Open Journal of Gastroenterology, 2013, 3, 64-71 OJGas Published Online February 2013 (
Disparity in clinical care for patients with inflammatory
bowel disease between specialists and non-specialists
Tomoko Hirakawa1, Jun Kato2, Sakuma Takahashi1, Hideyuki Suzuki1, Mitsuhiro Akita1,
Izumi Inoue2, Hisanobu Deguchi2, Sakiko Hiraoka1, Hiroyuki Okada3, Kazuhide Yamamoto1
1Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama, Japan
2Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
3Department of Endoscopy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama,
Received 25 October 2012; revised 24 November 2012; accepted 1 December 2012
Background: Although inflammatory bowel disease
(IBD) patients have been increasing and new thera-
peutic options for IBD have been developed, there are
relatively few clinicians who specialize in IBD. Pa-
tients treated by a non-specialist of IBD may not re-
ceive appropriate treatment. This study aimed to
compare disease and medication status between IBD
patients treated by a specialist and those treated by a
non-specialist. Methods: Medical charts of ambulat-
ing IBD patients in two hospitals were examined. All
patients in one hospital were treated by one of the
IBD specialists, while in the other hospital, patients
were treated by one of the gastroenterologists who
was a non-specialist of IBD. Results: The numbers of
IBD patients were 255 (hospital with specialists) and
74 (hospital without specialists), respectively. Disease
activity of the patients was not well-controlled in the
hospital without specialists compared to in the hospi-
tal with specialists (ulcerative colitis (UC): p = 0.0006
and Crohn’s disease: p = 0.012, respectively). The
proportion of UC patients who received an insuffi-
cient dose of mesalazine (Pentasa < 3 g/day or Asacol
< 3.6 g/day) was higher in the hospital without spe-
cialists (47% vs. 15%, p < 0.0001). In the hospital
without specialists, more patients received long-term
corticosteroids (UC: 23% vs. 5%, p < 0.0001), while
fewer patients received immunomodulators (UC: 8%
vs. 46%, p < 0.0001). Conclusions: IBD patients of the
hospital without specialists were not well-controlled
and were not prescribed appropriately with thera-
peutic drugs. Fostering and placement of the special-
ist of IBD is an urgent problem.
Keywords: Inflammatory Bowel Disease; Clinical Care;
Inflammatory bowel disease (IBD) involves ulcerative
colitis (UC) and Crohn’s disease (CD). UC is a chronic
disease characterized by diffuse mucosal inflammation
limited to the colon. Meanwhile, CD can affect any part
of the gastrointestinal tract with focal, asymmetric, trans-
mural, and occasionally, granulomatous inflammation.
Patients of either disease suffer from symptoms such as
diarrhea, abdominal pain, bloody stool, etc. unless ap-
propriate treatment is provided. There are approximately
1.4 million and 2.2 million IBD patients in the USA and
in Europe, respectively [1-3]. Moreover, in recent years a
drastic increase in IBD patients has been noted in Asian
countries. In Japan, the numbers of UC and CD patients
were approximately 23,000 and 6600 in 1990, respec-
tively, while in 2010, the numbers had increased to more
than 120,000 and 30,000, respectively [4,5].
Recently, new therapeutic agents have become avail-
able for the treatment of IBD. In particular, new immu-
nomodulators such as cyclosporine, tacrolimus, and bio-
logics such as infliximab and adalimumab have been
shown to be effective for aggressive and/or refractory
UC and CD [6-11]. On the other hand, although 5-ami-
nosalicylic acid (5-ASA), corticosteroids, and older im-
munomodulators such as azathioprine and 6-mercapto-
purine (AZA and 6-MP) have been widely used, it is
rather difficult to make full use of these agents while
avoiding adverse effects. Corticosteroids can induce vari-
ous serious side effects such as hyperglycemia, cushin-
goid features, infections, osteoporosis, emotional and
psychiatric disturbances, gastroduodenal mucosal injury,
glaucoma, and cataracts. In addition, patients on chronic
corticosteroids are at risk of adrenal insufficiency.
