Portal de Periódicos da CAPES

Natural History of Severe Ulcerative Colitis in a Community-Based Health Plan

2008; Elsevier BV; Volume: 6; Issue: 9 Linguagem: Inglês

10.1016/j.cgh.2008.05.022

1542-7714

J. Allison, Lisa J. Herrinton, Liyan Liu, Jenny L. Yu, James N. Lowder,

Helicobacter pylori-related gastroenterology studies

Background & Aims: We sought to evaluate long-term outcomes of patients with severe ulcerative colitis (UC) after their first hospitalization for the disease. Methods: A cohort of 656 patients hospitalized for UC during 1996 to 2004 was followed up for 9 years through 2004. Time-to-event was estimated using actuarial methods, and the proportions of those under follow-up evaluation who experienced outcomes at month 3, year 1, and year 5 were determined. Outcome measures studied were time to subsequent colectomy, rehospitalization for inflammatory bowel disease, and restarting steroid medication. We also used survival analysis to evaluate whether patient characteristics predicted the risk of rehospitalization and colectomy. Results: Among 656 patients initially hospitalized for severe UC, 20% (N = 129) underwent colectomy during their initial hospitalization. Of the remaining 527, a total of 95% (N = 498) were discharged on a steroid taper. At 1 year after discharge, 29% of those remaining under observation were rehospitalized for UC, and an additional 10% required colectomy. At 1 and 5 years after discharge, 34% and 26% received at least a 90-day supply of steroid in the preceding 9 months. Risk of rehospitalization and colectomy were unrelated to the patient's age, sex, or race/ethnicity. Conclusions: The risk for colectomy in patients hospitalized for the first time with severe UC is 20%. In the 3 months after hospitalization the risk for colectomy is 6%. After that, risks appear to decrease proportionate to the time since initial hospitalization. Background & Aims: We sought to evaluate long-term outcomes of patients with severe ulcerative colitis (UC) after their first hospitalization for the disease. Methods: A cohort of 656 patients hospitalized for UC during 1996 to 2004 was followed up for 9 years through 2004. Time-to-event was estimated using actuarial methods, and the proportions of those under follow-up evaluation who experienced outcomes at month 3, year 1, and year 5 were determined. Outcome measures studied were time to subsequent colectomy, rehospitalization for inflammatory bowel disease, and restarting steroid medication. We also used survival analysis to evaluate whether patient characteristics predicted the risk of rehospitalization and colectomy. Results: Among 656 patients initially hospitalized for severe UC, 20% (N = 129) underwent colectomy during their initial hospitalization. Of the remaining 527, a total of 95% (N = 498) were discharged on a steroid taper. At 1 year after discharge, 29% of those remaining under observation were rehospitalized for UC, and an additional 10% required colectomy. At 1 and 5 years after discharge, 34% and 26% received at least a 90-day supply of steroid in the preceding 9 months. Risk of rehospitalization and colectomy were unrelated to the patient's age, sex, or race/ethnicity. Conclusions: The risk for colectomy in patients hospitalized for the first time with severe UC is 20%. In the 3 months after hospitalization the risk for colectomy is 6%. After that, risks appear to decrease proportionate to the time since initial hospitalization. See Porter CK et al on page 781 for the companion article in the September 2008 issue of Gastroenterology. See Porter CK et al on page 781 for the companion article in the September 2008 issue of Gastroenterology. The clinical course of ulcerative colitis (UC) has been described. However, most of the information is based on studies performed before the advent of immune modulator or biologic therapy.1Moum B. Ekbom A. Vatn M.H. et al.Clinical course during the 1st year after diagnosis in ulcerative colitis and Crohn's disease.Scand J Gastroenterol. 1997; 32: 1005-1012Crossref PubMed Scopus (159) Google Scholar, 2Kornbluth A. Lichtiger S. Present D. et al.Long-term results of oral cyclosporine in patients with severe ulcerative colitis: a double-blind, randomized multicenter trial.Gastroenterology. 1994; 106: A714Google Scholar, 3Langholz E. Munkholm P. Davidsen M. et al.Course of ulcerative colitis: analysis of changes in disease activity over years.Gastroenterology. 1994; 107: 3-11Abstract PubMed Google Scholar, 4Selby W. The natural history of ulcerative colitis.Baillieres Clin Gastroenterol. 