€¦  · Web viewIncidence and prevalence of Psoriasis in Israelbetween 2011-2017. Running head: Incidence and Prevalence of Psoriasis in Israel 2011-2017. Word count: 2323. Table

Incidence and prevalence of Psoriasis in Israelbetween 2011-2017

Running head:Incidence and Prevalence of Psoriasis in Israel 2011-2017

Word count:2323

Table count:1

Figure count:4

Y. Schonmann1-3, D.M. Ashcroft4, I.Y.K. Iskandar4, R. Parisi4, S. Sde-Or2, D. Comaneshter2,

E. Batat2, M. Shani2,3, S. Vinker3, C. E.M. Griffiths5, A.D. Cohen2,6

1Department of Family Medicine, Rabin Medical Center, Clalit Health Services, Petach

Tikva, Israel

2Department of Quality Measurements and Research, Chief Physician’s Office, Clalit Health

Services, Tel Aviv, Israel

3Department of Family Medicine, Sackler Faculty of Medicine, Tel Aviv University,Tel

Aviv, Israel

4Centre for Pharmacoepidemiology and Drug Safety, School of Health Sciences, Faculty of

Biology, Medicine and Health, University of Manchester, Manchester Academic Health

Science Centre (MAHSC), Manchester, UK

5Dermatology Centre, NIHR Manchester Biomedical Research Centre, University of

Manchester, Manchester, UK

6Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences,

Ben-Gurion University of the Negev, Beer-Sheva, Israel

1

2

Corresponding author:

Yochai Schonmann, M.D

London School of Hygiene & Tropical Medicine

Keppel St, Bloomsbury, London WC1E 7HT

Tel: +44 7754 274676

Fax: +972 8 6477623

E-mail: [email protected]

ORCID ID - https://orcid.org/0000-0002-4483-2277

Funding: None.

Conflict of interest/disclosures:

Relationships relevant to this manuscript within the last three years:

Arnon D. Cohen received research grants from Janssen, Novartis, AbbVie, Janssen and

Sanofi. Prof. Arnon Cohen served as a consultant, advisor or speaker to AbbVie, Amgen,

Boehringer Ingelheim, Dexcel Pharma, Janssen, Kamedis, Lilly, Neopharm, Novartis,

Perrigo, Pfizer, Rafa, Samsung Bioepis, Sanofi, Sirbal and Taro.

Christopher E.M. Griffithshas received honoraria and/or research grants from Abbvie,

Almirall, Bristol Meyers Squibb, Celgene, Eli Lilly, Galderma, Janssen, Leo Pharma,

Novartis, Sandoz and UCB.

Darren M. Ashcrofthas received research grants from Abbvie, Almirall, Celgene, Eli Lilly,

Novartis, UCB and the Leo Foundation.

No conflict of interest to declare:Yochai Schonmann,Ireny Y.K. Iskandar, Rosa Parisi,

Shlomo Vinker, Shiri Sde-Or, Doron Comaneshter, Erez Batat, Michal Shani.

Type: Original article (epidemiology)

3

ABSTRACT

Background: Psoriasis is a common chronic inflammatory skin disease associated with a

heavy burden of morbidity, disability and cost. The occurrence of the disease in Israelhas not

been previously investigated.

Objectives

To provide standardised estimates of trends in psoriasis incidence, prevalence and mortality

among patients in Israel between 2011-2017.

Methods: Using electronic health records from Clalit Health Services, the largestnationwide

public health provider in Israel, we conducted a population-based study investigating trends

in the annual incidence and prevalenceof psoriasis between the years 2011-2017. We report

age- and sex-adjusted rates, using the standard Europeanpopulation as a reference.

Results: We identified 71,094 incident psoriasis cases.The mean (SD) age of onset was 42.4

(21.0) years with a bimodal distribution, peaking in the early ’30s, and early ‘60s. Late-onset

psoriasis, occurring after 40 years of age,accounted for 51.1% of incident cases. The annual

psoriasis incidence rate was constant throughout the study period (280/100,000 person-

years).Psoriasis prevalence rose from 2.5% in 2011 to 3.8% in 2017.

