Skip to main content
NCBI home page
Inflammatory Bowel Diseases logoLink to Inflammatory Bowel Diseases
. 2019 Oct 21;26(8):1225–1231. doi: 10.1093/ibd/izz247

Decreasing Colectomy Rate for Ulcerative Colitis in the United States Between 2007 and 2016: A Time Trend Analysis

Edward L Barnes 1,2,3,✉, Yue Jiang 4, Michael D Kappelman 2,3,5, Millie D Long 1,2,3, Robert S Sandler 1,3, Alan C Kinlaw 6,7,1, Hans H Herfarth 1,2,3,1
PMCID: PMC7365804  PMID: 31634390

Abstract

Background

Improved treatment approaches for ulcerative colitis (UC), including novel medications, might reduce the need for colectomy. We performed a retrospective cohort study of adult patients (age 18–64) with UC in the United States to examine time trends for colectomy and biologic use from 2007 to 2016.

Methods

We estimated quarterly rates for colectomy and biologic use using the IQVIA Legacy PharMetrics Adjudicated Claims Database. We used interrupted time series methods with segmented regression to assess time trends with 95% confidence intervals (CIs) for biologic use and colectomy before and after the emergence of newly available biologic therapies in 2014.

Results

Among 93,930 patients with UC, 2275 (2.4%) underwent colectomy from 2007 to 2016. Biologic use rates increased significantly from 2007 to 2016, from 131 per 1000 person-years in 2007 (95% CI, 121 to 140) to 589 per 1000 person-years in 2016 (95% CI, 575 to 604; P < 0.001). Colectomy rates decreased significantly between 2007 and 2016, from 7.8 per 1000 person-years (95% CI, 7.4 to 8.2) to 4.2 per 1000 person-years in 2016 (95% CI, 3.2 to 5.1; P < 0.001). An interruption in 2014 was associated with a positive trend deflection for biologic use (+72 treatments per 1000 person-years per year (95% CI, 61 to 83) and a negative trend deflection for colectomy (–0.76 per 1000 person-years per year; 95% CI, –1.47 to –0.05).

Conclusions

Among commercially insured patients in the United States from 2007 to 2016, biologic use rates increased, colectomy rates decreased, and both trends were impacted by the interruption in 2014. These findings suggest that new biologic therapies may have contributed to decreased colectomy rates.

Keywords: ulcerative colitis, inflammatory bowel diseases, interrupted time series, administrative claims, colectomy

In a study of commercially insured patients with ulcerative colitis from the United States from 2007 to 2016, biologic use rates increased, colectomy rates decreased, with significant changes were noted in 2014 using interrupted time series analysis methods.

INTRODUCTION

In the past 15 years, the number of medications available for the treatment of ulcerative colitis (UC) has increased significantly. These new therapies act through multiple mechanisms, and biologic therapies in particular are being utilized earlier in the disease course than in prior eras of treatment for UC. If these new approaches are effective in altering the clinical course of disease, the need for colectomy may decrease or be delayed.

Population-based estimates of the frequency of colectomy among patients with UC have varied considerably over time.1 Although early reports of the frequency of colectomy ranged as high as 20%–45% in patients up to 25 years after diagnosis,1 in other population-based or prospectively enrolled cohort studies, the risk of colectomy reported was lower.2–4 A recent meta-analysis estimated that the 10-year risk of surgery among patients with UC was 15.6%.5 Additionally, the indication for colectomy appears to have changed over time, with an increasing proportion of colectomies being performed for fulminant colitis or neoplasia compared with medically refractory disease.6

The therapeutic landscape for UC is rapidly evolving, with multiple new biologic and small molecule therapies approved since 2014.7, 8 Recent guidelines for the management of UC advocate for an evaluation of disease activity and an assessment of disease prognosis when choosing a therapy,9 perhaps leading to earlier treatment with biologic therapy. Infliximab, the first biologic therapy to be approved for the treatment of UC, has been associated with decreased rates of colectomy in retrospective and placebo-controlled studies.10–12 It is unknown whether overall colectomy rates in the United States have been meaningfully impacted by newer biologic therapies or the earlier introduction of biologic therapies into management algorithms for UC.13

The primary objective of this study was to evaluate the rates of colectomy for UC over time between 2007 and 2016 among commercially insured patients in the United States. Additionally, we examined trends over time in use of biologic therapies among patients with UC and the rate of colectomy performed for colorectal cancer.