1997; 11: 53-64Abstract Full Text PDF PubMed Scopus (32) Google Scholar, 5Hiwatashi N. Yao T. Watanabe H. et al.Long-term follow-up study of ulcerative colitis in Japan.J Gastroenterol. 1995; 30: 13-16PubMed Google Scholar Information of this kind could be important for planning patient follow-up evaluation and anticipating demands and costs of health services. However, incomplete case records and trends toward improved endoscopic evaluation limit the older studies' usefulness to today's investigators.1Moum B. Ekbom A. Vatn M.H. et al.Clinical course during the 1st year after diagnosis in ulcerative colitis and Crohn's disease.Scand J Gastroenterol. 1997; 32: 1005-1012Crossref PubMed Scopus (159) Google Scholar New therapies now available and some in development may alter the natural history of severe UC and prevent hospitalizations or the need for colectomy.2Kornbluth A. Lichtiger S. Present D. et al.Long-term results of oral cyclosporine in patients with severe ulcerative colitis: a double-blind, randomized multicenter trial.Gastroenterology. 1994; 106: A714Google Scholar, 6Jarnerot G. Hertervig E. Friis-Liby I. et al.Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.Gastroenterology. 2005; 128: 1805-1811Abstract Full Text Full Text PDF PubMed Scopus (941) Google Scholar, 7Loftus C.G. Egan L.J. Sandborn W.J. Cyclosporine, tacrolimus, and mycophenolate mofetil in the treatment of inflammatory bowel disease.Gastroenterol Clin North Am. 2004; 33: 141-169Abstract Full Text Full Text PDF PubMed Scopus (34) Google Scholar Colectomy may be associated with significant morbidity, both psychologic and physical, so knowledge of the clinical course of severe UC is important to patients, their families, clinicians, and to those who are looking for therapies that might prevent this outcome. The subsequent natural history of patients with disease severe enough to require hospitalization is not well understood. The specific aim of our study was to determine the clinical course and long-term outcomes of patients with UC after their first hospital admission for severe disease. We further sought to identify whether patient characteristics predicted poor outcomes. We selected patients with an initial hospitalization because this event provides a clearly defined time point for the physician to assess disease, make treatment decisions, and characterize outcomes. We conducted a retrospective cohort study of 656 members of Kaiser Permanente hospitalized with severe UC from 1996 to 2004 and were able to follow their clinical course for up to 9 years after first hospitalization. Outcomes assessed included prolonged steroid use, rehospitalization, and colectomy at initial hospitalization, 3 months, and 1 and 5 years after hospitalization. Kaiser Permanente is a private, nonprofit, group-model health maintenance organization that provides integrated medical care to 30% of the population of metropolitan San Francisco and Sacramento as well as less urbanized areas of northern California. Kaiser members have been compared with persons living in the Kaiser Permanente service area who were insured or uninsured, but whose insurance was not with Kaiser Permanente. Compared with the underlying population of non–Kaiser Permanente insured, the Kaiser Permanente membership has greater racial diversity, lower income, lower education, fewer smokers, and more obesity. Compared with the underlying population of non–Kaiser Permanente uninsured, it has similar racial diversity, although with fewer Latinos, higher income, greater education, and fewer smokers (data available: http://www.dor.kaiser.org/dor/mhsnet/public/Kaiser_Permanente_community.htm, accessed February 4, 2008.) The retrospective cohort study included Kaiser Permanente members of all ages who were included into our Inflammatory Bowel Diseases Registry. Eligibility criteria for the study were as follows: (1) hospitalization at Kaiser Permanente during the period from 1996 to 2004, with no prior hospitalization recorded during 1979 to 1995; (2) a principle diagnosis of UC (International Classification of Diseases 9th revision [ICD-9] code 556) or a principle diagnosis of noninfectious gastroenteritis or colitis (ICD-9 code 558) with an admitting diagnosis of UC (ICD-9 code 556); and (3) use of intravenous steroids at initial hospitalization, with this criterion being used to increase the probability that the hospitalization was for disease unresponsive to outpatient therapy and not for the surgical treatment or prophylaxis of colorectal