- Email: [email protected]
Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan
G Model DESC 3054 No. of Pages 6
Journal of Dermatological Science xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Journal of Dermatological Science journal homepage: www.jdsjournal.com
Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan Ting-Shun Wang, M.D.a,c , Chi-Feng Hsieh, Ph.D.b , Tsen-Fang Tsai, M.D.c,* a b c
Division of Dermatology, National Taiwan University Hospital, Yun-Lin Branch, Taiwan Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 5 July 2016 Received in revised form 15 August 2016 Accepted 24 August 2016
Background: Recent global data show an increasing prevalence of psoriasis and psoriatic arthritis in western countries. Objective: The current study analyzed the trend of prevalence rates of psoriasis and psoriatic arthritis in Taiwan and examined biologic prescription patterns by different specialties. Methods: Data were accessed from the national payer National Health Insurance Research Database in Taiwan. This study protocol was approved by Joint Institutional Review Board established by Medical Research Ethics Foundation (No 13-S-001). Results: Between 2003 and 2013, the prevalence of psoriasis and psoriatic arthritis increased by 41% (from 15.54 to 21.90 per 10,000 population) and 191% (from 0.45 to 1.31 per 10,000 population), respectively, while the prevalence of psoriatic arthritis among patients with psoriatic disease increased from 6.3% to 12.7%. Dermatologists are the main caregivers for patients with psoriasis and psoriatic arthritis; however, data suggest a decreasing trend in the proportion of dermatologists for psoriasis patients from 24.7% between 2003 and 2008 to 10.74% between 2008 and 2013, with a corresponding decrease in dermatologists for psoriatic arthritis patients from 62.30% to 44.65% during the same periods, respectively. In 2013, of the 51,191 patients with psoriasis, only 596 (1.16%) received biologics (73.3% by dermatologists and 25.8% by rheumatologists), while 1120 of the 7470 (14.99%) psoriatic arthritis patients received biologics (72.8% by rheumatologists and 22.3% by dermatologists). The proportion of biologics use was 1.12% and 7.75% among all patients with only psoriasis and 8.01% and 26.70% among all patients with psoriatic arthritis seen by dermatologists and rheumatologists, respectively. Conclusion: The prevalence of psoriasis and psoriatic arthritis is increasing in Taiwan. The use of biologics in patients with psoriatic arthritis was comparable to that reported in previous studies in the United States and Europe; however, the use of biologics remained low in patients with psoriasis in Taiwan. ã 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Biologics Healthcare policy Prevalence Payer Psoriasis Psoriatic arthritis
1. Introduction The reported incidence of psoriasis in East Asian populations has been relatively lower than in Caucasians [1]. Two independent, previous claim-based studies using the Taiwanese national payer National Health Insurance (NHI) database revealed the prevalence of psoriasis to be approximately 0.2% in 2006 [2,3]. Patients with psoriasis experience significant impact on physical, psychosocial,
* Corresponding author at: Department of Dermatology, National Taiwan University Hospital, No.7 Chung-Shan South Road, Taipei, Taiwan. E-mail address: [email protected] (T.-F. Tsai).
and economic functions [4–6]. However, despite the high impact of the disease, data from well-designed, large-scale, populationbased studies on the temporal trends in prevalence or treatment of psoriasis in Asia are lacking. NHI is a single-payer national program launched in 1995, and the NHI Research Database (NHIRD) maintains records of the number of cases, treatment patterns, and medical claims reported to the NHI for reimbursement [7]. Thus, the NHIRD affords the opportunity to investigate the dynamics of disease prevalence and treatment in real-world settings in a large population sample in Taiwan, and can help to create the evidence for formulating appropriate policy initiatives for psoriasis management.
http://dx.doi.org/10.1016/j.jdermsci.2016.08.535 0923-1811/ ã 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
2
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
Biologic agents have revolutionized the treatment of many diseases. Across all indications, biologics account for 6.8% of the overall pharmaceutical expenditure by the NHI, a figure only slightly lower than that reported in Europe (8%–10%) but much lower than that reported in North America (12.9%) [8]. The use of biologics has also changed the treatment paradigm of psoriasis, with treatment satisfaction with biologics being highest among patients with moderate to severe psoriasis compared to other modalities [9]. Recently, results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey in the United States showed that 7.9% (reported by patients) and 35.8% (answered by dermatologists) of patients were receiving biologics treatment for psoriasis, while 25.9% (reported by patients), 46.9% (reported by dermatologists), and 52.7% (reported by rheumatologists) of patients were receiving biologics treatment for psoriatic arthritis (PsA) [10]. However, the percentage of patients with psoriasis receiving biologics in Taiwan is unknown. In Taiwan, the NHI approved reimbursement of biologics use without co-payment for up to 180 days for psoriasis and for an unlimited period for PsA since 2009 in responding patients [7]. Starting in April 2015, the reimbursement for psoriasis was extended to 2 years. However, for psoriasis patients who still suffer from psoriasis with a psoriasis area and severity index (PASI) of at least 10 despite a >50% reduction of PASI from baseline, continuous treatment with biologics is granted. Understanding psoriatic disease treatment patterns with biologics could be the key to designing interventions both at the clinical practice and at the overall healthcare system levels for optimizing the use of biologics in Taiwan. The current study analyzed the NHIRD data to investigate the trend of both psoriasis and PsA prevalence and treatment patterns, focusing on the use of biologics between 2003 and 2013 in Taiwan. 2. Materials and methods 2.1. Data source This study protocol was approved by Joint Institutional Review Board established by Medical Research Ethics Foundation (No 13S-001). Data from national payer NHIRD was accessed, which covered over 99.9% of the nearly 23 million people in Taiwan from 2003 to 2013. The clinical setting range for the NHI payment spectrum includes preventive medicine, dental care services, outpatient and inpatient services, and prescription drugs and Chinese herbal remedies, representing a broad range of psoriasis and PsA patients across different health-seeking behavioral categories. The NHIRD database contains registration files and original reimbursement claims data, including demographic characteristics, dates of admission and discharge, diagnostic codes, procedures performed, and details of prescriptions and comorbidities. In addition, private information in the NHIRD regarding patients or care providers, including medical institutions and physicians, was de-identified.
psoriasis (i.e., PsA). For the study, all psoriatic disease was defined as “PsO” plus “PsO + PsA” plus “PsA”; the “PsO only” group was considered for analysis of skin psoriasis, while the “PsO + PsA” and “PsA” groups were considered together for analyzing overall PsA. Reimbursement data on the following biologics was included in the analyses: adalimumab for PsA (January 08, 2009), by rheumatologists only; adalimumab and etanercept for PsA (November 01, 2009), by rheumatologists only; etanercept for skin psoriasis (November 01, 2009), by dermatologists only; adalimumab and etanercept for PsA and etanercept for skin psoriasis (January 01, 2010), both by dermatologists and rheumatologists; adalimumab for skin psoriasis (July 01, 2011), both by dermatologists and rheumatologists; ustekinumab for skin psoriasis (May 01, 2012), both by dermatologists and rheumatologists; golimumab for PsA (February 01, 2013), both by dermatologists and rheumatologists. 2.3. Outcomes Data were analyzed for obtaining outcomes associated with (a) annual prevalence of psoriasis (PsO only) and PsA (“PsO + PsA” and “PsA”) in Taiwan between 2003 and 2013, based on prevalence analysis, and (b) biologics treatment patterns for psoriasis (PsO only) and PsA (“PsO + PsA” and “PsA”) based on the annual number of patients prescribed with biologics from 2009 to 2013. Data on biologics prescription patterns were analyzed from 2009 to 2013, since the NHI approval for biologics reimbursement for psoriasis and PsA was initiated in 2009. Records were stratified by disease type. Data on the number of patients receiving biologics prescriptions were stratified by the specialty of the prescribing physicians. The categorical strata for the specialty of the prescribing physician included rheumatologists, internal medicine specialists, dermatologists, and others. Statistical Analysis Software (SAS) version 9.3 (SAS institute, Cary, NC, USA) was used for all the statistical analyses. 3. Results 3.1. Prevalence of skin psoriasis and PsA In Taiwan, from 2003 to 2013, the number of patients with psoriasis (PsO only) increased from 35,132 to 51,191 and from 1014 to 3072 for PsA patients (“PsA”). Similarly, the number of patients with a co-diagnosis of psoriasis and PsA (“PsO + PsA”) increased from 1337 to 4398. Further, the prevalence rate of psoriasis (PsO only) increased from 15.54 to 21.90 per 10,000 people, and that of PsA (“PsA”) more than doubled from 0.45 to 1.31 per 10,000 people. Similarly, the prevalence rate of patients with a co-diagnosis of psoriasis and PsA (“PsO + PsA”) more than doubled from 0.59 to 1.88 per 10,000 people (Table 1). Fig. 1 presents the prevalence rate of all psoriatic disease (“PsO” plus “PsO + PsA” plus “PsA”), psoriasis (PsO only), and co-diagnosis of psoriasis and PsA (“PsO + PsA”) in Taiwan from 2003 to 2013.