Conclusions: Psoriasis prevalence isincreasingin Israel, although its incidence is stable.

Clinicians and policymakers should plan to address the growing demands in the clinical,

economic and societal burden of psoriasis.

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INTRODUCTION

Psoriasis is a common, chronic inflammatory skindisease, affecting individuals of all

ages,(1,2)causing discomfort, disfigurement and disability.(3–5)The World Health

Organization (WHO) recognised psoriasis as a serious non-communicable disease in 2014,(6)

reflecting a growing awareness of the disease’s burden; yet some epidemiological aspects

remain to be fullyexplored.

The onset of psoriasis is typically described as bimodal, with 75% of cases presenting

early, before 40 years of age,(7)butother patterns of age distribution have been reported.(8–

11) There have also been conflicting reports on whether psoriasis is more prevalent in women

or men.(1)Estimates of the incidence of psoriasis vary between 30 and 140 new cases per

100,000 person-years and prevalence rates of 0.1% to 5.1%have been reported worldwide.

(1,2)A recent cross-sectional analysis highlighted the demographic characteristics of psoriasis

patients in Israel and the high burden of health services utilisation(12). However, trends in the

incidence and prevalence of psoriasis in Israel have not been investigated.Clalit Health

Services (CHS) provides all tiers of medical care to 52% of the Israeli population;with a

unified electronic health record, offeringan opportunity for dermato-epidemiological

research.

Policy makers and health organisations require information on the magnitude and

temporal trends of psoriasis burden when planning and allocating resources.We, therefore,

aimed to provide standardised estimates of trends in psoriasis incidence and prevalence

among patients in Israel between 2011-2017, using data from CHS.

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METHODS

Data source

Israel operatesa national health insurance scheme with universal access, based on the

National Health Insurance Law of 1995. A comprehensive range of services is delivered to

each resident by one of four non-for-profit health providers.CHS, the largest of these

organisations, provides all-inclusive hospital- and community-based medical services for

4,496,240members(52% of Israel's population in 2017).(13)Since 1998 CHS has operated a

unified electronic medical file, continuously updated withadministrative and clinical data.

Diagnoses are based on the WHO International Classification of Disease, version 9 (ICD-9),

anddataareintegrated using a unique civil identification number, assigned to all Israeli

residents at birth or upon immigration. Community-based dermatology consultations by

board-certified specialists are provided as a highly accessibleprimary care service by all

Israeli health providers(i.e. without gate-keeping) (See Appendix 1for additional details).

Study Design and Study Population

We searched the medical files of CHS members of all agesfor a psoriasis

diagnosisentered by a dermatology specialistbetween 01/01/2002

and31/12/2017(psoriasis,696.0; other psoriasis [guttate, inverse, pustular, von Zumbusch,

vulgaris], 696.1). The indexdate was the date of the first recorded diagnosis, and individuals

were considered as prevalent cases from that date onward.Some of the participants had been

diagnosed by a paediatrician, general practitionerorat hospital discharge before their first

dermatologist consultation. In such cases,to avoid misclassification of prevalent cases, we

corrected the index date to reflect the earlier date of onset.We did not includethose who were

never diagnosed by a dermatologist (initial feasibility counts revealed that 88% of CHS

members with any record of a psoriasis diagnosis had a diagnosis registered by a

dermatologist).We limited our analysis to the period between 2011-2017 toassure reliable and

6

complete incidencedataand to avoid misclassification of prevalent psoriasis cases as incident

ones; and used the accumulated diagnoses from 2002-2011 as baseline prevalence.

