Disease burden of AIRDs in Korea

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An Increased Disease Burden of Autoimmune Inflammatory

Rheumatic Diseases in Korea

Hyoungyoung Kim , Soo-Kyung Cho , Jin Wook Kim ,

Sun-Young Jung , Eun Jin Jang , Sang-Cheol Bae ,
Dae-Hyun Yoo , Yoon-Kyoung Sung

PII: S0049-0172(19)30688-2
DOI: https://doi.org/10.1016/j.semarthrit.2019.11.007
Reference: YSARH 51564

To appear in: Seminars in Arthritis & Rheumatism

Please cite this article as: Hyoungyoung Kim , Soo-Kyung Cho , Jin Wook Kim , Sun-Young Jung ,
Eun Jin Jang , Sang-Cheol Bae , Dae-Hyun Yoo , Yoon-Kyoung Sung , An Increased Disease Bur-
den of Autoimmune Inflammatory Rheumatic Diseases in Korea, Seminars in Arthritis & Rheumatism
(2019), doi: https://doi.org/10.1016/j.semarthrit.2019.11.007

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 Disease burden of AIRDs in Korea

September 24, 2019

Seminars in arthritis and rheumatism

Full-length article

3,074 words

An Increased Disease Burden of Autoimmune Inflammatory Rheumatic Diseases in

Korea

Hyoungyoung Kim,a Soo-Kyung Cho,a Jin Wook Kim,b Sun-Young Jung,c Eun Jin Jang,d

Sang-Cheol Bae,a Dae-Hyun Yoo,a Yoon-Kyoung Sung a

a
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul;
b
Department of Statistics, Kyungpook National University, Daegu; c College of Pharmacy,
d
Chung-Ang University, Seoul; Department of Information Statistics, Andong National

University, Andong, Republic of Korea.

Running title

Disease burden of AIRDs in Korea

Funding Source

This research was supported by a grant from the Rheumatology Research Foundation, Korean

1
 Disease burden of AIRDs in Korea

College of Rheumatology (RRF-2016-01).

Address correspondence and reprint requests to

Yoon-Kyoung Sung, MD, PhD, MPH, Department of Rheumatology, Hanyang University

Hospital for Rheumatic Diseases, Seoul, 04763, South Korea. E-mail: sungyk@hanyang.ac.kr,

Tel.: +82-2-2290-9250, Fax: +82-2-2298-8231

2
 Disease burden of AIRDs in Korea

Abstract (250 words)

Objectives: To estimate the prevalence, medical utilization, and recent changes in the

economic burden of autoimmune rheumatic diseases (AIRDs) in Korea.

Methods: Using a nationwide claims database that includes all medical claims made by

approximately 50 million Korean residents, the prevalences of seropositive rheumatoid

arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and others

between 2012 and 2016 were calculated. Changes in medical utilization and the direct

medical costs of each AIRD from 2012 to 2016 were also evaluated.

Results: Based on the data for 2016, seropositive RA was the most common AIRD in Korea

with 96,330 cases (188.5/100,000 population), followed by AS (30,006, 58.7/100,000

population), SLE (19,441, 38.0/100,000 population), Behçet disease (BD, 14,943,

29.2/100,000 population), primary Sjögren syndrome (pSS, 12,018, 23.5/100,000 population),

and systemic sclerosis (SSc, 3,606, 7.1/100,000 population). In terms of medical utilization,

patients with eosinophilic granulomatosis with polyangiitis visited outpatient clinics the most

frequently (9.8 times/year/patient), while hospitalization was most frequent in Microscopic

polyangiitis patients (1.0 time/year/patient). Total medical costs for all AIRDs increased from

$154,348,011 in 2012 to $262,481,974 in 2016. The annual medical cost per patient in 2016

was highest in microscopic polyangiitis ($6,223/year), followed by psoriatic arthritis

($3,362/year), and granulomatosis with polyangiitis ($2,823/year).

Conclusions: In Korea, the most prevalent AIRD is seropositive RA, followed by AS, SLE,

BD, pSS, and SSc. The economic burden of AIRDs has risen substantially in the last 5 years

3
 Disease burden of AIRDs in Korea

due not only to an increase in their prevalence but also to an increase in medical costs per

patient.

Key words: Autoimmune diseases, Epidemiology, Health services research

4
 Disease burden of AIRDs in Korea

1
INTRODUCTION

2
Autoimmune rheumatic diseases (AIRDs) are a group of heterogeneous disorders caused by
3
dysregulation of tolerance to self-antigens leading to chronic systemic inflammatory
4
disorders involving the musculoskeletal system [1]. They include rheumatoid arthritis (RA),
5
ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc),
6
primary Sjögren's syndrome (pSS), idiopathic inflammatory myositis (IIM), and systemic
7
vasculitides. Osteoarthritis, gout, and fibromyalgia are also rheumatic diseases but they are
8
not disorders of the immune system, and are not classified as AIRDs.

