Patients with inflammatory bowel disease (IBD) are diagnosed with ankylosing spondylitis (AS) often. However, the disease course of patients with both IBD and AS is not well understood. This study aims to evaluate the effect of concomitant AS on IBD outcomes.
Among the 4,722 patients with IBD who were treated in 3 academic hospitals from 2004 to 2021, 55 were also diagnosed with AS (IBD-AS group). Based on patients’ electronic medical records, the outcomes of IBD in IBD-AS group and IBD group without AS (IBD-only group) were appraised.
The proportion of patients treated with biologics or small molecule therapies was significantly higher in IBD-AS group than the proportion in IBD-only group (27.3% vs. 12.7%,
Concomitant AS is associated with the high possibility of biologics or small molecule therapies for IBD. IBD patients who also had AS may need more careful examination and active treatment to alleviate the severity of IBD.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of gastrointestinal tract and is classified as ulcerative colitis (UC) and Crohn’s disease (CD). The pathogenesis of IBD is not well established but multiple factors, including genetic, immunologic, microbial, and environmental factors, might comprehensively develop and aggravate IBD [
Arthritis is one of the extragastrointestinal manifestations that can be observed in patients with IBD. Arthritis in IBD patients was divided into 2 different clinical patterns: peripheral arthritis and axial arthritis. Major clinical characteristics of ankylosing spondylitis (AS) are sacroiliitis, inflammation in the axial skeleton, peripheral arthritis, enthesitis, and anterior uveitis [
On the other hand, a considerable number of IBD patients have clinical manifestations related to AS. The prevalence of AS in patients with IBD was in a range of 4%–10%, which was higher than that in the general population (0.32%–0.07%) [
The data was extracted from the electronic medical records of 3 hospitals; Seoul National University Hospital (SNUH), Seoul National University Bundang Hospital (SNUBH), and Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center. A retrospective cohort study included all patients who were diagnosed with both IBD and AS (IBD-AS group) in the 3 hospitals. Patients with AS were first identified by an International Classification of Disease, Tenth Revision (ICD-10) code of M45.0-45.9. The diagnosis of AS was confirmed according to the modified New York criteria by rheumatologic specialists [
The initial data, which included outpatient and inpatient records, admission and discharge summaries, surgery records, nursing information, and examination results, were collected and organized. The following covariates were extracted: age, age at diagnosis for IBD or AS, sex, types of IBD, surgery, emergent room (ER) visit, biologics, small molecules, IMMs, and comorbidities.
Bowel resection was usually performed when patients failed their medical treatments or had medically intractable complications [
Surgery included any kinds of operations for IBD complications. Bowel resection included operations that removed all or part of the small intestine or colon. When an operation did not include procedures of bowel resection such as anal fistulectomy or sphincterotomy, it did not belong to bowel resection but to surgery. ER visit was defined as the cases in which patients visit ER because of the symptoms or complications of IBD. Biologics were defined as infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab [
Propensity score matching (PSM) was applied to match the IBD-AS group and IBD-only group due to the unequal distribution of demographics between 2 groups at their baselines. Age, sex, and type of IBD were used as the matching scores. The nearest neighbor method on the logit scale and the match of 1:2 ratio were used. After PSM, 55 patients were included in IBD-AS group and 110 patients in only IBD group. PSM matching was performed by R version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria).
Statistical analysis was done by R 4.2.1 (R Foundation for Statistical Computing) and IBM SPSS Statistics 25.0 (IBM Corp., Armonk, NY, USA). Patient characteristics and outcomes are summarized using standard summary statistics. Mean±standard deviation was used for continuous variables and number and percentage for categorical variables. Student
Among the patients with IBD, 36 patients from SNUH, 13 from SNUBH, and 6 from SMG-SNU Boramae Medical Center were diagnosed with AS. IBD-AS group consisted of 14 CD patients (25.5%) and 41 UC patients (74.5%) (
The number of patients treated with biologics or small molecules was significantly larger in IBD-AS group than IBD-only group. In IBD-AS group, 15 (68.2%) and 7 (31.8%) patients were prescribed biologics or small molecules for the treatment of IBD and AS, respectively. Nearly two-thirds of IBD-AS and IBD-only patients experienced the treatment with only one type of biologics or small molecules. Adalimumab and infliximab were the most widely used biologics or small molecules in IBD-AS group and IBD-only group, respectively. There were no significant differences in the number and type of biologics between biologics or small molecules-treated IBD-AS group and IBD-only group.