We retrieved information on sex and date of birth from the CHS electronic medical

file. Dates of death wereobtained through direct linkage of the medical fileto the Israeli

Ministry of Internal Affairs dataensuring no loss to follow-up (i.e. the date of death was also

available for residents who transferred out of CHS).We obtained the annual age-distribution,

and crude death rates of the entire CHS denominator population from the Israeli National

Insurance Institute reports. (Appendix 2)

Statistical analysis

We aggregated the first-diagnosis dates into calendar years to calculate annual

incidenceand prevalence. Wecalculatedagegroup- and sex-adjustedincidence and

prevalencerates per 100,000 person-years (and 95% confidence intervals)separately for each

year,with the denominator being the same year’s entire CHS population distribution (i.e.

period prevalence).We substracted prevalent cases from the denominator of their respective

age- and sex-strata to include only the psoriasis-free population at-risk when calculating

incidence rates.

To account for temporal changes in population distribution (e.g. population ageing)

and to allowfurther international comparisons, we directly standardised the annual rates,

using the WHO 2013 European Standard Population as a reference (Appendix 3).(14)We

also repeated the analysis using the 2017 CHS population structure,to explore the sensitivity

of the trends estimate to the choice reference population structure. We used the chi-square

test to compare the sex-distribution among members with early- and late-onset psoriasis. We

used Theil-Sen’s median slope estimator to assess for temporal trends in rates; a non-

parametric method, robust to the possibility of unequal variance in different calendar years.

(15)

7

Statistical analysis was performed using Stata, version 15.0 IC (StataCorp LP, College

Station, Texas).

Ethical approvalwas obtained from the CHS institutional ethics review board.

8

RESULTS

CHS had 4,059,758 million members in 2011, and 4,496,240in 2017 (see Appendix 2

for the calendar year-specific age-distribution of CHS members). There were 76,538

individuals with psoriasis at the beginning of 2011, and 141,515 by the end of 2017. Overall,

the analysis included 149,122 individuals with psoriasis (including those who had died or

transferred out of CHS during the study period), of whom71,095 were incident cases,

diagnosedin 2011 or later (Appendix 4).Most incident cases (94.3%)had their initial

diagnosis registered by a dermatologyspecialist; the rest had beendiagnosedinitially by a

paediatrician or a general practitioner and confirmed by a dermatologist at a later date.

Standardised incidence and prevalence rates for each calendar yearare presented in Table 1.

The mean age of onset was 42.4 (standard deviation [SD] 21.0) years.The age

distribution showed a bimodal pattern with the frequency of age at first-diagnosis peaking at

the early ‘30s, and early ‘60s (Fig.1). This pattern was similar for both males and females

(Appendix 5). Slightly less than half of the incident cases (48.9% [34,786]) were of early-

onset, i.e.psoriasis diagnosed before age 40 (mean age24.9, SD 10.4). The mean age of those

with late-onset psoriasis was 59.7(SD 12.3). Half (49.9%) of the patients were male, and the

crude sex distribution was similar for both early and late onsets (P=0.6).

The age- and sex-standardised incidence rates remained stable during the study period

(282 new cases per 100,000 person-years in 2011 [95% CI: 276-288] and 276/100,000

person-years in 2017 [95% CI: 270-281]; median slope=-1.04 [95% CI -3.75-1.45], P-

trend=0.153). Incidence rates were consistently higher among males, but the

incidencewasconstant regardless of sex(males: median slope=-0.24 [95% CI -0.87-0.69],

P=0.603;

females: median slope=-1.79 [95% CI -5.22-3.14], P=0.1.72) (Table 1, Fig. 2). The crude

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incidence rates (new cases per 100,000 per year) were 241 in 2011 and 233 in 2017

(Appendix 4)

The standardised prevalence rates increased steadily from 2.5% in 2011 (95% CI 2.5-

2.6%) to 3.8% in 2017 (95% CI 3.8-3.9%); median slope=0.22 (95% CI 0.21-0.23, P-

trend<0.01). Prevalence was higher among males, compared to females, but increased

similarlyin both sexes (males: median slope=0.22 [95% CI 0.21-0.24], P<0.01; females:

median slope=0.21 [95% CI 0.20-0.23], P<0.01)(Table 1, Fig. 3). The crude prevalence rates

(percent of prevalent in the entire CHS population) were 2.1% in 2011 and 3.1% in 2017

(Appendix 4).