Moreover, AZA and 6-MP are also not user-friendly be-
cause of frequent adverse effects including leukocyte-
penia, thrombocytopenia, alopecia, liver abnormalities,
T. Hirakawa et al. / Open Journal of Gastroenterology 3 (2013) 64-71 65
allergy, uncomfortable gastrointestinal symptoms, and
pancreatitis. Thus, more than ever highly specialized
knowledge and experience of biological and clinical fea-
tures of IBD are required for providing appropriate treat-
ment. Therefore, many guidelines have been made and
updated by various organizations in the USA [12,13],
Europe [14], and also in Japan [15,16].
In spite of these guidelines, however, inappropriate
treatments continue to be provided for many IBD pa-
tients because of the limited numbers of clinicians spe-
cializing in IBD. Even in the USA, considerable numbers
of patients who visited an IBD center for the purpose of
obtaining a second opinion were inappropriately treated,
e.g., with suboptimal doses of 5-ASA and immuno-
modulators, or with long-term corticosteroid therapy [17].
The situation is much worse in Japan, where there is now
a greater gap between the numbers of IBD specialists and
IBD patients because of the rapid increase in IBD pa-
tients. Because even gastroenterologists are in short sup-
ply in Japan, particularly in local areas, there is no opti-
mism in expectations for an increase of IBD specialists.
Thus, recent advances and traditional compassionate
care in providing therapeutic options of IBD can make a
great difference in the disease and status of IBD patients
according to the doctor’s skill, knowledge, and experi-
ence for IBD. Patients who are provided medications by
IBD non-specialists may harbor a poorer disease status.
If so, disseminating a standard therapeutic strategy may
be much more important than developing various guide-
lines in various organizations. The purpose of this study
was to compare the disease and treatment status of IBD
patients who were treated by specialists vs. non-special-
ists of IBD.
2.1. Patients
The activity status and medical prescriptions for ambu-
lating IBD patients were compared between two hospi-
tals. The first hospital is Okayama University Hospital in
Okayama City, a city with a population of 700,000 lo-
cated in the western mainland of Japan. The second hos-
pital is Wakayama Medical University Hospital in Wa-
kayama City, a city with a population of 350,000 located
in the midwest of the mainland of Japan. Both facilities
are tertiary medical centers of each city. All IBD patients
were provided medical care by one of the two IBD spe-
cialists at the first facility (hospital with specialists),
while IBD patients were seen by one of the seven gas-
troenterologists all of whom were non-specialists of IBD
at the second facility (hospital without specialists). The
medical records of all IBD patients who visited periodi-
cally at each of the two hospitals during the same time
point (November 2010) were examined. UC patients who
had undergone colectomy were excluded from the analy-
The analysis of clinical data of patients for medical
studies was approved by the Institutional Review Boards
of Okayama University Graduate School of Medicine,
Dentistry and Pharmaceutical Sciences, and Wakayama
Medical University.
2.2. Study Design
A review of patient records was conducted by one of the
authors at each hospital (T.H. at Okayama University
Hospital and J.K. at Wakayama Medical University Hos-
pital). The clinical information obtained from the patient
record consisted of patient demographic data, disease
duration, extent of disease, disease activity, and medical
prescriptions including allergic information at the last
hospital visit prior to the date of data collection. Disease
activity was evaluated according to the Amerian College
of Gastroenterology practice guidelines and European
Crohn’s and Colitis Organization’s grading, and classi-
fied into remission, mild disease, moderate disease, and
severe disease [12,13,18].
2.3. Use of 5-ASA
Brand and daily doses of 5-ASA were investigated. The
brands available in Japan were Pentasa, Asacol, and sa-
lazosulfapyridine for UC, and Pentasa only for CD. The
health insurance in Japan approved 4.0 g/day of Pentasa
and 3.6 g/day of Asacol as the upper limit doses for UC.
The maximum dose allowed of Pentasa for CD was 3.0
g/day. Use of topical therapy (enema or suppository) was
also investigated. Information on allergic history for 5-
ASA was collected, and patients with histories of allergic
reactions for 5-ASA were excluded from the analysis.
2.4. Use of Corticosteroids, Immunomodulators
and Biologics
Oral corticosteroids use and continuous duration of the
drug exposure were investigated. Use of immunomodu-
lators (AZA and 6-MP) and biologics was also investi-
gated. Biologics available in Japan were infliximab and
adalimumab for CD, and infliximab only for UC.