9
Identification of the exact numbers of prevalent cases of AIRDs is crucial for two reasons.
10
First, recent advances in immunology have contributed to improved diagnostic tests, and
11
higher diagnostic yields make it possible for physicians to diagnose rare diseases at an early
12
stage. Second, the shift of treatment paradigm from nonspecific immunosuppression to
13
tailored treatments enabled the development of innovative biologic agents. As more and more
14
clinical practice guidelines recommend early administration of biologic agents, the number of
15
patients in need of such agents also increases. Therefore, it is important to predict how much
16
the economic burden of AIRDs is likely to grow in our society.

17
The Korean government launched a national financial support program for patients with rare
18
diseases in 2001 [2], and a rare intractable disease registration (RIDR) system was started in
19
2009 [3]. A total of 138 specified rare disease were eligible for registration in the RIDR
20
program in 2017 [4]. To register, a physician’s diagnosis based on an overall clinical

5
 Disease burden of AIRDs in Korea

21
assessment of the patient is essential, and the considerable accuracy of the diagnoses permits
22
further insight into the disease burden from AIRDs in Korea.

23
In this study, we aimed to identify the prevalences of AIRDs and to estimate recent changes
24
in the resulting economic burden in Korea.

25

26
MATERIAL AND METHODS

27
Data source

28
The Korean National Health Insurance (NHI) Claims Database is a public health plan that
29
contains information on individual beneficiaries, in addition to healthcare service information
30
such as diagnoses, procedures, prescriptions, and tests [5]. The total population of Korea was
31
49,855,796 in 2016 [6], and Korea achieved universal health coverage in 1989 [7]. We
32
included all beneficiaries aged 0 to 99 years between 2012 and 2016, and used the inpatient
33
and outpatient claims data for the Korean NHI system.

34

35
Study population

36
Every patient in Korea is assigned a specific International Statistical Classification of
37
Diseases and Related Health Problems 10th Revision (ICD-10) diagnostic code by clinicians
38
before using medical services. Patients are eligible for the RIDR program if they meet the
39
specific entry criteria of the NHI system. The entry criteria for each disease include

6
 Disease burden of AIRDs in Korea

40
laboratory tests, radiologic tests, or biopsies, based on established diagnostic or classification
41
criteria as well as physicians’ clinical judgement (Supplementary Table 1). For example, SLE
42
patients are eligible if they fulfill the ACR 1997 or SLICC 2012 classification criteria, and AS
43
patients are eligible if they meet the 1984 modified New York criteria. Contrarily, some
44
AIRDs are not included in the RIDR program because of uncertainty over clinical diagnoses
45
or diagnostic codes; examples are seronegative RA, adult-onset Still’s disease (AOSD), non-
46
axial spondyloarthropathies, giant cell arteritis, IgG4-related disease, and few juvenile
47
arthritis.

48

49
Prevalence of AIRDs

50
We defined the prevalence of AIRDs as the annual frequency of claims under the ICD-10
51
diagnostic code along with the concomitant codes for the RIDR program. Changes in the
52
prevalence over time between 2012 and 2016 were also observed. Among them, six
53
commonly prevalent AIRDs were presented in order, and their distribution by age and sex
54
were additionally analyzed.

55

56
Medical utilization related to AIRDs

57
The pattern of medical utilization was evaluated by the number of hospitalization, average
58
length of hospitalization, and number of outpatient department (OPD) visits for the total set

7
 Disease burden of AIRDs in Korea

59
of patients and each individual. Medical utilization for the treatment of AIRDs was separately
60
analyzed. Annual changes of medical utilization are presented from 2012 to 2016.

61
Medical costs related to AIRDs

62
Total direct medical costs were calculated every year based on the claims for the treatment
63
of each AIRD from 2012 to 2016. Annual direct medical cost per patient was estimated by
64
dividing total direct medical costs by the number of patients with each AIRD for the
65
corresponding period. Details of medical expenditures related to each AIRD were assessed
66
with regard to laboratory examinations, radiologic examinations, and prescribed medication,
67
and each component was calculated for inpatient and outpatient settings.

68

69
Statistical analysis

70 The crude prevalence of AIRDs was estimated and converted to the number of patients per

71 100,000 population with 95% confidence interval (CI). The medical utilization was assessed

72 as the number of OPD visits and hospitalizations of all patients and each patient by type of

73 AIRD. Annual direct medical costs of all patients and each patient were also estimated and

74 the components of expenditure were analyzed. All cost values were given in US dollars

75 (USDs) at the exchange rate of 1,000 won (KRW) per 1 USD. All statistical analysis was

76 performed with SAS 9.2 (SAS Institute, Cary, NC, USA).

77

78
Ethical consideration

8
 Disease burden of AIRDs in Korea

79
This study was exempted from IRB review because we used existing, publicly available data
80
and the information on the subjects could not be identified directly or through identifiers
81
linked to the subjects (IRB file No. 2017-06-007). Informed consent was waived because we
82
used a de-identified database which was open to the public.