Crude age-specific incidence rates remained constant within the various age-strata

throughout the follow-up period. Incidence among children 0-14 years old was 92 new cases

per 100,000 person-years in 2017, compared to 305 new cases per 100,000 person-years

among those over age 65(age 0-14, median slope=1.67 [95% CI -3.00-4.00], P=0.264; age

15-54, median slope=1.17 [95% CI -2.00-2.00], P=0.568; age 45-64, median slope=-6.17

[95% CI -11.00 - -2.00], P=0.154; age 65+, median slope=-2.00 [95% CI -5.67-1.50],

P=0.251). Prevalence among children remained constant throughout the follow-up period at

approximately 0.5% but increased in all other age groups (age 0-14, median slope=0.01 [95%

CI 0.01-0.02], P<0.01; age 15-44, median slope=0.19 [95% CI 0.18-0.21], P<0.01; age 45-64,

median slope=0.25 [95% CI 0.23-0.29], P<0.01; age 65+, median slope=0.40 [95% CI 0.35-

0.42], P<0.01)(Fig. 3). Incidence and prevalence by narrower age-bands are presented in

Appendix 6.

The overall crude mortality rates per 100,000 among CHS members were 690 in 2011

and 640 in 2017 (P-trend 0.029). (Appendix7)

The analysis was repeated using the CHS population structure as reference

populations, with no noticeable effects on temporal trends (Appendix 8).

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11

DISCUSSION

Summary of main findings

We conducted a population-based study,with a simultaneous longitudinal analysis of

psoriasis incidence, prevalence and mortality among 4,439,997members ofthe largest health

care provider in Israel, this included 149,122 people with psoriasis.The standardisedincidence

of psoriasis in Israel was stable between the years 2011-2017, with an average annual rate of

280 new casesper 100,000 -person-years. The standardised prevalence increased from 2.5%

in 2011 to 3.9% in 2017, driven by rising prevalence among older adults and the

elderly.Psoriasis was slightly more common among men, and there was evidence of a distinct

bimodal distribution, with 48.9% of new cases presenting before age 40 (i.e. early-onset

psoriasis).

Strengths and limitations of the study

This study has several strengths. Diagnoses were made by dermatology specialists, a

validated and highly specific method to identify psoriasis cases,(16,17)and the use of recent

data (2011-2017) increased the study’s internal validity.(18)Since dermatology consultations

are a community-based primary care service in CHS we could report robust population-based

summaries; and standardisation to the WHO European standard population allows for further

international comparisons and integration with ongoing global research efforts.

Nevertheless, the study has some limitations. Prevalent casescould have been

misclassified as incident if individualsdid not consult a dermatologist shortly after the onset

of symptoms. We were able to address this by augmenting the specialist-registered diagnoses

with those made by paediatricians, family physicians, and in hospital discharge letters.

Furthermore, by restricting the analysis to the period between 2011-2017, we allowed ample

time for prevalent cases to aggregate in the register.(19,20)It is possible that the actual age of

incidence is systematically lower than our estimates, but we assumesuch an error would be

12

consistent and not affect the observed trends. Another limitation, common to all register-

based studies, is the use ofnon-standardised diagnostic coding and the possibility of missing

milder cases who did not present for medical care (i.e. low sensitivity to detect cases).

(21)This issue, however, is probably of lesser magnitude in our study, considering the unique

setting of highly-accessible primary-care dermatology consultations. The high incidence rate

of psoriasisin our study does not support substantial selection bias or under-diagnosis. Any

remaining diagnostic misclassification was probably non-differential (i.e. similarly biased

regardless of the calendar year), and therefore did not affect the estimated temporal trends.

We did not analyse psoriasis incidence and prevalence by disease severity, as

standardised measures of severityare not routinely captured in the CHS database.Finally, our

analysis of the CHS population may not fullyrepresent the entire Israeli population.