2.2. Study population
3.2. Care of psoriasis and PsA by different specialties
All patient records with information on at least two patient visits to any medical setting for psoriatic disease treatment were included in the analyses. Procedures and diagnoses were coded using the International Classification of Diseases, ninth revision, Clinical Modification (ICD-9 CM) convention. Claims containing an ICD-9-CM diagnosis code of 696.0 for PsA or 696.1 for other psoriasis were included in the analyses. Patients were classified into three groups: psoriasis without co-existing PsA (i.e., PsO only), both psoriasis and PsA (i.e., PsO + PsA), and only PsA without
Dermatologists are the main caregivers for patients with psoriasis (PsO only), but the trend of increase is mild in recent years: 24.70% between 2003 and 2008, and 10.74% between 2008 and 2013; in contrast, there is a more rapid increase, 218.50% and 145.49%, for rheumatologists, respectively. For overall PsA (“PsO + PsA” and “PsA”), dermatologists are also the main caregivers, and the corresponding proportion of increase is 62.30% and 44.65% for dermatologists and 107.61% and 154.42% and for rheumatologists, respectively.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
3
Table 1 Prevalence rate for “PsO,” “PsA,” and “PsO + PsA” from 2003 to 2013. Year
PsA
PsO
PsO + PsA
Population
PsA prevalence rate (per 10,000)
PsO prevalence rate (per 10,000)
PsO + PsA prevalence rate (per 10,000)
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
1014 1103 1300 1639 1732 1918 2024 2357 2603 2879 3072
35,132 40,009 41,435 42,547 44,003 44,134 45,676 46,647 48,747 51,360 51,191
1337 1619 1745 1977 2146 2369 2822 3188 3650 3982 4398
22,604,550 22,689,122 22,770,383 22,876,527 22,958,360 23,037,031 23,119,772 23,162,123 23,224,912 23,315,822 23,373,517
0.45 0.49 0.57 0.72 0.75 0.83 0.88 1.02 1.12 1.23 1.31
15.54 17.63 18.20 18.60 19.17 19.16 19.76 20.14 20.99 22.03 21.90
0.59 0.71 0.77 0.86 0.93 1.03 1.22 1.38 1.57 1.71 1.88
PsA, psoriatic arthritis; PsO, psoriasis.
3.3. Number of patients prescribed with biologics per year between 2009 and 2013
3.4. Number of patients prescribed with biologics per year by specialty type between 2009 and 2013
From 2009 to 2013, the number of patients prescribed with biologics increased from 0.1% (32/45,676) to 1.2% (596/51,191) for psoriasis (PsO only), from 2.0% (97/4846) to 15% (1120/7470) for overall PsA (“PsO + PsA” and “PsA”). Between 2009 and 2013, while the number of patients with psoriasis (PsO only) increased by only 12% (45,676 to 51,191), the number of patients receiving biologics increased significantly by nearly 18.6 times (32 to 596) (Table 2). Further, patients with overall PsA (“PsO + PsA” and “PsA”) receiving biologics increased by nearly 11.5 times (97 in 2009 to 1,120 in 2013) (Table 2).
The proportion of patients with all psoriatic diseases (“PsO only,” “PsO + PsA,” “PsA only,” or all psoriatic diseases) who were prescribed with biologics was consistently much lower in a dermatology setting compared to the rheumatology setting. In 2013, a total of 437 (73.3%) patients out of the 596 with psoriasis (PsO only) received biologics in a dermatology setting. In comparison, 815 (72.8%) of the 1120 overall PsA patients (“PsO + PsA” and “PsA”) received biologics in a rheumatology setting. However, the percentage of psoriasis (PsO only) patients who received biologics in a rheumatology setting reduced from 50.0% in
(a) 70,000 60,000 50,000 40,000 30,000 20,000 10,000 0
(b) All psoriatic disease
58,661
60,000 50,000
42,067
51,191
PsO
38,947
40,000 30,000
5,039
20,000 10,000
1,986
0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 All psoriatic disease patient number All psoriatic disease patient number_Dermatology All psoriatic disease patient number_Rheumatology
PsO patient number PsO patient number_Dermatology PsO patient number_Rheumatology
(c) 3,500 3,000 2,500 2,000 1,500 1,000 500 0
(d) 3,072
PsA
4,000 1,732 685
4,398
5,000
PsO+PsA
3,000
2,435
2,000
1,321
1,000 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
PsA patient number
PsO+PsA patient number
PsA patient number_Dermatology
PsO+PsA patient number_Dermatology
PsA patient number_Rheumatology
PsO+PsA patient number_Rheumatology
Fig. 1. Prevalence rate of (a) “all psoriatic disease,” (b) “PsO,” (c) “PsA,” and (d) “PsO + PsA” per year between 2003 and 2013. PsA, psoriatic arthritis; PsO, psoriasis.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
4
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
Table 2 Distribution of biologics prescription by specialty for “PsO,” “PsA,” and “PsO + PsA” from 2003 to 2013. “PsO” Year
Number of patients Patients who were prescribed biologics Biologics-treated patients/total patients Dermatology Internal Medicine
Others
Rheumatology
2009 2010 2011 2012 2013
45,676 46,647 48,747 51,360 51,191
0 1 1 2 3
16 60 82 115 154
32 156 250 374 596
0.1% 0.3% 0.5% 0.7% 1.2%
16 90 165 254 437
50% 57.7% 66.0% 67.9% 73.3%
0 5 2 3 2
0% 3.2% 0.8% 0.8% 0.3%
0% 0.6% 0.4% 0.5% 0.5%
50.0% 38.5% 32.8% 30.8% 25.8%
“PsA” and “PsO + PsA” Year
Number of patients Patients who were prescribed biologics Biologics-treated patients/total patients Dermatology Internal Medicine
Others
Rheumatology
2009 2010 2011 2012 2013
4846 5545 6253 6861 7470
2 6 4 2 7
89 297 464 629 815
97 353 560 799 1120
2.0% 6.4% 9.0% 11.6% 15.0%
6 48 84 136 250
6.2% 13.6% 15.0% 17.0% 22.3%
0 2 8 32 48
0.0% 0.6% 1.4% 4.0% 4.3%
2.1% 1.7% 0.7% 0.3% 0.6%
91.8% 84.1% 82.9% 78.7% 72.8%
PsA, psoriatic arthritis; PsO, psoriasis.
