Exposures to oral corticosteroids, azathioprine, or infliximab before admission were independent predictors of colectomy: OR 5.44 (95% CI, 3.03–9.75), OR 2.95 (95% CI, 1.42–6.09), and OR 5.12 (95% CI, 1.36–19.30), respectively. In contrast, receiving an induction dose of infliximab during hospitalization in biologic-naive patients was associated with reduced odds of colectomy: OR 0.28 (95% CI, 0.10–0.77).
In the sensitivity analysis that restricted the study population to the biologics era, previous infliximab use increased the odds of colectomy (OR 6.51; 95% CI, 1.63–26.00), whereas infliximab use in hospital was no longer significant (OR = 0.43; 95% CI, 0.15–1.25).
Optimizing medical therapy in UC is aimed at improving symptoms, preventing complications, and avoiding colectomy.16 Early identification of patients who are at higher risk of colectomy may help guide clinicians in targeting those patients who would require earlier aggressive therapy and more frequent monitoring. In this population-based study, we evaluated factors that may help identify patients at higher risk of colectomy and thus predict worse outcome in patients who require hospitalization for active UC within 3 years of diagnosis.
This is the first population-based study to evaluate clinical predictors of early colectomy among patients with severe UC requiring admission to hospital within 3 years of diagnosis. Overall analysis showed that patients who were males, diagnosed between the ages of 34 to 64 years with pancolitis, were more likely to require early colectomy. Although sex, age, and disease extent cannot be modified, they reflect a patient profile that warrants close monitoring during the early course following diagnosis of UC. Patients exposed to prednisone, azathioprine, and infliximab before hospitalization were more likely to need early colectomy. This suggests that UC patients with fulminant colitis may quickly progress to colectomy. In these cases, earlier introduction of biologics with immunomodulators may be required.
One-third of our population did not receive a course of oral prednisone before their index admission to hospital. This observation reflects the high disease severity of the study population. Patients who were not prescribed prednisone as outpatients were primarily those with UC who were diagnosed at their index hospital admission or who presented directly to the emergency department during their flare. Living in smaller towns or rural areas outside of the Calgary Health Zone increased the odds of colectomy. This finding suggests that those living in underserviced areas or areas requiring transfer to a tertiary care hospital are more likely to require surgery than those who have greater access to specialist care in hospital. The reasons for this could be delayed access to more effective therapy like anti-TNF or longer duration of exposure to steroids before transfer.
In a recent meta-analysis of 20 studies, Dias et al17 showed that gender, hospitalization, extent of UC, requirement for steroids, smoking habits, and CRP were associated with increased risk of colectomy. The studies included were heterogeneous with mixed prospective and retrospective design, and were not restricted to population-based studies. Using the population-based IBSEN data from Norway on patients diagnosed between 1990 and 1994 then followed-up for 10 years, Solberg et al18 showed that age ≤40 years, requirement of systemic steroids, pancolitis, and CRP ≥30 were associated with increased risk of colectomy over a course of 10 years following diagnosis. Our study is different as we report the relatively short-term colectomy outcome; that is, within 3 years of diagnosis.
The risk of colectomy reported in our cohort was relatively high, approaching 58%. This does not reflect the actual rate of colectomy among all patients with UC, which we have previously shown to be lower and decreasing significantly over time.12 A meta-analysis in 2013 revealed that colectomy rates were 4.9%, 11.6%, and 15.6% at 1, 5, and 10 years from diagnosis, respectively.5 Our study population focused on patients with severe disease requiring a hospital admission within 3 years of diagnosis. Among this population, 58% underwent early colectomy; however, this risk decreased throughout the course of study period. This likely reflects improvement in therapy optimization and early intervention based on identifying the risk factors for worse outcome. In addition, improved medical therapy for UC by the introduction of biologics early in the course of steroid, refractory acute severe UC might have contributed to this decrease over time. As our data collection started in 1996, many patients were treated in the pre-biologics era. In a retrospective study which evaluated a cohort of patients admitted with acute severe UC at different periods of time, it was shown that the early colectomy rate was >44% between 1976 and 2000, whereas it was 9.8% between 2000 and 2006.19 In addition, the risk of colectomy is highest in the first few years after diagnosis,12,18 and studies which have reported lower incidence of colectomy included patients with variable disease severity.