METHODS

Data Source

For this study of colectomy rates in the UC population, we used the IQVIA Legacy PharMetrics Adjudicated Claims Database, which contains longitudinal, de-identified, individual-level administrative claims for medical, surgical, and prescription drug services in the United States from January 1, 2007, to June 1, 2016. Approximately 100 health plans are included in this data source, with a total of 27,800,023 de-identified individuals represented. In prior published literature, this data source has been reported as representative of the commercially insured population in the United States on a variety of measures, including age, sex, geographic region, and health plan type.14, 15

Patient Selection

We identified adult patients age 18–64 with UC using previously described criteria.15, 16 Briefly, we extracted all claims with an International Classification of Diseases, 9th revision, Clinical Modification (ICD-9-CM) or ICD, 10th revision, Clinical Modification (ICD-10-CM) diagnosis code for UC (556.x for ICD-9-CM and K51.x for ICD-10-CM) and dispensing/administration of inflammatory bowel disease (IBD)–specific medications (mesalamine, olsalazine, balsalazide, sulfasalazine, azathioprine, mercaptopurine, infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab). We identified claims for these medications by searching their generic names and anatomical therapeutic chemical codes in the National Drug Data File (NDDF Plus; First Databank; www.firstdatabank.com) to ascertain National Drug Codes for prescription dispensation claims and CPT or Healthcare Common Procedure Coding System (HCPCS) codes for biologic procedure claims. To classify as having a diagnosis of UC, patients were required to have at least 1 diagnosis code for UC at 3 distinct health care encounters or at least 1 diagnosis code for UC with an accompanying claim for an IBD-specific medication.

Outcome Measures

The primary outcome of interest for this study was the rate of colectomy in patients with UC. We identified colectomy based on Current Procedural Terminology (CPT) codes for the first observed operation among 3 types of total colectomy procedures: total abdominal colectomy (44150, 44151, 44210), total proctocolectomy (44155, 44156, 44212), and total proctocolectomy with ileal pouch–anal anastomosis (IPAA; 44157, 44158, 44211). Similar methods of identifying patients with UC undergoing colectomy have been utilized in prior studies evaluating administrative claims data.17

Second, we measured the rate at which the following biologic medications were used by patients with UC: adalimumab, certolizumab, golimumab, infliximab, natalizumab, or vedolizumab. We analyzed use of biologic medications among the entire population of patients with UC and in separate evaluations of patients who underwent colectomy and those who did not undergo colectomy during the study period. In the evaluation of biologic use among colectomy patients, we evaluated biologic use in the quarter where colectomy occurred. Finally, we analyzed the annual and quarterly frequency of colectomy with a concomitant diagnosis of colorectal cancer during the study period. For the evaluation of colectomy for colorectal cancer among patients with UC, we identified patients with a diagnosis code of colorectal cancer (ICD-9-CM 153.x-154.8, 230.3, 230.4; ICD-10-CM C18, C19, C20)18 within the 3 months before colectomy.

Covariates

Available patient demographics included age, sex, and US Census region. We also used the Deyo Modification of the Charlson Comorbidity Index to assess comorbidities that potentially influence the likelihood of undergoing colectomy as a therapy for UC.19

Statistical Analysis

We estimated rates of biologic use and colectomy on a quarterly basis. The denominator for each quarterly rate was the accumulated person-years of follow-up with insurance coverage by patients with UC in that quarter. The numerator for each quarterly rate was the number of those patients who experienced the outcome. Follow-up for ascertainment of colectomy and biologic use began at the time of the patient’s first UC diagnosis code. Patient follow-up accrued until disenrollment from a health plan in the database, loss of prescription drug coverage for >1 month, age 65, or June 1, 2016—whichever came first. Among patients who underwent colectomy, follow-up for both outcomes was terminated at the time of their colectomy. We excluded patients who had <3 months of continuous insurance enrollment after UC diagnosis.

