New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond

Table 1 Summary of the literature findings about anti-inflammatory therapies in irritable bowel syndrome

Drug	Ref.	No. of patients	Study design	Outcome
Corticosteroids (prednisolone)	Dunlop et al[24]	29 patients with post-infectious irritable bowel syndrome	Randomized, double-blind, placebo-controlled trial of 3 wk of oral prednisolone, 30 mg/d	Not associated with any significant treatment-related improvement in abdominal pain, diarrhoea, frequency or urgency
Antibiotics (Rifaximin)	Pimentel et al[29]	623 IBS patients in TARGET 1 and 637 IBS in TARGET 2	Phase 3 trials, 14 d with rifaximin 550 mg 3 times daily	Significantly increased the percentage of relief of global IBS symptoms and improved IBS-related bloating and abdominal pain, discomfort, and loose or watery stools, with regard to placebo for up to 10 wk post-treatment
	Target 1 e 2
Antibiotics (norfloxacin)	Ghoshal et al[32]	80 IBS patients evaluate for SIBO	Randomized, double-blind, placebo-controlled trial; patients were randomized to 800 mg/d norfloxacin for 10 d or placebo	Although norfloxacin was more effective at reducing the symptom score at 1 mo among patients with compared with those without SIBO but not placebo, the scores were comparable at 6 mo. Symptoms more often resolved to turn Rome III negative in SIBO patients treated with norfloxacin compared with placebo at 1 mo
Mast cell stabilizers (Ketotifen)	Klooker et al[33]	60 IBS patiens	Case Control study; abarostat study to assess rectal sensitivity before and after 8 wk of treatment and, after the initial barostat, patients were randomised to receive ketotifen or placebo	Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity, but this effect was not observed in normosensitive patients with IBS. Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life
Mast cells stabilizers (DSCG)	Lobo et al[34]		Randomized, double-blind, placebo-controlled trial; with prolonged (6 mo) oral administration of DSCG	Induces Mast Cell-Mediated Recovery of Healthy-Like Innate Immunity Genes Expression Profile in the Jejunal Mucosa
Mast cells stabilizers (ebastin)	Wouters et al[35]	65 IBS patients	Double-blind placebo-controlled trial, after 2-wk run-in period, subjects were assigned randomly to groups ebastine (20 mg/d; n = 28) or placebo (n = 27) for 12 wk	Compared with subjects given placebo, those given ebastine had reduced visceral hypersensitivity, increased symptom relief, and reduced abdominal pain scores
Mesalazine	Barbara et al[39]	185 patients with IBS	A phase 3, multicentre, tertiary setting, randomised, double-blind, placebo-controlled trial in patients with Rome III confirmed IBS. Patients were randomly assigned to either mesalazine, 800 mg, or placebo, three times daily for 12 wk, and were followed for additional 12 wk	Mesalazine treatment was not superior than placebo on the study primary endpoint, but a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy
	Lam et al[40]	136 patients with IBS-D	A double-blind, randomised placebo-controlled trial of 2 g mesalazine twice daily compared with placebo for 3 mo	The authors concluded that mesalazine did not improve abdominal pain, stool consistency or percentage with satisfactory relief compared with placebo during the last 2 weeks’ follow-up, however a post hoc analysis in 13 post-infectious patients with IBS appeared to show benefit but this needs confirmation in a larger group[40]

IBS : Irritable bowel syndrome.