Insights from the Clalit Health Services database about Psoriasis Research using BIG DATA Arnon D. Cohen, MD, MPH, PHD

Transcription

1 Insights from the Clalit Health Services database about Psoriasis Research using BIG DATA Arnon D. Cohen, MD, MPH, PHD Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva Department of Quality Measurements and Research, Chief Physician's Office, Clalit Health Services, Tel-Aviv, Israel IPC, Barcelona, Spain, Friday, November 18, 2016

2 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

3 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

4 Population: ~8.6 Million Healthcare in Israel Health Insurance: Mandatory, Free Healthcare provision: 1 of 4 Sick Funds (insurer/provider) Non-for-profit, funding from state by capitation Clalit - Largest of the 4, unique in several aspects

5 Clalit Health Services Established in 1911 Public healthcare provider organization Members ~4,400,000 (>50% market share of Israel) Annual budget ~4 billion dollars 14 hospitals 1,400 community primary care clinics 550 consultation clinics Elderly (65+) 70% market share, 0.5 million Arab population 73% market share, 1 million 1.2 million dermatology visits per year

6 Tel Aviv Jerusalem Beer Sheva Haifa Tiberias Clalit Health Services Districts and hospitals Dan Petach Tikva Beilinson (782 beds) Golda (320 beds) Schneider (203 beds) Geha (166 beds) Shalvata (114 beds) Beit Rivka (276 beds) Northern District Ha'emek (425 beds) Haifa District Carmel (425 beds) Sharon Shomron District Meir (696 beds) Loewenstein (240 beds) Eilat Southern District Soroka (958 beds) Eilat Area Yoseftal (65 beds) Central District Kaplan Herzfeld (523 beds) (312 beds) Legend --General hospitals --Psychiatric hospitals --Geriatric & rehab

7 Clalit data warehouse Primary care visits Secondary care visits Medications Imaging Physiotherapy visits DATA WAREHOUSE Demographics Emergency room visits Outpatient visits Hospitalizations Dietician, social workers etc., Visits Laboratory tests

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9 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

10 Demonstrative psoriasis patient Mrs. Israela Levi, 56 year old, female Severe psoriasis, 3 years Obese Previous treatments: Acitretin, Phototherapy Current treatment: Adalimumab

11 General view screen

12 Clinic visits

13 Prescribed medications: Timeline

14 Problem List

15 Recent diagnoses

16 Blood tests

17 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

18 From psoriasis associated with drugs to psoriasis and the metabolic syndrome Cohen, A. D., et al. "Calcium channel blockers intake and psoriasis: a casecontrol study." Acta Derm.Venereol (2001): Cohen, A. D., et al. "Drug exposure and psoriasis vulgaris: case-control and case-crossover studies." Acta Derm.Venereol (2005):

19 From psoriasis associated with drugs to psoriasis and the metabolic syndrome Cohen, A. D., et al. "Psoriasis and the metabolic syndrome." Acta Derm.Venereol (2007): Cohen, A. D., et al. "Association between psoriasis and the metabolic syndrome. A cross-sectional study." Dermatology (2008):

20 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

21 Drug Exposure and Psoriasis Vulgaris: Case-Control and Case-Crossover Studies (2005) A case-control study 110 patients hospitalized for extensive psoriasis Control group (n =5515) - elective surgery A case-crossover study 98 patients hospitalized for extensive psoriasis Exposure to drugs was assessed during a hazard period (3 months before hospitalization) and compared to a control period in the patient s past.

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23 Drug Exposure and Psoriasis Vulgaris: Case-Control and Case-Crossover Studies psoriasis 2005 drugs

24 Drug Exposure and Psoriasis Vulgaris: Case-Control and Case-Crossover Studies psoriasis 2007 comorbdities drugs

25 Drug Exposure and Psoriasis Vulgaris: Case-Control and Case-Crossover Studies psoriasis 2007 comorbdities drugs

26 Drug Exposure and Psoriasis Vulgaris: Case-Control and Case-Crossover Studies Conclusions (2005): Extensive psoriasis may be associated with intake of ACE inhibitors, NSAIDs or beta-blockers

27 Drug Exposure and Psoriasis Vulgaris: Case-Control and Case-Crossover Studies Conclusions (2005): Extensive psoriasis may be associated with intake of ACE inhibitors, NSAIDs or beta-blockers Conclusions (Revisited): Psoriasis is associated with cardio-vascular disease and psoriatic arthritis