83

84
RESULTS

85
Prevalence of AIRDs

86
Based on the data for 2016, seropositive RA was the most common AIRD in Korea with
87
96,330 patients (188.5 per 100,000 population), followed by AS (30,006, 58.7 per 100,000
88
population), SLE (19,441, 38.0 per 100,000 population), Behçet disease (BD, 14,943, 29.2
89
per 100,000 population), Sjögren syndrome (pSS, 12,018, 23.5 per 100,000 population), and
90
SSc (3,606, 7.1 per 100,000 population). The prevalences of other AIRDs are listed in Table 1.

91
The prevalence of most AIRDs increased between 2012 and 2016 (Table 1). There was a
92
36.2% increase in overall AIRDs, representing an annual change of 19.7 per 100,000
93
population per year; the greatest increase was in RA, namely 9.8 per 100,000 population per
94
year, and the other major AIRDs, AS, SLE, BD, pSS, and SSc, increased from 0.4 to 3.7 per
95
100,000 population annually.

96 The overall distributions of the six most common AIRDs by age and sex were shown in

97 Figure 1. The prevalence of AIRDs generally increased for all ages and the increase was

98 predominant in women. The prevalence of female patients with seropositive RA was

9
 Disease burden of AIRDs in Korea

99 approximately 2.5 to 3.0 times higher than that of male patients. Systemic lupus

100 erythematosus was 10 times more frequent in females aged 20 to 40 than in males in the same

101 age, while other AIRDs were more prevalent in elderly people. Patients with pSS, BD, and

102 SSc were common in middle-aged female patients, whereas AS was 4 times more prevalent

103 in young male patients than in young females.

104

105
Medical utilization related to AIRDs

106
Patients with AIRDs were mainly managed in OPD settings instead of hospitalizations
107
(Table 2). Based on the data for 2016, they visited their doctors 7.4 times a year on average
108
for the management of underlying AIRDs; this varied between 5.3 and 9.8 times according to
109
the disease. Patients with eosinophilic granulomatosis with polyangiitis (EGPA) visited their
110
doctor most frequently, 9.8 times annually, followed by granulomatosis with polyangiitis
111
(GPA), SLE, polyarteritis nodosa, and relapsing polychondritis (Table 2). Total numbers of
112
OPD visits for the treatment of each AIRD have been increasing since 2012, whereas
113
numbers of OPD visits per patient varied, with a 21.4% reduction for eosinophilic fasciitis
114
patients but a 35.2% increase for juvenile dermatomyositis (JDM) patients.

115
In 2016, the total number of hospitalizations was highest in patients with seropositive RA
116
while the number of hospitalization per patient was the highest in patients with microscopic
117
polyangiitis, which was responsible for an average of 1.0 visit per year per patient (Table 3).
118
There was a general trend for an increase in the number of hospitalizations per patient
119
between 2012 and 2016, whereas hospitalization decreased in a few AIRDs, such as psoriatic

10
 Disease burden of AIRDs in Korea

120
arthritis, eosinophilic fasciitis, and relapsing polychondritis. Among the latter, JDM had the
121
highest increase with a 203.6% in the number of hospitalizations per patient in this period.

122
With regard to the average length of stay in hospital (ALOS), in most AIRDs with relatively
123
high prevalences there was a trend of increasing ALOS, while in less common diseases like
124
eosinophilic fasciitis, polyarteritis nodosa, and juvenile rheumatoid arthritis ALOS decreased
125
(Table 3). Patients with polymyalgia rheumatica stayed in hospital for the longest: 16.0 days
126
per hospitalization.

127
Systemic lupus erythematosus was largely responsible for the increased medical utilization
128
by the six most common AIRDs, with the most frequent OPD visits and the second most
129
frequent hospitalization per patient. Patients with SSc were admitted to hospital most often:
130
0.3 times per patient in 2016. Between 2012 and 2016, the number of hospitalizations per
131
patient increased most in seropositive RA, and the other common AIRDs, with the exceptions
132
of SLE and AS, displayed similar trends. However, the number of OPD visits per patient in
133
all six common AIRDs declined over 5 years (Table 3).

134

135
Medical costs related to AIRDs

136 The economic burden due to each AIRD was calculated in terms of total direct medical

137 costs (Table 3). According to the claims, the total direct medical costs of AIRDs were

138 $154,348,011 in 2012 and $262,481,974 in 2016, an increase of 70.1% over 5 years or

139 $21,626,793 per year. The six common AIRDs were responsible for over 90% of the total

140 medical costs: 91.8% in 2012 and 90.3% in 2016 (Figure 2A).

11
 Disease burden of AIRDs in Korea

141 For each AIRD, its prevalence mainly affected the total medical costs due to the disease

142 itself. Seropositive RA contributed the most to the total direct medical cost due to AIRDs,

143 which increased by 77.1%, from $60,561,119 in 2012 to $107,255,471 in 2016. During the

144 corresponding period, the costs for SLE increased by 43.2% and for AS by 59.2%, but there

145 was a 36.7% decrease in total direct medical costs due to eosinophilic fasciitis over the same

146 period (Table 3).