cancer. We assessed the following outcomes: (1) rehospitalization owing to UC, (2) colectomy at or after the initial UC hospitalization, (3) successful tapering from steroid medication, and (4) prolonged steroid exposure and an inability to wean off steroids or the necessity to restart steroid medication after tapering. Patients were followed up for outcomes until colectomy, disenrollment from the health plan, their 90th birthday, or death. Rehospitalization was defined using the same criteria as in the previous “Study Population” section: a principle diagnosis of UC (ICD-9 code 556) or principle diagnosis of noninfectious gastroenteritis or colitis (ICD-9 code 558) with an admitting diagnosis of UC (ICD-9 code 556). We further required a course of intravenous steroids during the hospitalization. Again, we required a course of intravenous steroids during the initial and subsequent hospitalization to increase the probability that all colectomies performed during these hospitalizations were for severe UC unresponsive to medications or for complications of severe UC such as toxic megacolon, perforation, or uncontrolled bleeding. Restarting steroid medication was examined only in persons who had tapered from steroids within 6 months of discharge from the initial hospitalization. Tapering was defined as documentation of no steroid use for 31 days or longer after discharge on steroids. The 31st day was used as the taper date. Rehospitalization was counted only if the principle or admitting diagnosis was UC, with the admission date serving as the event date. All information on UC, hospitalizations, procedures, pharmacy dispensing, laboratory tests, enrollment, and death, as well as patient characteristics, was ascertained through linkage of computerized administrative databases and clinical information obtained from chart review. Hospitalizations and colectomy procedures were identified from the computerized hospitalization file of admissions, discharges, and transfers that provides up to 13 diagnoses and 13 procedure codes for each hospitalization together with the date of admission and discharge. Length of stay in the hospital was calculated. Both partial (ICD-9 45.7) and total colectomy (ICD-9 45.8) were ascertained. We reviewed the computerized narrative pathology report to verify the diagnosis of severe UC for those patients who underwent a surgical procedure and to verify the procedure. In most patients, the surgical procedure involved removal of the rectum, colon, and a small portion of the terminal ileum; however, in a small number of patients, the rectum was spared. In several instances, the colectomy was a 2-stage procedure, in which case we coded the procedure as occurring on the date of the first surgery. Dispensing for outpatient medications associated with treatment of UC were ascertained from clinical pharmacy data (both inpatient and outpatient systems). The medications included steroids, mesalamine, sulfasalazine, 6-mercaptopurine, azathioprine, methotrexate, cyclosporine, and infliximab. For the outpatient medications, information included dates, preparations, and how many days for which the medication was supplied. For the inpatient medications, a start date was identified. We included drugs administered through intramuscular, intravenous, oral, and rectal routes. The computerized pharmacy data are essential for providing patient care and are highly reliable. Laboratory measures included the white blood cell count, as well as hemoglobin and serum albumin levels; these were obtained from computerized laboratory data that are essential for patient care. Patient age, sex, and length of enrollment were obtained from administrative membership data and the hospitalization record. We calculated the proportion of hospitalized patients who underwent colectomy during their initial hospitalization. Among those who did not, we also examined the proportion of patients who were rehospitalized and who underwent colectomy as a result of UC at 3 months, and at 1 and 5 years. In addition, we examined outpatient inflammatory bowel disease drug supply during the year before initial hospitalization, during the initial hospitalization, in the 3-month period immediately after discharge, and at years 1 and 5. The proportion of patients experiencing outcomes and their 95% confidence intervals were calculated using Kaplan–Meier plots using SAS software (SAS, Cary, NC). The relationship of patient characteristics (age, sex, and race/ethnicity) with risk of rehospitalization and colectomy was determined using survival analysis,8Kalbfleisch J.D. Prentice R.L. Estimation of the average hazard ratio.Biometrika. 