Advertisement

BMC Gastroenterology

, 19:145 | Cite as

Current diagnosis and management of Crohn’s disease in China: results from a multicenter prospective disease registry

  • Yue Li
  • Baili Chen
  • Xiang Gao
  • Naizhong Hu
  • Meifang Huang
  • Zhihua Ran
  • Zhanju Liu
  • Jie Zhong
  • Duowu Zou
  • Xiaoping Wu
  • Jianlin Ren
  • Jianqiu Sheng
  • Ping Zheng
  • Huahong Wang
  • Minhu Chen
  • Junrong Chen
  • Peng Xi
  • Jiajia Lu
  • Malcolm Handel
  • Yanfang Liu
  • Hua Fan
  • Jiaming QianEmail author
Open Access
Research article
Part of the following topical collections:
  1. Gastroesophageal disorders

Abstract

Background

This study aimed to understand the disease characteristics and treatment outcomes of Crohn’s disease (CD) in a real-world setting in China.

Methods

In this prospective, non-interventional, multicenter disease registry, adults (≥18 years) with existing and newly diagnosed CD were recruited from 14 medical centers across China from January 2015 to January 2017. The study consisted of the enrollment and follow-up periods, of 12 months each. Demographic, clinical characteristics, diagnostic duration and management of CD at enrollment were evaluated. Logistic regression analysis and stepwise multivariate logistic regression analysis used to assess the relationship between the risk factors and CD.

Results

Of 504 enrolled patients, 499 (99.0%) were eligible for analysis. The mean (SD) age at study enrollment was 32.3 (11.43) years and the majority (69.7%) of participants were male. In the past 15 years, a sustained decrease of the period of time in the diagnosis of CD was observed, at about 39.4 (24.11) months in 2010, which decreased to 3.1 (2.13) months in 2015. The most common presenting symptoms of CD included abdominal pain (78.0%), diarrhea (58.1%), weight loss (52.9%) and fever (30.1%). Oral ulcer (19.4%) and arthritis (9.8%) were the most common extra-intestinal manifestations. Non-stricturing non-penetrating (B1) (49.9%) behavior and ileocolonic involvement (L3) (56.2%) location were more frequent. Perianal disease was observed in 29.1% of the patients. Around 23.8% (119/499) patients had CD-related surgery other than perianal disease surgery. Older age at enrollment, longer disease course, complicated disease behavior and absence of perianal disease were all surgery risk factors (p < 0.05). The most common medications was immunomodulators (e.g., azathioprine) (41.5%), anti-TNFα agents (32.9%) and aminosalicylates (20.6%). The mean (SD) Crohn’s Disease Active Index (CDAI) score was 159.1 (91.45) and almost half of the patients (49.1%, 81/165) were in remission.

Conclusions

This study demonstrated the CD-disease characteristics, risk factors of CD-related surgery and perianal disease, and treatment strategies in a real-world setting in China and may help in developing programs to diagnose and manage patients with CD.

Keywords

China Crohn’s disease Disease registry Extraintestinal manifestations Treatment outcomes 

Abbreviations

B1

Non-stricturing non-penetrating

B2

Structuring

B3

Penetrating;

BMI

Body mass index

CD

Crohn’s disease

CDAI

Crohn’s Disease Active Index

CI

Confidence interval

FAS

Full analysis set

IBD

Inflammatory bowel disease

L1

Terminal ileum

L2

Colon

L3

Ileocolon

L4

Upper gastrointestinal tract

OR

Odds ratio

SD

Standard deviation

TNF

Tumor necrosis factor

Background

Crohn’s disease (CD) is a chronic, progressive and relapsing inflammatory bowel disease (IBD) that is often characterized by the presence of intestinal strictures, fistulas or abscesses [1]. The incidence rate of CD in Western countries has demonstrated a significant increasing trend, and it varies from 0.3 to 12.7 cases per 100,000 persons in Europe and 0 to 20.2 cases per 100,000 persons in North America [2, 3]. Similar to Western countries, the incidence of CD has increased over time in Asian countries [4, 5, 6, 7]. While CD is well known in Western countries, it was reported in China about 30 years later: the first case of CD was reported in China in 1956 [8]. Although the overall incidence of CD in China is much lower than in Western countries, the incidence is increasing rapidly with urbanization and socioeconomic development [9]. The current estimated incidence is 0.51–1.09 cases per 100,000 persons in China [10, 11]. In Hong Kong, the incidence of CD has tripled over the last 10 years [12]. Since most studies focused only on particular regions of China, existing data are inadequate to represent the actual incidence of CD at the national level.

According to available data on CD, there is a substantial difference in the incidence and disease characteristics of CD in southern and northern China, as well as in coastal and inland areas [13, 14]. China is also known as a high-risk area for infectious diseases, especially tuberculosis [15]. Due to similar clinical, morphological and histological features of intestinal tuberculosis and CD, the differential diagnosis between these two disorders remains challenging, and must also be considered in terms of treatment modalities and strategies. Intriguingly, while the epidemiology, phenotypic characteristics and management of CD in Asia have the same features as that of Western countries, they also possess certain specific characteristics. A comprehensive understanding of the demographics and disease characteristics as well as diagnosis and treatment status of patients with CD is of great significance to improve the disease management in China. Furthermore, understanding of these factors can likely help optimize diagnosis and treatment and provide the basis for making public health policy decisions.

There is a paucity of population-based epidemiological studies to demonstrate the disease status, diagnosis and treatment patterns of CD in China. The aim of the present study was to build a hospital-based CD registry that would help to analyze the disease characteristics, diagnosis and treatment patterns, and potentially support understanding of treatment strategies for CD in clinical practice in China. Results of this study would help optimize and develop management strategies based on characteristics of CD patients in China.

Methods

Patients

Patients aged ≥18 years were recruited from 14 tertiary teaching medical centers in China from January 2015 to January 2017 (Additional file 1: Table S1). Patients were included if they had a confirmed diagnosis of CD, attended the outpatient clinics and/or hospital wards and were adhering to the physician’s advice through follow-up for up to 1 year.

Study design

In this prospective, non-interventional, multicenter disease registry, patients with a confirmed diagnosis of CD were enrolled regardless of the treatments received. All the eligible patients were followed for 1 year.

Study objectives

The primary objectives of the study were to collect data related to patient demographics and clinical manifestations. Secondary objectives included risk factors for different disease behaviors and locations, and factors related to surgery and medical treatment.

Study evaluations

At baseline, data were collected for variables including patient demographics, nicotine use history, alcohol use history, medical history and comorbid medical conditions, disease onset and diagnosis time, CD symptom profile, details of prior treatment regimen and surgery history. Surgery history included CD-related surgery and perianal disease-related surgery. CD-related surgery referred to any bowel resection due to CD complications. Baseline data were collected upon entry into the registry. During the observational period, each patient was followed for 1 year and data were collected approximately every 3 months to observe their clinical progression.

Patients were grouped based on location of the medical centers as coastal cities: Shanghai, Hangzhou, Guangzhou, Xiamen, and inland cities: Beijing, Changsha, Wuhan, Hefei (Additional file 1: Table S1). The Montreal classification was used to define disease location as L1: terminal ileum, L2: colon, L3: ileocolon and L4: involving upper gastrointestinal tract. Disease behavior was defined as B1: non-stricturing non-penetrating, B2: stricturing and B3: penetrating [16]. The disease activity was assessed using the Crohn’s Disease Active Index (CDAI).

Demographics and disease characteristics such as age, sex, body mass index, nicotine and alcohol use, family and medical history, months from disease onset to enrollment and months from initial definite diagnosis to enrollment were correlated at baseline.