147 Patients with microscopic polyangiitis incurred the highest annual medical cost per patient

148 of $6,223 in 2016, followed by psoriatic arthritis (PsA, $3,362), GPA ($2,823), AS ($2,604),

149 and dermatomyositis ($2,469) (Table 3). Seropositive RA and SLE were responsible for the

150 relatively lower costs of $1,113 and $1,425 per patient, respectively. Juvenile

151 dermatomyositis made the highest contribution to the increase (177.6%) in annual medical

152 costs per patient between 2012 and 2016, followed by PsA (111.8%).

153
The contributions of the different disease entities to the various components of total direct
154
medical costs differed considerably. Patients with GPA were the most expensive of the
155
diseases in terms of laboratory examinations ($867 per patient in 2016), while microscopic
156
polyangiitis patients made the greatest contribution to the cost of radiologic examinations
157
($440 per patient in 2016), and systemic sclerosis patients were the biggest spenders on
158
prescription medications, $1,143 per patient in 2016 (Table 4). The six common AIRDs
159
contributed substantially to the costs of medications with most of the expenditures occurring
160
in OPD settings (Figure 2B). On average, patients with seropositive RA spent $811 on
161
medications, $223 on laboratory examinations, and $48 on radiologic examinations in 2016.

12
 Disease burden of AIRDs in Korea

162
However, patients with SLE incurred significant costs on laboratory examinations ($640 per
163
patient in 2016) as well as medications.

164

165
DISCUSSION

166
This is the first study focused on the current prevalence and the overall economic burden of
167
AIRDs in Korea. Seropositive RA was the most common AIRD, followed by AS, SLE, BD,
168
pSS, and SSc in that order. Most of them affected mainly women but AS mainly affected
169
males. Although other AIRDs are common in elderly people, AS and SLE are frequently
170
found in patients under 50. The prevalence of AIRDs has increased by 36.2% from 2012 to
171
2016, and this has resulted in a 70.1% increase in economic burden over the same period.
172
Seropositive RA contributed the highest proportion of the overall medical costs, accounting
173
for 20-fold more than SSc. The annual medical cost per patient was the highest in patients
174
with microscopic polyangiitis.

175
The prevalence of AIRDs differs depending on which definition of the disease was applied
176
to the analysis, and we defined them via their diagnostic and RIDR codes. Since prevalence
177
using diagnostic codes only is likely to be overestimated, some validated operational
178
definition including actual prescriptions of specific medications and tests is required when
179
using a claims database [8]. Fortunately, the Korean RIDR program yields relatively precise
180
prevalences because it has entry criteria for registration based on established diagnostic and
181
classification criteria. Moreover, it includes a regular re-registration process, and provides

13
 Disease burden of AIRDs in Korea

182
accumulated information on the current status of AIRDs. For RA or SLE, the numbers of
183
patients extracted by the two methods were almost similar (Supplementary Table 2).

184
The prevalences of RA, AS, and SLE in Korea differed from those in Western and Asian
185
countries. For RA, the prevalence in Korea was estimated to be 188.5 per 100,000 population,
186
lower than in the United States (1,070 per 100,000 population), Japan (600-1,000 per 100,000
187
population), European countries (310-500 per 100,000 population), and other developing
188
countries (350 per 100,000 population) [9-10]. This variation could be due to differences in
189
the case definition of RA in different studies. In addition, the prevalence of total RA patients
190
would increase considerably if we included seronegative patients. The prevalence of AS in
191
Korea was higher (58.7 per 100,000 population) than in Japan (6.5 per 100,000 population)
192
[11], but lower than in China (100 per 100,000 population) [12] and Western countries (319
193
per 100,000 population in the US and 238 in Europe) [13]. The prevalence of SLE in Korea
194
was estimated to be 38.0 per 100,000 population, comparable to the estimates for Taiwan
195
(37.0-567.4 per 100,000 population) [14-16], Europe (47-97 per 100,000 population) [17-19],
196
and the US (50.8-102.9 per 100,000 population) [20-22]. Koreans are rarely affected by PsA
197
and vasculitides. However, BD is more frequent in Korea (29.2/100,000 population) than in
198
the West; 4.2 per 100,000 population in Germany and 8.6 per 100,000 population in the US
199
[23-25].

200 The common AIRDs, in particular, seropositive RA, AS, and SLE, are responsible for most

201 of the medical costs. The direct medical costs of some AIRDs are comparable to those in

202 other countries, and may be affected by several factors. The direct medical cost of RA in

203 Korea were estimated at $1,113 per person in 2016, compared with $3,723 in the US and

14
 Disease burden of AIRDs in Korea

204 $4,022 in Japan, but their gross domestic products (GDP) per person were 1.5 to 2.0 times

205 higher than in Korea [26, 27]. However, Taiwan and Turkey with similar GDPs to Korea also

206 spent more than Korea on direct medical costs for each RA patient: $2,050 and $2,720 each

207 [28, 29]. It is thought that expenditures on medications may have been a cost driver after the

208 introduction of biologic DMARDs [30], and that this may have resulted in the differences in

209 medical costs between countires. Another societal factor, namely national insurance coverage,

210 may have affected access to biologic DMARDs and so influenced costs [31]. Further

211 international comparative studies are needed to analyze the differences in the structure of

212 medical costs between countries.