To estimate time trends in rates of biologic use and colectomy and to assess how these may have been impacted by newly available biologics, we conducted an interrupted time series analysis. This is a common study design to assess changes in time trends that take place after well-defined population-level changes (eg, new policies or guidelines), when randomization is not possible.20, 21 Three new biologic therapies were approved for the treatment of UC between 2012 and 2014 (adalimumab, golimumab, and vedolizumab). Given that vedolizumab was approved by the Food and Drug Administration (FDA) in May 2014, we allowed a 6-month lag until the fourth quarter of 2014 as the a priori “interruption” that would mark deflections in trends for biologic use and colectomy. We hypothesized that changes in rates of biologic use and colectomy would be gradual, and therefore did not model discontinuities between segments.22, 23

We used ordinary least squares for segmented linear regression models to estimate linear trends before and after the 2014 interruption, with 95% confidence intervals (CIs). We controlled for confounding by seasonality using a transformed cosine periodic function.24, 25 To account for autocorrelated error over time, we used Durbin-Watson tests (α = 0.05) lagged up to 3 years.26

We performed all data management and analysis using R, version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria), and SAS, version 9.4 (SAS Institute, Cary, NC, USA), including the AUTOREG and MODEL (with %AR macro) procedures to implement segmented regression. The study protocol was exempted by the Institutional Review Board at the University of North Carolina at Chapel Hill.

RESULTS

We identified 93,930 UC patients for this study. Clinical and demographic characteristics of the study population are reported in Table 1. Among all patients with UC, 51,393 (55%) were women with a median age of 55 years at the time of last follow-up [interquartile range (IQR) 44–63 years]. The median follow-up time for all patients with UC was 5.5 years (IQR 3.2–7.0 years).

TABLE 1.

Demographic and Clinical Characteristics of Patients with Ulcerative Colitis in the United States, IQVIA Legacy PharMetrics Adjudicated Claims Database, 2007–2016

Patients With UC (n = 93,930)
Median IQR
Age at last follow-up, y 55 (44–63)
Person-years of follow-up 5.5 (3.2–7.0)
No. %
Male sex 42,537 45.3
Census region
East 23,301 24.8
Midwest 26,599 28.3
South 28,638 30.5
West 15,392 16.4
Charlson Comorbidity Index
0 69,312 73.8
1 16,725 17.8
2 4103 4.4
≥3 3790 4.0
Open in a new tab

Among 93,930 patients with UC, 2275 (2.4%) underwent colectomy during the study period; 1082 patients (48%) underwent a total abdominal colectomy, 375 (16%) underwent a total proctocolectomy, and 818 (36%) underwent a total proctocolectomy with IPAA. The quarterly rate of colectomy among UC patients decreased between 2007 and 2016, from a peak of 8.4 per 1000 person-years in quarter 4 (Q4)–2007 to a minimum of 4.1 per 1000 person-years in Q2-2016 (Fig. 1).

FIGURE 1.

FIGURE 1.

Open in a new tab

Incidence rates of colectomy per 1000 person-years among patients with ulcerative colitis in the United States, IQVIA Legacy PharMetrics Adjudicated Claims Database, 2007–2016. P < 0.001.

Impact of Newly Available Biologics for Ulcerative Colitis

The rates of (A) biologic use and (B) colectomy in patients with UC are presented in Figure 2, along with seasonality-adjusted trend estimates from our interrupted time series analysis. In patients with UC, the rate of biologic use increased over time from 2007 (131 per 1000 person-years; 95% CI, 121 to 140) until the interruption in 2014 (402 per 1000 person-years; 95% CI, 393 to 411). During this pre-interruption period, the increasing trend for biologic use rates was 35 per 1000 person-years per year (95% CI, 33 to 37; P < 0.001). The interruption in 2014 was associated with a further positive trend deflection of +72 per 1000 person-years per year (95% CI, 61 to 83; P < 0.001; null impact of interruption would be 0 deflection). As a result, the postinterruption trend was 107 per 1000 person-years per year (95% CI, 97 to 117; P < 0.001). By 2016, the biologic use rate had reached 589 per 1000 person-years (95% CI, 575 to 604).