2.5. Statistical Analysis
Comparison of data from the two institutions was per-
formed by the chi-squared test or Fisher’s exact test for
categorical variables, and Wilcoxon signed-rank tests for
continuous variables. A two-sided P value of less than
0.05 was accepted as significant. Statistical analysis was
conducted using JMP 8 software (SAS Institute, Cary,
Copyright © 2013 SciRes. OPEN ACCESS
T. Hirakawa et al. / Open Journal of Gastroenterology 3 (2013) 64-71
Copyright © 2013 SciRes.
3.1. Patient Characteristics
The numbers of IBD patients who made regular visits to
the hospitals at the time of data collection were 255
(hospital with specialists) and 74 (hospital without spe-
cialists), respectively. Table 1 summarizes the demo-
graphics and disease conditions of the patients. Disease
duration was longer in patients of the hospital with spe-
cialists than in patients of the hospital without specialists
both for UC and CD (p = 0.038 and p = 0.038, respec-
tively). Extensive colitis, left-sided colitis, and proctitis
were nearly evenly distributed among UC patients of the
hospital with specialists, while approximately two thirds
of UC patients in the hospital without specialists had
extensive colitis (p = 0.0007).
Table 1. Clinical characteristics of patients.
Hospital with specialists Hospital without specialists p-value
All IBD patients 255 74
UC patients 187 48
Men 94 (50%) 27 (56%)
Women 93 (50%) 21 (44%)
Median (range) 41 (13 - 80) 45.5 (19 - 77) 0.17
Disease duration (year)
Median (range) 9 (0 - 42) 5.5 (0 - 37) 0.038
Extent of disease
Extensive colitis 65 (35%) 31 (65%)
Left-sided colitis 60 (32%) 10 (21%) 0.0007
Proctitis 62 (33%) 7 (15%)
Disease activity
Remission 39 (21%) 15 (31%)
Mild 134 (72%) 22 (46%)
Moderate 12 (6%) 11 (23%)
Severe 2 (1%) 0 (0%)
CD patients 68 26
Men 43 (63%) 18 (69%)
Women 25 (37%) 8 (31%)
Median (range) 38 (19 - 65) 33.5 (17 - 57) 0.081
Disease duration (year)
Median (range) 11.5 (2 - 35) 8 (0 - 25) 0.038
Extent of disease
Colonic involvement only 14 (21%) 4 (15%)
Small bowel involvement only 16 (24%) 6 (23%) 0.83
Small bowel and colonic dease 38 (56%) 16 (62%)
Disease activity
Remission 5 (7%) 2 (8%)
Mild 53 (78%) 14 (54%)
Moderate 10 (15%) 10 (38%)
Severe 0 (0%) 0 (0%)
IBD, inflammatory bowel disease; UC, ulcerative colitis; CD, Crohn’s disease. *Disease activity was compared between remission or mild
vs. moderate or severe.
T. Hirakawa et al. / Open Journal of Gastroenterology 3 (2013) 64-71 67
Disease activity of the patients treated at each hospital
was in sharp contrast. Patients of the hospital with spe-
cialists showed milder activity than patients of the hos-
pital without specialists for both UC and CD (Table 1).
In the hospital with specialists, the proportions of the
patients in remission or mild activity were 93% for UC
and 85% for CD, while the proportions of the patients
with moderate or severe activity were 7% for UC and
15% for CD. In contrast, in the hospital without special-
ists, the proportions of the patients in remission or mild
activity were 77% for UC and 62% for CD, while the
proportions of the patients with moderate or severe activ-
ity were 23% for UC and 38% for CD (hospital with
specialists vs. hospital without specialists: p = 0.0006 for
UC and p = 0.012 for CD, respectively). These results
suggest that the patients of the hospital without special-
ists were not as well-controlled as the patients of the
hospital with specialists.