213 The chronicity of AIRDs may lead to unpredictable expenditures. Although it is difficult to

214 make direct comparisons with other chronic illnesses, the economic burden of AIRDs is

215 comparable or even higher than the burdens due to others. For example, annual total medical

216 cost for each patient was $ 1,184.3 for kidney disorders [32], $868 for heart failure [33], $504

217 for chronic obstructive pulmonary disease [34], and $430 for musculoskeletal diseases in

218 Korea [35]. Inequities between chronic illnesses will matter in the near future, as the

219 prevalence of AIRDs is increasing and we have to allocate our limited medical resources to as

220 many patients as possible. Another problem is the inequality of access according to economic

221 level in patients with the same diseases. As the number of patients with AIRDs increases,

222 demand for biologic agents is expected to expand. Treatment disparities by income level and

223 extent of insurance coverage could create barriers to adopting the latest treatment strategies.

224 Thus, current clinical practice needs to be evaluated in terms of cost-effectiveness, by

225 adjusting the effective dosages and dosing intervals of new medications to provide proper

15
 Disease burden of AIRDs in Korea

226 care for patients from all economic levels.

227
This study has several strengths. First, we estimated the prevalence of overall AIRDs and its
228
medical requirements using a nationwide database including almost 100% of the Korean
229
population and patients. The findings concerning current trends in overall AIRDs are
230
expected to provide fundamental data for comparisons with other countries. Second, we tried
231
to ensure that the estimates of prevalence were close to the actual distribution of each AIRD,
232
by examining registrations in the RIDR, which reflect physicians’ diagnoses. Third, the well-
233
managed claims database helped us to make precise estimates of the direct medical costs of
234
AIRD patients by tracing changes in overall medical costs and the proportions of each
235
component of costs from 2012 to 2016.

236
The study also had some limitations. First, AIRDs which are not included in the RIDR were
237
excluded so there were limitations in determining the prevalences of a few AIRDs;
238
seronegative RA, AOSD, and IgG4-related diseases. The exclusion of those diseases could
239
have led to underestimating the direct medical cost of AIRDs. Second, we could not obtain
240
any information on direct non-medical costs and indirect medical costs, and some medical
241
costs not reimbursed by national insurance were also excluded. This also may have led to
242
underestimating the direct medical costs of AIRDs. Third, other comorbidities of patients
243
with AIRDs could have contributed to the total medical costs that we estimated. Though we
244
defined the total medical costs as any medical expenditures charged for treatment of AIRD,
245
additional disease conditions might have been listed on claims with the diagnostic code of the
246
AIRD. Fourth, patient-related factors were not evaluated because the study focused on

16
 Disease burden of AIRDs in Korea

247
medical costs only. A further population-based study is needed to identify factors influencing
248
the increase in medical costs.

249
The prevalence of AIRDs has been increasing, resulting in an increased economic burden.
250
This means that we need to consider ways of managing inequalities in the use of medical
251
utilization and costs between various AIRDs. Further study is required to examine how much
252
of the burden is borne by AIRDs that are ineligible for the RIRD program even though they
253
involve a considerable number of patients. It is important to employ our limited medical
254
resources to increase the number of patients with AIRDs who are receiving appropriate
255
clinical care, and to provide equitable access to health care services.

256

257 Contributors

258 YK Sung designed and supervised the study. H Kim, SK Cho, YK Sung contributed to

259 acquisition and interpretation of the data and wrote the manuscript. JW Kim, SY Jung, EJ

260 Jang analyzed the data. SC Bae and DH Yoo made substantial contributions to revising the

261 article. All authors were involved in drafting the article or revising it critically for important

262 intellectual content and final approval of the version to be submitted.

263

264 Competing interests

265 None of the authors have any conflicts of interest to declare.

266

17
 Disease burden of AIRDs in Korea

267 Patient consent for publication

268 Informed consent was waived because we used a de-identified database which was open to

269 the public.

270

271 Ethics approval

272
This study was exempted from IRB review because we used existing, publicly available data
273
and the information on the subjects could not be identified directly or through identifiers
274
linked to the subjects (IRB file No. 2017-06-007).

