Correspondence
Infliximab for Ulcerative Colitis
N Engl J Med 2006; 354:1424-1426March 30, 2006
- Article
To the Editor:
As Rutgeerts et al. mention in their article about infliximab for ulcerative colitis (Dec. 8 issue),1 nocturnal fecal incontinence in patients who have an ileoanal pouch is, indeed, an “inconvenience” that is reminiscent of their presurgery symptoms of colitis (but without the debilitating disease). However, Hahnloser et al. do not state the overall prevalence as 24 percent.2 Their data actually show that the proportion of patients with more than two episodes of nocturnal staining per week was 5 percent. The proportion increased to 24 percent only after 15 years, by which time the population had aged to a mean of 50 years and included patients up to 77 years of age. This increase mainly reflected postpartum and senescent decline in sphincter strength3-5 in a population that was 50 percent female and included patients 10 to 30 years older than those in the trial of Rutgeerts et al.
There is little to recommend changes in practice on the basis of this trial, considering that half the data are short term. Only one third of the patients achieved remission, approximately 10 to 24 percent had a serious adverse event, and long-term safety is not known. The cumulative risks and financial burden would be considerable for these young patients.
5 ReferencesConor J. Shields, M.D.
Desmond C. Winter, M.D.
University College Dublin, Dublin 00004, Ireland
dwinter@eircom.net 1
Rutgeerts P ,Sandborn WJ ,Feagan BG , et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med 2005;353:2462-2476
Full Text | Web of Science | Medline2
Hahnloser D ,Pemberton JH ,Wolff BG ,Larson DR ,Crownhart BS ,Dozois RR . The effect of ageing on function and quality of life in ileal pouch patients: a single cohort experience of 409 patients with chronic ulcerative colitis. Ann Surg 2004;240:615-623
Web of Science | Medline3
McHugh SM ,Diamant NE . Effect of age, gender, and parity on anal canal pressures: contribution of impaired anal sphincter function to fecal incontinence. Dig Dis Sci 1987;32:726-736
CrossRef | Web of Science | Medline4
Sultan AH ,Kamm MA ,Hudson CN ,Thomas JM ,Bartram CI . Anal-sphincter disruption during vaginal delivery. N Engl J Med 1993;329:1905-1911
Full Text | Web of Science | Medline5
Ryhammer A ,Laurberg S ,Sorensen FH . Effects of age on anal function in normal women. Int J Colorectal Dis 1997;12:225-229
CrossRef | Web of Science | Medline
To the Editor:
Although Rutgeerts et al. highlight a new use of infliximab, for ulcerative colitis, they misrepresent the outcomes of total proctocolectomy with ileal pouch–anal anastomosis as a curative option by citing unrealistically high rates of pouchitis1 and pouch failure2 from decade-old studies. These data from the 1980s do not reflect the technical advances that have resulted in the low rates of complications and high levels of patient satisfaction when the operation is performed by experienced surgeons today.
Our meta-analysis3 and another,4 both involving more than 9200 patients who underwent ileoanal anastomosis with the creation of an ileoanal pouch, show rates of pouchitis (23 percent and 18 percent, respectively) and pouch failure (5 percent and 6.8 percent, respectively) that are substantially lower than those cited by Rutgeerts et al. In our own series of more than 750 patients in whom the procedure was performed by a single surgeon (Dr. Becker), acute pouchitis occurred in 12 percent, chronic pouchitis in 10 percent, and pouch failure in 2 percent.5
The risks associated with the use of infliximab, including death, are considerable, and if medical therapy is compared with surgery, it should not be inferred that ileoanal anastomosis with the creation of an ileoanal pouch is a therapeutic option for which patients cannot expect a satisfactory outcome.
5 ReferencesJames M. Becker, M.D.
Scott G. Prushik, M.D.
Arthur F. Stucchi, Ph.D.
Boston University Medical Center, Boston, MA 02118
james.becker@bmc. org 1
Penna C ,Dozois R ,Tremaine W , et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut 1996;38:234-239
CrossRef | Web of Science | Medline2
McIntyre PB ,Pemberton JH ,Wolff BG ,Beart RW ,Dozois RR . Comparing functional results one year and ten years after ileal pouch-anal anastomosis for chronic ulcerative colitis. Dis Colon Rectum 1994;37:303-307
CrossRef | Web of Science | Medline3
Lehrmann J ,Stucchi AF ,LaMorte WW , et al. Complications and outcomes after ileal pouch−anal anastomosis (IPAA): a meta-analysis of more than 8300 patients. Gastroenterology 2003;124:A814-A814
CrossRef | Web of Science4
Hueting WE ,Buskens E ,van der Tweel I ,Gooszen HG ,van Laarhoven CJ . Results and complications after ileal pouch anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients. Dig Surg 2005;22:69-79
CrossRef | Web of Science | Medline5
Becker JM ,Stucchi AF . Proctocolectomy with ileoanal anastomosis. J Gastrointest Surg 2004;8:376-386
CrossRef | Web of Science | Medline
To the Editor:
The study by Rutgeerts et al. showed a modest but significant effect in the induction and maintenance of remission in patients with moderate-to-severe ulcerative colitis. Patients with active disease despite concurrent therapy with corticosteroids alone or in combination with the immunosupressant azathioprine or mercaptopurine were studied. The real challenge is in the treatment of patients with chronic active ulcerative colitis that is refractory to azathioprine or mercaptopurine. Forty-six percent of the study population was treated with azathioprine or mercaptopurine before inclusion in the study, without success, but it is not shown how many of the patients with disease that was refractory to azathioprine or mercaptopurine responded to the infliximab therapy. Without these data the real therapeutic potential of infliximab in patients with ulcerative colitis is not clear.