Interpretation of the findings and comparison with existing literature

We observed a bimodal age-distribution of psoriasis onset, compatible with early- and

late-onset presentations.Interestingly, late-onset psoriasis is slightly more common than the

early onset-type, contrary to the often quoted convention that 75% of new psoriasis cases

present before age 40 (i.e. early-onset).(7)While the predominance of early-onset psoriasis

was confirmed in samples from dermatology departments,outpatient clinics and self-reported

patient surveys,(11,22–26)recent population-based estimates suggested that late-onset

psoriasiswasthe more commonform.(27–29)The high frequency of late-onset psoriasis among

incident cases probably reflects the underlying population age-distribution, with late-onset

psoriasis more common as the general population becomes older. The discrepancy could also

be explained by over-representation of the more severe early-onset presentation in studies of

highly-selected populations.(7,22,24)Our results suggest increased incidence and prevalence

rates of psoriasis among men, compared to women; in-line with some,(30–32) but not all

13

previous reports.(27,28) However, the absolute magnitude of the sex-difference is small, and

its clinical implications are therefore questionable.

Recent studies showed that the average incidence of psoriasisper 100,000 person-

years ranged between 38 new cases in Taiwan,(30)90 new cases in Canada,(32) 139 in

Denmark,(27)156 in the UK,(28) and 230-320 in Italy.(33)Thesubstantially higher incidence

rate in CHS could reflectthe high accessibility of dermatological consultations (i.e. milder

cases are more likely to be captured).However, different reference populations, together with

other methodological and health-system variationspreclude direct comparisons. Our data

showed a 30% increase in psoriasis prevalence between 2013 and 2017, considerably higher

than the 4-17% increase observed in the final 5-year follow-up periods of previous reports.

(27,28,32) This may reflect some unique demographic aspects of the Israeli population. Israel

has the lowest proportion of elderly in Europe (89% of the population under age 65),(34)and

overall mortality rates among CHS members are consistently declining (Appendix 7). While

severe psoriasis may be associated with excess mortality, more than 95% of CHS members

with psoriasis have mild to moderate disease.(12,35,36)The substantial increase in psoriasis

prevalence among CHS members in the presence of stable incidenceis, therefore, compatible

withincreased overall longevity andlonger disease duration.Rising psoriasis prevalence

implies that the future economic burdens of psoriasis will continue to increaseand may be of

major importance to policymakers.(37)

Conclusions

We presented updated standardised and age-specific estimates of the current incidence

and prevalence of psoriasis in Israel, as well as their temporal trends in the past seven

years,addingvaluable information to the global efforts to describe the epidemiology of the

disease.The rising prevalence of psoriasis will likely result in increasing clinical, economic

and societal burden. In contrast to previous convention, late-onset psoriasis seems to be the

14

more common presentation among CHS members. More research is needed to characterise

and phenotype the epidemiology of psoriasis by the age of onset and severity, specifically,

addressing issues of disability and quality of life.

15

Yochai Schonmanntakes responsibility for the integrity of the work as a whole, from

inception to published article.

Acknowledgements:

The authors acknowledge the substantial contribution of the Global Psoriasis Atlas

(GPA) Project teams at the University of Manchester to the administration of the project. The

authors also acknowledge the key role played by the GPA Collaborating Organisations in the

establishment and organisation of the GPA: the International Psoriasis Council; the

International Federation of Psoriasis Associations; the International League of

Dermatological Societies. The views and opinions expressed herein are those of the authors

and do not necessarily reflect those of the GPA Collaborating Organisations.

The authors are grateful to the members of the GPA Executive Committee: Chris

Griffiths - GPA Project Director, Darren Ashcroft – Workstream 1 Lead, Matthias Augustin

Workstream 2 Lead and Rebekah Swan – Programme Manager.

Finally, we acknowledge the enthusiastic collaboration of all of the members of the

GPA Board of Governors, Steering Committee, Regional Coordinators and other

dermatologists worldwide who provided the data.

This Study was not funded by the GPA.

The Global Psoriasis Atlas (GPA) is coordinated by the University of Manchester on

behalf of the three GPA Collaborating Organisations (the International Psoriasis Council, the

International Federation of Psoriasis Associations and the International League of

Dermatological Societies). The GPA is funded through contributions from the GPA

Collaborating Organisations and through income from the Leo Foundation, Abbvie, Eli Lilly

and Company and Novartis. All decisions concerning analysis, interpretation, and publication

are made independently of any industrial contribution.