2009 to 25.8% in 2013 (Table 2). In 2013, 1.12% (437/38,947), 8.01% (250/3120), and 1.63% (687/42067) of patients with psoriasis, PsA (“PsA” and “PsO + PsA”), and psoriatic diseases, respectively, were receiving biologics under the care of a dermatologist, while 7.75% (154/1986), 26.70% (815/3053), and 19.23% (969/5039) were receiving biologics under the care of a rheumatologist (Table 2). 4. Discussion In Taiwan, biologics are indicated/reimbursed as second line systemic treatment for psoriasis (Psoriasis Area Severity Index [PASI] at least 10) and psoriatic arthritis (peripheral PsA, swollen and tender joints counts each 3; sacroiliitis grade 2 two sides or grade 3 one side with erythrocyte sedimentation rate [ESR] or Creactive protein [CRP]) after failure, contra-indicated or intolerant to the first line systemic therapies.: i.e acitretin, methotrexate, cyclosporine and photo(chemo)therapy for psoriasis, and nonsteroidal anti-inflammatory drugs [NSAIDs], sulfasalazine, methotrexate, cyclosporine and leflunomide for PsA. In 2013, etanercept, adalimumab and ustekinumab were reimbursed for psoriasis and each was used in about the same proportion. For psoriasis, loading of etanercept (50 mg twice weekly for 12 weeks) and adalimumab (80 mg followed by 40 mg a week later) was allowed, but not for PsA. Etanercept, adalimumab and golimumab were reimbursed for PsA, and both etanercept and adalimumab were mainly used. However, ustekinumab might also be reimbursed for PsA and golimumab for psoriasis on a case-by-case application process. No copayment was needed for biologic use in Taiwan [11]. Although the epidemiology of psoriasis and PsA in Taiwan at specific time points has been reported previously [2,3], no studies have specifically evaluated the trends in epidemiology over an extended duration for either skin psoriasis or PsA in Taiwan. Between 2003 and 2013, the prevalence of skin psoriasis (PsO only) increased by 41%, while that of overall PsA (“PsO + PsA” and “PsA”) increased by 191%. Increasing trends have been reported for both skin psoriasis and PsA [12]. The prevalence of psoriasis has been reported to be rapidly increasing both in the United Kingdom [13] and the United States [14], possibly attributable to changes in lifestyle and environmental factors, or an increased awareness of the disease. Moreover, the prevalence of PsA is also increasing, and the increase is more rapid than that of psoriasis. However, the increase in PsA
might be largely due to under diagnosis as 41% of patients had not received a diagnosis until visiting a rheumatologist in a large series [15]. In Japan, an increased trend of PsA was reported among dermatological clinics in Japan, corresponding to 1% during 1982– 2001 [16], 3.3% during 2002–2008 [17], 7.4% in 2012 [18], and 10.5% during April 2014 and March 2015 [19]. Across shared dermatologist and rheumatology clinics, the mean prevalence ratio was up to 14.3% in 2014 [20]. No recent reports are available on the trend of PsA prevalence in Taiwan. While the current data are comparable with previous reports from other parts of East Asia in terms of the point prevalence of PsA [20–22], the current study shows that the rate of increase in the prevalence of overall PsA (“PsO + PsA” and “PsA”) was higher than that of psoriasis (PsO only). During 2003–2013, the absolute prevalence of overall PsA (“PsO + PsA” and “PsA”) increased by 217.74%, mainly due to better recognition by rheumatologists (428.20% increase) as compared to dermatologists (134.76% increase). Although PsA is generally considered a rheumatologic disease, dermatologists are the main caregivers for patients with overall PsA (“PsO + PsA” and “PsA”) during all time points in Taiwan. However, in more recent years, rheumatologists are diagnosing more patients with PsA. Similarly, the absolute prevalence of only PsA increased by 1.4 times, while that of coexisting diagnoses (“PsO + PsA”) increased by nearly 3.18 times during 2003–2013. No disproportional increase in the prevalence of psoriasis (PsO only) was noted after the reimbursement of biologics for psoriasis. However, there was an increase in diagnosis of overall PsA (“PsO + PsA” and “PsA”) among rheumatologists, especially after the reimbursement of biologics for PsA. Approximately 8% of patients with psoriasis in this study had PsA (“PsO + PsA” and “PsA” over “PsO” plus “PsO + PsA” plus “PsA”), which falls within the range of psoriasis and PsA co-prevalence among Caucasians, rather than the lower ranges attributed to Asian populations [23]. Of the 51,191 patients with psoriasis (PsO only), only 596 (1.16%) received biologics prescription, while 1120 of the 7470 (15%) overall PsA (“PsO + PsA” and “PsA”) patients received biologics. Most patients with psoriatic disease received their biologics prescription from rheumatologists. In the current study, approximately 2.9% (1716/58,661) of all psoriatic patients (“PsO” plus “PsO + PsA” plus “PsA”) were prescribed biologics in 2013, which is much lower than the
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
corresponding rates of biologics prescription rates elsewhere in countries with biologics reimbursement, and 7.75% (154/1986) psoriasis patients (“PsO” only) visiting rheumatologists were given biologics by rheumatologists in 2013. This value is much higher than that reported in a German study, in which 2% of all patient visits resulted in the prescription of biologics for psoriasis [24]. However, according to the United States Medicare data, systemic treatments (phototherapy and oral systemic or biologic therapies) were received by 27.3% of the total psoriasis sample, of whom 37.2% used biologics [25]. For the treatment of PsA, although dermatologists are seeing more patients than rheumatologists, the proportion of biologics use is also much higher under rheumatologists (26.70%, 813/3053) compared to dermatologists (8.01%, 250/3120). In contrast, a recent United States study shows similar prescription rate of biologics for PsA among dermatologists (46.9%) and rheumatologists (52.7%) [10]. In the present study, rheumatology was the specialty associated with the most biologics prescriptions. The steep difference in the number and/or proportion of biologic prescriptions given by rheumatologists and dermatologists in Taiwan is not known but may be due to either disease-seeking behavior favoring more severe diseases to visit rheumatologists. Alternatively, rheumatologists may be more aggressive in disease treatment. Difference in reimbursement may also exist, since the use of biologics is approved by the same applying specialists despite the same reimbursement criteria. The current study is an observational study and hence may reflect a sampling bias of patients filing claims in the NHIRD. The health-seeking behavior of psoriasis patients may impact the interpretability of the data, as many patients with