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The Risk of Cancer in Patients with Psoriasis a Population-Based Cohort Study in the Health Improvement Network

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The Risk of Cancer in Patients with Psoriasis a Population-Based Cohort Study in the Health Improvement Network Research Original Investigation The Risk of Cancer in Patients With Psoriasis A Population-Based Cohort Study in the Health Improvement Network Zelma C. Chiesa Fuxench, MD; Daniel B. Shin, MS; Alexis Ogdie Beatty, MD, MSCE; Joel M. Gelfand, MD, MSCE IMPORTANCE The risk of cancer in patients with psoriasis remains a cause of special concern due to the chronic inflammatory nature of the disease, the use of immune-suppressive treatments and UV therapies, and the increased prevalence of comorbid, well-established risk factors for cancer, such as smoking and obesity, all of which may increase the risk of carcinogenesis. OBJECTIVE To compare the overall risk of cancer, and specific cancers of interest, in patients with psoriasis compared with patients without psoriasis. DESIGN, SETTING, AND PARTICIPANTS Population-based cohort study of patients ages 18 to 89 years with no medical history of human immunodeficiency virus, cancer, organ transplants, or hereditary disease (albinism and xeroderma pigmentosum), prior to the start date, conducted using The Health Improvement Network, a primary care medical records database in the United Kingdom. The data analyzed had been collected prospectively from 2002 through January 2014. The analysis was completed in August 2015. EXPOSURES OF INTEREST Patients with at least 1 diagnostic code for psoriasis were classified as having moderate-to-severe disease if they had been prescribed psoralen, methotrexate, cyclosporine, acitretin, adalimumab, etanercept, infliximab, or ustekinumab or phototherapy for psoriasis. Patients were classified as having mild disease if they never received treatment with any of these agents. MAIN OUTCOMES AND MEASURES Incident cancer diagnosis. RESULTS A total of 937 716 control group patients without psoriasis, matched on date and practice visit, and 198 366 patients with psoriasis (186 076 with mild psoriasis and 12 290 with moderate-to-severe disease) were included in the analysis. The adjusted hazard ratios (aHRs) with 95% CIs for any incident cancer excluding nonmelanoma skin cancer (NMSC) were 1.06 (95% CI, 1.02-1.09), 1.06 (95% CI, 1.02-1.09), and 1.08 (95% CI, 0.96-1.22) in the overall, mild, and severe psoriasis group. The aHRs for incident lymphoma were 1.34 (95% CI, Author Affiliations: Departments of Dermatology, University of 1.18-1.51), 1.31 (95% CI, 1.15-1.49), and 1.89 (95% CI, 1.25-2.86); for NMSC, 1.12 (95% CI, Pennsylvania Perelman School of 1.07-1.16), 1.09 (95% CI, 1.05-1.13), and 1.61 (95% CI, 1.42-1.84); and for lung cancer, 1.15 (95% Medicine, Philadelphia (Chiesa CI, 1.03-1.27), 1.12 (95% CI, 1.01-1.25), and 1.62 (95% CI, 1.16-2.28) in the overall, mild, and Fuxench, Shin, Gelfand); severe psoriasis groups, respectively. No significant association was seen with cancer of the Epidemiology and Biostatistics, Center for Clinical Epidemiology and breast, colon, prostate, or leukemia. Biostatistics, University of Pennsylvania Perelman School of CONCLUSIONS AND RELEVANCE The association between psoriasis and cancer, albeit small, Medicine, Philadelphia (Chiesa Fuxench, Ogdie Beatty, Gelfand); was present in our cohort of patients with psoriasis. This association was primarily driven by Department of Rheumatology, NMSC, lymphoma, and lung cancer. University of Pennsylvania Perelman School of Medicine, Philadelphia (Ogdie Beatty). Corresponding Author: Zelma C. Chiesa Fuxench, MD, Department of Dermatology, University of Pennsylvania, Perelman School of Medicine, 3400 Spruce St, 1107 Dulles, Philadelphia, PA 19104 JAMA Dermatol. 2016;152(3):282-290. doi:10.1001/jamadermatol.2015.4847 (zelma.chiesafuxench Published online December 16, 2015. @uphs.upenn.edu). 282 (Reprinted) jamadermatology.com Copyright 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 The Risk of Cancer in Patients With Psoriasis Original Investigation Research he risk of cancer in patients with psoriasis has been of ferred out of the practice prior to the implementation of EMR. special concern owing to the chronic inflammatory na- Each patient with psoriasis was matched to up to 5 unex- T ture of the disease, use of immune suppressive treat- posed controls that were also 18 to 89 years at the start date ments and UV therapies, and the increased prevalence of and were from the same practice. Unexposed controls were as- comorbid, well-established risk factors for cancer, such as signed a “diagnosis” date based on having a recorded visit with smoking, all of which may increase the risk of carcinogenesis.1 the GP within 6 months (ie, ±180 days) of the corresponding Indeed, studies2-8 have previously demonstrated that pa- patient’s visit date to the GP. This algorithm was designed to tients with more severe psoriasis are at an increased risk of minimize bias by ensuring that exposed patients and unex- cancer-related mortality, and psoriasis has been associated with posed controls were followed by similar clinicians during simi- an increased risk