1981; 68: 105-112Crossref Scopus (72) Google Scholar with year of initial hospitalization evaluated as a potential confounding variable. Follow-up evaluation began on the date of discharge. Event times for the Kaplan–Meier plots were defined as described earlier. Patients were censored on the earliest of the following dates: (1) their 90th birthday, (2) the date of disenrollment from the health plan, (3) the date of colectomy, (4) the date of death, or (5) December 31, 2004. Demographic characteristics of the patients are shown in Table 1. The study population was evenly distributed between men and women, with the number of hospitalizations slightly increasing every year (as did the level of membership). Among 656 patients initially hospitalized for severe UC, the average white blood count was 11.9 × 109 cells/L (SD, 5.0 × 109 cells/L) and the average hemoglobin level was 11.5 g/dL (SD, 2.3 g/dL), with 37.2% of patient having high white blood counts and 57.6% having low hemoglobin levels. Among the 53% with an albumin measurement, the average level was 2.7 g/dL (SD, 0.7 g/dL), with 87.4% having low albumin. Among the 656 patients, 20% (N = 133) underwent colectomy during the initial hospitalization. Three patients had no subsequent follow-up information. Of the 527 who were discharged, a total of 95% (N = 498) were discharged on steroid taper. Among these 527, 35% were followed up for less than 1 year before censoring or colectomy and 25% were followed up for 4 years or longer.Table 1Demographic Characteristics Among 656 Kaiser Permanente Members With UC Who Were Hospitalized for Glucocorticoid Therapy (1996–2004)N = 656N%Age at first hospitalization for UC, y 0–2915423.5 30–4926340.1 50–8923936.4Sex Male32850.0 Female32850.0Race/ethnicity, mean across block group Caucasian47272.0 African American396.0 Asian/Pacific Islander406.0 Hispanic8513.0 Other/unknown race203.0Year of first hospitalization of UC 1996–199815623.8 1999–200121933.4 2002–200428142.8White blood count at initial hospitalizationaFor 10 patients, there was no white blood count; for 7 patients there was no hemoglobin level; and for 308 patients there was no albumin level recorded. Normal (3.5–12.5 per 109cells/L)39861.6 High24037.2 Low81.2Hemoglobin level at initial hospitalizationaFor 10 patients, there was no white blood count; for 7 patients there was no hemoglobin level; and for 308 patients there was no albumin level recorded. Normal (male, 13.0–17.0 g/dL; female, 11.5–15.0 g/dL)26941.5 High60.9 Low37457.6Albumin level at initial hospitalizationaFor 10 patients, there was no white blood count; for 7 patients there was no hemoglobin level; and for 308 patients there was no albumin level recorded. Normal (3.3–4.7 g/dL)4412.6 Low30487.4Length of follow-up evaluation after initial hospitalization, ybAmong 527 with an intact colon after the initial hospitalization. <113525.6 1–216831.9 2–410820.5 4–67113.5 6–9458.5Length of stay of initial hospitalization, d Mean (SD)9.0 (9.3) 25th percentile3 50th percentile6 75th percentile11 90th percentile19 95th percentile26a For 10 patients, there was no white blood count; for 7 patients there was no hemoglobin level; and for 308 patients there was no albumin level recorded.b Among 527 with an intact colon after the initial hospitalization. Open table in a new tab Inpatient and outpatient drug use before, during, and after surgery is shown in Table 2. Before the initial hospitalization, 69% of patients used aminosalicylates, and among users the average supply during the 12 months before hospitalization was 212 days. Also during this time period, 16% used immune modulators (average supply among users, 193 days), and 67% used steroids (average supply among users, 153 days). During the initial hospitalization, 2% received cyclosporine; 2% received off-label use of infliximab.Table 2Drug Supply Preceding and During the IBD Hospitalization, and at Selected Time Points Thereafter, 656 Kaiser Permanente Members With UC Who Were Hospitalized for Severe UC (1996–2004)IBD-related drugAny use in the 12 mo before initial hospitalization for IBD (N = 656), %Any use during the initial IBD hospitalization (N = 656), %aDrug supply during hospitalization included both inpatient and outpatient prescriptions. Other time periods were considered as outpatient prescriptions only.Any use 0–3 mo after discharge (N = 527), %bExcludes patients who died, disenrolled, had their 90th birthday, or