Max Reinshagen, M.D.
Klinikum Braunschweig, 38124 Braunschweig, Germany
m.reinshagen@klinikum-braunschweig. de Author/Editor Response
The categorizations of fecal incontinence (i.e., one to two episodes of incontinence per week, more than two episodes per week, or daytime vs. nighttime occurrence) in the study cited by Drs. Shields and Winter, which evaluated the ileal pouch–anal anastomosis procedure in patients with ulcerative colitis,1 do not take into account the effect of fecal incontinence on the quality of life of the patient. The reality is that approximately 25 percent of patients have fecal incontinence at least once weekly and at least 50 percent have a stool frequency exceeding seven bowel movements in 24 hours. Although it can be argued that a decline in sphincter function is related to aging, the authors themselves state that increased fecal incontinence may be a function of the operation, the result of aging, or due to a combination of both factors.1
The letter from Becker et al. cites the study by Hueting et al., which reports a low rate of pouchitis and pouch failure. Other studies of the cumulative frequency of pouchitis, adjusted for time since colectomy, report pouchitis in 40 to 50 percent of patients within 5 years after colectomy, a rate similar to those reported by Hahnloser et al. of 38 percent within 10 years and 47 percent within 15 years after surgery.1,2 Within 10 years after surgery, 53 percent of patients require one or more reoperations for postoperative complications, and 10 percent of patients require pouch excision by 10 years. Despite all these limitations to the ileoanal-pouch procedure, we believe the procedure remains a valuable treatment option for patients. However, now that an acceptably safe and effective medical treatment exists, we believe that all patients with medically refractory ulcerative colitis should be offered both colectomy and infliximab as treatment options.
Dr. Reinshagen inquires about the efficacy of infliximab therapy in patients whose disease is refractory to therapy with azathioprine or mercaptopurine. In the pooled databases of the Active Ulcerative Colitis Trials 1 and 2, the proportions of patients in the infliximab treatment groups who were receiving azathioprine or mercaptopurine and had a clinical response or remission at weeks 8 and 30 (response, 63.4 percent and 53.3 percent, respectively; remission, 26.9 percent and 35.2 percent, respectively) were similar to the proportions of patients who were not receiving azathioprine or mercaptopurine and had a clinical response or remission at weeks 8 and 30 (response, 68.5 percent and 51.8 percent, respectively; remission, 38.5 percent and 31.1 percent, respectively). We conclude that, at both week 8 and week 30, a similar proportion of patients who were treated with infliximab had a clinical response or clinical remission whether or not they were receiving immunomodulators (azathioprine or mercaptopurine) at baseline.
2 ReferencesPaul Rutgeerts, M.D., Ph.D.
University Hospital Gasthuisberg, 3000 Leuven, Belgium
paul.rutgeerts@uz. kuleuven. ac. be William J. Sandborn, M.D.
Mayo Clinic, Rochester, MN 55905Allan Olson, M.D.
Centocor, Malvern, PA 193551
Hahnloser D ,Pemberton JH ,Wolff BG ,Larson DR ,Crownhart BS ,Dozois RR . The effect of ageing on function and quality of life in ileal pouch patients: a single cohort experience of 409 patients with chronic ulcerative colitis. Ann Surg 2004;240:615-623
Web of Science | Medline2
Svaninger G ,Nordgren S ,Oresland T ,Hulten L . Incidence and characteristics of pouchitis in the Kock continent ileostomy and the pelvic pouch. Scand J Gastroenterol 1993;28:695-700
CrossRef | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
C. W. LEES, D. HEYS, G. T. HO, C. L. NOBLE, A. G. SHAND, C. MOWAT, R. BOULTON-JONES, A. WILLIAMS, N. CHURCH, J. SATSANGI, I. D. R. ARNOTT, . (2007) A retrospective analysis of the efficacy and safety of infliximab as rescue therapy in acute severe ulcerative colitis. Alimentary Pharmacology & Therapeutics 26:3, 411-419
CrossRef
