Objective Measures of Psoriasis Severity Predict Mortality: A Prospective Population-Based Cohort Study

A broad and growing body of literature suggests that psoriasis is associated with higher rates of major comorbidities, including mortality (Gelfand et al., 2007Gelfand J.M. Troxel A.B. Lewis J.D. Kurd S.K. Shin D.B. Wang X. et al.The risk of mortality in patients with psoriasis: results from a population-based study.Arch Dermatol. 2007; 143: 1493-1499Crossref PubMed Scopus (449) Google Scholar, Lee et al., 2017Lee M.S. Yeh Y.C. Chang Y.T. Lai M.S. All-cause and cause-specific mortality in patients with psoriasis in Taiwan: a nationwide population-based study.J Invest Dermatol. 2017; 137: 1468-1473Abstract Full Text Full Text PDF PubMed Scopus (39) Google Scholar, Lindegard, 1989Lindegard B. Mortality and causes of death among psoriatics.Dermatologica. 1989; 179: 91-92Crossref PubMed Scopus (22) Google Scholar, Ogdie et al., 2014Ogdie A. Haynes K. Troxel A.B. Love T.J. Hennessy S. Choi H. et al.Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study.Ann Rheum Dis. 2014; 73: 149-153Crossref PubMed Scopus (81) Google Scholar, Poikolainen et al., 1999Poikolainen K. Karvonen J. Pukkala E. Excess mortality related to alcohol and smoking among hospital-treated patients with psoriasis.Arch Dermatol. 1999; 135: 1490-1493Crossref PubMed Scopus (166) Google Scholar, Salahadeen et al., 2015Salahadeen E. Torp-Pedersen C. Gislason G. Hansen P.R. Ahlehoff O. Nationwide population-based study of cause-specific death rates in patients with psoriasis.J Eur Acad Dermatol Venereol. 2015; 29: 1002-1005Crossref PubMed Scopus (22) Google Scholar, Springate et al., 2017Springate D.A. Parisi R. Kontopantelis E. Reeves D. Griffiths C.E. Ashcroft D.M. Incidence, prevalence and mortality of patients with psoriasis: a U.K. population-based cohort study.Br J Dermatol. 2017; 176: 650-658Crossref PubMed Scopus (129) Google Scholar, Stern and Huibregtse, 2011Stern R.S. Huibregtse A. Very severe psoriasis is associated with increased noncardiovascular mortality but not with increased cardiovascular risk.J Invest Dermatol. 2011; 131: 1159-1166Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar, Svedbom et al., 2015Svedbom A. Dalen J. Mamolo C. Cappelleri J.C. Mallbris L. Petersson I.F. et al.Increased cause-specific mortality in patients with mild and severe psoriasis: a population-based Swedish register study.Acto Derm Venereol. 2015; 95: 809-815PubMed Google Scholar). Most current literature does not adjust for major mortality risk factors such as obesity, and critically, to our knowledge there are no studies that evaluate how direct measures of psoriasis severity influence risk of death. Therefore, the objective of this study is to examine the risk of mortality in psoriasis patients compared with adults without psoriasis, stratified by simple physician-reported objective measures of disease severity while adjusting for major mortality risk factors routinely collected in clinical practice. We conducted a prospective, population-based, cohort study using The Health Improvement Network, an electronic medical records database in the United Kingdom. Within The Health Improvement Network, we created a nested cohort of patients with psoriasis, who were followed prospectively as the Incident Heath Outcomes and Psoriasis Events (i.e., iHOPE) study, as previously described (Yeung et al., 2013Yeung H. Takeshita J. Mehta N.N. Kimmel S.E. Ogdie A. Margolis D.J. et al.Psoriasis severity and the prevalence of major medical comorbidity: a population-based study.JAMA Dermatol. 