of inflammatory bowel disease patient education and medical information sheets: serving an unmet need.

Inflammatory bowel disease is a chronic gastrointestinal condition that necessitates life-long healthcare engagement and management. Empowering patients with knowledge is fundamental to enhance health literacy, improve health outcomes and facilitate complex decision-making regarding medication and potential surgery. A working group was formed to develop concise, comprehensive patient information sheets to meet this unmet need in the Australian setting.

Faecal microbiota transplantation for recurrent Clostridioides difficile infection: an Australian experience - effective, safe, yet room for improvement.

Faecal microbiota transplantation (FMT) is reportedly effective and safe for the management of recurrent or refractory Clostridioides difficile infection (CDI), yet real-world data of outcomes of FMT in Australia are limited. In this series, FMT safely resulted in resolution of CDI in 19 patients with reduced healthcare utilisation after 25 FMT, but one patient was diagnosed with an anti-nuclear antibody-positive constitutional illness and Hashimoto thyroiditis following FMT. Further prospective evaluation of the utility of FMT earlier in CDI treatment algorithms to minimise cost and morbidity, and recipient follow up for immune-mediated conditions, is required.

Altered bowel habit and rectal bleeding in pregnancy: the importance of recognising undiagnosed inflammatory bowel disease.

Worsening of disease activity during pregnancy in patients with known inflammatory bowel disease, especially ulcerative colitis (UC), is well recognised, but the diagnosis of new-onset or previously undiagnosed UC in pregnancy has been inadequately studied to date. Recognition of gastrointestinal symptoms in pregnancy as potentially indicating UC is of paramount importance, as this allows appropriate investigation and instigation of therapies to optimise maternal and foetal outcomes. Here, we report three cases of women with gastrointestinal symptoms in pregnancy with disparate outcomes.

Imbalance of the renin-angiotensin system may contribute to inflammation and fibrosis in IBD: a novel therapeutic target?

OBJECTIVE: We evaluated the influence of the renin-angiotensin system (RAS) on intestinal inflammation and fibrosis. DESIGN: Cultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1-7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies. RESULTS: Human colonic myofibroblast proliferation was reduced by Ang (1-7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1-7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson's trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=-0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation. CONCLUSIONS: The RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.

Hypophosphataemia after ferric carboxymaltose is unrelated to symptoms, intestinal inflammation or vitamin D status.

BACKGROUND: Intravenous iron replacement is recommended for iron-deficient patients with inflammatory bowel disease (IBD), but may be associated with hypophosphataemia, predisposing to osteomalacia and fractures. This study aimed to evaluate the incidence and risk factors for hypophosphataemia following intravenous ferric carboxymaltose (FCM) in patients with IBD. METHODS: This prospective observational study of patients with and without IBD evaluated serum phosphate for 28 days following intravenous FCM, and assessed associations with symptoms, markers of inflammation and vitamin D status. RESULTS: Twenty-four patients with IBD (11 with Crohn's disease [CD], 13 with ulcerative colitis [UC], mean age 45 years [range 19-90], 7 female), and 20 patients without IBD (mean age 56 [22-88] y, 11 female), were included. Overall, serum phosphate declined by a mean of 36% at Day 7, with a mean fall of 42% (SD 19%) at some time point over 28 days (p <  0.001). Twenty-four of 44 (55%) patients developed moderate to severe hypophosphataemia (serum phosphate < 0.6 mmol/L). No differences between patients with and without IBD were seen, but patients with CD had greater decline in phosphate than those with UC. There was no association between hypophosphataemia and symptomatic adverse events, faecal calprotectin, C-reactive protein, albumin, platelet count, 25(OH) vitamin D, or 1,25(di-OH) vitamin D. Serum phosphate < 1.05 mmol/L on Day 2 predicted susceptibility to moderate-severe hypophosphataemia (OR 7.0). CONCLUSIONS: Hypophosphataemia following FCM is common, unrelated to symptomatic adverse events, baseline intestinal or systemic inflammation, or vitamin D status.

Poor predictive value of breath hydrogen response for probiotic effects in IBS.

BACKGROUND AND AIMS: Previous observations suggested that an early rise in breath hydrogen after lactulose (ERBHAL) may identify patients with irritable bowel syndrome (IBS) likely to respond to probiotics. Therefore, we aimed to (i) investigate whether treatment with a probiotic changes breath hydrogen response in patients with ERBHAL and (ii) whether these changes identify patients who may benefit symptomatically from probiotics. METHODS: In a randomized, double-blind, placebo-controlled trial, patients with IBS (Rome III) were randomized to either 65 mL/day fermented milk product containing probiotic (FMPP) or placebo for 6 weeks, followed by 6 weeks' open-label treatment and 6 weeks' withdrawal. Breath hydrogen responses to lactulose (15 g) and liquid-gastric emptying time were evaluated before and at the end of each treatment period. Symptoms were measured using a 100-mm visual analog scale. RESULTS: Loss of ERBHAL occurred in 36% of 23 patients receiving FMPP and 41% of 22 receiving placebo (P = 1.00). Amongst 40 patients who completed open-label FMPP treatment, ERBHAL was lost in a further 38%, continued in 25%, and regained in 10%. Similar variability occurred in the withdrawal phase. Variability was unrelated to changes in gastric emptying. No differences in symptom response were seen between treatment groups nor in relation to the loss or retention of ERBHAL. CONCLUSIONS: Breath hydrogen patterns after lactulose are poorly reproducible. No FMPP-specific effects on fermentation patterns or symptoms were observed. The presence of ERBHAL is not useful to predict symptomatic response to probiotic therapy in patients with IBS.