FIGURE 2.

FIGURE 2.

Open in a new tab

Segmented trends over calendar time for quarterly incidence rates of (A) biologic use and (B) colectomy per 1000 person-years among patients with ulcerative colitis in the United States, IQVIA Legacy PharMetrics Adjudicated Claims Database, 2007–2016. A, Biologic use: pre-interruption period, P < 0.001; trend deflection at interruption, P < 0.001; postinterruption period, P < 0.001. B, Colectomy: pre-interruption period, P < 0.001; trend deflection at interruption, P = 0.044; postinterruption period, P = 0.005. Pointwise quarterly rates (circles), pre- and postinterruption trend segments (solid lines), and projected postinterruption trend based on pre-interruption trend (dashed lines) are shown separately in each panel for each outcome.

The colectomy rate in UC patients decreased by 24% from 2007 (7.8 per 1000 person-years; 95% CI, 7.4 to 8.2) until the interruption in 2014 (5.9 per 1000 person-years; 95% CI, 5.5 to 6.3). During this pre-interruption period, the decreasing trend for colectomy rates was –0.24 per 1000 person-years per year (95% CI, –0.33 to –0.15; P < 0.001). The interruption in 2014 was associated with a further negative trend deflection of –0.76 per 1000 person-years per year (95% CI, –1.47 to –0.05; P = 0.044; null association would be 0 deflection). As a result, the postinterruption trend was –1.00 per 1000 person-years per year (95% CI, –1.66 to –0.35; P = 0.005). By 2016, the colectomy rate had reached its nadir, at 4.2 per 1000 person-years (95% CI, 3.2 to 5.1). In a subanalysis of patients with UC undergoing colectomy, there was no significant difference in the rate of colectomy performed for colorectal cancer during the study period (Supplementary Fig. 1).

Figure 3 shows the quarterly proportion of patients with UC who used each biologic. From 2007 to 2016, use of infliximab increased from 2.9% to 4.9% among patients with UC, whereas use of adalimumab increased from 0.3% in 2007 to 2.6% in 2012 to 6.3% in 2016. After FDA approval of vedolizumab in 2014, the proportion of patients with claims for vedolizumab reached a maximum of 1.4% of patients with UC by 2016. Among patients undergoing colectomy, the percentage of patients with a biologic claim in the same quarter increased by a mean of 0.23 absolute percentage points per quarter (linear trend test, P = 0.024) during the study period, whereas the percentage of patients who did not undergo colectomy with a biologic claim increased by 0.24 absolute percentage points per quarter (linear trend test, P < 0.001) during the study period.

FIGURE 3.

FIGURE 3.

Open in a new tab

Trends in percentage of patients with claims for biologic therapies over time, among patients with ulcerative colitis in the IQVIA Legacy PharMetrics Adjudicated Claims Database, analyzed by regimen. Other biologics: golimumab, certolizumab, natalizumab.

DISCUSSION

In this evaluation of health care claims from more than 90,000 commercially insured patients with UC in the United States, we observed a decrease over time in the rate of colectomy between 2007 and 2016. This decrease was demonstrated on multiple analyses, including segmented regression of interrupted time series data based on an interruption in 2014 representing the emergence of newly available biologic medications. During the same time period, rates of biologic use significantly increased among patients with UC. The decrease in colectomy rate during the study period represents one of the first evaluations of colectomy patterns in a commercially insured population in the United States during the current biologic era, when earlier and more aggressive biologic treatment regimens have been advocated.27