psoriasis may remain untreated. According to a United States survey, the proportion of untreated psoriasis patients ranged from 36.6% to 49.2% among patients with mild psoriasis, from 23.6% to 35.5% among patients with moderate psoriasis, and from 9.4% to 29.7% among patients with severe psoriasis [26]. This reasoning also underlies the supposition that the current prevalence rate may be an underestimate, and may prove to be useful in real-world policy making as it represents a conservative minimum value of the prevalence rate. Another pitfall in the study is the difficulty in accurately differentiating between the use of biologics for psoriasis (PsO only) and PsA. Theoretically, the dosage and duration of biologics use as well as the different need of failure to prior treatments are all different between psoriasis and PsA. However, the co-existence of psoriasis and PsA may result in shifting in the claimed diagnosis for reimbursement in cases which fulfill both reimbursement criteria. In the current study, all biologics use in patients with both psoriasis and PsA was categorized as users for PsA, and this may result in an overestimate of biologics users for PsA. However, it is our belief that patients fulfilling both reimbursement criteria of biologics for skin psoriasis and PsA are more likely to apply under the diagnosis of PsA due to the unrestricted duration of treatment period as compared to 6 months for psoriasis. The current study is one of the first studies to report the yearly prevalence of psoriasis and PsA over a period of 11 years from a comprehensive national-level database, and addresses important gaps in the knowledge of psoriasis treatment in Taiwan. Despite the limitations, based on the presented data, it is clear that a trend of progressive increase in psoriasis (PsO only) and PsA prevalence exists. The higher rate of increase in the proportion of patients with co-existing diagnoses (“PsO + PsA”) compared with psoriasis (PsO only) most likely indicates an improved patient and/or physician awareness of PsA in the Taiwanese population. The much lower percentage of biologics use for psoriasis and PsA by dermatologists compared to other countries and among rheumatologists in
5
Taiwan also suggests a need for re-consideration of the NHI reimbursement policy to optimize the rational use of biologics. 5. Conflict of interest Dr. Tsai has conducted clinical trials or received honoraria for serving as a consultant for Pfizer, Novartis, Celgene, Eli-Lilly and Janssen-Cilag Pharmaceuticals and received speaker fees from Abbvie. Dr. Wang has received speaker fees from Abbvie and Janssen-Cilag Pharmaceuticals. Mr. Hsieh has no conflict of interest. Funding sources Novartis provided funding on the acquisition of the study database. Acknowledgments This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health, and managed by National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health, or National Health Research Institutes. The authors would like to thank Mr. Wei-Chin Hsu (Novartis Taiwan) for valuable discussions on the design of the study and Rukaiyya Khan, Ph.D. (Novartis Healthcare Private) for providing editorial assistance. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.jdermsci. 2016. 08.535. References [1] S.P. Raychaudhuri, E.M. Farber, The prevalence of psoriasis in the world, J. Eur. Acad. Dermatol. Venereol. 15 (2001) 16–17. [2] T.F. Tsai, T.S. Wang, S.T. Hung, P.I. Tsai, B. Schenkel, M. Zhang, et al., Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan, J. Dermatol. Sci. 63 (2011) 40–46. [3] Y.T. Chang, T.J. Chen, P.C. Liu, Y.C. Chen, Y.J. Chen, Y.L. Huang, et al., Epidemiological study of psoriasis in the national health insurance database in Taiwan, Acta Derm. Venereol. 89 (2009) 262–266. [4] E.A. Brezinski, J.S. Dhillon, A.W. Armstrong, Economic burden of psoriasis in the United States: a systematic review, JAMA Dermatol. 151 (2015) 651–658. [5] Y. Poulin, P. Sheth, Y. Gu, H.D. Teixeira, Health-related quality of life worsens disproportionately to objective signs of psoriasis after withdrawal of adalimumab therapy, Dermatol. Ther. (Heidelb) 4 (2014) 33–42. [6] K.C. Chen, S.T. Hung, C.W. Yang, T.F. Tsai, C.H. Tang, The economic burden of psoriatic diseases in Taiwan, J. Dermatol. Sci. 75 (2014) 183–189. [7] www.nhird.nhri.org.tw/en/ (last accessed 05.09.15). [8] C.C. Chi, S.H. Wang, Efficacy and cost-efficacy of biologic therapies for moderate to severe psoriasis: a meta-analysis and cost-efficacy analysis using the intention-to-treat principle, Biomed. Res. Int. 2014 (2014) 862851. [9] O.D. van Cranenburgh, J. de Korte, M.A. Sprangers, M.A. de Rie, E.M. Smets, Satisfaction with treatment among patients with psoriasis: a web-based survey study, Br. J. Dermatol. 169 (2013) 398–405. [10] M.G. Lebwohl, A. Kavanaugh, A.W. Armstrong, A.S. Van Voorhees, US Perspectives in the management of psoriasis and psoriatic arthritis: patient and physician results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, Am. J. Clin. Dermatol. 17 (2016) 87–97. [11] S.W. Youn, T.F. Tsai, C. Theng, S.E. Choon, B.E. Wiryadi, A. Pires, et al., The MARCOPOLO study of ustekinumab utilization and efficacy in a real-world setting: treatment of patients with plaque psoriasis in Asia-Pacific countries, Ann. Dermatol. 28 (2016) 222–231. [12] R. Parisi, D.P. Symmons, C.E. Griffiths, D.M. Ashcroft, Global epidemiology of psoriasis: a systematic review of incidence and prevalence, J. Invest. Dermatol. 133 (2013) 377–385.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
6
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
[13] K. Danielsen, A.O. Olsen, T. Wilsgaard, A.S. Furberg, Is the prevalence of psoriasis increasing? A 30-year follow-up of a population-based cohort, Br. J. Dermatol. 168 (2013) 1303–1310. [14] M. Icen, C.S. Crowson, M.T. McEvoy, F.J. Dann, S.E. Gabriel, H. Maradit Kremers, Trends in incidence of adult-onset psoriasis over three decades: a populationbased study, J. Am. Acad. Dermatol. 60 (2009) 394–401. [15] P.J. Mease, D.D. Gladman, K.A. Papp, M.M. Khraishi, D. Thaci, F. Behrens, et al., Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics, J. Am. Acad. Dermatol. 69 (2013) 729–735. [16] A. Kawada, T. Tezuka, Y. Nakamizo, H. Kimura, H. Nakagawa, M. Ohkido, et al., A survey of psoriasis patients in Japan from 1982 to 2001, J. Dermatol. Sci. 31 (2003) 59–64. [17] H. Takahashi, K. Nakamura, F. Kaneko, H. Nakagawa, H. Iizuka, Analysis of psoriasis patients registered with the Japanese Society for Psoriasis Research from 2002–2008, J. Dermatol. 38 (2011) 1125–1129. [18] A. Morita, Therapeutic choices of TNF-alpha blockers for psoriasis arthropathica (psoriatic arthritis), Pract. Dermatol. 36 (2014) 290–296. [19] T. Yamamoto, M. Ohtsuki, S. Sano, A. Igarashi, A. Morita, R. Okuyama, et al., Epidemiological analysis of psoriatic arthritis patients in Japan, J. Dermatol. (2016).