Statistical analysis

A sample size of approximately 500 patients from 14 tertiary medical centers was needed to obtain data that was representative of CD patients in China. Eligible patients were enrolled in the registry irrespective of their treatments, and as this was a descriptive study, no formal hypotheses were tested in this registry. The sample size was determined by pragmatic considerations including feasibility and cost. Effectiveness outcomes were based on the full analysis set (FAS), which included patients who entered the registry and had at least one assessment visit during the treatment period. Baseline data were presented and analyzed in this study. All continuous variables were summarized using mean (standard deviation [SD]). All categorical variables were summarized using frequencies and percentages. Logistic regression analysis and a stepwise multivariate logistic regression analysis was conducted to examine the relationship between the risk factors and CD with entry α = 0.5 and stay α = 0.2 as the selection criteria. The 95% confidence interval (CI) and odds ratio (OR) were calculated. Statistically significant (p < 0.05) results obtained from this analysis of correlation factors using logistic regression model are presented here.

Ethical considerations

This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The Independent Ethics Committee or the Institutional Review Board at each study site approved the trial design and eligible patients provided written informed consent before participating.

Results

Enrollment and demographic characteristics

During the study period, 504 patients were screened and 499 patients were eligible. Among those 499 patients, 421 (84.4%) completed the registry and 1-year observational phase; 78 patients were excluded from the analysis mainly due to loss to follow-up (n = 60) and withdrawal of consent (n = 12) (Additional file 1: Table S2). Among 499 patients, 32.9% (164/499) were from South China, 28.9% (144/499) from East China, 21.1% (106/499) from Central China and 17.0% (85/499) from North China (Additional file 1: Table S1). About 61.7% (308/499) of patients were enrolled in centers located in coastal cities, and 38.3% (191/499) enrolled in centers in inland cities. The mean (SD) age was 32.3 (11.43) years (median: 30.0, range: 18 to 77 years), and a higher proportion of patients were male (69.7%, n = 348, male vs. female ratio: 2.30:1). The majority of patients never used nicotine (86.4%, n = 382) and never consumed alcohol (90.5%, n = 401). Patents enrolled in inland medical centers had a higher proportion of smoking (current user 10.3% vs. 6.9%, former user 9.7% vs. 2.9%, p = 0.0036) and drinking (former user 9.0% vs. 1.8%, p = 0.0023) than that of patients enrolled in coastal cities (Table 1). At baseline, hepatitis B was reported in 19 (3.8%) patients. Appendicitis and medical history of nephrolithiasis were reported in 10 (2.0%) patients each (Table 1).
Table 1

Demographic and clinical characteristics of patients with Crohn’s disease at baseline

Variable

Total

Inland city

Coastal city

P value

N (%)

499

191 (38.3%)

308 (61.7%)

 

Age at enrollment (years), mean (SD)

32.3 (11.43)

34.3 (13.03)

31.1 (10.14)

0.0022

Male, n (%)

348 (69.7%)

138 (72.3%)

210 (68.2%)

 

Ethnicity, n (%)

 Chinese Han

495 (99.2%)

187 (97.9%)

308 (100.0%)

 

 Other Chinese minority

4 (0.8%)

4 (2.1%)

0

 

BMI (kg/m2), mean (SD)

19.10 (3.198)

18.80 (2.676)

19.29 (3.479)

 

Nicotine use history, n (%)

   

0.0036

 N

442

165

277

 

 Never used

382 (86.4%)

132 (80.0%)

250 (90.3%)

 

 Current user

36 (8.1%)

17 (10.3%)

19 (6.9%)

 

 Former user

24 (5.4%)

16 (9.7%)

8 (2.9%)

 

Alcohol use history, n (%)

   

0.0023

 N

443

166

277

 

 Never used

401 (90.5%)

143 (86.1%)

258 (93.1%)

 

 Current user

22 (5.0%)

8 (4.8%)

14 (5.1%)

 

 Former user

20 (4.5%)

15 (9.0%)

5 (1.8%)

 

Medical history reported, n (%)

 Any medical history

180 (36.1%)

76 (39.8%)

104 (33.8%)

 

 Hepatitis B

19 (3.8%)

7 (3.7%)

12 (3.9%)

 

 Appendicitis

10 (2.0%)

5 (2.6%)

5 (1.6%)

 

 Hypertension

8 (1.6%)

3 (1.6%)

5 (1.6%)

 

 Nephrolithiasis

10 (2.0%)

7 (3.7%)

3 (1.0%)

 

CD-related surgery history, n (%)

119 (23.8%)

51 (26.7%)

68 (22.1%)

0.2071

Perianal disease related surgery, n (%)

79 (15.8%)

21 (11.0%)

58 (18.8%)

0.0023

Family history of IBD, n (%)

 N

6

2

4

 

 Crohn’s disease

5 (83.3%)

2 (100%)

3 (75.0%)

 

 Ulcerative colitis

1 (16.7%)

0

1 (25.0%)

 

Age at disease onset (years), n (%)

   

0.0291

  ≤ 16

29 (5.8%)

15 (7.9%)

14 (4.5%)

 

 17–39

401 (80.4%)

142 (74.3%)

259 (84.1%)

 

  ≥ 40

69 (13.8%)

34 (17.8%)

35 (11.4%)

 

Age at initial diagnosis (years), n (%)

   

0.0083

  ≤ 16

6 (1.2%)

4 (2.1%)

2 (0.6%)

 

 17–39

418 (83.8%)

148 (77.5%)

270 (87.7%)

 

  ≥ 40

75 (15.0%)

39 (20.4%)

36 (11.7%)

 

Time from disease onset to initial diagnosis (months), mean (SD)

32.0 (46.43)

39.9 (58.84)

27.0 (35.93)

0.0255

Location, n (%)

   

< 0.0001

 N

493

190

303

 

 L1

137 (27.8%)

69 (36.3%)

68 (22.4%)

 

 L2

71 (14.4%)

38 (20.0%)

33 (10.9%)

 

 L3

277 (56.2%)

82 (43.2%)

195 (64.4%)

 

 L4

8 (1.6%)

1 (0.5%)

7 (2.3%)

 

Behavior, n (%)

   

< 0.0001

 N

495

190

305

 

 B1

247 (49.9%)

110 (57.9%)

137 (44.9%)

 

 B2

148 (29.9%)

45 (23.7%)

103 (33.8%)

 

 B3

100 (20.2%)

35 (18.4%)

65 (21.3%)

 

 Perianal disease

144 (29.1%)

32 (16.8%)

112 (36.7%)

 

Crohn’s Disease Activity Index at baseline, n (%)

   

0.0094

 N

165

80

85

 

  < 150

81 (49.1%)

37 (46.3%)

44 (51.8%)

 

 150–220

43 (26.1%)

28 (35.0%)

15 (17.6%)

 

 221–400

39 (23.6%)

13 (16.3%)

26 (30.6%)

 

  > 400

2 (1.2%)

2 (2.5%)

0

 

Crohn’s disease treatment information at baseline, n (%)

 Any Crohn’s disease treatment

441 (88.4%)

161 (84.3%)

280 (90.9%)

0.0308

 Immunomodulators

207 (41.5%)

78 (40.8%)

129 (41.9%)

0.8179

 Anti-TNF agents

164 (32.9%)

50 (26.2%)

114 (37.0%)

0.0123

 Aminosalicylates

103 (20.6%)

47 (24.6%)

56 (18.2%)

0.0847

 Steroids

99 (19.8%)

53 (27.7%)

46 (14.9%)

0.0005

 Enteral nutrition

69 (13.8%)

6 (3.1%)

63 (20.5%)

< 0.0001

 Antibiotics

65 (13.0%)