Although historically the lifetime risk of colectomy for an individual patient has been estimated to be ≥25% for patients with UC in population-based cohorts,1, 28 more recent analyses have demonstrated a lower risk of colectomy at 10 years after diagnosis (~15%).5 Thus far, the impact of early and more aggressive use of biologic therapy on long-term outcomes such as colectomy among patients with UC in the United States has not been well established. A prior study from Kaplan et al. demonstrated a decreased rate of elective colectomy among patients with UC in Alberta, Canada, from 1997 to 2009, along with a significant increase in thiopurine (1997–2009) and infliximab use (2005–2009).9 Although a decrease in early colectomy rates was noted from 1998 to 2005 in a Dutch population-based cohort when compared with previous years, there were no differences in late colectomy rates between 1991 and 2010.2

In an evaluation from Ontario, Canada, using data from 1995 to 2012, the marketplace introduction of infliximab was not associated with a decrease in colectomy among patients with UC,29 whereas a study from Edmonton, Canada, demonstrated a decrease in colectomy rate after 2005, which paralleled the increased use of infliximab.30 In our study of a more recent decade (2007–2016), we have evaluated the early biologic era after the approval of infliximab for the treatment of UC and the current biologic era, which includes additional anti-TNF therapies and a new mechanism of action in the form of anti-integrin therapy. Additionally, this more modern era of analysis likely incorporates current practice patterns where earlier introduction of biologic therapy into the treatment paradigm is favored if not recommended.27, 31 A recent study from Japan demonstrated a similar increase in anti-TNF therapy and calcineurin inhibitor use during a similar time period, along with a decrease in surgery rates for UC.32

Our segmented regression analyses demonstrated that colectomy rates decreased from 2007 until the interruption in 2014, with an even more precipitous decrease noted after the interruption through the end of the study period in 2016. Biologic use rates were also meaningfully impacted by the interruption in 2014, after which the increasing trend in biologic use became even steeper. We identified this interruption a priori under the hypothesis that 2014 was a period of introduction and increased utilization of the newest biologic therapies for UC (adalimumab, golimumab, and vedolizumab). Prior studies utilizing administrative claims data from the United States have also demonstrated a consistent rise in biologic use for UC during this same time period.33 Changes in the pattern of colectomies among inpatients in the United States during an early portion of this time period have been reported using the HCUP Nationwide Inpatient Sample13; however, this data source lacks a mechanism to follow patients longitudinally and does not include medications. Whether the trends demonstrated in our study represent a significant shift in the natural history of UC or a temporary delay in surgery with a potential rebound in colectomy rates in the future is unknown. This question will require vigilant follow-up in future iterations of this data source and confirmation in other large, population-based longitudinal cohorts.

In our evaluation of the rate of colectomy performed for colorectal cancer among patients with UC, there was no significant change from 2007 to 2016. A recent evaluation of colectomy patterns in Helsinki demonstrated a similar decrease in colectomy rate during the current biologic era, without a significant difference in the percentage of colectomies performed for colorectal cancer or dysplasia.34 There have been several recent changes in the approach to specific findings on surveillance colonoscopy among patients with UC, including recommendations from the SCENIC consensus statement,35 in which surveillance colonoscopy is recommended over colectomy in multiple scenarios. Despite the overall decrease in colectomy rates for UC, the impact of these recommendations and other changes in practice patterns may not be fully captured in administrative claims data.

The findings of this study are ecological, and they may be influenced by other temporal changes in the clinical treatment of UC. They may be influenced by other temporal changes in clinical treatment of UC. Increased access to IBD specialist care may also improve long-term outcomes among patients with UC.36 This is particularly true when recognizing comorbid conditions that might also increase the risk of colectomy such as cytomegalovirus infection or nontherapy interventions such as access to a nutritionist, social worker, psychologist, or other resources. In addition to an overall use of biologic therapies, changes in how these biologic therapies are utilized may also significantly impact outcomes, including an increase in the use of combination therapy,37 treat-to-target strategies,38, 39 and potentially therapeutic drug monitoring.40