3.2. Comparison of 5-ASA Use
Prescriptions of 5-ASA were compared in patients ex-
cluding 19 cases with 5-ASA allergy (Table 2). The
proportion of patients using salazosulfapyridine was sig-
nificantly higher in UC patients of the hospital with spe-
cialists than in UC patients of the hospital without spe-
cialists (30% vs. 7%, p = 0.0022). In UC patients using
mesalazine, significantly more patients were prescribed
with insufficient doses of the agents (Pentasa < 3 g/day
or Asacol < 3.6 g/day) in the hospital without specialists
than in the hospital with specialists (47% vs. 15%, p <
0.0001). This result was almost unchanged when ana-
lyzed in patients who had active disease (i.e., excluding
patients in remission) (52% vs. 22%, p = 0.0031). Topi-
cal therapy was less frequently used for UC patients of
the hospital without specialists (2% vs. 17%, p = 0.013).
These results suggest that 5-ASA agents were not suffi-
ciently utilized for patients in the hospital without spe-
cialists. For CD patients, the manner for prescribing
5-ASA agents did not significantly differ between the
two hospitals (Table 2).
3.3. Comparison of Corticosteroids Use
Oral corticosteroids were prescribed in 10% of the UC
patients and in 7% of the CD patients of the hospital with
specialists, and in 27% of the UC patients and in 23% of
the CD patients of the hospital without specialists (Table
3). Because many guidelines insist that long-term corti-
costeroids should be avoided in the treatment of IBD, the
proportion of patients who continuously received corti-
costeroids for more than 6 months was investigated. Both
in UC and CD patients, the proportion of patients re-
ceiving long-term corticosteroids was higher in the hos-
pital without specialists than in the hospital with special-
ists (UC: 23% vs. 5%, p < 0.0001, CD: 23% vs. 4%, p =
0.012, respectively).
Table 2. Use of 5-aminosalicylic acid.
Hospital with specialists Hospital without specialists p-value
UC patients 174 45
Oral administration
Salazosulfapyridine 53 (30%) 3 (7%)
Pentasa 3 g/day or Asacol 3.6 g/day 89 (51%) 15 (33%)
Pentasa 3 g/day > or Asacol 3.6 g/day > 26 (15%) 21 (47%) <0.0001**
None 6 (4%) 6 (13%)
Topical (enema or suppository)
Yes 29 (17%) 1 (2%)
No 145 (83%) 44 (98%)
CD patients 65 26
Oral administration
Salazosulfapyridine 4 (6%) 2 (8%)
Pentasa 3 g/day 25 (38%) 15 (58%)
Pentasa 3 g/day > 26 (40%) 6 (23%) 0.082**
None 10 (15%) 3 (12%)
UC, ulcerative colitis; CD, Crohn’s disease. Patients with 5-aminosalicylic acid allergy were excluded from this analysis. *Salazosulfapyridine use
vs. mesalazine use; **Pentasa 3 g/day or Asacol 3.6 g/day vs. Pentasa 3 g/day > or Asacol > 3.6 g/day, or none.
Copyright © 2013 SciRes. OPEN ACCESS
T. Hirakawa et al. / Open Journal of Gastroenterology 3 (2013) 64-71
3.4. Comparison of Immunomodulators and
Biologics Use
Table 4 indicates the conditions of use of immunomodu-
lators (AZA or 6-MP) and biologics (infliximab or
adalimumab) in the two hospitals. Immunomodulators
were less frequently used in the hospital without special-
ists (UC + CD; 14% vs. 44%, p < 0.0001). The differ-
ence was markedly lower in UC patients of the hospital
without specialists (8% vs. 46%, p < 0.0001). Biologics
in CD were used more frequently in the hospital with
specialists (46% vs. 15%, p = 0.0083).
In this study, we demonstrated that IBD patients who
were treated by an IBD non-specialist were likely to be
in an uncontrolled disease status. In addition, those pa-
tients were likely to be provided medications inappropri-
ately, e.g., insufficient doses of 5-ASA, longer corticos-
teoroids administration, and less frequent prescriptions of
immunomodulators. Although the difference in clinical
characteristics between the two groups may have af-
fected the treatment strategy, the result that UC patients
of the hospital without specialists were likely to show
extensive colitis may also indicate that inappropriate
treatment strategy extended the area of active disease.
Details of differences in medical care for IBD patients
between specialists and non-specialists elucidated in this
study can be helpful in education of doctors and conse-
quently improvement of clinical care for IBD patients.
Table 3. Use of corticosteroids.