According to the Montreal classification, more than half of CD-AS patients showed colon-involving disease extent (57.1%) and non-stricturing and non-penetrating behavior (57.1%). In UC patients, the most common disease extent was proctitis (41.2%) and the second most disease extent was left-side colitis (32.4%). The number of HLA-B27-positive patients was the same as in HLA-B27-negative patients in IBD-AS group. In IBD-AS group, 2 patients were diagnosed with pyoderma gangrenosum, 2 were diagnosed with uveitis, and 1 was diagnosed with non-axial arthritis. Most patients with IBD-AS (n = 44) took nonsteroidal anti-inflammatory drugs (NSAIDs) to relieve their axial arthralgia. Eight IBD-AS patients did not require the prescription of NSAIDs because their pain was tolerable without medication. The NSAIDs prescription information of 3 IBD-AS patients was not available.
Among IBD-AS patients, 37 patients were diagnosed with IBD before the onset of AS, and 15 patients were diagnosed with AS before the onset of IBD. There were no significant differences in age, age at diagnosis, sex, type of IBD, bowel resection, ER visit, treatment of biologics or small molecules, and C-reactive protein at diagnosis between patients who were diagnosed with IBD before the onset of AS and those who were diagnosed AS before the onset of IBD. However, the number of patients prescribed IMMs was significantly larger in patients who were diagnosed with AS before the onset of IBD than in those who were diagnosed with IBD before the onset of AS (
After PSM, 55 patients of IBD-AS group and 110 patients of IBD-only group, whose age, sex, and IBD type matched, were identified (
The characteristics of UC-AS group and matched only UC group was evaluated (
Univariable logistic regression analysis was performed to reveal risk factors for biologics or small molecule therapies (
Our present study revealed the characteristics and outcomes of IBD-AS patients, compared to patients with only IBD. IBD-AS patients had a higher risk of starting biologics or small molecules for IBD treatment than patients with only IBD. UC patients were likely to be treated with biologics or small molecules when they were also diagnosed with AS. There was no significant difference in IBD outcomes between CD-AS patients and patients with only CD.
Some studies showed similar results to our study. A Swiss cohort study reported that IBD patients with sacroiliitis or AS had more possibility to need anti-TNF agents or surgery for IBD treatment [
Patients with IBD and AS have a high risk of severe IBD because of pathophysiological correlation between IBD and AS. First, IBD and AS have similar genetic polymorphisms. Single-nucleotide polymorphism research revealed that IL23R and kinase proteins related to IL23R signaling, STAT3, and JAK2 were associated with AS [
IBS and AS share similar immunologic pathogenesis. CD4+ T cells and CD68+ macrophages were observed in inflammatory sacroiliac joints, entheses, and peripheral joint synovium from AS patients [
Severe colitis in IBD patients with AS can be explained by leaky gut theory. High permeability of intestinal barrier is one of the characteristics observed in the bowel from IBD patients. The higher intestinal permeability was correlated with the higher severity of experimental colitis in the murine model [
To our knowledge, this is the only study evaluating the characteristics and disease course of IBD patients with concomitant AS in Asia, where the prevalence of IBD and AS is increasing [
In conclusion, IBD patients with concomitant AS had a higher risk of the biologics or small molecule therapies for IBD than those without AS. Based on our study, clinicians should pay more attention to IBD patients with concomitant AS.
The authors received no financial support for the research, authorship, and/or publication of this article.