28 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

29 Psoriasis and diabetes: a population-based crosssectional study (JEADV 2008)

30 Psoriasis and diabetes: a population-based cross-sectional study (JEADV 2008)

31 Psoriasis and diabetes: a population-based cross-sectional study (JEADV 2008)

32 Psoriasis and the Risk of Diabetes Mellitus (Armstrong, JAMA 2013)

33 Psoriasis and the Risk of Diabetes Mellitus (Armstrong, JAMA 2013)

34 Psoriasis and the Risk of Diabetes Mellitus (Armstrong, JAMA 2013)

35 Thank you April! (Armstrong, JAMA 2013)

36 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

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38 Osteoporosis Prevalence in females (psoriasis vs. controls) 22.3 vs 20.2%, P=0.008, OR 1.1;

39 Osteoporosis Prevalence in females (psoriasis vs. controls) 22.3 vs 20.2%, P=0.008, OR 1.1; Prevalence in males (psoriasis vs. controls) 3.1 vs 1.7%, p=0.001, OR 1.86;

40 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

41 Logistic mistakes - example

42 Logistic mistakes - example

43 Logistic mistakes - example

44 Logistic mistakes - example

45 Human mistakes - example

46 Human mistakes - example

47 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

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49 A cross-sectional study was performed utilizing the database of Maccabi Healthcare Services, a large health provider organization in Israel. The study included 46,095 patients with psoriasis and 1,579,037 subjects without psoriasis (control patients)

50 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

51 Herpes Zoster 1. Dreiher, J., et al. "Risk of Herpes zoster in patients with psoriasis treated with biologic drugs." J.Eur.Acad.Dermatol.Venereol (2012): Shalom, G., et al. "Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500,000 Person-year Study." JAMA Dermatol (2015): Zisman, D., et al. "Psoriatic arthritis treatment and the risk of herpes zoster." Ann.Rheum.Dis (2016):

52 Herpes Zoster Paper I Dreiher, J., et al. "Risk of Herpes zoster in patients with psoriasis treated with biologic drugs." J.Eur.Acad.Dermatol.Venereol (2012):

53 psoriasis patients 215,656 person-years 1321 herpes zoster Exposure window: <30 days following prescription (three months for infliximab) 53

54 Incidence rates by type of treatment Treatment Incidence rate P-value vs. control UVB 6.0 NS PUVA 10.1 NS Acitretin 5.4 <0.01 Cyclosporine 48.4 <0.01 MTX 17.0 <0.001 Alefacept 0 NS Efalizumab 0 NS Etanercept 13.9 NS Infliximab 19.3 NS Adalimumab 0 NS Corticosteroids 25.7 <0.001 Control period 4.6 Reference All

55 Cox proportional hazard model Characteristics HR 95% CI P-value Age <0.001 Female sex Psoriasis severity Low 1 Reference Intermediate <0.001 High <0.001 Corticosteroids <

56 Cox proportional hazard model (Cont.) Characteristics HR 95% CI P-value Control period 1 Reference --- UVB PUVA Acitretin Cycloporine MTX Alefacept Efalizumb Etanercept Infliximab Adalimumab

57 Herpes Zoster Paper II Shalom, G., et al. "Systemic Therapy for Psoriasis and the Risk of Herpes Zoster: A 500,000 Person-year Study." JAMA Dermatol (2015):

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59 Committed to Lead Participants 95,941 patients with psoriasis 12 years of follow-up (January June 2013) 522,616 person-years 47,069 males (49%) Age, mean (SD) 45.8 (20.5) Zoster events - 4,636 (4,425 in the control group)

60 Committed to Lead Results Crude incidence rates of herpes zoster per 1000 person-years for each Tx. Total Control Systemic 32.3 Biologic Combination Control group UVB (N=2,895) PUVA (N=1,063) Methotrexate Acitretin (N=4,094) Cyclosporine (N=148) Etanercept (N=1,030) Adalimumab (N=719) Infliximab (N=392) Ustekinumab (N=63) Efalizumab (N=38) Alefacept (N=21) Mtx and bio. Med. Acitretin and bio. Photo. and bio. Photo. and Mtx. Photo. and Acitretin 8.9 Total (N=95,941)

61 Committed to Lead Results Treatment Herpes Zoster episodes (N) Time to herpes zoster event, mean (SD) a Control group (N=) 94,073 4, (35.5) UVB (N=2,895) (4.3) PUVA (N=1,063) (2.8) MTX (N=4,320) (22.7) Acitretin (N=4,094) (22) Cyclosporine (N=148) (30.8) Etanercept (N=1,030) (19.9) Adalimumab (N=719) (14.4) Infliximab (N=392) (17.9) Ustekinumab (N=63) (7) Efalizumab (N=38) 0 - Alefacept (N=21) 0 - MTX and biologics (N=739) (14.2) Acitretin and biologics (N=54) (12.3) Phototherapy & biologics (N=26) (2.5) Phototherapy & MTX (N=71) (3.1) Phototherapy & Acitretin(N=327) (4.3) Total (N=95,941) 4, (37)