[20] Y. Ohara, M. Kishimoto, N. Takizawa, K. Yoshida, M. Okada, H. Eto, et al., Prevalence and clinical characteristics of psoriatic arthritis in Japan, J. Rheumatol. 42 (2015) 1439–1442. [21] J.T. Liu, H.M. Yeh, S.Y. Liu, K.T. Chen, Psoriatic arthritis: epidemiology, diagnosis, and treatment, World J. Orthop. 5 (2014) 537–543. [22] Q. Yang, L. Qu, H. Tian, Y. Hu, J. Peng, X. Yu, et al., Prevalence and characteristics of psoriatic arthritis in Chinese patients with psoriasis, J. Eur. Acad. Dermatol. Venereol. 25 (2011) 1409–1414. [23] L.S. Tam, Y.Y. Leung, E.K. Li, Psoriatic arthritis in Asia, Rheumatology (Oxford) 48 (2009) 1473–1477. [24] A. Nast, N. Reytan, S. Rosumeck, R. Erdmann, B. Rzany, Low prescription rate for systemic treatments in the management of severe psoriasis vulgaris and psoriatic arthritis in dermatological practices in Berlin and Brandenburg, Germany: results from a patient registry, J. Eur. Acad. Dermatol. Venereol. 22 (2008) 1337–1342. [25] J. Takeshita, J.M. Gelfand, P. Li, L. Pinto, X. Yu, P. Rao, et al., Psoriasis in the US Medicare population: prevalence, treatment, and factors associated with biologic use, J. Invest. Dermatol. 135 (2015) 2955–2963. [26] A.W. Armstrong, A.D. Robertson, J. Wu, C. Schupp, M.G. Lebwohl, Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from the National Psoriasis Foundation surveys, 2003–2011, JAMA Dermatol. 149 (2013) 1180–1185.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
Journal of Dermatological Science xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Journal of Dermatological Science journal homepage: www.jdsjournal.com
Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan Ting-Shun Wang, M.D.a,c , Chi-Feng Hsieh, Ph.D.b , Tsen-Fang Tsai, M.D.c,* a b c
Division of Dermatology, National Taiwan University Hospital, Yun-Lin Branch, Taiwan Institute of Health and Welfare Policy, National Yang-Ming University, Taipei, Taiwan Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
A R T I C L E I N F O
A B S T R A C T
Article history: Received 5 July 2016 Received in revised form 15 August 2016 Accepted 24 August 2016
Background: Recent global data show an increasing prevalence of psoriasis and psoriatic arthritis in western countries. Objective: The current study analyzed the trend of prevalence rates of psoriasis and psoriatic arthritis in Taiwan and examined biologic prescription patterns by different specialties. Methods: Data were accessed from the national payer National Health Insurance Research Database in Taiwan. This study protocol was approved by Joint Institutional Review Board established by Medical Research Ethics Foundation (No 13-S-001). Results: Between 2003 and 2013, the prevalence of psoriasis and psoriatic arthritis increased by 41% (from 15.54 to 21.90 per 10,000 population) and 191% (from 0.45 to 1.31 per 10,000 population), respectively, while the prevalence of psoriatic arthritis among patients with psoriatic disease increased from 6.3% to 12.7%. Dermatologists are the main caregivers for patients with psoriasis and psoriatic arthritis; however, data suggest a decreasing trend in the proportion of dermatologists for psoriasis patients from 24.7% between 2003 and 2008 to 10.74% between 2008 and 2013, with a corresponding decrease in dermatologists for psoriatic arthritis patients from 62.30% to 44.65% during the same periods, respectively. In 2013, of the 51,191 patients with psoriasis, only 596 (1.16%) received biologics (73.3% by dermatologists and 25.8% by rheumatologists), while 1120 of the 7470 (14.99%) psoriatic arthritis patients received biologics (72.8% by rheumatologists and 22.3% by dermatologists). The proportion of biologics use was 1.12% and 7.75% among all patients with only psoriasis and 8.01% and 26.70% among all patients with psoriatic arthritis seen by dermatologists and rheumatologists, respectively. Conclusion: The prevalence of psoriasis and psoriatic arthritis is increasing in Taiwan. The use of biologics in patients with psoriatic arthritis was comparable to that reported in previous studies in the United States and Europe; however, the use of biologics remained low in patients with psoriasis in Taiwan. ã 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Keywords: Biologics Healthcare policy Prevalence Payer Psoriasis Psoriatic arthritis
1. Introduction The reported incidence of psoriasis in East Asian populations has been relatively lower than in Caucasians [1]. Two independent, previous claim-based studies using the Taiwanese national payer National Health Insurance (NHI) database revealed the prevalence of psoriasis to be approximately 0.2% in 2006 [2,3]. Patients with psoriasis experience significant impact on physical, psychosocial,
* Corresponding author at: Department of Dermatology, National Taiwan University Hospital, No.7 Chung-Shan South Road, Taipei, Taiwan. E-mail address: [email protected] (T.-F. Tsai).
and economic functions [4–6]. However, despite the high impact of the disease, data from well-designed, large-scale, populationbased studies on the temporal trends in prevalence or treatment of psoriasis in Asia are lacking. NHI is a single-payer national program launched in 1995, and the NHI Research Database (NHIRD) maintains records of the number of cases, treatment patterns, and medical claims reported to the NHI for reimbursement [7]. Thus, the NHIRD affords the opportunity to investigate the dynamics of disease prevalence and treatment in real-world settings in a large population sample in Taiwan, and can help to create the evidence for formulating appropriate policy initiatives for psoriasis management.
http://dx.doi.org/10.1016/j.jdermsci.2016.08.535 0923-1811/ ã 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
2
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
Biologic agents have revolutionized the treatment of many diseases. Across all indications, biologics account for 6.8% of the overall pharmaceutical expenditure by the NHI, a figure only slightly lower than that reported in Europe (8%–10%) but much lower than that reported in North America (12.9%) [8]. The use of biologics has also changed the treatment paradigm of psoriasis, with treatment satisfaction with biologics being highest among patients with moderate to severe psoriasis compared to other modalities [9]. Recently, results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey in the United States showed that 7.9% (reported by patients) and 35.8% (answered by dermatologists) of patients were receiving biologics treatment for psoriasis, while 25.9% (reported by patients), 46.9% (reported by dermatologists), and 52.7% (reported by rheumatologists) of patients were receiving biologics treatment for psoriatic arthritis (PsA) [10]. However, the percentage of patients with psoriasis receiving biologics in Taiwan is unknown. In Taiwan, the NHI approved reimbursement of biologics use without co-payment for up to 180 days for psoriasis and for an unlimited period for PsA since 2009 in responding patients [7]. Starting in April 2015, the reimbursement for psoriasis was extended to 2 years. However, for psoriasis patients who still suffer from psoriasis with a psoriasis area and severity index (PASI) of at least 10 despite a >50% reduction of PASI from baseline, continuous treatment with biologics is granted. Understanding psoriatic disease treatment patterns with biologics could be the key to designing interventions both at the clinical practice and at the overall healthcare system levels for optimizing the use of biologics in Taiwan. The current study analyzed the NHIRD data to investigate the trend of both psoriasis and PsA prevalence and treatment patterns, focusing on the use of biologics between 2003 and 2013 in Taiwan. 2. Materials and methods 2.1. Data source This study protocol was approved by Joint Institutional Review Board established by Medical Research Ethics Foundation (No 13S-001). Data from national payer NHIRD was accessed, which covered over 99.9% of the nearly 23 million people in Taiwan from 2003 to 2013. The clinical setting range for the NHI payment spectrum includes preventive medicine, dental care services, outpatient and inpatient services, and prescription drugs and Chinese herbal remedies, representing a broad range of psoriasis and PsA patients across different health-seeking behavioral categories. The NHIRD database contains registration files and original reimbursement claims data, including demographic characteristics, dates of admission and discharge, diagnostic codes, procedures performed, and details of prescriptions and comorbidities. In addition, private information in the NHIRD regarding patients or care providers, including medical institutions and physicians, was de-identified.
psoriasis (i.e., PsA). For the study, all psoriatic disease was defined as “PsO” plus “PsO + PsA” plus “PsA”; the “PsO only” group was considered for analysis of skin psoriasis, while the “PsO + PsA” and “PsA” groups were considered together for analyzing overall PsA. Reimbursement data on the following biologics was included in the analyses: adalimumab for PsA (January 08, 2009), by rheumatologists only; adalimumab and etanercept for PsA (November 01, 2009), by rheumatologists only; etanercept for skin psoriasis (November 01, 2009), by dermatologists only; adalimumab and etanercept for PsA and etanercept for skin psoriasis (January 01, 2010), both by dermatologists and rheumatologists; adalimumab for skin psoriasis (July 01, 2011), both by dermatologists and rheumatologists; ustekinumab for skin psoriasis (May 01, 2012), both by dermatologists and rheumatologists; golimumab for PsA (February 01, 2013), both by dermatologists and rheumatologists. 2.3. Outcomes Data were analyzed for obtaining outcomes associated with (a) annual prevalence of psoriasis (PsO only) and PsA (“PsO + PsA” and “PsA”) in Taiwan between 2003 and 2013, based on prevalence analysis, and (b) biologics treatment patterns for psoriasis (PsO only) and PsA (“PsO + PsA” and “PsA”) based on the annual number of patients prescribed with biologics from 2009 to 2013. Data on biologics prescription patterns were analyzed from 2009 to 2013, since the NHI approval for biologics reimbursement for psoriasis and PsA was initiated in 2009. Records were stratified by disease type. Data on the number of patients receiving biologics prescriptions were stratified by the specialty of the prescribing physicians. The categorical strata for the specialty of the prescribing physician included rheumatologists, internal medicine specialists, dermatologists, and others. Statistical Analysis Software (SAS) version 9.3 (SAS institute, Cary, NC, USA) was used for all the statistical analyses. 3. Results 3.1. Prevalence of skin psoriasis and PsA In Taiwan, from 2003 to 2013, the number of patients with psoriasis (PsO only) increased from 35,132 to 51,191 and from 1014 to 3072 for PsA patients (“PsA”). Similarly, the number of patients with a co-diagnosis of psoriasis and PsA (“PsO + PsA”) increased from 1337 to 4398. Further, the prevalence rate of psoriasis (PsO only) increased from 15.54 to 21.90 per 10,000 people, and that of PsA (“PsA”) more than doubled from 0.45 to 1.31 per 10,000 people. Similarly, the prevalence rate of patients with a co-diagnosis of psoriasis and PsA (“PsO + PsA”) more than doubled from 0.59 to 1.88 per 10,000 people (Table 1). Fig. 1 presents the prevalence rate of all psoriatic disease (“PsO” plus “PsO + PsA” plus “PsA”), psoriasis (PsO only), and co-diagnosis of psoriasis and PsA (“PsO + PsA”) in Taiwan from 2003 to 2013.