2013; 149: 1173-1179Crossref PubMed Scopus (342) Google Scholar). Physician survey was used to confirm the diagnosis of psoriasis and classify, a priori, the extent of disease based on standard categories used by the Centers for Disease Control and Prevention and the National Psoriasis Foundation for epidemiological studies of psoriasis. The outcome of interest was death. Data were collected prospectively from the date of physician survey until the individual died, transferred out of the practice, or reached the end of the data collection period. Covariates of interest included age, sex, body mass index (BMI), alcohol use, smoking, and medical comorbidities from the Charlson comorbidity index (CCI) (Charlson et al., 1987Charlson M.E. Pompei P. Ales K.L. MacKenzie C.R. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chron Dis. 1987; 40: 373-383Abstract Full Text PDF PubMed Scopus (34492) Google Scholar). The CCI classifies comorbid health conditions that may affect the risk of mortality and has been previously validated to be a strong predictor of 5-year mortality in UK medical records databases (Khan et al., 2010Khan N.F. Perera R. Harper S. Rose P.W. Adaptation and validation of the Charlson Index for Read/OXMIS coded databases.BMC Fam Pract. 2010; 11: 1Crossref PubMed Scopus (233) Google Scholar). Descriptive statistics were used to examine age, sex, and comorbidity distribution between psoriasis patients and control subjects. The mortality rate was calculated by dividing number of deaths over the total observation time, in 1,000 person-years. Cox proportional hazard regression models, adjusted for age, sex, and CCI, were created to determine the adjusted risk of death in psoriasis. Sensitivity analyses controlling for BMI, alcohol and tobacco use, and use of systemic therapy were performed. Statistical analysis was performed in STATA 14.2 (StataCorp, College Station, TX). The analysis included 8,760 adults with psoriasis and 87,600 adults without psoriasis (Table 1). Psoriasis patients were more likely to be male and had a slightly higher BMI, but the average age was similar in both groups. Psoriasis patients had higher rates of chronic kidney disease, chronic obstructive pulmonary disease, diabetes, and history of myocardial infarction. Among the 8,760 patients with psoriasis there were 125 deaths, which resulted in a mortality rate of 3.35 deaths per 1,000 person-years (95% CI = 2.81–3.99). In 87,600 adults without psoriasis, there were 1,188 total deaths or 3.24 deaths per 1,000 person-years (95% CI = 3.06–3.43) (Table 2).Table 1Baseline characteristics of psoriasis patients and controlsCharacteristicsControlsN = 87,600All PsoriasisN = 8760P-ValueFemale, n (%)46,352 (52.9)4,330 (49.4)<0.001Age in years, mean (SD)45.3 (11.1)45.4 (11.1)0.596BMI, mean (SD)27.1 (5.7)27.9 (6.1)<0.001Alcohol use<0.001 Never8,659 (9.9)733 (8.4) Current/former68,739 (78.5)7,076 (80.8) Missing10,202 (11.7)951 (10.7)Smoking<0.001 Never42,609 (48.6)3,209 (36.6) Current/former43,616 (49.8)5,474 (62.5) Missing1,375 (1.6)77 (0.88)Medical comorbidities, n (%) Cerebrovascular disease969 (1.1)108 (1.2)0.282 Chronic kidney disease1,889 (2.1)233 (2.66)0.002 Congestive heart failure251 (0.3)32 (0.4)0.194 Chronic obstructive pulmonary disease15,434 (17.6)1,622 (18.5)0.036 Dementia39 (0.04)6 (0.07)0.322 Diabetes3,831 (4.4)461 (5.3)<0.001 Hemiplegia114 (0.2)8 (0.1)0.100 HIV11 (0.01)1 (0.01)0.927 History of myocardial infarction908 (1.0)129 (1.5)<0.001 Peripheral vascular disease528 (0.6)75 (0.9)0.004 Liver disease695 (0.8)93 (1.06)0.008 Malignancy2,188 (2.5)185 (2.1)0.026Charlson Comorbidity Index, n (%)<0.001 063,201 (72.0)6,097 (69.6) 1–221,728 (24.8)2,310 (26.4) 3–42,316 (2.6)291 (3.3) >5454 (0.5)62 (0.7)Abbreviations: BMI, body mass index; SD, standard deviation. Open table in a new tab Table 2Hazard ratio of morality based on physician-reported psoriasis BSAControlsn = 87,600<3% BSAn = 4,5393–10% BSAn = 3,133>10% BSAn = 1,088Number of deaths1,188583829Average follow-up time, years (SD)4.17 (1.64)4.25 (1.56)4.31 (1.50)4.16 (1.53)Mortality