Lee HJ and Kang HW are editorial board members of the journal but were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Not applicable.
Conceptualization: Yoon H, Koh SJ, Park JW, Kang HW. Formal analysis: Jun YK, Kim AH, Kim KW. Methodology: Yoon H, Koh SJ, Park JW, Kang HW. Project administration: Lee HJ, Im JP, Park YS, Kim JS. Writing - original draft: Jun YK. Writing - review & editing: Jun YK, Yoon H, Koh SJ. Approval of final manuscript: all authors.
The authors are grateful to Seulji Kim, Hosun Yu, Young Yi Choi, Jaewook Shin, and Minji Oh for their supports of SIRN research works.
Supplementary materials are available at the Intestinal Research website (
Supplementary Table 1. Characteristics of Patients Diagnosed with IBD after the Onset of AS and Those before the Onset of AS
Supplementary Table 2. Characteristics Patients with UC and CD after Propensity Score Matching
Flow diagram of patients selected and matched in IBD-AS group and IBD-only group. IBD, inflammatory bowel disease; AS, ankylosing spondylitis; UC, ulcerative colitis; CD, Crohn’s disease.
Characteristics of IBD Patients with or without AS
Characteristics | IBD-AS group (n = 55) | IBD-only group (n = 4,665) | |
---|---|---|---|
Age (yr) | 42.7 ± 14.3 | 49.8 ± 18.7 | < 0.001 |
Age at diagnosis (yr) | < 0.001 | ||
IBD | 31.7 ± 14.2 | 42.2 ± 15.7 | |
AS | 34.0 ± 12.0 | ||
Sex | 0.676 | ||
Male | 36 (65.5) | 2,783 (59.7) | |
Female | 19 (34.5) | 1,882 (40.3) | |
Types of IBD | 0.073 | ||
Crohn’s disease | 14 (25.5) | 1,386 (29.8) | |
Ulcerative colitis | 41 (74.5) | 3,269 (70.2) | |
Diagnosis order | |||
IBD-AS | 35 (63.6) | ||
AS-IBD | 17 (30.9) | ||
Unknown | 3 (5.5) | ||
No. of patients treated with biologics or small molecules | 22 (40.0) | 653 (14.0) | 0.006 |
Cause for biologics or small molecules | |||
IBD | 15 (68.2) | ||
AS | 7 (31.8) | ||
No. of biologics or small molecules | 0.324 | ||
1 | 17 (77.3) | 484 (74.1) | |
2 | 3 (13.6) | 140 (19.6) | |
3 | 1 (4.5) | 17 (4.5) | |
More than 3 | 1 (4.5) | 12 (1.8) | |
Types of biologics or small molecules | 0.253 | ||
Adalimumab | 14 (63.6) | 239 (36.6) | |
Golimumab | 2 (9.1) | 41 (6.3) | |
Infliximab | 9 (40.9) | 461 (70.5) | |
Tofacitinib | 1 (4.5) | 17 (27.0) | |
Ustekinumab | 1 (4.5) | 41 (6.3) | |
Vedolizumab | 4 (18.2) | 64 (9.8) |
Values are presented as mean±standard deviation or number (%).
IBD, inflammatory bowel disease; AS, ankylosing spondylitis.
