Use of medical record databases to study psoriasis

Transcription

1 Use of medical record databases to study psoriasis Joel M. Gelfand, MD, MSCE Professor of Dermatology and Epidemiology Vice Chair for Clinical Research Medical Director, Clinical Studies Unit Director, Psoriasis and Phototherapy Treatment Center University of Pennsylvania Perelman School of Medicine

2 Disclosure and funding statement Investigator and/or consultant for Amgen, Abbvie, Jansen, Merck (DSMB), Pfizer, Lilly, Celgene, Coherus (DSMB), Novartis, Sanofi, Valeant, and Astrazenaca Patent Resiquimod for CTCL This presentation is the sole work of Dr. Gelfand

3 Overview of epidemiology Epidemiology is the basic science underlying much of public health, preventative medicine, and individual patient care decisions Requirements: Large numbers of patients to detect clinically relevant relationships Methods to minimize selection and information bias as well as adjust for confounding (internal validity) Representative samples to enhance generalizability (external validity)

4 Population based studies: Unifying theory for analytical studies o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o o allocation process Exposed Unexposed End of observation period Study population Error Sources: Confounding & Selection Bias study time = Study outcome Information Bias

5 Study Designs in Epidemiology 1. Clinical Trial 2. Cohort 3. Case-control 4. Cross-sectional/ecologic 5. Case series 6. Case reports Analytic Descriptive

6 Use of Automated databases for epidemiological research Advantages Rapid access to large numbers of patients Well defined population May have co-variates of interest Disadvantages Validity should be established System may be open Data on co-variates may be incomplete or missing

7 Types of automated databases Claims Based on bills for health care services from hospitals, pharmacies, physicians Often has very accurate pharmacy data as this is subject to intense audits in US Hospital discharge diagnoses generally accurate (but can be skewed), outpatient diagnoses generally less accurate Short follow up Medical record Generally more accurate as diagnoses reflect the medical record Often has data on smoking, body weight, blood pressure Follow up may be longer Completeness of data can be a problem

8 Medical Record Databases: UK Examples UK is an ideal model for use of medical records data Virtually all are registered with a GP Gatekeeper model: GPs coordinate care capturing data from specialists and hospitals Early adopters of electronic medical records Performance measures often result in high capture for some disease states

9 Medical Record Databases: GCPRD and THIN General Practice Research Database established 1987 (now called Clinical Practice Research Datalink) run by UK government 12 million + patients 67+ million person years 600+ practices broadly representative of UK Ongoing quality checks of data BMI, smoking, alcohol use captured Many outcomes validated by chart review publications! The Health Improvement Network (THIN) is a related system run by IMS Health

10 Cardinal Rule #1: Understand your data and its validity Random sample of 100 patients with psoriasis code: confirmation rate 92% Prevalence of Psoriasis by Age and Sex Prevalence yr 10-20yr 20-29yr 30-39yr 40-49yr Age 50-59yr 60-69yr 70-79yr yr 89yr Male Female Gelfand JM et al Arch Derm 2005;141: Gelfand JM et al Arch Derm 2003;139:

11 Validation of the PsA Codes! Patients with PsA (not Juv. PsA) and aged ,045 *There are 6 codes for PsA Randomly Selected Practices that Contribute to Additional Information Services 100 Surveys Returned 87 Confirmed PsA 74 PsA also Confirmed by Rheumatologist 62 PPV: 85.1% 83.8% Slide courtesy of A. Ogdie MD Ogdie et al Pharmacoepidemiol Drug Saf 2014;23:

12 Psoriasis: a risk factor for CAD and MI? Psoriasis CVD Smoking HTN DM Obesity Lipids PET/MRI courtesy of NN Mehta

13 40 Prevalence of cardiovascular risk factors Controls Mild Severe OR (severe vs. control) DM HTN Lipids Smoking BMI BMI> Neimann et al. JAAD 2006;55:

14 Gelfand 1.0: Cardiometabolic disease in GPRD Mortality Curve Mortality Curve Outcome! Abuabara, K., et al. Br. J. Dermatol. 2010; 163(3):586 Adj.!RR! Mild! Adj.!RR! Severe! MI 1$ Stroke 2$ CV$Death 3 $ Not done 1.6 MACE 4 $ Not done 1.5 Diabetes 5$ Analytical Approach: Match on practice and start date Severity based on use of systemic or phototherapy Multivariable modeling to adjust for BMI, smoking, HTN, HL, DM Sensitivity analyses 1. Gelfand, J.M., et al. JAMA. 2006; 296: Gelfand, J.M., et al. J. Invest. Derm. 2009; 129: Mehta, N.N., et al. Eur. Heart J. 2010; 31: Mehta, N.N., et al. Am. J. Med. 2011; 124:775.e Azfar R, et al.. Arch Derm 2012; 148:

15 Cardinal rule #2: Good science requires confirmation- MACE in more severe psoriasis CPRD CPRD THIN HR MACE 1.28 * HR MACE 1.29 HR MACE 1.42 HR MACE 1.46 # * Not significant # Exclude PsA