275

18
 Disease burden of AIRDs in Korea

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direct medical and nonmedical costs for care of rheumatoid arthritis patients using the large

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 Disease burden of AIRDs in Korea

Figure Legends

24
 Disease burden of AIRDs in Korea

25
 Disease burden of AIRDs in Korea

Figure 1. The prevalence of the six most common AIRDs in 2016 by age and sex

26
 Disease burden of AIRDs in Korea

27
 Disease burden of AIRDs in Korea

Figure 2. Comparison of total direct medical costs and components of annual direct medical cost per patient related to AIRD

Table 1. Trends in the prevalence of AIRDs in Korea from 2012 to 2016

Number of patients (N/100,000)

Mean change of
Change from
the annual
Category of disease 2012 to 2016 a
prevalence b
(%)
2012 2013 2014 2015 2016 (N/100,000)

Seropositive rheumatoid arthritis 70,276 (139.6) 76,441 (151.2) 83,322 (164.2) 90,280 (177.2) 96,330 (188.5) 35.0 9.8

Systemic lupus erythematosus 15,287 (30.4) 16,304 (32.2) 17,484 (34.4) 18,245 (35.8) 19,441 (38.0) 25.3 1.5

Ankylosing spondylitis 20,132 (40.0) 22,362 (44.2) 24,794 (48.8) 27,311 (53.6) 30,006 (58.7) 46.8 3.7

Polymyositis 763 (1.5) 810 (1.6) 896 (1.8) 935 (1.8) 1,036 (2.0) 33.7 0.1

Dermatomyositis 1,028 (2.0) 1,107 (2.2) 1,159 (2.3) 1,237 (2.4) 1,369 (2.7) 31.2 0.1

28
 Disease burden of AIRDs in Korea

Systemic sclerosis 2,648 (5.3) 2,873 (5.7) 3,126 (6.2) 3,271 (6.4) 3,606 (7.1) 34.1 0.4

Primary Sjögren syndrome 6,727 (13.4) 7,687 (15.2) 8,756 (17.2) 10,255 (20.1) 12,018 (23.5) 76.0 2.0

Psoriatic arthritis 760 (1.5) 900 (1.8) 1,136 (2.2) 1,476 (2.9) 1,672 (3.3) 116.6 0.4

Polymyalgia rheumatic 1,133 (2.3) 1,370 (2.7) 1,582 (3.1) 1,770 (3.5) 2,112 (4.1) 83.6 0.4

Behçet disease 13,254 (26.3) 13,754 (27.2) 14,444 (28.5) 14,562 (28.6) 14,943 (29.2) 11.1 0.6

Polyarteritis nodosa 222 (0.4) 231 (0.5) 265 (0.5) 265 (0.5) 276 (0.5) 22.5 0.02

Eosinophilic granulomatosis with

330 (0.7) 349 (0.7) 398 (0.8) 420 (0.8) 457 (0.9) 27.7 0.04
polyangiitis

Granulomatosis with polyangiitis 260 (0.5) 305 (0.6) 338 (0.7) 364 (0.7) 376 (0.7) 42.5 0.04

Microscopic polyangiitis 114 (0.2) 147 (0.3) 204 (0.4) 259 (0.5) 323 (0.6) 179.1 0.1

Aortic arch syndrome 1,199 (2.4) 1,285 (2.5) 1,393 (2.7) 1,460 (2.9) 1,562 (3.1) 28.3 0.1

Overlap syndrome or MCTD 875 (1.7) 937 (1.9) 995 (2.0) 1,111 (2.2) 1,281 (2.5) 44.2 0.2

Eosinophilic fasciitis 27 (0.1) 26 (0.1) 28 (0.1) 33 (0.1) 35 (0.1) 27.7 0.003

29
 Disease burden of AIRDs in Korea

Relapsing polychondritis 186 (0.4) 210 (0.4) 229 (0.5) 280 (0.5) 324 (0.6) 71.6 0.1

Juvenile rheumatoid arthritis 1,520 (3.0) 1,619 (3.2) 1,729 (3.4) 1,773 (3.5) 1,950 (3.8) 26.4 0.2

Juvenile ankylosing spondylitis 136 (0.3) 134 (0.3) 156 (0.3) 152 (0.3) 197 (0.4) 42.7 0.02

Juvenile arthritis with systemic onset 68 (0.1) 81 (0.2) 82 (0.2) 96 (0.2) 100 (0.2) 44.9 0.01

Juvenile dermatomyositis 113 (0.2) 121 (0.2) 121 (0.2) 124 (0.2) 122 (0.2) 6.3 0.003

The prevalences of AIRDs that provide access to the RIRD are presented as N/100,000 population.
a
Rate of increase in prevalence from 2012 to 2016.
b
Mean percentage change of the annual prevalence defined as the mean difference in prevalence between 2012 and 2016, defined as N/100,000 population.

AIRD, autoimmune rheumatic diseases; RIDR, Rare Intractable Disease registration; MCTD, mixed connective tissue diseases.