62 Committed to Lead Results Effect of covariates on herpes zoster incidence (Poisson regression model) Exposures Rate ratio 95% CI P-value Control group Reference - - UVB NS PUVA NS Methotrexate NS Acitretin <0.01 Cyclosporine NS Etanercept NS Adalimumab NS Infliximab Ustekinumab NS Methotrexate + biologics Acitretin + biologics NS Systemic steroids <0.01 Charlson's Comorbidity Index score <0.01 Psoriasis severity Ø Adjusted for Gender, Age, Socioeconomic Status <0.01

63 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

64 Herpes Zoster Paper III Zisman, D., et al. "Psoriatic arthritis treatment and the risk of herpes zoster." Ann.Rheum.Dis (2016):

65 3128 patients with PsA Study period: ,096 person-years 182 zoster events (9.06/1000 person years)

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69 Cox regression analysis (Model 1): Combination of anti-tnf-α and DMARDs increased zoster risk Cox regression analysis (Model 2): Combination of etanercept and c-dmards: increased zoster risk Combination of MAB-anti-TNF-α and c-dmards: no increased zoster risk

70 Cox regression analysis (Model 1): Combination of anti-tnf-α and DMARDs increased zoster risk (20 zoster events) Cox regression analysis (Model 2): Combination of etanercept and c-dmards: increased zoster risk (9 zoster events) Combination of MAB-anti-TNF-α and c-dmards: no increased zoster risk (11 zoster events)

71 Herpes Zoster Paper III Zisman, D., et al. "Psoriatic arthritis treatment and the risk of herpes zoster." Ann.Rheum.Dis (2016): INSIGHT Even with BIG DATA the cells may become small

72 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

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74 Risk of Herpes Zoster in Psoriasis Patients: Results From PSOLAR Study Poster presented at EADV, September 2016, Vienna, Austria

75 Risk of Herpes Zoster in Psoriasis Patients: Results From PSOLAR Study Poster presented at EADV, September 2016, Vienna, Austria

76 Herpes Zoster Comparison between Clalit and PSOLAR INSIGHT Big data captures more zoster cases

77 Psoriasis registry vs. database Inclusion Data source Number of patients Parameters Follow up Attrition Cost Severe patients Interviews Psoriasis registry 1,000-20,000 (each) Psoriasis specific X1-2 Year 5%-30% Expensive All patients Computerized 100,000 Clalit database Utilization based Continuous 1% Marginal Insignificant 77

78 Psoriasis registry vs. database: Zoster diagnosis Psoriasis registry Clalit database Incidence Herpes diagnosis Severe patients More zoster events? Clinical Reflects all psoriasis patients Clinical + treatment Laboratory confirmation Not used Not used Miss zoster events Possible Exceptional Wrong zoster diagnosis Possible Possible 78

79 Psoriasis registry vs. database: Parameters important in Zoster Demographics Psoriasis severity Systemic steroids Phototherapy Zoster characteristics: Multi dermatomal Psoriasis registry + PASI - +/- +/- Clalit database + Defined by utilization + + +/- 79

80 Lecture outline 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

81 Herpes Zoster and TOFACITINIB Therapy in Patients With Psoriasis Poster presented at EADV, October 2015, Copenhagen, Denmark

82 Herpes Zoster and TOFACITINIB Therapy in Patients With Psoriasis Poster presented at EADV, October 2015, Copenhagen, Denmark 3623 tofacitinib-treated patients patient-years of exposure 130 cases of zoster 8/1217 cases in tofacitinib 5 mg BID - 1/100 py 20/1219 cases in tofacitinib 10 mg BID 2.3/100 py Most herpes zoster cases were Non-serious Resolved without needing tofacitinib discontinuation

83 Herpes Zoster and TOFACITINIB Therapy in Patients With Psoriasis Poster presented at EADV, October 2015, Copenhagen, Denmark

84 Herpes Zoster and TOFACITINIB Therapy in Patients With Psoriasis Poster presented at EADV, October 2015, Copenhagen, Denmark

85 Herpes Zoster Comparison between Clalit and Tofacitinib Phase III studies INSIGHT Even in big phase III studies the cells may become small

86 Lecture Summary 1. Clalit Health Services Database 2. Clalit - Demonstrative psoriasis patient 3. Beginning of psoriasis research in Clalit database 4. Confounding occurs even in BIG DATA 5. Keep it simple e.g. Diabetes 6. Stratification is needed even in BIG DATA 7. Database mistakes: human, logistic 8. Don t use all database 9. Herpes Zoster studies 10. Zoster: Even with BIG DATA the cells may become small 11. Zoster: Comparison between Clalit and PSOLAR 12. Zoster: Comparison between Clalit and Tofacitinib Phase III studies

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88 The largest health care organization in Israel WORKS FOR YOU