underwent colectomy before the interval.Any use 3–12 mo after discharge (N = 452), %bExcludes patients who died, disenrolled, had their 90th birthday, or underwent colectomy before the interval.Any use 4–5 y after discharge (N = 131), %bExcludes patients who died, disenrolled, had their 90th birthday, or underwent colectomy before the interval.None20051530Aminosalicylates6961787256Immune modulators1614252923SteroidscIncludes oral, rectal, and subcutaneous routes of administration.6799915838Steroids, 90+ d44N/A393426Cyclosporine02110Infliximab02110IBD, inflammatory bowel disease; N/A, not applicable.a Drug supply during hospitalization included both inpatient and outpatient prescriptions. Other time periods were considered as outpatient prescriptions only.b Excludes patients who died, disenrolled, had their 90th birthday, or underwent colectomy before the interval.c Includes oral, rectal, and subcutaneous routes of administration. Open table in a new tab IBD, inflammatory bowel disease; N/A, not applicable. Of the 527 patients free of colectomy who were followed up after their initial hospitalization, 480 (91%) were discharged on steroid taper. Of these, 293 successfully tapered within the first year (272 of whom tapered within the first 6 months). However, 82% (N = 224 of 272) of them had to restart steroids during the latter half of the first year, and at 1 year after discharge 58% of patients under observation had used steroids during the previous 9 months, 34% of these having been dispensed a supply of 90 days or more over the course of the preceding 9 months. At year 5 the proportion of patients on corticosteroids was 38%, with 26% having received a supply of 90 days or more during the preceding year (Table 2). During the first 3 months after discharge, 21% of the 527 patients under observation were rehospitalized, and an additional 6% required colectomy (Figure 1 and Table 3). By 1 year after discharge, 29% were rehospitalized, and an additional 10% required colectomy. At 5 years, rehospitalization increased to 39%, with an additional 15% requiring colectomy.Table 3Outcomes at 3 Months, 12 Months, and 5 Years, Kaiser Permanente Members With UC Who Were Hospitalized for Severe UC (1996–2004) and Discharged With an Intact ColonEventFollow-up periodInitial hospitalization3 mo12 mo5 yNumber observed at start of period656527505505Number observed at end of period527505505252Number rehospitalized during period (%)aThe percentage is relative to the number who entered follow-up evaluation at the beginning of the follow-up period (shown in the column heading).—100 (21%)146 (29%)197 (39%)Number with a colectomy during period (%)aThe percentage is relative to the number who entered follow-up evaluation at the beginning of the follow-up period (shown in the column heading).131 (20%)32 (6%)51 (10%)76 (15%)a The percentage is relative to the number who entered follow-up evaluation at the beginning of the follow-up period (shown in the column heading). Open table in a new tab In multivariable modeling, we observed no effect of age, sex, or race/ethnicity on risk of rehospitalization or colectomy (Table 4).Table 4Predictors of Rehospitalization and Colectomy, 656 Kaiser Permanente Members With UC Who Were Hospitalized for Severe UC (1996–2004)*VariableColectomyRehospitalizationRelative risk95% CIP valueRelative risk95% CIP valueAge, per year1.000.98–1.01.541.000.99–1.00.33Men1.00Reference—1.00Reference—Women0.960.62–1.50.870.960.74–1.23.72White1.00Reference—1.00Reference—Black1.130.48–2.64.780.900.52–1.55.70Hispanic0.790.39–1.59.510.890.76–1.56.65Asian0.530.17–1.69.280.700.38–1.28.25Other race0.390.05–2.79.351.270.62–2.57.52CI, confidence interval. Open table in a new tab CI, confidence interval. There is abundant literature on the colectomy rate of patients with UC whose disease requires hospitalization and administration of inpatient corticosteroid therapy, but the number of patients studied in each was small (N = 13–189) and the follow–up was short term.9Turner D. Walsh C.M. Steinhart A.H. et al.Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression.Clin Gastroenterol Hepatol. 2007; 5: 103-110Abstract Full Text Full Text PDF PubMed Scopus (476) Google Scholar Our study's strengths include its large size and its very long follow-up period. It found that such patients are at increased risk for colectomy at first hospitalization. For those who are discharged with their colon, prolonged steroid exposure, rehospitalization for failure of medical treatment, and subsequent colectomy are common within the first 3 months after hospitalization. Actuarial risk estimates for outcomes as we have presented in Figure 1 have been reported in only one other study.3Langholz E. Munkholm P. Davidsen M. et al.Course of ulcerative colitis: analysis of changes in disease activity over years.Gastroenterology. 