6 (3.1%)

59 (19.2%)

< 0.0001

 Anti-tuberculosis

27 (5.4%)

1 (0.5%)

26 (8.4%)

< 0.0001

 Anti-hepatitis

3 (0.6%)

2 (1.0%)

1 (0.3%)

0.5613

 Other agentsa

115 (23.0%)

7 (3.7%)

108 (35.1%)

< 0.0001

B1 non-stricturing non-penetrating, B2 stricturing, B3 penetrating, BMI body mass index, CD Crohn’s disease, IBD inflammatory bowel disease, L1 terminal ileum, L2 colon, L3 ileocolon, L4 upper gastrointestinal tract, n total number of participants in a subset, N total sample size, SD standard deviation, TNF tumor necrosis factor

aOther agents including traditional Chinese medicine, et al

Abdominal pain (78.0%, 389/499), diarrhea (58.1%, 290/499), weight loss (52.9%, 264/499) and fever (30.1%, 150/499) were the most common symptoms of CD. Less common symptoms were bloody stool (25.1%, 125/499), anemia (22.8%, 114/499) and mucus or pus in stools (12.4%, 62/499) (Fig. 1a). Oral ulcer (19.4%, 97/499) and arthritis (9.8%, 49/499) were the most common extra-intestinal manifestations. Skin lesions such as nodular erythema and uveitis were relatively uncommon (Fig. 1b).
Fig. 1

Symptom and complication profile (a) and extraintestinal manifestations (b) in patients with Crohn’s disease

Time from disease onset to definite diagnosis

The mean (SD) time from disease onset to definite diagnosis was 32.0 (46.43) months, patients enrolled in inland centers had a longer duration for diagnosis (39.9 [58.84] vs. 27.0 [35.93] months, p = 0.0255) than patients enrolled in coastal centers. The patients with data available for different time periods were grouped by the year of disease onset (Table 2). The mean (SD) duration from disease onset to initial definitive diagnosis decreased significantly over the period of time from 79.4 (67.03) months before 2010, to 39.4 (24.11) months in 2010, and to 3.1 (2.13) months in 2015 (Table 2 and Fig. 2). There was a significant shortening of diagnostic duration in recent years.
Table 2

Crohn’s disease diagnosis information - grouped by duration from disease onset to date of initial definite diagnosis

Year of disease onset

n

Age (years) at disease onseta

Months from disease onset to definite diagnosisb

Before 2010

130

27.0 (10.82)

79.4 (67.03)

2010

34

28.1 (11.73)

39.4 (24.11)

2011

38

26.4 (10.65)

28.7 (20.81)

2012

41

28.6 (10.07)

21.0 (13.57)

2013

74

26.3 (8.48)

17.3 (8.99)

2014

104

28.7 (10.74)

7.7 (5.41)

2015

78

30.5 (11.53)

3.1 (2.13)

All values are mean (standard deviation) unless otherwise stated

n total number of participants in a subset

aAge at disease onset is calculated as (date of disease onset-date of birth+ 1)/365.25, rounded to integer

bTime from disease onset to definite diagnosis, measured by (date of definite diagnosis-date of disease onset), rounded to integer

Fig. 2

Months from disease onset to definite diagnosis

Surgery history

Of the total 499 patients, 23.8% (119/499) had a history of CD-related surgery, and 15.8% (19/499) had a history of perianal disease related surgery. Demographics and baseline characteristics were comparable between patients with history of CD-related surgery and patients without. Patients who had a CD-related surgery history were older at disease onset (30.8 ± 10.98 vs. 27.0 ± 10.37 years, p = 0.0006), at initial definite diagnosis (34.1 ± 11.45 vs. 29.5 ± 10.66 years, p < 0.0001), and at enrollment (37.3 ± 11.95 vs. 30.8 ± 10.81 years, p < 0.0001) than patients without CD-related surgery history (Table 3). Time from disease onset to initial diagnosis (39.4 ± 47.57 vs. 29.6 ± 45.89 months, p = 0.0457) as well as time from disease onset to enrollment (78.6 ± 73.29 vs. 44.4 ± 51.32 months, p < 0.0001) were significantly longer in patients with a history of CD-related surgery. Fistulizing or penetrating CD behavior (B3) was higher (43.5% vs. 13.2%, p < 0.0001) in patients with history of CD-related surgery than in patients without history of CD-related surgery. On the contrary, patients with a CD-related surgery history had lower presence of perianal disease (16.8%, n = 20 vs. 32.6%, n = 124, p = 0.0009). Logistic model for correlation analysis revealed older age at enrollment (OR = 1.047, p < 0.01), longer disease course (months from disease onset to enrollment, OR = 1.009, p < 0.01), stricturing behavior (B2 vs. B1, OR = 2.815, p < 0.001), penetrating behavior (B3 vs B1, OR = 8.147, p < 0.001; B3 vs. B2, OR = 2.895, p < 0.001) and perianal disease (OR = 0.419, p < 0.001) were associated with CD-related surgery (Table 4).
Table 3

Demographic and clinical characteristics - grouped by baseline surgery information

Variable

Total

Patients with surgery history

Patients without surgery history

P value

N (%)

499

119 (23.8%)

380 (76.2%)

 

Age (years), mean (SD)

32.3 (11.43)

37.3 (11.95)

30.8 (10.81)

< 0.0001

Male, n (%)

348

91 (76.5%)

257 (67.6%)

0.0670

BMI (kg/m2), mean (SD)

19.10 (3.198)

18.81 (3.119)

19.19 (3.223)

0.3898

Age at disease onset (years), mean (SD)

27.9 (10.63)

30.8 (10.98)

27.0 (10.37)

0.0006

Age group at disease onset (years), n (%)

   

0.0007

 N

499

119

380

 

  ≤ 16

29 (5.8%)

6 (5.0%)

23 (6.1%)

 

 17–39

401 (80.4%)

84 (70.6%)

317 (83.4%)

 

  ≥ 40

69 (13.8%)

29 (24.4%)

40 (10.5%)

 

Age at initial definite diagnosis (years), mean (SD)

30.6 (11.01)

34.1 (11.45)

29.5 (10.66)

< 0.0001

Time from disease onset to initial diagnosis (months), mean (SD)

32.0 (46.43)

39.4 (47.57)

29.6 (45.89)

0.0457

Time from initial diagnosis to enrollment (months), mean (SD)

20.6 (39.06)

39.3 (61.42)

14.8 (26.24)

< 0.0001

Time from disease onset to enrollment (months), mean (SD)

52.6 (59.08)

78.6 (73.29)

44.4 (51.32)

< 0.0001

Nicotine use history, n (%)

   

0.4698

 N

442

99

343

 

 Never used

382 (86.4%)

83 (83.8%)

299 (87.2%)

 

 Current user

36 (8.1%)

11 (11.1%)

25 (7.3%)

 

 Former user

24 (5.4%)

5 (5.1%)

19 (5.5%)

 

Alcohol use history, n (%)

   

0.0760

 N

443

99

344

 

 Never used

401 (90.5%)

84 (84.8%)

317 (92.2%)

 

 Current user

22 (5.0%)

8 (8.1%)

14 (4.1%)

 

 Former user

20 (4.5%)

7 (7.1%)

13 (3.8%)

 

Location, n (%)

   

0.4628

 N

493

115

378

 

 L1

137 (27.8%)

27 (23.5%)

110 (29.1%)

 

 L2

71 (14.4%)

21 (18.3%)

50 (13.2%)

 

 L3

277 (56.2%)

65 (56.5%)

212 (56.1%)

 

 L4

8 (1.6%)

2 (1.7%)

6 (1.6%)

 