This study has several strengths. Our interrupted time series analysis examined a critical 10-year period in the management of UC, during which several new medications became available. We leveraged reliable administrative claims data to analyze a large sample of patients with UC using validated case-finding definitions, records of medication dispensing and infusion, and colectomies. However, it is recognized that disease extent influences risk of colectomy,41 and we were unable to assess for disease extent or severity. Similarly, due to the restrictions of administrative claims data, we were only able to evaluate those patients with a diagnosis of colorectal cancer before colectomy. There are also limitations when analyzing biologic use using administrative claims. There may be incomplete capture of inpatient biologic utilization, given that bundling of inpatient costs may occur. Furthermore, if patients utilized manufacturer assistance programs, biologic use patterns would not be completely captured. Both of these measurement limitations would suggest that our estimates of sharp increasing trends for biologic use are underestimations, if they are indeed biased. When identifying patients with UC, we recognize that some patients will potentially continue to have documented diagnosis codes for UC despite having previously undergone colectomy (potentially before enrollment). Although this likely represents a small subset of this population, this could inflate the total number of patients with UC while not representing true eligibility for colectomy. Due to the lack of granularity in this regard in the available claims data, we could not overcome this limitation for this study.

In conclusion, among a large, geographically diverse sample of patients with UC from the United States, we demonstrated a significant decrease in the rate of colectomy from 2007 to 2016, which became more precipitous after the interruption in 2014. The use of biologics increased throughout the study period, and began to increase more rapidly in 2014. Although other nontherapy factors may have contributed to the decrease in colectomy rates, these data suggest that more widespread use of biologic therapy has reduced the rate of colectomy.

Supplementary Material

izz247_suppl_Supplementary_Material
Click here for additional data file. (102.3KB, docx)

Supported by: This work was supported by the Nickolas Bunn Boddie, Sr., and Lucy Mayo Boddie Foundation (to E.L.B.), the Crohn’s and Colitis Foundation (grant number 567497 to E.L.B.), and the National Institutes of Health (P30DK034987).

Conflicts of interest: E.L.B.: speaking for AbbVie, Inc.; Y.J.: no disclosures; M.D.K.: consulting for AbbVie, Inc., Eli Lilly; M.D.L.: consulting for Pfizer, AbbVie, Takeda, Janssen, Salix, Valeant, Target Pharmasolutions, Prometheus, UCB; R.S.S.: no disclosures; A.C.K.: no disclosures; H.H.H.: consulting for Alivio, AMAG, Finch, Gilead, Merck, Pfizer, Celltrion, Lycera, Boehringer-Ingelheim, Seres, and Otsuka and research support from Pfizer and Artizan.