rate, per 1,000 person-years (95% CI)3.24 (3.06–3.43)3.00 (2.32–3.88)2.81 (2.04–3.86)6.39 (4.45–9.21)Unadjusted HRREF0.92 (0.71–1.20)0.87 (0.63–1.20)2.00 (1.38–2.89)Adjusted for age and sexREF0.89 (0.70–1.17)0.87 (0.63–1.20)2.12 (1.46–3.07)Adjusted for age, sex, and CCIREF0.87 (0.67–1.13)0.79 (0.57–1.09)1.79 (1.23–2.59)Attributable risk1Adjusted for age, sex, and CCI.N/AN/AN/A2.56 per 1,000 person-yearsSensitivity analysesAdjusted for BMIREF0.90 (0.69–1.18)0.77 (0.54–1.08)1.81 (1.23–2.68)Adjusted for smoking and alcohol useREF0.80 (0.61–1.06)0.70 (0.49–0.99)1.76 (1.21–2.57)Adjusted for cardiovascular risk factors2Adjusted for age, sex, smoking, diabetes, history of myocardial infarction, and history of stroke.REF0.82 (0.63–1.08)0.76 (0.55–1.06)1.87 (1.29–2.70)Excluding those who received any systemic therapy (UV, oral systemic, or biologic)n = 4,478n = 2,944n = 856Fully adjusted1Adjusted for age, sex, and CCI.0.89 (0.68–1.15)0.78 (0.55–1.09)1.68 (1.08–2.61)Excluding those who received oral systemic or biologic therapyn = 4,509n = 3,062n = 988Fully adjusted1Adjusted for age, sex, and CCI.0.88 (0.68–1.15)0.78 (0.56–1.08)1.87 (1.26–2.75)Abbreviations: BSA, body surface area; CI, confidence interval; CCI, Charlson Comorbidity Index; HR, hazard ratio; N/A, not applicable; REF, reference; SD, standard deviation.1 Adjusted for age, sex, and CCI.2 Adjusted for age, sex, smoking, diabetes, history of myocardial infarction, and history of stroke. Open table in a new tab Abbreviations: BMI, body mass index; SD, standard deviation. Abbreviations: BSA, body surface area; CI, confidence interval; CCI, Charlson Comorbidity Index; HR, hazard ratio; N/A, not applicable; REF, reference; SD, standard deviation. After stratification by physician-reported body surface area (BSA), there were 58, 38, and 29 deaths in the <3%, 3–10%, and >10% psoriasis groups, respectively (Table 2). In age and sex- adjusted models, only those with more than 10% BSA had a statistically significant increased risk of death (hazard ratio = 2.12, 95% confidence interval = 1.46–3.07). The risk of mortality in those with BSA greater than 10% remained elevated when adjusting for CCI (hazard ratio = 1.79, 95% confidence interval = 1.23–2.59). Results were robust to sensitivity analyses adjusting for BMI, alcohol and tobacco use, and use of systemic therapy (Table 2). In this large, population-based, prospective study from the United Kingdom, patients with psoriasis BSA of more than 10% had 1.79 times increased risk of death, compared with age- and sex-matched adults without psoriasis after controlling for baseline predictors of mortality. Those with less than 10% BSA may be at a higher risk for clinically important comorbidities, but not with elevated mortality. Based on our results, we estimate there is 1 excess death in every 390 psoriasis patients with a BSA greater than 10% annually that cannot be explained by traditional risk factors identified in routine medical practice. The findings are consistent with what can be inferred from the existing mortality literature. Previously published population-based studies found an increased risk of death in psoriasis patients compared with control subjects; however, this was using treatment received as a proxy for psoriasis severity (Gelfand et al., 2007Gelfand J.M. Troxel A.B. Lewis J.D. Kurd S.K. Shin D.B. Wang X. et al.The risk of mortality in patients with psoriasis: results from a population-based study.Arch Dermatol. 2007; 143: 1493-1499Crossref PubMed Scopus (449) Google Scholar, Ogdie et al., 2014Ogdie A. Haynes K. Troxel A.B. Love T.J. Hennessy S. Choi H. et al.Risk of mortality in patients with psoriatic arthritis, rheumatoid arthritis and psoriasis: a longitudinal cohort study.Ann Rheum Dis. 2014; 73: 149-153Crossref PubMed Scopus (81) Google Scholar, Salahadeen et al., 2015Salahadeen E. Torp-Pedersen C. Gislason G. Hansen P.R. Ahlehoff O. Nationwide population-based study of cause-specific death rates in patients with psoriasis.J Eur Acad Dermatol Venereol. 