Behavior, n (%)

   

< 0.0001

 N

495

115

380

 

 B1

247 (49.9%)

27 (23.5%)

220 (57.9%)

 

 B2

148 (29.9%)

38 (33.0%)

110 (28.9%)

 

 B3

100 (20.2%)

50 (43.5%)

50 (13.2%)

 

Perianal disease, n (%)

144 (28.9%)

20 (16.8%)

124 (32.6%)

0.0009

B1 non-stricturing non-penetrating, B2 stricturing, B3 penetrating, BMI body mass index, L1 terminal ileum, L2 colon, L3 ileocolon, L4 upper gastrointestinal tract, SD standard deviation

Table 4

Logistic model for each correlation factors to baseline CD-related surgery history (has surgery history vs. no surgery history)

Variable

OR

95% CI for OR

Parameter estimates (standard error)

Corresponding 95% CI

P value

Age (years)

1.047

1.029, 1.066

0.046 (0.009)+

0.029, 0.064

< 0.001*

Sex (male vs. female)

1.549

0.963, 2.491

0.438 (0.242)+

−0.037, 0.913

0.071

BMI (18.5 - < 24 vs. < 18.5 kg/m2)

0.845

0.482, 1.481

−0.169 (0.287)

−0.731, 0.393

0.555

BMI (≥24 vs. < 18.5 kg/m2)

0.713

0.225, 2.260

− 0.339 (0.589)

−1.493, 0.815

0.565

Nicotine use (former vs. Never)

0.951

0.345, 2.624

−0.050 (0.518)

−1.065, 0.965

0.923

Nicotine use (current vs. Never)

1.591

0.752, 3.367

0.464 (0.382)+

−0.285, 1.214

0.225

Alcohol use (former vs. Never)

2.038

0.789, 5.270

0.712 (0.485)+

−0.238, 1.662

0.142

Alcohol use (current vs. Never)

2.163

0.878, 5.328

0.772 (0.460)+

−0.130, 1.673

0.093

Time from disease onset to enrollment (months)

1.009

1.005, 1.013

0.009 (0.002)+

0.005, 0.012

< 0.001*

Time from initial definite diagnosis to enrollment (months)

1.015

1.009, 1.021

0.015 (0.003)+

0.009, 0.021

< 0.001*

Disease behavior (B2 vs. B1)

2.815

1.634, 4.848

1.035 (0.278)+

0.491, 1.579

< 0.001*

Disease behavior (B3 vs. B1)

8.147

4.655, 14.261

2.098 (0.286)+

1.538, 2.658

< 0.001*

Disease behavior (B3 vs. B2)

2.895

1.690, 4.959

1.063 (0.275)+

0.525, 1.601

< 0.001*

Disease location (L3 vs. L1)

1.260

0.761, 2.087

0.231 (0.257)

−0.273, 0.736

0.368

Disease location (L3 vs. L2)

0.730

0.408, 1.304

−0.315 (0.296)+

−0.895, 0.266

0.288

Perianal disease (yes vs. no)

0.419

0.247, 0.709

−0.871 (0.268)+

−1.397, − 0.344

0.001*

“No surgery history” is the reference level. +: standard error is not larger than parameter estimates. *: P < 0.05. B1 non-stricturing non-penetrating, B2 stricturing, B3 penetrating, BMI body mass index, CI confidence interval, L1 terminal ileum, L2 colon, L3 ileocolon, OR odds ratio

Disease behavior and location

At baseline, non-stricturing non-penetrating (B1) disease behavior (49.9%, 247/495) was the highest. Centers in coastal cities were taking care of more patients with B2 (33.8% vs. 23.7%), B3 (21.2% vs. 18.4%) behavior and perianal disease (36.7% vs. 16.8%) than inland centers (p < 0.0001). Increase in duration from disease onset to enrollment and increase in duration from disease initial definite diagnosis to enrollment in registry were risk factors associated with patients of B2 and B3 behavior (OR = 1.006, p = 0.002; and OR = 1.007, p = 0.009, respectively). Currently smoking (OR = 2.454, p = 0.020) was also associated with patients with B2 and B3 behavior (Additional file 1: Table S3).

CD was classified as being localized in the L3 region in the majority of patients (56.2%, 277/493) (Fig. 3). Former smokers had higher probability of having CD localized in terminal ileal (L1) region than ileocolonic (L3) region (OR = 0.205, p = 0.004, Additional file 1: Table S4). Body mass index (BMI) in normal range (18.5–24 kg/m2) was associated with colonic (L2) location compared with L1 location (OR = 0.404, p = 0.017).
Fig. 3

Disease behavior (a) and disease location (b) classification of patients with Crohn’s disease. B1: non-stricturing non-penetrating; B2: stricturing; B3: penetrating; L1: terminal ileum; L2: colon; L3: ileocolon; L4: upper gastrointestinal tract

Patients who had perianal disease were younger at disease onset (25.3 ± 9.40 vs. 29.0 ± 10.92 years, p = 0.0003), at initial definite diagnosis (27.7 ± 10.02 vs. 31.8 ± 11.19 years, p = 0.0001), and at enrollment (28.9 ± 10.05 vs. 33.7 ± 11.67 years, p < 0.0001) than patients without perianal disease (Table 5). Duration from initial diagnosis to enrollment (14.8 ± 24.97 vs. 22.9 ± 43.29 months, p = 0.0345) and duration from disease onset to enrollment (43.8 ± 44.55 vs. 56.2 ± 63.75 months, p = 0.0341) were significantly shorter in patients with perianal disease. Logistic model for correlation analysis revealed that younger age at enrollment (OR = 0.957, p < 0.001), shorter disease course (time from disease onset to enrollment, OR = 0.996, p = 0.036), smoking (former vs. never, OR = 0.209, p = 0.036), B2 disease behavior (OR = 0.514, p = 0.006), and L3 disease location (OR = 3.052, p < 0.001) were associated with perianal disease (Table 6). Patients with perianal disease had higher proportion of anti-tumor necrosis factor α (TNFα) agents use (41.7% vs. 29.6%, p = 0.0098) and antibiotics use (20.8% vs. 10.0%, p = 0.0012).
Table 5

Demographic and clinical characteristics - grouped by baseline perianal disease

Variable

Total

Patients with perianal disease

Patients without perianal disease

P value

N (%)

499

144 (28.9%)

355 (71.1%)

 

Age (years), mean (SD)

32.3 (11.43)

28.9 (10.05)

33.7 (11.67)

< 0.0001

Male, n (%)

348 (69.7%)

102 (70.8%)

246 (69.3%)

0.7348

BMI (kg/m2), mean (SD)

19.10 (3.198)

19.29 (3.254)

19.04 (3.182)

0.5446

Age at disease onset (years), mean (SD)

27.9 (10.63)

25.3 (9.40)

29.0 (10.92)

0.0003

Age group at disease onset (years), n (%)

   

0.0556

 N

499

144

355

 

  ≤ 16

29 (5.8%)

7 (4.9%)

22 (6.2%)

 

 17–39

401 (80.4%)

125 (86.8%)

276 (77.7%)

 

  ≥ 40

69 (13.8%)

12 (8.3%)

57 (16.1%)

 

Age at initial definite diagnosis (years), mean (SD)

30.6 (11.01)

27.7 (10.02)

31.8 (11.19)

0.0001

Time from disease onset to initial diagnosis (months), mean (SD)

32.0 (46.43)

29.0 (38.54)

33.2 (49.27)

0.3672

Time from initial diagnosis to enrollment (months), mean (SD)

20.6 (39.06)

14.8 (24.97)

22.9 (43.29)

0.0345

Time from disease onset to enrollment (months), mean (SD)