of cancer, including lymphoma. However, lar time periods. Patients were initially excluded from the en- these studies have generally not controlled for important con- tire cohort if they had a personal history of any cancer, organ founders, and have often failed to examine the rates of spe- transplant, or human immunodeficiency virus (HIV) and/or cific cancers or the impact of disease severity on cancer risk. AIDS, or had a diagnosis of hereditary diseases that have an Furthermore, there have often been conflicting data on the increased susceptibility for developing malignant abnormali- risk of specific cancers including lymphoma.1,3,4,6,9 Addi- ties, including albinism and xeroderma pigmentosum. tional studies are necessary to further define the risk of cancer in patients with this disease. Protection of Study Subjects We performed a population-based cohort study using a na- This study was developed in accordance with the STROBE tionwide, electronic medical records database from the United guidelines and was approved by the institutional review board Kingdom to evaluate the association between psoriasis and of the University of Pennsylvania and by the Scientific Re- cancer. In addition, our study also evaluated whether the risk view Committee of CSD Medical Research, United Kingdom. of cancer in patients with psoriasis could be explained by a spe- This study was a population-based study using data already cific group of cancers and if this risk was higher in patients with collected for these purposes. Data were collected by a third more severe disease. party and deidentified before they were made available for re- search purposes. Because our study analyzed data already col- lected for these purposes, patient consent was not required. Methods Definition of Exposure This study is a population-based cohort study analyzing data Patients with psoriasis were identified by the presence of at that had been collected prospectively since 2002 through Janu- least one diagnostic Read code for psoriasis in the patient’s ary 2014 by general practitioners (GPs) in the United King- medical file. Read codes are a comprehensive numerical sys- dom who were unaware of the hypothesis being tested. tem developed in the United Kingdom to record diagnosis, symptoms, and tests, and is similar to the International Clas- Data Source sification of Disease (ICD) codes.16 The use of Read codes for Our source of data was The Health Improvement Network modeling disease outcomes in patients with psoriasis has been (THIN), an electronic medical records (EMR) database that con- previously validated in THIN.13 Severity of psoriasis was clas- tains anonymized medical record information from nearly 11.9 sified as mild or moderate-to-severe depending on whether the million patients across the United Kingdom. THIN has been patient was prescribed systemic therapy or phototherapy for extensively used for epidemiological research, and prior psoriasis. Patients were classified as having moderate-to- studies10-13 have validated the diagnostic accuracy of psoria- severe psoriasis if they had ever received any prescription for sis and malignant disease codes used in THIN. Participants psoralen, phototherapy, methotrexate, cyclosporine, acitre- within THIN are considered to be representative of the gen- tin, adalimumab, etanercept, infliximab, and/or ustekinumab. eral population of the United Kingdom in terms of their age, Patients were classified as having mild disease if they had never sex, geography, and medical diagnoses.14 Information re- received treatment with any of these agents. This approach has corded includes patient demographics, medical diagnosis, and been used in previous studies as a proxy for estimating treatments prescribed, as well as referrals to specialists, hos- disease severity.4,17 pitalizations, and laboratory results. THIN has the advantage over administrative claims databases (ie, Medicare) because Person-Time Calculation it contains information on important risk factors for cancer, For exposed patients (ie, those who received at least 1 diag- such as smoking, alcohol intake, and body mass index (BMI).15 nostic code for psoriasis) the start of follow-up time occurred at the latest of the following: date of first diagnostic code for Study Population psoriasis in THIN; 180 days after patient registration with the Our initial cohort within THIN consisted of all patients with a practice; or when the practice began recording information diagnosis of psoriasis and unexposed controls (ie, those with using Vision software. For unexposed patients (ie, those with no recorded diagnosis of psoriasis). All patients with psoria- no diagnosis of psoriasis) the start time occurred at the latest sis who were ages 18 to 89 years at the start date and had ob- of 3 dates: 180 days after patient registration, when the prac- servation time within THIN, after implementation of the EMR, tice began recording information using Vision software, or the were included. Patients were excluded if they died or trans- closest corresponding visit to the exposed patient’s visit date jamadermatology.com (Reprinted) JAMA Dermatology March 2016 Volume 152, Number 3 283 Copyright 2016 American Medical Association.
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