1994; 107: 3-11Abstract PubMed Google Scholar We further evaluated the role of patient characteristics in risk of colectomy and rehospitalization, observing no evidence for a relationship. The key strengths of the study were as follows: (1) the community-based setting; (2) the study size and up to 9 years of follow-up evaluation; (3) the stability of the population, including those on Medicare; (4) the availability of electronic records to obtain detailed information on UC, hospitalizations, and drugs; and (5) generalizability to the population of northern California. The limitations of the study were that it was retrospective and based on computerized data. Some of our study patients may not have been severely ill, although we were able to review the underlying diagnosis for those patients who underwent surgical procedures. To the extent we included patients with mild disease, our study may have underestimated the risk of outcomes. Also, because the findings were determined from clinical databases and not from chart review, we do not have information on the nature of the patients' UC, the extent of disease in those who did not undergo surgery, or symptoms, and our information on medications was limited to the time period from 1994 onward. Finally, there likely was some misclassification of disease, although this was minimal. Regarding our effort to evaluate risk factors for colectomy and rehospitalization, observational studies are poor for assessing the relationship of clinical variables (such as laboratory measures) or medication use with subsequent outcomes because of confounding by severity of disease, with severity being associated both with the decision to admit or treat the patient, as well as with the outcomes.10Petri H. Urquhart J. Channeling bias in the interpretation of drug effects.Stat Med. 1991; 10: 577-581Crossref PubMed Scopus (194) Google Scholar Only 16 % of the patients in this study were treated with immune-modulating drugs such as azathioprine or 6-mercaptopurine during the 12 months before their index hospitalization. In our community setting, the usefulness of immunomodulators in steroid-resistant UC was perhaps slower to be recognized and accepted. The patients in this study were unresponsive to glucocorticoids by definition. It is unknown whether prior use of immunomodulator predicts for the incidence of colectomy during a hospitalization for refractory disease. It would appear from the short- and long-term outcomes in this study that our patient population was of similar severity to those reported in other studies. Selby4Selby W. The natural history of ulcerative colitis.Baillieres Clin Gastroenterol. 1997; 11: 53-64Abstract Full Text PDF PubMed Scopus (32) Google Scholar points out that the proportion of patients requiring colectomy varies among studies, from about 15% to 40% or higher, and speculated that the highest rates were in those centers where the patient has been referred for surgery or drug-resistant disease. A Norwegian study published in 200611Henriksen M. Jahnsen J. Lygren I. et al.Ulcerative colitis and clinical course: results of a 5-year population-based follow-up study (the IBSEN study).Inflamm Bowel Dis. 2006; 12: 543-550Crossref PubMed Scopus (214) Google Scholar reported a colectomy rate in 454 patients of 7.5% over 5 years of follow-up evaluation, but the patients studied were a cohort of UC patients with variable disease activity and extent of disease. Only 7% of these patients were on steroids and only 4% were on azathioprine. A population-based study from Sweden and another from Denmark both estimated a cumulative colectomy risk of 20% after 5 years in their populations.12Leijonmarck C.E. Persson B.G. Hellers G. Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.Gut. 1990; 31: 329-333Crossref PubMed Scopus (174) Google Scholar The Langholz et al3Langholz E. Munkholm P. Davidsen M. et al.Course of ulcerative colitis: analysis of changes in disease activity over years.Gastroenterology. 