REFERENCES

  • 1. Fumery M, Singh S, Dulai PS, et al. Natural history of adult ulcerative colitis in population-based cohorts: a systematic review. Clin Gastroenterol Hepatol. 2018;16:343–356.e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. Jeuring SF, Bours PH, Zeegers MP, et al. Disease outcome of ulcerative colitis in an era of changing treatment strategies: results from the Dutch population-based IBDSL cohort. J Crohns Colitis. 2015;9:837–845. [DOI] [PubMed] [Google Scholar]
  • 3. Eriksson C, Cao Y, Rundquist S, et al. Changes in medical management and colectomy rates: a population-based cohort study on the epidemiology and natural history of ulcerative colitis in Örebro, Sweden, 1963-2010. Aliment Pharmacol Ther. 2017;46:748–757. [DOI] [PubMed] [Google Scholar]
  • 4. Parragi L, Fournier N, Zeitz J, et al. ; Swiss IBD Cohort Study Group Colectomy rates in ulcerative colitis are low and decreasing: 10-year follow-up data from the Swiss IBD Cohort Study. J Crohns Colitis. 2018;12:811–818. [DOI] [PubMed] [Google Scholar]
  • 5. Frolkis AD, Dykeman J, Negrón ME, et al. Risk of surgery for inflammatory bowel diseases has decreased over time: a systematic review and meta-analysis of population-based studies. Gastroenterology. 2013;145:996–1006. [DOI] [PubMed] [Google Scholar]
  • 6. Samuel S, Ingle SB, Dhillon S, et al. Cumulative incidence and risk factors for hospitalization and surgery in a population-based cohort of ulcerative colitis. Inflamm Bowel Dis. 2013;19:1858–1866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Feagan BG, Rutgeerts P, Sands BE, et al. GEMINI 1 Study Group Vedolizumab as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2013;369:699–710. [DOI] [PubMed] [Google Scholar]
  • 8. Sandborn WJ, Su C, Sands BE, et al. OCTAVE Induction 1, OCTAVE Induction 2, and OCTAVE Sustain Investigators Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2017;376:1723–1736. [DOI] [PubMed] [Google Scholar]
  • 9. Kaplan GG, Seow CH, Ghosh S, et al. Decreasing colectomy rates for ulcerative colitis: a population-based time trend study. Am J Gastroenterol. 2012;107:1879–1887. [DOI] [PubMed] [Google Scholar]
  • 10. Sandborn WJ, Rutgeerts P, Feagan BG, et al. Colectomy rate comparison after treatment of ulcerative colitis with placebo or infliximab. Gastroenterology. 2009;137:1250–1260; quiz 1520. [DOI] [PubMed] [Google Scholar]
  • 11. Aratari A, Papi C, Clemente V, et al. Colectomy rate in acute severe ulcerative colitis in the infliximab era. Dig Liver Dis. 2008;40:821–826. [DOI] [PubMed] [Google Scholar]
  • 12. Clemente V, Aratari A, Papi C, Vernia P. Short term colectomy rate and mortality for severe ulcerative colitis in the last 40 years. Has something changed? Dig Liver Dis. 2016;48:371–375. [DOI] [PubMed] [Google Scholar]
  • 13. Geltzeiler CB, Lu KC, Diggs BS, et al. Initial surgical management of ulcerative colitis in the biologic era. Dis Colon Rectum. 2014;57:1358–1363. [DOI] [PubMed] [Google Scholar]
  • 14. Stempel DA, Mauskopf J, McLaughlin T, et al. Comparison of asthma costs in patients starting fluticasone propionate compared to patients starting montelukast. Respir Med. 2001;95:227–234. [DOI] [PubMed] [Google Scholar]
  • 15. Kappelman MD, Rifas-Shiman SL, Kleinman K, et al. The prevalence and geographic distribution of Crohn’s disease and ulcerative colitis in the United States. Clin Gastroenterol Hepatol. 2007;5:1424–1429. [DOI] [PubMed] [Google Scholar]
  • 16. Bernstein CN, Blanchard JF, Rawsthorne P, Wajda A. Epidemiology of Crohn’s disease and ulcerative colitis in a central Canadian province: a population-based study. Am J Epidemiol. 1999;149:916–924. [DOI] [PubMed] [Google Scholar]
  • 17. Kulaylat AS, Kulaylat AN, Schaefer EW, et al. Association of preoperative anti-tumor necrosis factor therapy with adverse postoperative outcomes in patients undergoing abdominal surgery for ulcerative colitis. JAMA Surg. 2017;152:e171538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Peery AF, Cools KS, Strassle PD, et al. Increasing rates of surgery for patients with nonmalignant colorectal polyps in the United States. Gastroenterology. 2018;154:1352–1360.e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45:613–619. [DOI] [PubMed] [Google Scholar]
  • 20. Shadish W, Cook T, Campbell D.. Experimental and Quasi-Experimental Designs for Generalized Causal Inference. 2nd ed. Boston: Houghton-Mifflin; 2001. [Google Scholar]
  • 21. Wagner AK, Soumerai SB, Zhang F, Ross-Degnan D. Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther. 2002;27:299–309. [DOI] [PubMed] [Google Scholar]