Hospital with specialists Hospital without specialists p-value
No 168 (90%) 35 (73%)
<6 months 9 (5%) 2 (4%)
6 months 10 (5%) 11 (23%)
No 63 (93%) 20 (77%)
<6 months 2 (3%) 0 (0%)
6 months 3 (4%) 6 (23%)
UC, ulcerative colitis; CD, Crohn’s disease. *No or < 6 months vs. 6 months.
Table 4. Immunomodulators and biologics use.
Hospital with specialists Hospital without specialists p-value
Yes 85 (46%) 4 (8%)
No 102 (56%) 44 (92%)
Yes 28 (41%) 6 (23%)
No 40 (58%) 20 (77%)
Yes 11 (6%) 1 (2%)
No 176 (94%) 47 (98%)
Yes 31 (46%) 4 (15%)
No 37 (54%) 22 (85%)
UC, ulcerative colitis; CD, Crohn’s disease.
Copyright © 2013 SciRes. OPEN ACCESS
T. Hirakawa et al. / Open Journal of Gastroenterology 3 (2013) 64-71 69
Many studies have shown that IBD benefited consid-
erably from treatment with 5-ASA [19,20]. Several stud-
ies showed that the efficacy of 5-ASA for UC is dose-
dependent [21-23]. In addition, a recent guideline indi-
cated that greater clinical improvement for UC is associ-
ated with doses > 3 g/day of mesalazine [14]. In this
context, our results showed that 5-ASA prescribed by
non-specialists of IBD was not sufficient. These physi-
cians may be fearful of adverse events due to a high-dose
5-ASA, although it has been shown that the incidence of
adverse events of 5-ASA is not dose-dependent [21].
Otherwise, they reduced doses of 5-ASA early after
achieving remission. Because patients who were treated
by a non-specialist were likely to have more active dis-
ease, those doctors should have prescribed more doses of
5-ASA and for longer duration.
IBD specialists were more likely than non-specialists
to prescribe salazosulfapyridine for UC patients. Previ-
ous studies have showed that salazosulfapyridine is more
effective for UC, but more frequently show adverse ef-
fects such as headache, rash, nausea, and liver and renal
dysfunction than mesalazine [24-26]. Because specialists
were familiar with handling these adverse effects, they
could prescribe this agent with the expectation of derive-
ing a better response than with mesalazine.
Topical therapy of 5-ASA is effective for UC when
used either as a topical therapy alone or used in combi-
nation with oral 5-ASA [27]. Because topical administra-
tion is occasionally burdensome for patients, adequate
education and explanation for the patients are necessary.
It is more likely that patients would accept the use of
topical preparations when the instructions and explana-
tions are provided by the specialists than the non-spe-
cialists. Thus, for 5-ASA for IBD patients, guidelines
may have to stipulate the optimal dose and the optimal
way of application in more detail, including handling of
salazosulfapyridine and topical therapy.
The difference in oral corticosteroids use was one of
the most striking results of this study. Corticosteroids are
potent anti-inflammatory agents for moderate to severe
relapses of both UC and CD. However, long-term and/or
repeated administrations of corticosteroids induce vari-
ous adverse events including diabetes, osteoporosis, oph-
thalmologic diseases, and psychiatric disorders. There-
fore, all of the guidelines insist that long-term and/or
repeated use of corticosteroids should be avoided for
IBD patients. Nevertheless, non-specialists were likely to
use corticosteroids in spite of the guidelines. Several
reasons may account for this inappropriate practice. First,
a considerable part of IBD patients are likely to go into a
steroid-dependent course unless appropriate steroid-spar-
ing medications are given. In fact, Faubion et al. reported
that 22% of UC patents and 28% of CD patients fell into
a steroid-dependent course [28]. Awkwardness of ster-
oid-sparing agents such as AZA and 6-MP facilitate ster-
oid-dependence. Next, maintenance therapy with corti-
costeroids is not so rare when treating other diseases than
IBD. In fact, maintenance with long-term corticosteroids
is allowed in the treatment of autoimmune hepatitis and
immune thrombocytopenic purpura [29,30]. IBD experts
must inform non-specialists of appropriate methods of
using corticosteroids with consideration of the particular
features for IBD treatment. In addition, it should be
known that UC patients have a chance of cure without
any more corticosteroids by undergoing colectomy.