2015; 29: 1002-1005Crossref PubMed Scopus (22) Google Scholar, Springate et al., 2017Springate D.A. Parisi R. Kontopantelis E. Reeves D. Griffiths C.E. Ashcroft D.M. Incidence, prevalence and mortality of patients with psoriasis: a U.K. population-based cohort study.Br J Dermatol. 2017; 176: 650-658Crossref PubMed Scopus (129) Google Scholar). In our psoriasis patients, only 21% of those with BSA of greater than 10% had a history of treatment with systemic therapy (phototherapy, oral systemic medication, or biologic), showing the need to use objective measures of disease severity to more fully capture patient experience. One previous study has examined mortality risk, using physician-reported objective measures of psoriasis severity. The PUVA Follow-Up Study prospectively followed 1,376 adults with severe psoriasis enrolled in a clinical trial for treatment with psoralens and ultraviolet-A (PUVA) (Stern et al., 1984Stern R.S. Laird N. Melski J. Parrish J.A. Fitzpatrick T.B. Bleich H.L. Cutaneous squamous-cell carcinoma in patients treated with PUVA.New Engl J Med. 1984; 310: 1156-1161Crossref PubMed Scopus (399) Google Scholar). Our results confirm what was shown in the PUVA Follow-Up Study: a one-time measurement of psoriasis severity is a powerful predictor of future mortality (Stern and Huibregtse, 2011Stern R.S. Huibregtse A. Very severe psoriasis is associated with increased noncardiovascular mortality but not with increased cardiovascular risk.J Invest Dermatol. 2011; 131: 1159-1166Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar). In summary, patients with psoriasis affecting more than 10%of BSA are at an increased risk of death compared with the general population, even after controlling for standard mortality risk factors. Our findings support the existing literature showing that patients with severe psoriasis have an increased risk of death and show that a one-time, simple clinical assessment can be predictive of future mortality. Based on these results, psoriasis patients identified in the clinic with BSA of greater than 10% should be targeted for preventative health interventions. Additionally, future research is needed to better elucidate the specific causes of mortality in patients with extensive psoriasis and determine the effects of psoriasis treatment on mortality risk. Megan H Noe: http://orcid.org/0000-0001-8481-4711 In the previous 12 months, JMG served as a consultant for Coherus (DSMB), Dermira, Janssen Biologics, Merck (DSMB), Novartis Corp., Regeneron, Dr Reddy’s labs, Sanofi and Pfizer Inc., receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from Abbvie, Janssen, Novartis Corp., Regeneron, Sanofi, Celgene, and Pfizer Inc.; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly and Abbvie. JMG is a co-patent holder of resiquimod for treatment of cutaneous T-cell lymphoma. MHN, DBS, and MTW state no conflict of interest. Back to the Future: Looking at the Skin to Predict Death—A Lesson from PsoriasisJournal of Investigative DermatologyVol. 138Issue 1PreviewNoe et al. have documented that an objective measure of psoriasis severity, the body surface area as assessed at a single time point, could predict the risk of all-cause mortality in psoriatic patients. The results have important implications for disease management. Socioeconomic variables may, in part, confound the association between severe psoriasis and increased mortality. Full-Text PDF Open ArchiveAddendumJournal of Investigative DermatologyVol. 138Issue 4PreviewObjective Measures of Psoriasis Severity Predict Mortality: A Prospective Population-Based Cohort Study Full-Text PDF Open Archive