52.6 (59.08)

43.8 (44.55)

56.2 (63.75)

0.0341

Nicotine use history, n (%)

   

0.0188

 N

442

124

318

 

 Never used

382 (86.4%)

116 (93.5%)

266 (83.6%)

 

 Current user

36 (8.1%)

6 (4.8%)

30 (9.4%)

 

 Former user

24 (5.4%)

2 (1.6%)

22 (6.9%)

 

Alcohol use history, n (%)

   

0.3203

 N

443

124

319

 

 Never used

401 (90.5%)

116 (93.5%)

285 (89.3%)

 

 Current user

22 (5.0%)

3 (2.4%)

19 (6.0%)

 

 Former user

20 (4.5%)

5 (4.0%)

15 (4.7%)

 

Location, n (%)

   

< 0.0001

 N

493

143

350

 

 L1

137 (27.8%)

23 (16.1%)

114 (32.6%)

 

 L2

71 (14.4%)

14 (9.8%)

57 (16.3%)

 

 L3

277 (56.2%)

105 (73.4%)

172 (49.1%)

 

 L4

8 (1.6%)

1 (0.7%)

7 (2.0%)

 

Behavior, n (%)

   

0.0309

 N

495

144

351

 

 B1

247 (49.9%)

84 (58.3%)

163 (46.4%)

 

 B2

148 (29.9%)

32 (22.2%)

116 (33.0%)

 

 B3

100 (20.2%)

28 (19.4%)

72 (20.5%)

 

Crohn’s disease treatment information at baseline, n (%)

 Immunomodulators

207 (41.5%)

64 (44.4%)

143 (40.7%)

0.4480

 Anti-TNF agents

164 (32.9%)

60 (41.7%)

104 (29.6%)

0.0098

 Aminosalicylates

103 (20.6%)

23 (16.0%)

80 (22.8%)

0.0896

 Steroids

99 (19.8%)

24 (16.7%)

75 (21.4%)

0.2350

 Enteral nutrition

69 (13.8%)

24 (16.7%)

45 (12.8%)

0.2618

 Antibiotics

65 (13.0%)

30 (20.8%)

35 (10.0%)

0.0012

 Anti-tuberculosis

27 (5.4%)

11 (7.6%)

16 (4.6%)

0.1705

 Other agentsa

115 (23.0%)

40 (27.8%)

75 (21.4%)

0.1251

aOther agents including traditional Chinese medicine, et al. B1 non-stricturing non-penetrating, B2 stricturing, B3 penetrating, BMI body mass index, L1 terminal ileum, L2 colon, L3 ileocolon, L4 upper gastrointestinal tract

Table 6

Logistic model for each correlation factors to baseline perianal disease (has perianal disease vs. no perianal disease)

Variable

OR

95% CI for OR

Parameter estimates (standard error)

Corresponding 95% CI

P value

Age (years)

0.957

0.937, 0.977

−0.044 (0.011)+

−0.065, −0.023

<.001*

Sex (male vs. female)

1.072

0.701, 1.638

0.069 (0.216)

−0.355, 0.493

0.749

BMI (18.5 - < 24 vs. < 18.5 kg/m2)

1.082

0.632, 1.854

0.079 (0.275)

−0.459, 0.617

0.773

BMI (≥24 vs. < 18.5 kg/m2)

1.795

0.688, 4.683

0.585 (0.489)+

−0.373, 1.544

0.231

Nicotine use (former vs. Never)

0.209

0.048, 0.904

−1.564 (0.747)+

−3.028, −0.100

0.036*

Nicotine use (current vs. Never)

0.460

0.187, 1.136

−0.776 (0.461)+

−1.679, 0.127

0.092

Alcohol use (former vs. Never)

0.822

0.292, 2.313

−0.196 (0.528)

−1.231, 0.839

0.710

Alcohol use (current vs. Never)

0.389

0.113, 1.341

−0.943 (0.631)+

−2.180, 0.293

0.135

Time from disease onset to enrollment (months)

0.996

0.992, 1.000

−0.004 (0.002)+

−0.008, − 0.000

0.036*

Time from initial definite diagnosis to enrollment (months)

0.993

0.986, 1.000

−0.007 (0.003)+

−0.014, − 0.000

0.039*

Disease behavior (B2 vs. B1)

0.514

0.320, 0.827

−0.665 (0.243)+

−1.141, − 0.190

0.006*

Disease behavior (B3 vs. B1)

0.755

0.453, 1.256

−0.282 (0.260)+

−0.791, 0.228

0.279

Disease behavior (B3 vs. B2)

1.468

0.814, 2.646

0.384 (0.301)+

−0.206, 0.973

0.202

Disease location (L3 vs. L1)

3.052

1.834, 5.079

1.116 (0.260)+

0.607, 1.6252

<.001*

Disease location (L3 vs. L2)

2.485

1.320, 4.681

0.911 (0.323)+

0.277, 1.544

0.005*

“No perianal disease” is the reference level. +: standard error is not larger than parameter estimates. *: P < 0.05. B1 non-stricturing non-penetrating, B2 stricturing, B3 penetrating, BMI body mass index, CI confidence interval, L1 terminal ileum, L2 colon, L3 ileocolon, OR odds ratio

Medical treatment and disease activity

At baseline, the mean (SD) CDAI score was 159.1 (91.45) and half of the patients (49.1%, 81/165) were in disease remission. Severe CDAI scores at baseline were reported in only 1.2% (2/165) of the patients. Patients enrolled in coastal medical centers had a higher proportion of moderate active disease (30.6% vs. 16.3%), and a smaller proportion of mild active disease (17.6% vs. 35.0%) than patients enrolled in inland centers (p = 0.0094).

At baseline, most of the patients (88.4%, 441/499) had a history of using any medicine for CD management. Less than 50% of patients were receiving immunomodulators (41.5%, n = 207; e.g., azathioprine) or anti-TNFα agents (32.9%, n = 164). About one-fifth of patients were on aminosalicylates (20.6%, n = 103) or steroids (19.8%, n = 99) (Table 1). Compared with inland centers, coastal centers had a higher use of anti-TNF agents (37.0% vs. 26.2%, p = 0.0123), enteral nutrition (20.5% vs. 3.1%, p < 0.0001), antibiotics (19.2% vs. 3.1%, p < 0.0001), anti-tuberculosis (8.4% vs. 0.5%, p < 0.0001) and other agents including traditional Chinese medicine (35.1% vs. 3.7%, p < 0.0001), but with a lower use of steroids (14.9% vs. 27.7%, p = 0.0005).

Discussion

To our knowledge, this is one of the largest registry studies of CD in China till now, and the results reveal the disease characteristics, behaviors and treatment strategies of CD in China, including difference between inland and coastal medical centers. The results may be helpful to understand the current situation of CD in China. This registry study demonstrated that the number of male patients outweighed the number of female patients, which may reflect a higher prevalence of CD in men. Commonly reported symptoms of CD were abdominal pain, diarrhea, weight loss and fever. More than half of the patients had ileocolonic involvement, and half of the patients were of the non-stricturing non-penetrating behavior. Age, disease duration, B2 or B3 disease behavior and perianal disease were associated with CD-related surgery. This registry study also demonstrated that the diagnosis period was significantly shortened during the recent years in China.