16 Cardinal rule #3: Good science requires challenging your assumptions: Sensitivity analyses Seen at least 1x per year Exclude PsA Restrict on treatments to define severe disease Use of multiple imputation for missing data Time varying models, propensity scores, inception design Figure adopted from Ogdie et al Ann Rheum Dis 2015;74:326-32

17 Cardinal rule #4: Large sample size allows more precise analysis of outcomes Mild psoriasis N=149,203 Severe psoriasis N=3,994 Lymphoma all HR 1.34 HR 1.59 (ns) Non-Hodgkin s HR 1.15 (ns) HR 0.73 (ns) Hodgkin s HR 1.42 HR 3.18 Cutaneous T cell HR 4.1 HR 10.75

18 Epidemiology of Psoriasis in THIN Seminara NM et al BJD 2011;164:602-9

19 Risk of cancer and lymphoma in psoriasis THIN data: Similar findings to older GPRD data Fuxench ZC et al JAMA Derm 2016;152:

20 Gelfand 2.0: Disease severity assessed directly by GP in THIN, simultaneous RA comparisons The Incident Health Outcomes and Psoriasis Events study (ihope) Prospective study ages at least one psoriasis code (or visit to GP for controls) within 2 years of random sample 10,474 eligible psoriasis patients, 10,026 surveys returned (95.7% response rate)

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22 Disease severity in ihope 9035 confirmed to have psoriasis (90.1%) Severity: 4,523 (51.8%) mild 3,122 (35.8%) moderate 1,081 (12.4%) severe 19% have disease severe enough to require systemic or phototherapy

23 Use of validation data to develop algorithms when surveys are not available Algorithms allow PPV of 90% for confirmation of diagnosis by dermatology Seminara NM et al BJD 2011;164:602-9

24 Algorithm for predicting BSA >10%: Good Discrimination but limited predictive value Seminara NM et al BJD 2011;164:602-9

25 Prevalence of CVD increases with increasing body surface area affected by psoriasis in ihope Odds Ratio Yeung H et al. Psoriasis severity and the prevalence of major medical comorbidity. JAMA Derm 2013;149:1173-9

26 Metabolic syndrome components increase with affected BSA Langan SM, Seminara, NM, Shin, DB, Troxel A, Kimmel SE, Mehta NN, Margolis DJ, and Gelfand JM: Prevalence of metabolic syndrome in patients with psoriasis: A population based study in the United Kingdom. Journal of Investigative Dermatology 2012 Mar;132:

27 CV risk factors are under screened and under managed in psoriasis patients P for trend = Prevalence of Uncontrolled Hypertension (%) No Psoriasis Psoriasis Overall Mild (<2%) Moderate (3-10%) Severe (>10%) Takeshita, J et al. JAMA Dermatology 2015;151:161-9

28 Moderate to Severe Psoriasis is a risk factor for chronic kidney disease Nearly 2 fold risk of chronic kidney disease >4 fold risk of dialysis Risks are independent of diabetes, hypertension and nephrotoxic meds Prevalence of CKD Wan J, Wang S, Denburg MR, Shin DB, Gelfand JM. Risk of moderate to advanced kidney disease in patients with psoriasis. BMJ 2013;15;347:f5961

29 Comparison of cardiometabolic outcomes: Psoriasis vs. RA vs. PsA Søren Lund Kristensen et al. Ann Rheum Dis 2015;74: Ogdie A et al. Ann Rheum Dis Jan;73(1): Ogdie A et al. Ann Rheum Dis. 2015;74: Dubreuil M et al Rheumatology 2014 Feb;53(2):

30 What s new? BSA predicts death! HR Death Mild Moderate Severe BSA 2% BSA 3-10% BSA >10% p= 0.43 p=0.32 p<0.001

31 Gelfand 3.0: RCTs evaluating impact of psoriasis treatment on CV risk Vascular Inflammation in Psoriasis Trials (VIP) Does treatment with ADALIMUMAB or PHOTOTHERAPY lower vascular inflammation and improve lipid metabolism in patients with moderate to severe psoriasis? (NCT ) Does treatment with USTEKINUMAB lower vascular inflammation and improve lipid metabolism in patients with moderate to severe psoriasis (NCT ) Does treatment with SECUKINUMAB lower vascular inflammation and improve lipid metabolism in patients with moderate to severe psoriasis (NCT )

32 Acknowledgements Collaborators D. Margolis, B. Strom, A. Troxel, N. Mehta, A. Ogdie A. Van Voorhees, D. Shin, A. Alavi Post Docs A. Neimann, R. Azfar, S. Langan, J. Takeshita Z. Chiesa, M Noe Pre Docs S. Kurd, N. Smith, E. Dommasch, K Abuabara, S. Wang N. Seminara, J. Wan, H. Yeung, J. Chung, S. Grewal Coordinators S Baez VanderBeek, M Papadopoulos, J. Alvarez, P Kim Funding support NIH NIAMS F32, K23, K24, RC1 and NHLBI R01HL and R01HL Funding support Industry Abbvie, Amgen, Lilly, Jansen, Pfizer, Novartis Funding support foundations National Psoriasis Foundation, Dermatology Foundation, American Skin Association, Psoriasis Research Association in memory of Herman Beerman