30
 Disease burden of AIRDs in Korea

Table 2. Changes in health care utilization related to AIRDs in Korea from 2012 to 2016

Hospitalization OPD visit

Number of Number of Average length of Number of Number of OPD visits

hospitalizations hospitalization hospitalization b OPD visits per patient a
Category of disease per patient a
Change Change Change Change Change
2012 2016 from 2012 2016 from 2012 2016 from 2012 2016 from 2012 2016 from
2012 to 2012 to 2012 to 2012 to 2012 to
2016 c 2016 c 2016 c 2016 c 2016 c
Seropositive rheumatoid arthritis 7,308 (%)
12,296 68.3 0.10 0.13 (%)
22.7 12.3 14.0 (%)
13.8 550,410 724,568 (%)
31.6 7.8 7.5 (%)
-4.0

Systemic lupus erythematosus 4,845 5,833 20.4 0.32 0.30 -5.3 10.4 10.7 2.6 135,174 166,741 23.4 8.8 8.6 -3.0

Ankylosing spondylitis 1,927 2,780 44.3 0.10 0.09 -3.2 12.1 12.9 6.5 139,838 206,276 47.5 6.9 6.9 -1.0

Polymyositis 421 652 54.9 0.55 0.63 14.1 13.8 13.3 -4.0 5,857 8,498 45.1 7.7 8.2 6.9

Dermatomyositis 512 679 72.2 0.50 0.50 -0.4 13.9 14.5 4.3 7,721 10,655 51.4 7.5 7.8 3.6

Systemic sclerosis 768 1,139 48.3 0.29 0.32 8.9 10.2 11.0 7.5 20,544 27,535 34.0 7.8 7.6 -1.6

Primary Sjögren syndrome 592 1,217 105.6 0.09 0.10 15.1 12.2 13.6 11.2 45,471 79,123 74.0 6.8 6.6 -2.6

Psoriatic arthritis 63 95 50.8 0.08 0.06 -31.5 9.1 11.1 21.6 5,409 11,679 115.9 7.1 7.0 -1.9

Polymyalgia rheumatica 256 547 113.7 0.23 0.26 14.6 15.4 16.0 4.1 8,132 13,573 66.9 7.2 6.4 -10.5

Behçet disease 1,815 2,387 31.5 0.14 0.16 16.7 11.7 11.6 -0.7 97,446 109,601 12.5 7.4 7.3 -0.2

31
 Disease burden of AIRDs in Korea

Polyarteritis nodosa 98 91 -7.1 0.44 0.33 -25.3 11.1 7.2 -35.4 1,807 2,362 30.7 8.1 8.6 5.1

Eosinophilic granulomatosis with

227 315 38.8 0.69 0.69 0.2 10.3 11.6 12.7 3,715 4,471 20.3 11.3 9.8 -13.1
polyangiitis

Granulomatosis with polyangiitis 199 305 53.3 0.77 0.81 6.0 11.7 9.9 -15.7 2,360 3,644 54.4 9.1 9.7 6.8

Microscopic polyangiitis 97 329 239.2 0.85 1.02 19.7 11.3 12.8 13.1 762 2,244 194.5 6.7 6.9 3.9

Aortic arch syndrome 179 299 67.0 0.15 0.19 28.2 9.8 11.1 14.0 8,908 10,763 20.8 7.4 6.9 -7.3

Overlap syndrome or MCTD 164 255 55.5 0.19 0.20 6.2 11.1 10.2 -8.1 5,573 7,398 32.7 6.4 5.8 -9.3

Eosinophilic fasciitis 13 11 -15.4 0.48 0.31 -34.7 17.3 4.2 -75.8 206 210 1.9 7.6 6.0 -21.4

Relapsing polychondritis 86 108 25.6 0.46 0.33 -27.9 14.4 11.6 -18.9 1,536 2,777 80.8 8.3 8.6 3.8

Juvenile rheumatoid arthritis 218 398 82.6 0.14 0.20 42.3 9.9 6.7 -32.1 9,811 12,162 24.0 6.5 6.2 -3.4

Juvenile ankylosing spondylitis 12 15 25.0 0.09 0.08 -13.7 10.3 8.5 -18.1 656 1,046 59.5 4.8 5.3 10.1

Juvenile arthritis with systemic onset 20 36 80.0 0.29 0.36 22.4 10.0 7.3 -26.9 527 788 49.5 7.8 7.9 1.7

Juvenile dermatomyositis 18 59 227.8 0.16 0.48 203.6 13.4 11.1 -17.4 689 1,006 46.0 6.1 8.2 35.2

Hospitalizations and OPD visits for the treatment of each AIRD were considered in the analysis.
a
Presented as number per patient.
b
Presented as days per patient.
c
Changes in numbers of OPD visits (per patient) are given in percentages.

32
 Disease burden of AIRDs in Korea

AIRD, autoimmune rheumatic diseases; OPD, outpatient department; MCTD, mixed connective tissue diseases.