Data of the present study demonstrated a male predominance in CD, with a male vs. female ratio of 2.30:1, which is consistent with the previous studies in Asian countries including data from Korea [7], Japan [17], India [18], Sri Lanka [19], Singapore [20] and others [21, 22]. In contrast, the incidence of CD in women is greater or equal to that in men in Western countries [23, 24, 25]. Thus far, no explanation is available for such discrepancies between Asian and Western populations, but this could be attributed to differences in genetic susceptibility and men having a greater possibility of seeking job opportunities in industrialized areas at a younger age, thus being exposed to potential environmental risk factors early in life. The peak incidence of CD observed in this study was in the fourth decade of life (32.3 years), consistent with previous reports from China [10, 26]. Studies in Western population have demonstrated a bimodal distribution in the age at onset of CD, with a peak occurring at 20–39 years and another peak at 50–79 years [27, 28, 29, 30]. Studies in Asian populations have demonstrated either a less prominent second peak [7, 31, 32] or no second peak [33]. The exact reason for the bimodal distribution in the Western population is unclear, but it may be attributed to passive and active smoking in childhood and adulthood and sensitivities of different age groups to certain infectious factors [30, 34].

In terms of disease location, 56.2% patients had ileocolonic disease, whereas only 14.4% of the patients had colonic disease, which is consistent with the results from a single-center study from China [29]. Ileocolonic disease is also the most common CD phenotype in other Asian countries like Japan (65.8%) [35] and South Korea (77.7%) [7]. In Western countries, data on the disease location are relatively homogeneous largely with colonic, upper gastrointestinal and intestinal involvement. A population-based study from Hungary demonstrated that disease location for patients with CD was greatest in ileocolon (44.2%), followed by colon (35.6%), ileum (20.2%) and upper gastrointestinal region (2.4%) [36]. Disease behavior was clinically relevant as it is associated with the development of CD-related complications and need for surgery. At baseline, the disease behavior phenotypes (49.9% B1, 29.9% B2 and 20.2% B3) were concordant with a previous study from China and other studies from Asian countries [11, 33, 36]. Studies in western population have demonstrated that B1 was the most frequently observed behavior, with a frequency of nearly 80%. This difference might due to our registry patients who were not newly diagnosis CD patients, and the disease had already progressed to a more severe behavior. Accordingly, a larger proportion of patients change their behavior pattern to a more aggressive type (B2 and B3) after 5, 10 and 15 years of follow-up [37], and this may be attributed to increased smoking, disease location and clinical activity of the disease.

In concordance with other studies in the Asian population [36, 38, 39], abdominal pain, diarrhea and weight loss were the leading presenting symptoms of CD noted in the present study population. In the Western population, the incidence of diarrhea was the highest (79%), followed by abdominal pain (63%) and weight loss (21%) [40]. Certain extraintestinal manifestations such as oral ulcer, arthritis, skin lesions and uveitis often occur in patients with CD. The prevalence of extraintestinal manifestations was lower in the Asian population compared with the Western population (11% vs. 25–40%) [41, 42, 43]. Less frequent extraintestinal manifestations may be associated with relatively better prognosis among patients from Asian countries as compared with patients from Western countries.

Of the 499 patients, 23.8% (119/499) had history of CD-related surgery other than perianal disease surgery (15.8%). Older age at enrollment, longer disease duration, longer duration from disease onset to initial diagnosis and penetrating behavior were all risk factors related to CD surgery. A delayed diagnosis could result in missing the best timing for treatment, thus affecting the prognosis and increasing the risk of CD-related surgery [44]. Thus, diagnostic delay of CD is a challenge in several parts of the world. In Switzerland [45], the diagnostic delay was reported about 24 months. The analysis of the CD diagnosis period in the present registry revealed that the diagnostic period was significantly shortened in recent years. The current study found that patients with CD-related surgery history had a relatively lower presence of perianal disease. In the literature, patients with perianal disease carry a higher risk of surgery and this suggests a more severe disease course. [46] In the present study, patients with perianal disease also had a younger age at disease onset and a shorter duration from disease onset to enrollment, as well as a higher use of anti-TNF agents. These differences indicate that the presence of perianal disease may be shortened the diagnosis awareness and be helpful in differentiating from intestinal tuberculosis. A shorter diagnostic duration and a higher proportion of anti-TNF use might explain the negative association between perianal disease and bowel surgery.

In the present disease registry, immunomodulators were used frequently (41.5%) for the treatment of CD. A retrospective review in a population from East China demonstrated that 26.9% (61/227) patients had indications for immunomodulator use; however, such agents were prescribed to 34.4% of patients, of which, 37.5% received a subtherapeutic dose with no attempt of dose escalation [46]. The use of immunomodulators early in the course of the disease has been reported to be more effective in achieving clinical remission than conventional step-up therapy, but not in preventing relapse [47]. In Asia, anti-TNFs are used less frequently for the treatment of patients with CD. Sung et al. demonstrated that physicians in Asia favored anti-TNFs as a second-line therapy for CD [48]. A retrospective study from Korea, conducted from 1991 to 2007, reported that only 8.6% of patients with CD used infliximab [36]. Another study comparing the management of CD between Melbourne and Hong Kong demonstrated that a significantly higher percentage of patients were on anti-TNFs therapy in Melbourne than in Hong Kong (40% vs. 11%) [49]. Anti-TNFs are effective in inducing and maintaining clinical remission of CD [50, 51], and the use in the current study was higher (32.9%) than in other Asian countries. Thus, these results indicate that the update of new treatment paradigms was well adopted in China, especially in coastal medical centers. This multicenter study definitely helps inform a strategy for prevention and management programs for patients with CD in China by stratifying disease risk factors.

In the current study, because only baseline data were analyzed, disease progression and treatment effect could not be observed. Hence, further studies are warranted to describe the long-term disease progression. In addition, the small sample size of the current study may likely be interpreted as a selection bias. Patients were recruited from selected medical centers but not from national or regional registry. Since young patients < 18 years of age and women with pregnancy were excluded, the present study may not exactly reflect the profiles of the whole population. Adjuvant therapy such as enteral nutrition therapy, antibiotics and immunosuppressants may also affect the prognosis and disease behaviors.

Conclusions

This multicenter, observational study was conducted in China to analyze the nationwide disease characteristics, clinical behavior and treatment strategies in patients with CD. This study indicated that the clinical features of CD in China were different from those in Western countries in terms of age, sex distribution, disease location, disease behavior, the prevalence of extra-intestinal manifestations and treatment practices. These findings have important implications for local resource allocation, healthcare planning and to further update the clinical guidelines for management of CD in China.

Notes

Acknowledgements

The authors thank the study participants, without whom the study would never have been accomplished.

Authors’ contributions

JQ: principal investigator, who contributed to study design, study supervision and editing of the manuscript. YL: study design, protocol development, data interpretation, and drafting and editing of the manuscript. BC, XG, NH, MFH, ZR, ZL, JZ, DZ, XW, JR, JS, PZ, HW, MC, and JC: study design and implementation, protocol development, and data collection. PX, JL, MH, YFL, and HF: statistical analyses and data interpretation. All authors read and approved the final manuscript.

Funding

This work was supported by Xi’an Janssen Pharmaceutical Ltd., Beijing, China. The funding body had a role in data analysis and data interpretation.

Ethics approval and consent to participate

This study was conducted in accordance with the ethical principles originating in the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The Institutional Review Board at each study site approved the trial design.(see the REMICADECRD4018 CSR IRB-IEC List).

All the eligible patients provided written informed consent before participating in the study.

Consent for publication

Not applicable.

Competing interests

This work was supported by Xi’an Janssen Pharmaceutical Ltd., Beijing, China. The funding body had a role in data analysis and data interpretation. No other competing interests exist.