Only 7% of patients hospitalized with UC were prescribed infliximab in hospital because our study period spanned 1996 to 2009. Routine prescription of infliximab in our health region started in 2005. In the overall analysis, patients who received induction infliximab during hospitalization had lower risk of proceeding to colectomy; however, this association lost significance when analysis was restricted to the biological era. In part, the loss of significance was due to reduced small sample size. In addition, in the first few years of infliximab use in hospital, induction dosing with rapid dose escalation to 10 mg/kg and dose optimization following measurement of drug levels were not performed. Other studies demonstrated that early introduction of infliximab in the course of refractory severe UC was associated with a reduction in colectomy rates,19–21 even up to 75% reduction in one study.22 Infliximab was found to be effective in significantly reducing the risk of colectomy.12,19,23–27 Rescue therapy with infliximab has preferential outcome in terms of lower colectomy risk for longer follow up.25 Nonresponders to infliximab rescue therapy, however, were shown to have worse outcomes.28,29
In our study, smoking status did not influence the need for early colectomy. This is in agreement with the findings of the IBSEN study as well as others,30,31 which demonstrated no effect of smoking status on risk of colectomy during the first 10 years of UC diagnosis. On the other hand, several other studies demonstrated that smoking status affects the need for a colectomy32–35 with an increased risk of colectomy in nonsmokers and those who quit smoking before their diagnosis with UC. In part, the inconsistencies may be driven by study design, as our population was focused on those with severe UC early in the course of diagnosis.
This study has some limitations. Firstly, a retrospective chart review cannot adequately control for disease severity. Although we evaluated some indirect proxies of disease severity like anemia and pancolitis, other biomarkers (e.g., C-reactive protein) were not reliably measured in our study population. Nonetheless, by restricting our study population to those who were admitted to hospital early after diagnosis, our patients were universally considered to have severe or fulminant colitis. In addition, less than 10% of our cohort was exposed to infliximab because routine prescription of infliximab in UC started in 2006. Further, Berkson's fallacy may be a source of bias in our study population. Study populations arising from hospitalized patients, rather than the general population, may result in a selection bias that leads to a false negative association between a risk factor and a disease. Therefore, the findings of our study should be generalized to hospitalized patients with severe disease, and not to those with milder disease activity and who did not require hospitalization. Further studies with prospective design should be undertaken to validate the predictive clinical factors.
Among patients hospitalized with UC within 3 years of diagnosis, the need for colectomy is high. Importantly, this risk is decreasing across time. The profile of a patient at a higher risk of early colectomy includes middle-aged men with pancolitis, a finding that clinicians can use for risk stratification at diagnosis of UC. As well, patients from rural areas had higher odds of colectomy. Programs to support patients living in underserviced areas should be evaluated to improve access to specialist care.
Disclosures: G. G. Kaplan has served as a speaker for Jansen, Merck, Schering-Plough, Abbvie, and UCB Pharma. He has participated in advisory board meetings for Jansen, Abbvie, Merck, Schering-Plough, Shire, and UCB Pharma. G. G. Kaplan has received research support from GlaxoSmith Kline, Abbvie, and Shire. R. Panaccione has served as a speaker, a consultant, and an advisory board member for Abbott Laboratories, Merck, Schering-Plough, Shire, Centocor, Elan Pharmaceuticals, and Procter and Gamble. He has served as a consultant and speaker for Astra Zeneca. He has served as a consultant and an advisory board member for Ferring and UCB. He has served as a consultant for Glaxo-Smith Kline and Bristol Meyers Squibb. He has served as a speaker for Byk Solvay, Axcan, Jansen, and Prometheus. He has received research funding from Merck, Schering-Plough, Abbott Laboratories, Elan Pharmaceuticals, Procter and Gamble, Bristol Meyers Squibb, and Millennium Pharmaceuticals. He has received educational support from Merck, Schering-Plough, Ferring, Axcan, and Jansen. C. H. Seow has served as a speaker for Janssen, Merck, Schering-Plough, and Warner Chilcott. She has participated in advisory board meetings for Janssen, Abbvie, Merck, and Schering-Plough. Y. Leung has served as a speaker for Ferring, Abbvie, Takeda, Jannsen, and Shire. K. Novak has received research support (independent investigator award) from AbbVie, in addition to consultancy and/or speaker fees from Abbvie, Janssen, UCB Canada, Pfizer, Pendopharm, Takeda, and Merck. A. Al-Darmaki, A. Aziz Shaheen, and J. Hubbard have no disclosures.
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Keywords:© Crohn's & Colitis Foundation
ulcerative colitis; colectomy; predicators; inflammatory bowel disease