2.2. Study population
3.2. Care of psoriasis and PsA by different specialties
All patient records with information on at least two patient visits to any medical setting for psoriatic disease treatment were included in the analyses. Procedures and diagnoses were coded using the International Classification of Diseases, ninth revision, Clinical Modification (ICD-9 CM) convention. Claims containing an ICD-9-CM diagnosis code of 696.0 for PsA or 696.1 for other psoriasis were included in the analyses. Patients were classified into three groups: psoriasis without co-existing PsA (i.e., PsO only), both psoriasis and PsA (i.e., PsO + PsA), and only PsA without
Dermatologists are the main caregivers for patients with psoriasis (PsO only), but the trend of increase is mild in recent years: 24.70% between 2003 and 2008, and 10.74% between 2008 and 2013; in contrast, there is a more rapid increase, 218.50% and 145.49%, for rheumatologists, respectively. For overall PsA (“PsO + PsA” and “PsA”), dermatologists are also the main caregivers, and the corresponding proportion of increase is 62.30% and 44.65% for dermatologists and 107.61% and 154.42% and for rheumatologists, respectively.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
3
Table 1 Prevalence rate for “PsO,” “PsA,” and “PsO + PsA” from 2003 to 2013. Year
PsA
PsO
PsO + PsA
Population
PsA prevalence rate (per 10,000)
PsO prevalence rate (per 10,000)
PsO + PsA prevalence rate (per 10,000)
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
1014 1103 1300 1639 1732 1918 2024 2357 2603 2879 3072
35,132 40,009 41,435 42,547 44,003 44,134 45,676 46,647 48,747 51,360 51,191
1337 1619 1745 1977 2146 2369 2822 3188 3650 3982 4398
22,604,550 22,689,122 22,770,383 22,876,527 22,958,360 23,037,031 23,119,772 23,162,123 23,224,912 23,315,822 23,373,517
0.45 0.49 0.57 0.72 0.75 0.83 0.88 1.02 1.12 1.23 1.31
15.54 17.63 18.20 18.60 19.17 19.16 19.76 20.14 20.99 22.03 21.90
0.59 0.71 0.77 0.86 0.93 1.03 1.22 1.38 1.57 1.71 1.88
PsA, psoriatic arthritis; PsO, psoriasis.
3.3. Number of patients prescribed with biologics per year between 2009 and 2013
3.4. Number of patients prescribed with biologics per year by specialty type between 2009 and 2013
From 2009 to 2013, the number of patients prescribed with biologics increased from 0.1% (32/45,676) to 1.2% (596/51,191) for psoriasis (PsO only), from 2.0% (97/4846) to 15% (1120/7470) for overall PsA (“PsO + PsA” and “PsA”). Between 2009 and 2013, while the number of patients with psoriasis (PsO only) increased by only 12% (45,676 to 51,191), the number of patients receiving biologics increased significantly by nearly 18.6 times (32 to 596) (Table 2). Further, patients with overall PsA (“PsO + PsA” and “PsA”) receiving biologics increased by nearly 11.5 times (97 in 2009 to 1,120 in 2013) (Table 2).
The proportion of patients with all psoriatic diseases (“PsO only,” “PsO + PsA,” “PsA only,” or all psoriatic diseases) who were prescribed with biologics was consistently much lower in a dermatology setting compared to the rheumatology setting. In 2013, a total of 437 (73.3%) patients out of the 596 with psoriasis (PsO only) received biologics in a dermatology setting. In comparison, 815 (72.8%) of the 1120 overall PsA patients (“PsO + PsA” and “PsA”) received biologics in a rheumatology setting. However, the percentage of psoriasis (PsO only) patients who received biologics in a rheumatology setting reduced from 50.0% in
(a) 70,000 60,000 50,000 40,000 30,000 20,000 10,000 0
(b) All psoriatic disease
58,661
60,000 50,000
42,067
51,191
PsO
38,947
40,000 30,000
5,039
20,000 10,000
1,986
0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 All psoriatic disease patient number All psoriatic disease patient number_Dermatology All psoriatic disease patient number_Rheumatology
PsO patient number PsO patient number_Dermatology PsO patient number_Rheumatology
(c) 3,500 3,000 2,500 2,000 1,500 1,000 500 0
(d) 3,072
PsA
4,000 1,732 685
4,398
5,000
PsO+PsA
3,000
2,435
2,000
1,321
1,000 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
PsA patient number
PsO+PsA patient number
PsA patient number_Dermatology
PsO+PsA patient number_Dermatology
PsA patient number_Rheumatology
PsO+PsA patient number_Rheumatology
Fig. 1. Prevalence rate of (a) “all psoriatic disease,” (b) “PsO,” (c) “PsA,” and (d) “PsO + PsA” per year between 2003 and 2013. PsA, psoriatic arthritis; PsO, psoriasis.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
4
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
Table 2 Distribution of biologics prescription by specialty for “PsO,” “PsA,” and “PsO + PsA” from 2003 to 2013. “PsO” Year
Number of patients Patients who were prescribed biologics Biologics-treated patients/total patients Dermatology Internal Medicine
Others
Rheumatology
2009 2010 2011 2012 2013
45,676 46,647 48,747 51,360 51,191
0 1 1 2 3
16 60 82 115 154
32 156 250 374 596
0.1% 0.3% 0.5% 0.7% 1.2%
16 90 165 254 437
50% 57.7% 66.0% 67.9% 73.3%
0 5 2 3 2
0% 3.2% 0.8% 0.8% 0.3%
0% 0.6% 0.4% 0.5% 0.5%
50.0% 38.5% 32.8% 30.8% 25.8%
“PsA” and “PsO + PsA” Year
Number of patients Patients who were prescribed biologics Biologics-treated patients/total patients Dermatology Internal Medicine
Others
Rheumatology
2009 2010 2011 2012 2013
4846 5545 6253 6861 7470
2 6 4 2 7
89 297 464 629 815
97 353 560 799 1120
2.0% 6.4% 9.0% 11.6% 15.0%
6 48 84 136 250
6.2% 13.6% 15.0% 17.0% 22.3%
0 2 8 32 48
0.0% 0.6% 1.4% 4.0% 4.3%
2.1% 1.7% 0.7% 0.3% 0.6%
91.8% 84.1% 82.9% 78.7% 72.8%
PsA, psoriatic arthritis; PsO, psoriasis.