Supplementary material

12876_2019_1057_MOESM1_ESM.doc (112 kb)
Additional file 1 : Table S1. List of participating centers; Full analysis set. Table S2. Subject dispositions; Screened analysis set. Table S3. Logistic model for each correlation factor to Crohn’s disease behavior (B1 vs. B2 + B3); Full analysis set. Table S4. Logistic model for each correlation factors to Crohn’s disease localization (L1 vs. L2 vs. L3 vs. L4); Full analysis set. (DOC 111 kb)

References

  1. 1.
    Ha F, Khalil H. Crohn’s disease: a clinical update. Ther Adv Gastroenterol. 2015;8(6):352–9.CrossRefGoogle Scholar
  2. 2.
    Ananthakrishnan AN. Epidemiology and risk factors for IBD. Nat Rev Gastroenterol Hepatol. 2015;12(4):205–17.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 2012;142(1):46–54 e42 quiz e30.CrossRefGoogle Scholar
  4. 4.
    Chuang CH, Lin SH, Chen CY, Sheu BS, Kao AW, Wang JD. Increasing incidence and lifetime risk of inflammatory bowel disease in Taiwan: a nationwide study in a low-endemic area 1998-2010. Inflamm Bowel Dis. 2013;19(13):2815–9.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Ng SC. Emerging trends of inflammatory bowel disease in Asia. Gastroenterol Hepatol. 2016;12(3):193–6.Google Scholar
  6. 6.
    Wei SC, Lin MH, Tung CC, Weng MT, Kuo JS, Shieh MJ, Wang CY, Ho WC, Wong JM, Chen PC. A nationwide population-based study of the inflammatory bowel diseases between 1998 and 2008 in Taiwan. BMC Gastroenterol. 2013;13:166.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Yang SK, Yun S, Kim JH, Park JY, Kim HY, Kim YH, Chang DK, Kim JS, Song IS, Park JB, et al. Epidemiology of inflammatory bowel disease in the Songpa-Kangdong district, Seoul, Korea, 1986-2005: a KASID study. Inflamm Bowel Dis. 2008;14(4):542–9.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Wen S. A case report of gastric, duodenal and jejunal crohn’s disease. Chinese Med J. 1956;5:379–581.Google Scholar
  9. 9.
    Wang PQ, Hu J, Al Kazzi ES, Akhuemonkhan E, Zhi M, Gao X, de Paula Pessoa RH, Ghazaleh S, Cornelius T, Sabunwala SA, et al. Family history and disease outcomes in patients with Crohn’s disease: a comparison between China and the United States. World J Gastrointest Pharmacol Ther. 2016;7(4):556–63.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Zeng Z, Zhu Z, Yang Y, Ruan W, Peng X, Su Y, Peng L, Chen J, Yin Q, Zhao C, et al. Incidence and clinical characteristics of inflammatory bowel disease in a developed region of Guangdong Province, China: a prospective population-based study. J Gastroenterol Hepatol. 2013;28(7):1148–53.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Zhao J, Ng SC, Lei Y, Yi F, Li J, Yu L, Zou K, Dan Z, Dai M, Ding Y, et al. First prospective, population-based inflammatory bowel disease incidence study in mainland of China: the emergence of “western” disease. Inflamm Bowel Dis. 2013;19(9):1839–45.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Lakatos L, Kiss LS, David G, Pandur T, Erdelyi Z, Mester G, Balogh M, Szipocs I, Molnar C, Komaromi E, et al. Incidence, disease phenotype at diagnosis, and early disease course in inflammatory bowel diseases in Western Hungary, 2002-2006. Inflamm Bowel Dis. 2011;17(12):2558–65.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Hu D, Ren J, Wang G, Gu G, Liu S, Wu X, Chen J, Ren H, Hong Z, Li J. Geographic mapping of Crohn’s disease and its relation to affluence in Jiangsu province, an eastern coastal province of China. Gastroenterol Res Pract. 2014;2014:590467.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Yang H, Li Y, Wu W, Sun Q, Zhang Y, Zhao W, Lv H, Xia Q, Hu P, Li H, et al. The incidence of inflammatory bowel disease in northern China: a prospective population-based study. PLoS One. 2014;9(7):e101296.PubMedPubMedCentralCrossRefGoogle Scholar
  15. 15.
    Jia Z, Cheng S, Ma Y, Zhang T, Bai L, Xu W, He X, Zhang P, Zhao J, Christiani DC. Tuberculosis burden in China: a high prevalence of pulmonary tuberculosis in household contacts with and without symptoms. BMC Infect Dis. 2014;14:64.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Satsangi J, Silverberg MS, Vermeire S, Colombel JF. The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut. 2006;55(6):749–53.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Yao T, Matsui T, Hiwatashi N. Crohn’s disease in Japan: diagnostic criteria and epidemiology. Dis Colon Rectum. 2000;43(10 Suppl):S85–93.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Das K, Ghoshal UC, Dhali GK, Benjamin J, Ahuja V, Makharia GK. Crohn’s disease in India: a multicenter study from a country where tuberculosis is endemic. Dig Dis Sci. 2009;54(5):1099–107.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Subasinghe D, Nawarathna NM, Samarasekera DN. Disease characteristics of inflammatory bowel disease (IBD): findings from a tertiary care Centre in South Asia. J Gastrointest Surg. 2011;15(9):1562–7.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Lee YM, Fock K, See SJ, Ng TM, Khor C, Teo EK. Racial differences in the prevalence of ulcerative colitis and Crohn’s disease in Singapore. J Gastroenterol Hepatol. 2000;15(6):622–5.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Makharia GK, Ramakrishna BS, Abraham P, Choudhuri G, Misra SP, Ahuja V, Bhatia SJ, Bhasin DK, Dadhich S, Dhali GK, et al. Survey of inflammatory bowel diseases in India. Indian J Gastroenterol. 2012;31(6):299–306.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Malekzadeh MM, Vahedi H, Gohari K, Mehdipour P, Sepanlou SG, Ebrahimi Daryani N, Zali MR, Mansour-Ghanaei F, Safaripour A, Aghazadeh R, et al. Emerging epidemic of inflammatory bowel disease in a middle income country: a nation-wide study from Iran. Arch Iran Med. 2016;19(1):2–15.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Kyle J. Crohn’s disease in the northeastern and northern isles of Scotland: an epidemiological review. Gastroenterology. 1992;103(2):392–9.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Shivananda S, Pena AS, Nap M, Weterman IT, Mayberry JF, Ruitenberg EJ, Hoedemaeker PJ. Epidemiology of Crohn’s disease in Regio Leiden, the Netherlands. A population study from 1979 to 1983. Gastroenterology. 1987;93(5):966–74.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Wu D, Chen C, Wu S, DAI L, XIA L, CHEN X. A retrospective study on clinical characteristics of paediatric Crohn’s disease. HK J Paediatr. 2014;19:169–74.Google Scholar
  26. 26.
    Zheng JJ, Zhu XS, Huangfu Z, Shi XH, Guo ZR. Prevalence and incidence rates of Crohn’s disease in mainland China: a meta-analysis of 55 years of research. J Dig Dis. 2010;11(3):161–6.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Ekbom A, Helmick C, Zack M, Adami HO. The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden. Gastroenterology. 1991;100(2):350–8.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Loftus CG, Loftus EV Jr, Harmsen WS, Zinsmeister AR, Tremaine WJ, Melton LJ 3rd, Sandborn WJ. Update on the incidence and prevalence of Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000. Inflamm Bowel Dis. 2007;13(3):254–61.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Mocanu D, Catuneanu AM, Diculescu M, Gologan S, Sporea I. Current epidemiologic trends in Crohn’s disease: data from a tertiary referral Centre in Bucharest: (Fundeni institute, Center of Gastroenterology and Hepatology). Maedica (Buchar). 2010;5(2):95–101.Google Scholar
  30. 30.
    Park SJ, Kim WH, Cheon JH. Clinical characteristics and treatment of inflammatory bowel disease: a comparison of eastern and Western perspectives. World J Gastroenterol. 2014;20(33):11525–37.PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Asakura K, Nishiwaki Y, Inoue N, Hibi T, Watanabe M, Takebayashi T. Prevalence of ulcerative colitis and Crohn’s disease in Japan. J Gastroenterol. 2009;44(7):659–65.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Ng SC, Tang W, Ching JY, Wong M, Chow CM, Hui AJ, Wong TC, Leung VK, Tsang SW, Yu HH, et al. Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn’s and colitis epidemiology study. Gastroenterology. 2013;145(1):158–65 e152.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Moon CM, Park DI, Kim ER, Kim YH, Lee CK, Lee SH, Kim JH, Huh KC, Jung SA, Yoon SM, et al. Clinical features and predictors of clinical outcomes in Korean patients with Crohn’s disease: a Korean association for the study of intestinal diseases multicenter study. J Gastroenterol Hepatol. 2014;29(1):74–82.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Wang YF, Zhang H, Ouyang Q. Clinical manifestations of inflammatory bowel disease: east and west differences. J Dig Dis. 2007;8(3):121–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Oriuchi T, Hiwatashi N, Kinouchi Y, Takahashi S, Takagi S, Negoro K, Shimosegawa T. Clinical course and longterm prognosis of Japanese patients with Crohn’s disease: predictive factors, rates of operation, and mortality. J Gastroenterol. 2003;38(10):942–53.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Ye BD, Yang SK, Cho YK, Park SH, Yang DH, Yoon SM, Kim KJ, Byeon JS, Myung SJ, Yu CS, et al. Clinical features and long-term prognosis of Crohn’s disease in Korea. Scand J Gastroenterol. 2010;45(10):1178–85.PubMedCrossRefGoogle Scholar
  37. 37.
    Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, Gendre JP. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis. 2002;8(4):244–50.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Li X, Song P, Li J, Tao Y, Li G, Li X, Yu Z. The Disease Burden and Clinical Characteristics of Inflammatory Bowel Disease in the Chinese Population: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2017;14(3).PubMedCentralCrossRefGoogle Scholar
  39. 39.
    Jiang L, Xia B, Li J, Ye M, Yan W, Deng C, Ding Y, Luo H, Hou W, Zhao Q, et al. Retrospective survey of 452 patients with inflammatory bowel disease in Wuhan city, Central China. Inflamm Bowel Dis. 2006;12(3):212–7.PubMedCrossRefGoogle Scholar
  40. 40.
    Penn KA, Whittle DO, Lee MG. Inflammatory bowel disease in Jamaica. Ann Gastroenterol. 2013;26(3):239–42.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Ephgrave K. Extra-intestinal manifestations of Crohn’s disease. Surg Clin North Am. 2007;87(3):673–80.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Hsu YC, Wu TC, Lo YC, Wang LS. Gastrointestinal complications and extraintestinal manifestations of inflammatory bowel disease in Taiwan: a population-based study. J Chin Med Assoc. 2017;80(2):56–62.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Luo CH, Wexner SD, Liu QS, Li L, Weiss E, Zhao RH. The differences between American and Chinese patients with Crohn’s disease. Color Dis. 2011;13(2):166–70.CrossRefGoogle Scholar
  44. 44.
    Li Y, Ren J, Wang G, Gu G, Wu X, Ren H, Hong Z, Hu D, Wu Q, Li G, et al. Diagnostic delay in Crohn’s disease is associated with increased rate of abdominal surgery: a retrospective study in Chinese patients. Dig Liver Dis. 2015;47(7):544–8.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Vavricka SR, Spigaglia SM, Rogler G, Pittet V, Michetti P, Felley C, Mottet C, Braegger CP, Rogler D, Straumann A, et al. Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease. Inflamm Bowel Dis. 2012;18(3):496–505.PubMedCrossRefGoogle Scholar
  46. 46.
    Huang LJ, Zhu Q, Lei M, Cao Q. Current use of immunosuppressive agents in inflammatory bowel disease patients in East China. World J Gastroenterol. 2009;15(24):3055–9.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Kwak MS, Kim DH, Park SJ, Kim TI, Hong SP, Kim WH, Cheon JH. Efficacy of early immunomodulator therapy on the outcomes of Crohn’s disease. BMC Gastroenterol. 2014;14:85.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Sung JJ, Kamm MA, Marteau P. Asian perspectives in the management of inflammatory bowel disease: findings from a recent survey. J Gastroenterol Hepatol. 2010;25(1):183–93.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Prideaux L, Kamm MA, De Cruz P, Williams J, Bell SJ, Connell WR, Brown SJ, Lust M, Desmond PV, Chan H, et al. Comparison of clinical characteristics and management of inflammatory bowel disease in Hong Kong versus Melbourne. J Gastroenterol Hepatol. 2012;27(5):919–27.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, et al. Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial. Lancet. 2002;359(9317):1541–9.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Schreiber S, Khaliq-Kareemi M, Lawrance IC, Thomsen OO, Hanauer SB, McColm J, Bloomfield R, Sandborn WJ, Investigators PS. Maintenance therapy with certolizumab pegol for Crohn’s disease. N Engl J Med. 2007;357(3):239–50.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© The Author(s). 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors and Affiliations