  • 22. Gillings D, Makuc D, Siegel E. Analysis of interrupted time series mortality trends: an example to evaluate regionalized perinatal care. Am J Public Health. 1981;71:38–46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Piegorsch W, Bailer J.. Nonlinear Regression. 1st ed. Chichester, UK:John Wiley & Sons, Ltd; 2005. [Google Scholar]
  • 24. Brookhart MA, Rothman KJ. Simple estimators of the intensity of seasonal occurrence. BMC Med Res Methodol. 2008;8:67. doi:10.1186/1471-2288-8-67 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25. Nam J-m. Efficient method for identification of cyclic trends in incidence. Comm Statist Theory Methods. 1983;12:1053–1068. [Google Scholar]
  • 26. DURBIN J, WATSON GS. Testing for serial correlation in least squares regression. I. Biometrika. 1950;37:409–428. [PubMed] [Google Scholar]
  • 27. Berg DR, Colombel JF, Ungaro R. The role of early biologic therapy in inflammatory bowel disease. Inflamm Bowel Dis. 2019;15:1896–1905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Langholz E, Munkholm P, Davidsen M, Binder V. Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology. 1994;107:3–11. [DOI] [PubMed] [Google Scholar]
  • 29. Murthy SK, Begum J, Benchimol EI, et al. Introduction of anti-TNF therapy has not yielded expected declines in hospitalisation and intestinal resection rates in inflammatory bowel diseases: a population-based interrupted time series study. Gut. In press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Reich KM, Chang HJ, Rezaie A, et al. The incidence rate of colectomy for medically refractory ulcerative colitis has declined in parallel with increasing anti-TNF use: a time-trend study. Aliment Pharmacol Ther. 2014;40:629–638. [DOI] [PubMed] [Google Scholar]
  • 31. Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG clinical guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114:384–413. [DOI] [PubMed] [Google Scholar]
  • 32. Uchino M, Ikeuchi H, Hata K, et al. Changes in the rate of and trends in colectomy for ulcerative colitis during the era of biologics and calcineurin inhibitors based on a Japanese nationwide cohort study. Surg Today. In press. [DOI] [PubMed] [Google Scholar]
  • 33. Yu H, MacIsaac D, Wong JJ, et al. Market share and costs of biologic therapies for inflammatory bowel disease in the USA. Aliment Pharmacol Ther. 2018;47:364–370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Kolehmainen S, Lepisto A, Farkkila M. Impact of anti-TNF-alpha therapy on colectomy rate and indications for colectomy in ulcerative colitis: comparison of two patient cohorts from 2005 to 2007 and from 2014 to 2016. Scand J Gastroenterol. 2019;54:707–711. [DOI] [PubMed] [Google Scholar]
  • 35. Laine L, Kaltenbach T, Barkun A, et al. SCENIC Guideline Development Panel SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology. 2015;148:639–651.e28. [DOI] [PubMed] [Google Scholar]
  • 36. Regueiro M, Click B, Anderson A, et al. Reduced unplanned care and disease activity and increased quality of life after patient enrollment in an inflammatory bowel disease medical home. Clin Gastroenterol Hepatol. 2018;16:1777–1785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Panaccione R, Ghosh S, Middleton S, et al. Combination therapy with infliximab and azathioprine is superior to monotherapy with either agent in ulcerative colitis. Gastroenterology. 2014;146:392–400.e3. [DOI] [PubMed] [Google Scholar]
  • 38. Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): determining therapeutic goals for treat-to-target. Am J Gastroenterol. 2015;110:1324–1338. [DOI] [PubMed] [Google Scholar]
  • 39. Ungaro R, Colombel JF, Lissoos T, Peyrin-Biroulet L. A treat-to-target update in ulcerative colitis: a systematic review. Am J Gastroenterol. 2019;114:874–883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Colombel JF, D’Haens G, Lee WJ, Petersson J, Panaccione R. Outcomes and strategies to support a treat-to-target approach in inflammatory bowel disease: a systematic review. J Crohns Colitis. In press. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41. Romberg-Camps MJ, Dagnelie PC, Kester AD, et al. Influence of phenotype at diagnosis and of other potential prognostic factors on the course of inflammatory bowel disease. Am J Gastroenterol. 2009;104:371–383. [DOI] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

izz247_suppl_Supplementary_Material
Click here for additional data file. (102.3KB, docx)

Articles from Inflammatory Bowel Diseases are provided here courtesy of Oxford University Press

RESOURCES