1994; 107: 3-11Abstract PubMed Google Scholar study reported a cumulative colectomy rate of 24% at 10 years after diagnosis, but a 9% rate in the year of diagnosis, 3% per year in the following 4 years, and a trend toward a more benign course with increasing disease duration in the noncolectomy patients. The indication for surgery was failure of medical treatment in 98% of their patients. A recent systematic review of the literature and meta-analysis reported that the short-term colectomy rate in severe UC has remained stable at about 27%.9Turner D. Walsh C.M. Steinhart A.H. et al.Response to corticosteroids in severe ulcerative colitis: a systematic review of the literature and a meta-regression.Clin Gastroenterol Hepatol. 2007; 5: 103-110Abstract Full Text Full Text PDF PubMed Scopus (476) Google Scholar The 26% colectomy rate observed in this study for the first 3 months after admission is consistent with this number. Outcomes in UC and Crohn's disease were reported from Olmsted County, Minnesota, where residents were diagnosed during 1970 to 1993 and were followed up for 1 year after an initial treatment with corticosteroids.13Faubion W.A. Loftus E.V. Harmsen W.S. et al.The natural history of corticosteroid therapy for inflammatory bowel disease: a population-based study.Gastroenterology. 2001; 121: 255-260Abstract Full Text Full Text PDF PubMed Scopus (1036) Google Scholar It is difficult to compare those results with ours because there were significant differences in study design and the populations studied. In most of the Olmsted County patients the steroids were administered orally. The total number of UC patients studied was only 183, and only 63 (34%) required any corticosteroid therapy. In those that did, 18 (29%) required surgery within the first year of treatment, remarkably similar to the percentage requiring surgery in our study (30%). Our acute and 1-year colectomy rates (20% and 30%, respectively) were consistent with what might be expected in a cohort of severely ill patients requiring intravenous inpatient corticosteroid therapy. Our study was performed in a prepaid, integrated, health care organization without a special referral center for those with the most severe disease. Our results are most representative of what one would find in a culturally diverse, community health care setting. Only 16% received prior immunomodulators. Only 2% were treated as inpatients with cyclosporine and 2% with infliximab. The study period antedated articles showing the potential usefulness of infliximab as rescue therapy in severe to moderately severe UC.6Jarnerot G. Hertervig E. Friis-Liby I. et al.Infliximab as rescue therapy in severe to moderately severe ulcerative colitis: a randomized, placebo-controlled study.Gastroenterology. 2005; 128: 1805-1811Abstract Full Text Full Text PDF PubMed Scopus (941) Google Scholar Despite the continued need for glucocorticoid therapy, the risk for colectomy decreased over time from initial hospitalization (Figure 1), a finding widely reported in the literature.5Hiwatashi N. Yao T. Watanabe H. et al.Long-term follow-up study of ulcerative colitis in Japan.J Gastroenterol. 1995; 30: 13-16PubMed Google Scholar, 12Leijonmarck C.E. Persson B.G. Hellers G. Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study.Gut. 1990; 31: 329-333Crossref PubMed Scopus (174) Google Scholar The number of patients in our study who were steroid-dependent also was large. The 59% successful taper rate for patients discharged with their colons intact looked good but 83% of them had to restart within 1 year and 35% required rehospitalization. The use of infliximab was limited (2%) in our study population but use of other immune modulators was 16% before hospitalization and increased to 29% in the 1 year after hospitalization. It is unclear whether a subset of UC patients could be so severe that medical management may never succeed. Strategies to manage those patients who become acutely ill and resistant to glucocorticoids are clearly necessary. In this study, 70% of colectomies occurred during the first acute hospitalization. Better agents for treatment of intravenous steroid-refractory disease are necessary. In addition, management of patients who are discharged after this initial hospitalization with their colons intact must be focused on steroid-sparing regimens. The natural history of the disease may reduce in intensity over time if the patient's colon can be preserved. In conclusion, UC is a disease of variable severity and course. Disease activity requiring hospitalization for inpatient intravenous administration of corticosteroids is a marker of poor prognosis. The development of more immune-modulator or biologic therapy targeted to such patients would be a welcome addition to the clinician's armamentarium.