  • Yue Li
    • 1
  • Baili Chen
    • 2
  • Xiang Gao
    • 3
  • Naizhong Hu
    • 4
  • Meifang Huang
    • 5
  • Zhihua Ran
    • 6
  • Zhanju Liu
    • 7
  • Jie Zhong
    • 8
  • Duowu Zou
    • 9
  • Xiaoping Wu
    • 10
  • Jianlin Ren
    • 11
  • Jianqiu Sheng
    • 12
  • Ping Zheng
    • 13
  • Huahong Wang
    • 14
  • Minhu Chen
    • 2
  • Junrong Chen
    • 3
  • Peng Xi
    • 15
  • Jiajia Lu
    • 16
  • Malcolm Handel
    • 17
  • Yanfang Liu
    • 18
  • Hua Fan
    • 19
  • Jiaming Qian
    • 1
    Email author
  1. 1.Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.The First Affiliated Hospital, Sun Yat-sen UniversityGuangzhouChina
  3. 3.The Sixth Affiliated Hospital, Sun Yat-sen UniversityGuangzhouChina
  4. 4.The First Affiliated Hospital of Anhui Medical UniversityHefeiChina
  5. 5.Zhongnan Hospital of Wu Han UniversityWuhanChina
  6. 6.Renji Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  7. 7.Shanghai Tenth Peoples Hospital of Tongji UniversityShanghaiChina
  8. 8.Ruijin Hospital, Shanghai Jiao Tong University School of MedicineShanghaiChina
  9. 9.Changhai Hospital, Second Military Medical UniversityShanghaiChina
  10. 10.The Second Xiangya Hospital of Central South UniversityChangshaChina
  11. 11.Zhongshan Hospital, Xiamen UniversityXiamenChina
  12. 12.Army General HospitalBeijingChina
  13. 13.Dongfang Hospital of Tongji UniversityShanghaiChina
  14. 14.Peking University First HospitalBeijingChina
  15. 15.Medical Affairs, Xi’an Janssen Pharmaceutical Ltd.BeijingChina
  16. 16.Johnson & Johnson (China) Investment Ltd. Janssen China R&D CenterBeijingChina
  17. 17.Janssen Asia-PacificSydneyAustralia
  18. 18.Janssen Asia-PacificSingaporeSingapore
  19. 19.Medical Affairs, Takeda ChinaShanghaiChina

Personalised recommendations