16

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22

Table 1 Psoriasis prevalence and incidence rates per 100,000 person-years, adjusted for age and sex (95% confidence intervals)

Total Male Female

YEAR CHS members

Prevalence* (95% CIs)

Incidence*(95% CIs)

CHS members

Prevalence*(95% CIs)

Incidence*(95% CIs)

CHS members

Prevalence*(95% CIs)

Incidence*(95% CIs)

2011 4,059,758 2529 (2512-2546) 282 (276-288) 1,984,179 2653 (2627-2679) 296 (287-305) 2,075,579 2405 (2382-2428) 268 (261-276)

2012 4,133,410 2764 (2746-2782) 278 (272-284) 2,021,693 2889 (2862-2915) 283 (275-292) 2,111,717 2639 (2616-2663) 273 (265-281)

2013 4,215,118 2997 (2978-3015) 291 (285-297) 2,063,319 3125 (3098-3153) 304 (295-312) 2,151,799 2868 (2843-2892) 278 (270-286)

2014 4,296,843 3213 (3194-3232) 276 (271-282) 2,104,748 3350 (3321-3378) 290 (281-298) 2,192,095 3076 (3051-3101) 263 (256-271)

2015 4,355,775 3434 (3414-3453) 273 (267-279) 2,134,630 3580 (3551-3608) 289 (280-297) 2,221,145 3288 (3262-3314) 257 (250-265)

2016 4,426,534 3647 (3627-3666) 281 (276-287) 2,170,840 3797 (3768-3826) 294 (286-302) 2,255,694 3496 (3470-3523) 269 (261-276)

2017 4,496,240 3847 (3827-3867) 276 (270-281) 2,206,226 4003 (3973-4033) 288 (280-296) 2,290,014 3692 (3665-3719) 263 (256-271)

Total number of patients, and sex-specific estimates by calendar year.

* RATES ARE PRESENTED PER 100,000 PERSON-YEARS/ ADJUSTED RATES WERE DERIVED THROUGH DIRECT STANDARDISATION, USING WHO 2013

EUROPEAN STANDARD POPULATION.(14)

23

Figure 1. Age Distribution of all Incident psoriasis cases in CHS (2011-2017), n=71,087

24

0.0%

0.5%

1.0%

1.5%

2.0%1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61 64 67 70 73 76 79 82 85 88 91 94 97 100

Freq

uenc

y

Age, years

Figure 2. Age-standardised sex-specific incidence of psoriasis among CHS members, 2011-2017

296283

304290 289 294 288

268 273 278263 257

269 263

0

50

100

150

200

250

300

350

2011 2012 2013 2014 2015 2016 2017Psor

iasis

new

cas

es p

er 1

00,0

00 p

erso

n-ye

ars

Year

Males

Females

Error bars indicate 95% confidence intervals rates, directly standardised using the World Health Organisation 2013 European Standard Population.(14)

Figure 3. Age-standardised* prevalence of psoriasis among CHS members (2011-2017)

2.72.9

3.13.3

3.63.8

4.0

2.42.6

2.93.1

3.33.5

3.7

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

2011 2012 2013 2014 2015 2016 2017

Psor

iasis

cas

es, %

Year

Males

Females

Error bars indicate 95% confidence intervals rates, directly standardised using the World Health Organisation 2013 European Standard Population.(14)

25

Figure 4. Crude age-specific incidence(a) and prevalence (b) of psoriasis among CHS members between 2011-2017

26

0

50

100

150

200

250

300

350

400

2011 2012 2013 2014 2015 2016 2017

Case

s per

100

,000

per

son-

year

s

Year

(a)

0

1

2

3

4

5

6

7

2011 2012 2013 2014 2015 2016 2017

Case

s, %

Year

Age 0-14

Age 15-44

Age 45-64

Age 65+

(b)

27