2009 to 25.8% in 2013 (Table 2). In 2013, 1.12% (437/38,947), 8.01% (250/3120), and 1.63% (687/42067) of patients with psoriasis, PsA (“PsA” and “PsO + PsA”), and psoriatic diseases, respectively, were receiving biologics under the care of a dermatologist, while 7.75% (154/1986), 26.70% (815/3053), and 19.23% (969/5039) were receiving biologics under the care of a rheumatologist (Table 2). 4. Discussion In Taiwan, biologics are indicated/reimbursed as second line systemic treatment for psoriasis (Psoriasis Area Severity Index [PASI] at least 10) and psoriatic arthritis (peripheral PsA, swollen and tender joints counts each 3; sacroiliitis grade 2 two sides or grade 3 one side with erythrocyte sedimentation rate [ESR] or Creactive protein [CRP]) after failure, contra-indicated or intolerant to the first line systemic therapies.: i.e acitretin, methotrexate, cyclosporine and photo(chemo)therapy for psoriasis, and nonsteroidal anti-inflammatory drugs [NSAIDs], sulfasalazine, methotrexate, cyclosporine and leflunomide for PsA. In 2013, etanercept, adalimumab and ustekinumab were reimbursed for psoriasis and each was used in about the same proportion. For psoriasis, loading of etanercept (50 mg twice weekly for 12 weeks) and adalimumab (80 mg followed by 40 mg a week later) was allowed, but not for PsA. Etanercept, adalimumab and golimumab were reimbursed for PsA, and both etanercept and adalimumab were mainly used. However, ustekinumab might also be reimbursed for PsA and golimumab for psoriasis on a case-by-case application process. No copayment was needed for biologic use in Taiwan [11]. Although the epidemiology of psoriasis and PsA in Taiwan at specific time points has been reported previously [2,3], no studies have specifically evaluated the trends in epidemiology over an extended duration for either skin psoriasis or PsA in Taiwan. Between 2003 and 2013, the prevalence of skin psoriasis (PsO only) increased by 41%, while that of overall PsA (“PsO + PsA” and “PsA”) increased by 191%. Increasing trends have been reported for both skin psoriasis and PsA [12]. The prevalence of psoriasis has been reported to be rapidly increasing both in the United Kingdom [13] and the United States [14], possibly attributable to changes in lifestyle and environmental factors, or an increased awareness of the disease. Moreover, the prevalence of PsA is also increasing, and the increase is more rapid than that of psoriasis. However, the increase in PsA
might be largely due to under diagnosis as 41% of patients had not received a diagnosis until visiting a rheumatologist in a large series [15]. In Japan, an increased trend of PsA was reported among dermatological clinics in Japan, corresponding to 1% during 1982– 2001 [16], 3.3% during 2002–2008 [17], 7.4% in 2012 [18], and 10.5% during April 2014 and March 2015 [19]. Across shared dermatologist and rheumatology clinics, the mean prevalence ratio was up to 14.3% in 2014 [20]. No recent reports are available on the trend of PsA prevalence in Taiwan. While the current data are comparable with previous reports from other parts of East Asia in terms of the point prevalence of PsA [20–22], the current study shows that the rate of increase in the prevalence of overall PsA (“PsO + PsA” and “PsA”) was higher than that of psoriasis (PsO only). During 2003–2013, the absolute prevalence of overall PsA (“PsO + PsA” and “PsA”) increased by 217.74%, mainly due to better recognition by rheumatologists (428.20% increase) as compared to dermatologists (134.76% increase). Although PsA is generally considered a rheumatologic disease, dermatologists are the main caregivers for patients with overall PsA (“PsO + PsA” and “PsA”) during all time points in Taiwan. However, in more recent years, rheumatologists are diagnosing more patients with PsA. Similarly, the absolute prevalence of only PsA increased by 1.4 times, while that of coexisting diagnoses (“PsO + PsA”) increased by nearly 3.18 times during 2003–2013. No disproportional increase in the prevalence of psoriasis (PsO only) was noted after the reimbursement of biologics for psoriasis. However, there was an increase in diagnosis of overall PsA (“PsO + PsA” and “PsA”) among rheumatologists, especially after the reimbursement of biologics for PsA. Approximately 8% of patients with psoriasis in this study had PsA (“PsO + PsA” and “PsA” over “PsO” plus “PsO + PsA” plus “PsA”), which falls within the range of psoriasis and PsA co-prevalence among Caucasians, rather than the lower ranges attributed to Asian populations [23]. Of the 51,191 patients with psoriasis (PsO only), only 596 (1.16%) received biologics prescription, while 1120 of the 7470 (15%) overall PsA (“PsO + PsA” and “PsA”) patients received biologics. Most patients with psoriatic disease received their biologics prescription from rheumatologists. In the current study, approximately 2.9% (1716/58,661) of all psoriatic patients (“PsO” plus “PsO + PsA” plus “PsA”) were prescribed biologics in 2013, which is much lower than the
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
corresponding rates of biologics prescription rates elsewhere in countries with biologics reimbursement, and 7.75% (154/1986) psoriasis patients (“PsO” only) visiting rheumatologists were given biologics by rheumatologists in 2013. This value is much higher than that reported in a German study, in which 2% of all patient visits resulted in the prescription of biologics for psoriasis [24]. However, according to the United States Medicare data, systemic treatments (phototherapy and oral systemic or biologic therapies) were received by 27.3% of the total psoriasis sample, of whom 37.2% used biologics [25]. For the treatment of PsA, although dermatologists are seeing more patients than rheumatologists, the proportion of biologics use is also much higher under rheumatologists (26.70%, 813/3053) compared to dermatologists (8.01%, 250/3120). In contrast, a recent United States study shows similar prescription rate of biologics for PsA among dermatologists (46.9%) and rheumatologists (52.7%) [10]. In the present study, rheumatology was the specialty associated with the most biologics prescriptions. The steep difference in the number and/or proportion of biologic prescriptions given by rheumatologists and dermatologists in Taiwan is not known but may be due to either disease-seeking behavior favoring more severe diseases to visit rheumatologists. Alternatively, rheumatologists may be more aggressive in disease treatment. Difference in reimbursement may also exist, since the use of biologics is approved by the same applying specialists despite the same reimbursement criteria. The current study is an observational study and hence may reflect a sampling bias of patients filing claims in the NHIRD. The health-seeking behavior of psoriasis patients may impact the interpretability of the data, as many patients with psoriasis may remain untreated. According to a United States survey, the proportion of untreated psoriasis patients ranged from 36.6% to 49.2% among patients with mild psoriasis, from 23.6% to 35.5% among patients with moderate psoriasis, and from 9.4% to 29.7% among patients with severe psoriasis [26]. This reasoning also underlies the supposition that the current prevalence rate may be an underestimate, and may prove to be useful in real-world policy making as it represents a conservative minimum value of the prevalence rate. Another pitfall in the study is the difficulty in accurately differentiating between the use of biologics for psoriasis (PsO only) and PsA. Theoretically, the dosage and duration of biologics use as well as the different need of failure to prior treatments are all different between psoriasis and PsA. However, the co-existence of psoriasis and PsA may result in