Characteristics and Comorbidities of Patients with IBD after Propensity Score Matching
Characteristics | IBD-only group (n = 110) | IBD-AS group (n = 55) | ||
---|---|---|---|---|
Age (yr) | 44.0 ± 12.8 | 42.7 ± 14.3 | 0.544 | |
Age at IBD diagnosis (yr) | 31.3 ± 11.7 | 31.7 ± 14.2 | 0.858 | |
Sex | Male | 78 (70.9) | 36 (65.5) | 0.592 |
Female | 32 (29.1) | 19 (34.5) | ||
IBD | CD | 27 (24.5) | 14 (25.5) | 1.000 |
UC | 83 (75.5) | 41 (74.5) | ||
Surgery | No | 91 (82.7) | 49 (89.1) | 0.398 |
Yes | 19 (17.3) | 6 (10.9) | ||
1 | 8 (42.1) | 2 (33.3) | 0.535 | |
2 | 2 (10.5) | 2 (33.3) | ||
3 | 3 (15.8) | 1 (16.7) | ||
4 | 2 (10.5) | 1 (16.7) | ||
5 | 1 (5.3) | 0 | ||
Bowel resection | No | 98 (89.1) | 49 (89.1) | 1.000 |
Yes | 12 (10.9) | 6 (10.9) | ||
1 | 10 (83.3) | 4 (66.7) | 0.688 | |
2 | 1 (8.3) | 2 (33.3) | ||
3 | 1 (8.3) | 0 | ||
Emergency room | No | 75 (68.2) | 42 (76.4) | 0.363 |
Yes | 35 (31.8) | 13 (23.6) | ||
1 | 14 (40.0) | 5 (38.5) | 0.342 | |
2 | 9 (25.7) | 2 (15.4) | ||
3 | 5 (14.3) | 0 | ||
4 | 0 | 3 (23.1) | ||
5 | 2 (5.7) | 0 | ||
≥6 | 5 (14.3) | 3 (23.1) | ||
Biologics or small molecules | No | 96 (87.3) | 40 (72.7) | 0.036 |
Yes | 14 (12.7) | 15 (27.3) | ||
1 | 8 (57.1) | 10 (66.7) | 0.024 | |
2 | 4 (28.6) | 3 (20.0) | ||
3 | 1 (7.1) | 1 (6.7) | ||
4 | 1 (7.1) | 0 | ||
5 | 0 | 1 (6.7) | ||
Immunomodulators | No | 74 (67.3) | 38 (69.1) | 0.953 |
Yes | 36 (32.7) | 17 (30.9) | ||
1 | 21 (58.3) | 1 (5.9) | 0.002 | |
2 | 15 (41.7) | 16 (94.1) | ||
Hypertension | No | 106 (96.4) | 52 (94.5) | 0.687 |
Yes | 4 (3.6) | 3 (5.5) | ||
Type 2 DM | No | 100 (90.9) | 53 (96.4) | 0.203 |
Yes | 10 (9.1) | 2 (3.6) | ||
Dyslipidemia | No | 109 (99.1) | 54 (98.2) | 0.615 |
Yes | 1 (0.9) | 1 (1.8) | ||
Immune-mediated disease |
No | 102 (92.7) | 50 (90.9) | 0.683 |
Yes | 8 (7.3) | 5 (9.1) | ||
Gastrointestinal cancer | No | 108 (98.2) | 55 (100.0) | 0.314 |
Yes | 2 (1.8) | 0 |
Values are presented as mean±standard deviation or number (%).
Immune-mediated disease included Behçet’s disease, Wegener’s disease, systemic lupus, multiple sclerosis, polymyositis, autoimmune hemolytic anemia, thrombocytopenic purpura, Henoch-Schonlein purpura, vitiligo, Graves’ disease, type 1 DM, psoriasis, erythema nodosum, pyoderma gangrenosum, celiac disease, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, polymyalgia rheumatica, rheumatoid arthritis, and hidradenitis.
IBD, inflammatory bowel disease; AS, ankylosing spondylitis; CD, Crohn’s disease; UC, ulcerative colitis; DM, diabetes mellitus.
Factors Associated with the Biologics or Small Molecules for IBD Evaluated by Univariable Logistic Regression Analysis
Biologics or small molecules | OR (95% CI) | |
---|---|---|
Only IBD group | Reference | < 0.001 |
IBD-AS group | 4.099 (1.863–9.021) | |
Ulcerative colitis | Reference | 0.002 |
Crohn’s disease | 3.552 (1.590–7.934) |
IBD, inflammatory bowel disease; OR, odds ratio; CI, confidence interval; AS, ankylosing spondylitis.