33
 Disease burden of AIRDs in Korea

Table 3. Changes in direct medical costs related to AIRDs from 2012 to 2016

Total direct medical cost (USD) a Annual medical cost per patient (USD) a
Category of disease Change from Change from
2012 2016 2012 2016
2012 to 2016 (%) b 2012 to 2016 (%) b

Seropositive rheumatoid arthritis 60,561,119 107,255,471 77.1 862 1,113 29.2

Systemic lupus erythematosus 19,341,580 27,694,324 43.2 1,265 1,425 12.6

Ankylosing spondylitis 49,072,799 78,133,501 59.2 2,438 2,604 6.8

Polymyositis 1,286,381 2,553,297 98.5 1,686 2,465 46.2

Dermatomyositis 1,903,431 3,379,388 77.5 1,852 2,469 33.3

Systemic sclerosis 2,661,717 5,191,029 95.0 1,005 1,440 43.2

Primary Sjögren syndrome 3,380,327 7,730,515 128.7 503 643 28.0

Psoriatic arthritis 1,206,120 5,620,815 366.0 1,587 3,362 111.8

Polymyalgia rheumatica 811,376 1,731,316 113.4 716 820 14.5

34
 Disease burden of AIRDs in Korea

Behçet disease 6,663,256 11,026,314 65.5 503 738 46.8

Polyarteritis nodosa 416,913 420,409 0.8 1,878 1,523 -18.9

Eosinophilic granulomatosis with

608,468 1,010,317 66.0 1,844 2,211 19.9
polyangiitis

Granulomatosis with polyangiitis 780,686 1,061,500 36.0 3,003 2,823 -6.0

Microscopic polyangiitis 507,064 2,010,130 296.4 4,448 6,223 35.8

Aortic arch syndrome 841,213 1,488,292 76.9 702 953 39.9

Overlap syndrome or MCTD 853,097 1,201,832 40.9 975 938 -3.8

Eosinophilic fasciitis 27,795 17,591 -36.7 1,029 503 -51.2

Relapsing polychondritis 285,603 507,308 77.6 1,535 1,566 2.0

Juvenile rheumatoid arthritis 2,729,230 3,779,430 38.5 1,796 1,938 7.9

Juvenile ankylosing spondylitis 227,254 269,118 18.4 1,671 1,366 -18.2

Juvenile arthritis with systemic onset 111,253 186,884 68.0 1,636 1,869 14.2

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 Disease burden of AIRDs in Korea

Juvenile dermatomyositis 71,140 213,191 199.7 630 1,747 177.6

a
United States dollars (USDs) at the exchange rate of 1,000 won (KRW) per 1 USD.
b
Percentage increase in medical costs between 2012 and 2016.
AIRD, autoimmune inflammatory rheumatic disease; MCTD, mixed connective tissue diseases.

36
 Disease burden of AIRDs in Korea

Table 4. Comparison of components of direct medical costs per patient related to AIRDs from 2012 to 2016

Laboratory examination Radiologic examination Medications

Category of disease Change Change Change

2012 2016 from 2012 2016 from 2012 2016 from
2012 to 2012 to 2012 to
2016 (%) 2016 (%) 2016
Seropositive rheumatoid (%)
164 223 35.7 43 48 12.4 843 811 -3.8
arthritis

Systemic lupus
554 640 15.6 73 76 3.8 868 897 3.4
erythematosus

Ankylosing spondylitis 132 181 37.1 54 52 -3.1 360 341 -5.2

Polymyositis 496 757 52.6 106 148 39.3 771 912 18.4

Dermatomyositis 552 737 33.5 128 117 -9.0 708 776 9.6

Systemic sclerosis 303 487 60.4 92 114 24.2 1046 1143 9.2

Primary Sjögren syndrome 205 268 30.3 38 41 7.1 670 576 -14.0

Psoriatic arthritis 142 144 1.8 33 26 -21.9 523 432 -17.5

Polymyalgia rheumatica 215 252 17.2 52 53 1.7 545 438 -19.6

Behçet disease 176 236 34.2 40 44 9.8 487 498 2.2

Polyarteritis nodosa 613 389 -36.5 189 113 -40.1 635 547 -13.8

Eosinophilic granulomatosis
551 662 20.3 134 138 3.3 840 795 -5.4
with polyangiitis

Granulomatosis with
778 867 11.4 229 246 7.1 637 609 -4.4
polyangiitis

Microscopic polyangiitis 938 780 -16.8 919 440 -52.1 594 612 3.0

Aortic arch syndrome 233 461 98.0 112 143 27.8 642 655 2.1

Overlap syndrome or
355 390 9.9 66 76 14.7 770 762 -1.0
MCTD

Eosinophilic fasciitis 260 234 -10.1 30 60 104.2 335 236 -29.6

Relapsing polychondritis 461 480 4.3 111 98 -11.4 654 585 -10.5

37
 Disease burden of AIRDs in Korea

Juvenile rheumatoid
201 240 19.4 43 38 -11.2 293 249 -14.9
arthritis

Juvenile ankylosing
112 159 41.6 49 44 -9.4 168 144 -14.6
spondylitis

Juvenile arthritis with

437 436 -0.1 61 61 0.0 450 385 -14.5
systemic onset

Juvenile dermatomyositis 221 458 107.5 28 65 129.3 239 251 5.0

Presented in United States dollars (USDs) at the exchange rate of 1,000 won (KRW) per 1 USD.

Since the Korean National Health Insurance (NHI) Claims Database does not offer actual amounts of payment
for each component, this is cited using information on requests for medical care cost by health care institutions.

AIRDs, autoimmune inflammatory rheumatic diseases; MCTD, mixed connective tissue diseases.

38