In this study, IBD patients of the hospital without spe-
cialists were more likely to be treated by a psychiatrist
than patients of the hospital with specialists (data not
shown). Patients who suffer from a long-term incurable
disease with difficult symptoms may be likely to develop
psychiatric disorders. However, there may be patients
who had psychiatric disorders induced by inappropriate
use of corticosteroids.
Immunomodulators (AZA or 6-MP) are widely used in
maintenance therapy for both UC and CD. The use of
these agents is particularly indispensable for patients
with a steroid-dependent course. However, these agents
can easily cause adverse events including leukocytopenia,
thrombocytopenia, alopecia, and gastrointestinal uncom-
fortable symptoms, which hamper prescriptions by non-
specialists. These agents have more difficulties in elicit-
ing responses: very slow onset of effectiveness and di-
versity of proper doses among subjects. The onset of the
effects of these agents usually takes two or three months.
Such long periods make non-specialist doctors unaware
of the efficacy of the agents.
The diversity in proper dose of the agents is a very
challenging problem. In Western countries, the recom-
mended maintenance dose of AZA is 2 - 2.5 mg/kg/day
and that of 6-MP is 0.75 - 1.5 mg/kg/day [31]. For Japa-
nese patients, however, the appropriate maintenance doses
were lower: 50 - 100 mg/day in AZA and 30 - 50 mg/day
in 6-MP [32,33]. Dose diversity within ranges of lower
amounts makes adjustment of doses more difficult.
Moreover, an excess dose of the agents can easily cause
adverse events. Therefore, dose adjustment of the agents
may be more difficult for Japanese doctors than Western
doctors. Although measurement of 6-thioguanine levels
and allele diversity of thiopurine methyltransferase has
been reported to be helpful in determining doses of the
agents [34], these are not routinely examined in the ma-
jority of hospitals. In addition, several reports suggested
that these indices are not reliable, particularly for Japa-
nese patients [35,36]. Thus, many obstacles have caused
non-specialist doctors to hesitate about issuing prescript-
tions for these agents. However, it should be noticed that
specialist doctors more frequently encounter severe ad-
verse events due to AZA/6-MP in their patients than
Copyright © 2013 SciRes. OPEN ACCESS
T. Hirakawa et al. / Open Journal of Gastroenterology 3 (2013) 64-71
non-specialist doctors (data not shown). It seems an ad-
ditional problem is that 6-MP is not covered by the
health insurance in Japan, although 6-MP generally
causes less frequent adverse events and is more tolerable
in IBD patients than AZA [36-38].
Biologics were more frequently used for CD patients
in the hospital with specialists. This suggests that the
proportion of the patients with more severe activity who
require biologics therapy was larger in the hospital with
specialists. However, an additional consideration is that
non-specialist doctors prescribed corticosteroids inade-
quately for severe CD patients. Because biologics use for
UC only became available in 2010 in Japan, the use was
limited in both institutes.
There are several potential limitations of this study,
which preclude broad generalizations concerning the
quality of care of patients with IBD. First, areas where
each hospital located are different. The difference may
cause biases in patient demographics and manners in
receiving medical care including medications. In this
context, disease duration of the patients of the hospital
without specialists was shorter than that of the patients of
the hospital with specialists. However, this result may
indicate that patients who were treated by a non-special-
ist had hoped to visit other hospitals. Second, because
this study was performed in Japan, direct generalizations
of the results to other countries may not be valid. How-
ever, the many guidelines issued in Western countries in
itself suggests the paucity of IBD specialists even in
those countries. Moreover, our results would be particu-
larly valuable in Asian countries where IBD patients are
currently showing an increasing trend.
In conclusion, our study found that the IBD patients of
the hospital without specialists were not well-controlled
and were not prescribed therapeutic drugs appropriately
when compared to the patients of the hospital with spe-
cialists. Many parallel guidelines are not necessary. Fos-
tering and placement of the IBD specialist is an urgent
problem in countries where IBD patients are increasing
as well as in Western countries. In addition, to verify our
findings, multicentric surveillance studies for medical
care for IBD would be expected.
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