Insights from the Kaiser Permanente database Jashin J. Wu, M.D. Founding Director of Dermatology Research Director, Psoriasis Clinic Department of Dermatology Kaiser Permanente Los Angeles Medical Center Los Angeles, CA jashinwu@gmail.com
Potential conflicts of interest Company Research Consultant AbbVie X X Amgen X X AstraZeneca Boehringer Ingelheim Celgene Coherus Biosciences Dermira X X Eli Lilly X X Janssen LEO Pharma Merck Novartis Pfizer X X Regeneron X X Sandoz Sun Pharmaceutical Industries X X Valeant Pharmaceuticals X X X X X X X X X X
Goals of this lecture Discuss background on Kaiser Permanente Pros and cons of database research at Kaiser Permanente Discuss some of my research findings using the Kaiser Permanente database
Kaiser Permanente Founded in 1945 Large pre-paid managed health care system that spans 7 regions Over 10.6 million patients 38 hospitals 630 medical offices Workforce 18,652 physicians (about 300 dermatologists) 51,010 nurses 193,171 employees Annual operating revenue 2015: 60.7 billion
Business structure Kaiser Foundation Health Plans Nonprofit, public benefit corporations that contract with individuals and groups for prepaid, comprehensive health care services The Health Plans contract exclusively with the Permanente Medical Groups and Kaiser Foundation Hospitals for medical and hospital services for members and patients http://www.kaiserpermanentejobs.org/our-business-structure.aspx
Business structure Kaiser Foundation Hospitals Nonprofit, public benefit corporation that owns and operates community hospitals in California, Oregon, and Hawaii owns outpatient facilities in several states provides or arranges hospital services sponsors charitable, educational, and research activities http://www.kaiserpermanentejobs.org/our-business-structure.aspx
Business structure Permanente Medical Groups Partnerships or professional corporations of physicians, represented nationally by The Permanente Federation, which contract exclusively with the Kaiser Foundation Health Plans For profit I am a partner physician of Southern California Permanente Medical Group (SCPMG) http://www.kaiserpermanentejobs.org/our-business-structure.aspx
Kaiser Permanente regions Health plan members by region (June 2016) Southern California (KPSC): 4,224,958 Northern California (KPNC): 3,962,636 Colorado: 666,934 Mid-Atlantic States (VA, MD, DC): 664,877 Northwest (Oregon/Washington): 545,676 Georgia: 291,699 Hawaii: 247,477 Group Health Cooperative (Seattle-based) was acquired in 2016, will add 600,000 patients https://share.kaiserpermanente.org/article/fast-facts-about-kaiser-permanente/
Kaiser Permanente Southern California KPSC has served approximately 3.1-4.2 million members in each of the last 10 years KPSC comprises approximately 20% of the region s population and is representative of California Attrition averages about 10% per year Health plan members receive the majority of their health care at KPSC-owned facilities More than 92% of members obtain their prescription medications from a KPSC pharmacy
Kaiser Permanente Southern California Demographics of KPSC Hispanic 40.7% Non-hispanic white 35.8% Asian/pacific islanders 10.8% Black 9.2% Others 3.5%
KPSC advantages Generalizable to an insured population Linked records from inpatient, outpatient, emergency, mentalhealth settings, all laboratory and radiological tests, and all prescribed treatments Can open individual patient charts to fully validate and verify various diagnoses, labs, medications, etc. Research scientists (usually PhDs) who can help formulate the research question, protocol, analysis If on formulary, minimal restrictions for biologics Constantly growing membership due to the Affordable Care Act Higher numbers = more power
KPSC challenges Difficult to study disease severity Unable to capture over-the-counter or alternative treatments Mortality data may lag 12-18 months Limited number of programmers and statisticians If want to collaborate with other regions of Kaiser Permanente, would need to find a local PI with their own team of programmers and statisticians Retrospective studies can not determine causality
Autoimmune diseases The study aim was to determine whether patients with psoriasis with or without psoriatic arthritis were at increased risk for autoimmune diseases Retrospective cohort study of KPSC from 2004 to 2011 25341 patients with 2+ diagnosis codes for psoriasis (with or without psoriatic arthritis) Matched in 1:5 ratio with controls Wu JJ, et al. The association of psoriasis with autoimmune diseases. J Am Acad Dermatol. 2012 Nov;67(5):924-30.
