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Re: Unmet needs for IBS therapies

Dear Editor,

We have read with great interest the recent manuscript published in GUT by Professor Tack and colleagues entitled “A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation (IBS-C)”.[Tack et al. 2005] To date, this is the largest clinical trial assessing the efficacy and safety of repeated tegaserod therapy in women with IBS-C. Furthermore, it is currently the only published trial to address the recent guidelines from the CHMP (formerly known as the CPMP, and the following article is published under this name) regarding the design and performance of IBS therapies for short-term, repeated treatment.[CPMP 2003]

Data from this large, placebo-controlled trial demonstrate that tegaserod provides relief of overall symptoms of IBS, and relief of individual IBS symptoms including abdominal pain, bloating and constipation. The effects of tegaserod were rapid, being significantly greater than placebo during the first week of treatment, and were sustained throughout the duration of treatment. Patients who experienced symptom recurrence following cessation of initial treatment received a further cycle of tegaserod or placebo. It is noteworthy that tegaserod appeared even more effective at alleviating patients’ IBS symptoms during retreatment, the effect being approximately 16% greater than observed with placebo for both overall IBS-C symptoms and abdominal pain relief. This finding is of considerable importance given that IBS is a chronic, intermittent disorder, and therefore, likely to require long-term, intermittent therapy.

Most physicians in Europe agree that IBS is not adequately treated, if indeed it is treated at all. The therapies IBS-C patients in Europe generally receive include antispasmodics, unspecified stool softeners, or laxatives, coupled with dietary recommendations. While some patients’ symptoms are managed effectively by such means, others feel their symptoms are not properly addressed. Furthermore, the safety and efficacy of many of these agents have not been established in clinical trials, and some are associated with side effects that exacerbate other symptoms of IBS, such as increased bloating and abdominal pain.[Brandt et al. 2002] Given the multiple symptoms that IBS patients experience, based on the complex aetiology of this disorder, it is quite clear that the needs of some patients with IBS cannot be met satisfactorily by simple measures such as bulking agents and reassurance.

Consequently, it is fortunate that this study,[Tack et al. 2005] together with clinical experiences in countries where tegaserod is available, show that previously unmet needs of IBS-C patients can be significantly improved by intermittent cycles of tegaserod therapy during symptom relapse. Firstly, the most intriguing clinical symptoms of IBS-C, namely abdominal pain and discomfort, can be significantly improved by a relatively short period of treatment. Secondly, patients experience sustained improvements in bowel movement frequency and associated constipation problems. Thirdly, additional positive clinical effects can be observed, including relief of long-term symptoms such as bloating, and improvements in patients’ satisfaction with treatment, work productivity and quality of life (QoL) following treatment with tegaserod. These observations are of considerable importance, given the substantial burden IBS places on sufferers’ QoL and their daily activities.

From the patient´s point of view, these data suggest a clear-cut advance in the complicated and frequently undertreated clinical setting of IBS, at least for a large subgroup of women with IBS-C-like symptoms. The publication of these data is welcomed as it gives valuable information on the efficacy of this new treatment in a setting relevant to clinical practice.

The efficacy and safety data from this large trial, together with other international clinical trials and the post-marketing experience, (tegaserod was first licensed in the US in 2002 and is currently approved for IBS-C in over 50 countries), demonstrate that tegaserod offers considerable benefits to patients. It has a scientifically established efficacy with a favourable safety profile. Even by using a very critical appraisal, a growing number of clinical researchers and IBS experts agree that this pharmacologic treatment should also be made available in the European Union, where it will resolve at least some of the unmet needs that the majority of patients with IBS-C experience. The efficacy and safety of tegaserod, together with the improvements observed in patients’ treatment satisfaction, work productivity, and QoL following treatment, strongly call for licensing of the drug by the CHMP. Licensing of this drug may also help to reduce the use of multiple, suboptimal agents, which do not have established safety profiles, in this patient population.

References

Brandt LJ, Bjorkman D, Fennerty B, Locke R, Olden K, Peterson W, Quigley E, Schoenfield P, Schuster M Talley N. Systematic review on the management of irritable bowel syndrome in North America. Am J Gastroenterol 2002;97 (11 Suppl):S7–S26.

CPMP. Points to consider on the evaluation of medicinal products for the treatment of irritable bowel syndrome. 2003;(CPMP/EWP/785/97).