shifting in the claimed diagnosis for reimbursement in cases which fulfill both reimbursement criteria. In the current study, all biologics use in patients with both psoriasis and PsA was categorized as users for PsA, and this may result in an overestimate of biologics users for PsA. However, it is our belief that patients fulfilling both reimbursement criteria of biologics for skin psoriasis and PsA are more likely to apply under the diagnosis of PsA due to the unrestricted duration of treatment period as compared to 6 months for psoriasis. The current study is one of the first studies to report the yearly prevalence of psoriasis and PsA over a period of 11 years from a comprehensive national-level database, and addresses important gaps in the knowledge of psoriasis treatment in Taiwan. Despite the limitations, based on the presented data, it is clear that a trend of progressive increase in psoriasis (PsO only) and PsA prevalence exists. The higher rate of increase in the proportion of patients with co-existing diagnoses (“PsO + PsA”) compared with psoriasis (PsO only) most likely indicates an improved patient and/or physician awareness of PsA in the Taiwanese population. The much lower percentage of biologics use for psoriasis and PsA by dermatologists compared to other countries and among rheumatologists in
5
Taiwan also suggests a need for re-consideration of the NHI reimbursement policy to optimize the rational use of biologics. 5. Conflict of interest Dr. Tsai has conducted clinical trials or received honoraria for serving as a consultant for Pfizer, Novartis, Celgene, Eli-Lilly and Janssen-Cilag Pharmaceuticals and received speaker fees from Abbvie. Dr. Wang has received speaker fees from Abbvie and Janssen-Cilag Pharmaceuticals. Mr. Hsieh has no conflict of interest. Funding sources Novartis provided funding on the acquisition of the study database. Acknowledgments This study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health, and managed by National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health, or National Health Research Institutes. The authors would like to thank Mr. Wei-Chin Hsu (Novartis Taiwan) for valuable discussions on the design of the study and Rukaiyya Khan, Ph.D. (Novartis Healthcare Private) for providing editorial assistance. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.jdermsci. 2016. 08.535. References [1] S.P. Raychaudhuri, E.M. Farber, The prevalence of psoriasis in the world, J. Eur. Acad. Dermatol. Venereol. 15 (2001) 16–17. [2] T.F. Tsai, T.S. Wang, S.T. Hung, P.I. Tsai, B. Schenkel, M. Zhang, et al., Epidemiology and comorbidities of psoriasis patients in a national database in Taiwan, J. Dermatol. Sci. 63 (2011) 40–46. [3] Y.T. Chang, T.J. Chen, P.C. Liu, Y.C. Chen, Y.J. Chen, Y.L. Huang, et al., Epidemiological study of psoriasis in the national health insurance database in Taiwan, Acta Derm. Venereol. 89 (2009) 262–266. [4] E.A. Brezinski, J.S. Dhillon, A.W. Armstrong, Economic burden of psoriasis in the United States: a systematic review, JAMA Dermatol. 151 (2015) 651–658. [5] Y. Poulin, P. Sheth, Y. Gu, H.D. Teixeira, Health-related quality of life worsens disproportionately to objective signs of psoriasis after withdrawal of adalimumab therapy, Dermatol. Ther. (Heidelb) 4 (2014) 33–42. [6] K.C. Chen, S.T. Hung, C.W. Yang, T.F. Tsai, C.H. Tang, The economic burden of psoriatic diseases in Taiwan, J. Dermatol. Sci. 75 (2014) 183–189. [7] www.nhird.nhri.org.tw/en/ (last accessed 05.09.15). [8] C.C. Chi, S.H. Wang, Efficacy and cost-efficacy of biologic therapies for moderate to severe psoriasis: a meta-analysis and cost-efficacy analysis using the intention-to-treat principle, Biomed. Res. Int. 2014 (2014) 862851. [9] O.D. van Cranenburgh, J. de Korte, M.A. Sprangers, M.A. de Rie, E.M. Smets, Satisfaction with treatment among patients with psoriasis: a web-based survey study, Br. J. Dermatol. 169 (2013) 398–405. [10] M.G. Lebwohl, A. Kavanaugh, A.W. Armstrong, A.S. Van Voorhees, US Perspectives in the management of psoriasis and psoriatic arthritis: patient and physician results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey, Am. J. Clin. Dermatol. 17 (2016) 87–97. [11] S.W. Youn, T.F. Tsai, C. Theng, S.E. Choon, B.E. Wiryadi, A. Pires, et al., The MARCOPOLO study of ustekinumab utilization and efficacy in a real-world setting: treatment of patients with plaque psoriasis in Asia-Pacific countries, Ann. Dermatol. 28 (2016) 222–231. [12] R. Parisi, D.P. Symmons, C.E. Griffiths, D.M. Ashcroft, Global epidemiology of psoriasis: a systematic review of incidence and prevalence, J. Invest. Dermatol. 133 (2013) 377–385.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535
G Model DESC 3054 No. of Pages 6
6
T.-S. Wang et al. / Journal of Dermatological Science xxx (2016) xxx–xxx
[13] K. Danielsen, A.O. Olsen, T. Wilsgaard, A.S. Furberg, Is the prevalence of psoriasis increasing? A 30-year follow-up of a population-based cohort, Br. J. Dermatol. 168 (2013) 1303–1310. [14] M. Icen, C.S. Crowson, M.T. McEvoy, F.J. Dann, S.E. Gabriel, H. Maradit Kremers, Trends in incidence of adult-onset psoriasis over three decades: a populationbased study, J. Am. Acad. Dermatol. 60 (2009) 394–401. [15] P.J. Mease, D.D. Gladman, K.A. Papp, M.M. Khraishi, D. Thaci, F. Behrens, et al., Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics, J. Am. Acad. Dermatol. 69 (2013) 729–735. [16] A. Kawada, T. Tezuka, Y. Nakamizo, H. Kimura, H. Nakagawa, M. Ohkido, et al., A survey of psoriasis patients in Japan from 1982 to 2001, J. Dermatol. Sci. 31 (2003) 59–64. [17] H. Takahashi, K. Nakamura, F. Kaneko, H. Nakagawa, H. Iizuka, Analysis of psoriasis patients registered with the Japanese Society for Psoriasis Research from 2002–2008, J. Dermatol. 38 (2011) 1125–1129. [18] A. Morita, Therapeutic choices of TNF-alpha blockers for psoriasis arthropathica (psoriatic arthritis), Pract. Dermatol. 36 (2014) 290–296. [19] T. Yamamoto, M. Ohtsuki, S. Sano, A. Igarashi, A. Morita, R. Okuyama, et al., Epidemiological analysis of psoriatic arthritis patients in Japan, J. Dermatol. (2016).
[20] Y. Ohara, M. Kishimoto, N. Takizawa, K. Yoshida, M. Okada, H. Eto, et al., Prevalence and clinical characteristics of psoriatic arthritis in Japan, J. Rheumatol. 42 (2015) 1439–1442. [21] J.T. Liu, H.M. Yeh, S.Y. Liu, K.T. Chen, Psoriatic arthritis: epidemiology, diagnosis, and treatment, World J. Orthop. 5 (2014) 537–543. [22] Q. Yang, L. Qu, H. Tian, Y. Hu, J. Peng, X. Yu, et al., Prevalence and characteristics of psoriatic arthritis in Chinese patients with psoriasis, J. Eur. Acad. Dermatol. Venereol. 25 (2011) 1409–1414. [23] L.S. Tam, Y.Y. Leung, E.K. Li, Psoriatic arthritis in Asia, Rheumatology (Oxford) 48 (2009) 1473–1477. [24] A. Nast, N. Reytan, S. Rosumeck, R. Erdmann, B. Rzany, Low prescription rate for systemic treatments in the management of severe psoriasis vulgaris and psoriatic arthritis in dermatological practices in Berlin and Brandenburg, Germany: results from a patient registry, J. Eur. Acad. Dermatol. Venereol. 22 (2008) 1337–1342. [25] J. Takeshita, J.M. Gelfand, P. Li, L. Pinto, X. Yu, P. Rao, et al., Psoriasis in the US Medicare population: prevalence, treatment, and factors associated with biologic use, J. Invest. Dermatol. 135 (2015) 2955–2963. [26] A.W. Armstrong, A.D. Robertson, J. Wu, C. Schupp, M.G. Lebwohl, Undertreatment, treatment trends, and treatment dissatisfaction among patients with psoriasis and psoriatic arthritis in the United States: findings from the National Psoriasis Foundation surveys, 2003–2011, JAMA Dermatol. 149 (2013) 1180–1185.
Please cite this article in press as: T.-S. Wang, et al., Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan, J Dermatol Sci (2016), http://dx.doi.org/10.1016/j.jdermsci.2016.08.535