Conclusions Psoriasis and/or psoriatic arthritis was positively associated with 17 of the 21 studied autoimmune diseases 14 of these associations were statistically significant The study gives evidence for a common genetic or environmental etiology among these autoimmune diseases
Risk of myocardial infarction Patients with psoriasis or PsA (n = 8845) between January 1, 2004 and November 30, 2010 were placed into one of 3 groups: TNF inhibitor (n = 1673) Oral therapy or phototherapy (n = 2097) Topical therapy (n = 5075) (reference) TNF inhibitor group had a lower risk of MI (adjusted HR: 0.50, 95% CI: 0.43-0.79) Wu JJ, et al. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012 Nov;148(11):1244-50.
CRP Retrospective cohort study from January 1, 2002 to July 31, 2011 of KPSC population Psoriasis, psoriatic arthritis, or rheumatoid arthritis Had CRP at baseline and at end of study TNF inhibitor + MTX (n=294) vs MTX (n=979) TNF inhibitors + MTX was associated with a clinically and statistically significant decrease (-5.18 mg/dl) in CRP compared to baseline Not seen in MTX group Wu JJ, et al. Association between tumor necrosis factor inhibitor therapy and changes in C-reactive protein, blood pressure, and alanine aminotransferase among patients with psoriasis, psoriatic arthritis, or rheumatoid arthritis. J Am Acad Dermatol 2015;72(5):917-9.
Other markers No changes in: BMI blood pressure fasting glucose, hemoglobin A1C total cholesterol, LDL, HDL, triglycerides alanine aminotransferase (ALT) Wu JJ, et al. No association between tumor necrosis factor inhibitor therapy and hemoglobin A1C and fasting glucose among psoriasis, psoriatic arthritis, and rheumatoid arthritis patients. J Drugs Dermatol 2015;14 159-66. Wu JJ, et al. Total cholesterol, HDLc, LDLc and triglyceride levels in TNF inhibitor-treated patients with psoriasis, psoriatic arthritis, and rheumatoid arthritis. Int J Dermatol 2015; Oct;54(10):e442-5. Wu JJ, et al. Initiation of TNF inhibitor therapy and change in physiologic measures in psoriasis. J Eur Acad Dermatol Venereol 2014;28:1380-7.
Risk of major adverse cardiovascular events Psoriasis or PsA patients (n = 15,354) between January 1, 2004 and December 31, 2014 were placed into one of 3 groups: TNF inhibitor (n = 1605) Oral therapy or phototherapy (n = 3399) Topical therapy (n = 10,350) (reference) Wu JJ, et al. Association between tumor necrosis factor inhibitor therapy and reduced risk of major adverse cardiovascular events in patients with psoriasis. Poster 2658. 74th Annual Meeting of the American Academy of Dermatology, Washington, DC, March 4-8, 2016.
Incidence rates and relative risks of MACE Treatment Person- Years Number of Events Incidence Rate per 1000 Person- Years Unadjusted HR (95% CI) Topical 73,777 922 12.50 1.00 (Reference) Oral/ Phototherap y TNF inhibitor 24,220 300 12.39 0.98 (0.86, 1.11) 12,438 114 9.17 0.71 (0.59, 0.86) Propensity Score- Adjusted HR (95% CI) 1.00 (Reference) 0.98 (0.86, 1.11) 0.60 (0.48, 0.76)
Sensitivity analysis to exclude oral agents Treatment Person- Years Number of Events Incidence Rate per 1000 Person- Years Unadjusted HR (95% CI) Propensity Score- Adjusted HR (95% CI) Topical 73,777 922 12.50 1.00 (Reference) Phototherap y TNF inhibitor 8,078 90 11.14 0.88 (0.71, 1.10) 12,438 114 9.17 0.73 (0.60, 0.88) 1.00 (Reference) 0.98 (0.84, 1.15) 0.59 (0.49, 0.70)
Sensitivity analysis to exclude phototherapy, cyclosporine, acitretin Treatment Person- Years Number of Events Incidence Rate per 1000 Person- Years Unadjusted HR (95% CI) Propensity Score- Adjusted HR (95% CI) Topical 73,777 922 12.50 1.00 (Reference) Methotrexat e TNF inhibitor 10,403 136 13.07 1.04 (0.87, 1.24) 12,438 114 9.17 0.73 (0.60, 0.88) 1.00 (Reference) 0.99 (0.85, 1.14) 0.59 (0.49, 0.70)
Take home points Kaiser Permanente is a big player in big data research Many advantages but a few disadvantages Showed that TNF inhibitors may improve cardiovascular endpoints
Thank you for your attention! I m happy to answer your questions. Jashin J. Wu, M.D. Founding Director of Dermatology Research Director, Psoriasis Clinic Department of Dermatology Kaiser Permanente Los Angeles Medical Center jashinwu@gmail.com