Clinical trial: Combination allopurinol-thiopurine versus standard thiopurine in patients with IBD escalating to immunomodulators (the DECIDER study).

BACKGROUND: Thiopurines are established treatments for inflammatory bowel disease (IBD), yet concerns remain regarding their safety. AIM: To evaluate the use of thiopurine-allopurinol combination therapy compared to standard thiopurine therapy in IBD. METHODS: We performed a multicentre, randomised, placebo-controlled trial to compare the efficacy and safety of thiopurine-allopurinol versus thiopurine with placebo for adults commencing a thiopurine for IBD. Patients had active disease at baseline; dosing of therapy was based on a pre-specified regimen and subsequent metabolites. The primary outcome was the proportion of patients achieving a composite of symptomatic disease activity remission (Harvey Bradshaw Index <5 for Crohn's disease, Simple Clinical Colitis Activity Index <4 for ulcerative colitis) and a faecal calprotectin <150 µg/g after 26 weeks of treatment. RESULTS: The trial was terminated early due to slow recruitment. We randomised 102 participants (54 thiopurine-allopurinol, 48 thiopurine with placebo) with similar age (median 42 vs 48 years) and sex distribution (46% women per group). A higher proportion achieved the primary outcome in the thiopurine-allopurinol group (50% vs 35%, p = 0.14) and fewer participants stopped their allocated therapy due to adverse events (11% vs 29%, p = 0.02). Also, within the thiopurine-allopurinol group, thiopurine dose adjustments were less frequent (69% vs 92%, p = 0.03), a higher proportion achieved an early therapeutic 6-TGN level at week 6 (71% vs 53%, p = 0.19), and adverse events attributed to therapy were less frequent (15% vs 44%, p = 0.002). CONCLUSION: Thiopurine-allopurinol therapy is safe and mitigates thiopurine adverse effects, thus enhancing tolerability without compromising efficacy (ACTRN12613001347752).

Factors associated with long-term healthcare expense and steroid exposure in patients admitted with acute severe ulcerative colitis.

Background and Aim: Acute severe ulcerative colitis (ASUC) remains a significant cause of morbidity and healthcare utilization. This study aimed to characterize the total healthcare costs of ASUC, explore factors associated with significant cost over the 12 months following an index admission, and document outcomes including corticosteroid exposure. Methods: Patients admitted from January 2016 until January 2021 for ASUC to a tertiary inflammatory bowel disease (IBD) center in Australia were identified via retrospective chart review. Costs were calculated over a 12-month period following index admission. Results: Seventy-two patients (30 [42%] female, median age 39 [IQR 27-54] years) were included. The median length of stay of index admission was 6 days (IQR 5-10 days). The median cost of index admission was 7829 AUD, which was driven by the initial length of stay (P < 0.01) and requirement for colectomy (P < 0.01). Median total healthcare cost over the first 12 months was 13 873 AUD (IQR 9684-19 936 AUD), again predominately driven by the length of stay (P < 0.01) and requirement for colectomy (P < 0.01). Median cumulative corticosteroid use over 12 months inclusive of index hospitalization was 1760 mg (IQR 1560-2350 mg). Requirement for inpatient medical salvage therapy with infliximab was associated with increased corticosteroid requirement (P = 0.01). Conclusion: Healthcare expense related to ASUC remains high, driven predominantly by the length of stay during initial hospitalization and need for colectomy. From a healthcare cost perspective, novel methods to reduce inpatient hospital stay as well as need for colectomy may help reduce the economic and steroid burden of ASUC.

Network meta-analysis: efficacy and safety of treatments for fistulising Crohn's disease.

INTRODUCTION: Fistulas are a debilitating complication of Crohn's disease and treatment options remain limited. There is a lack of head-to-head comparisons between treatments. To our knowledge, this is the first network meta-analysis on the efficacy of medical therapies in achieving fistula remission and maintenance of fistula closure in Crohn's disease. METHODS: Biomedical databases and the Cochrane Central Registry were searched between 1978 and 2022 for randomized controlled trials (RCTs) reporting on treatments. A network meta-analysis was performed using the frequentist model with pooled relative risks (RRs) and P -scores used to rank treatments. RESULTS: Twenty-five RCTs were included for analysis with 2239 patients included. At the 16-24 week time point, infliximab produced the only statistically significant result with the 5 mg/kg dose proving the most effective [RR, 2.30; 95% confidence interval (CI), 1.40-3.77]. At 44 weeks, ustekinumab was found to be most superior with it being 2.38 times (RR, 2.38; 95% CI, 1.24-4.56) more superior to placebo, with adalimumab (RR, 2.06; 95% CI, 1.06-3.99) and infliximab 5 mg/kg (RR, 1.68; 95% CI, 1.03-2.75) also producing a statistically significant result. CONCLUSION: Despite infliximab being favoured in international guidelines for the treatment of perianal fistulising Crohn's disease, biologics such as ustekinumab, vedolizumab and adalimumab show promising results.

Biologics recommendations in the ECCO guidelines on therapeutics in Crohn's disease: medical treatment.

In 2019, the European Crohn's and Colitis Organisation released guidelines for the medical management of Crohn's disease, concerning the induction of remission, the maintenance of remission and the treatment of fistulising perianal disease. This review summarises the key recommendations regarding the use of biologics in these settings.