key: cord-0718550-xymvz9hg
authors: Mahil, Satveer K.; Dand, Nick; Mason, Kayleigh J.; Yiu, Zenas ZN.; Tsakok, Teresa; Meynell, Freya; Coker, Bola; McAteer, Helen; Moorhead, Lucy; Mackenzie, Teena; Rossi, Maria Teresa; Rivera, Raquel; Mahe, Emmanuel; Carugno, Andrea; Magnano, Michela; Rech, Giulia; Balogh, Esther A.; Feldman, Steven R.; De La Cruz, Claudia; Choon, Siew Eng; Naldi, Luigi; Lambert, Jo; Spuls, Phyllis; Jullien, Denis; Bachelez, Hervé; McMahon, Devon E.; Freeman, Esther E.; Gisondi, Paolo; Puig, Luis; Warren, Richard B.; Di Meglio, Paola; Langan, Sinéad M.; Capon, Francesca; Griffiths, Christopher EM.; Barker, Jonathan N.; Smith, Catherine H.
title: Factors associated with adverse COVID-19 outcomes in patients with psoriasis – insights from a global registry-based study
date: 2020-10-16
journal: J Allergy Clin Immunol
DOI: 10.1016/j.jaci.2020.10.007
sha: 1ae261d19a0d7396ed2408b789c586bbbd13cd98
doc_id: 718550
cord_uid: xymvz9hg

Background The multi-morbid burden and use of systemic immunosuppressants in people with psoriasis may confer greater risk of adverse COVID-19 outcomes but data are limited. Objective Characterize the course of COVID-19 in psoriasis and identify factors associated with hospitalization. Methods Clinicians reported psoriasis patients with confirmed/suspected COVID-19 via an international registry, PsoProtect. Multiple logistic regression assessed the association between clinical/demographic characteristics and hospitalization. A separate patient-facing registry characterized risk-mitigating behaviours. Results Of 374 clinician-reported patients from 25 countries, 71% were receiving a biologic, 18% a non-biologic and 10% no systemic treatment for psoriasis. 348 (93%) fully recovered from COVID-19, 77 (21%) were hospitalized and nine (2%) died. Increased hospitalization risk was associated with older age (multivariable-adjusted OR 1.59 per 10 years, 95% CI 1.19-2.13), male sex (OR 2.51, 95% CI 1.23-5.12), non-white ethnicity (OR 3.15, 95% CI 1.24-8.03) and comorbid chronic lung disease (OR 3.87, 95% CI 1.52-9.83). Hospitalization was more frequent in patients using non-biologic systemic therapy than biologics (OR 2.84, 95% CI 1.31-6.18). No significant differences were found between biologic classes. Independent patient-reported data (n=1,626 across 48 countries) suggested lower levels of social isolation in individuals receiving non-biologic systemic therapy compared to biologics (OR 0.68, 95% CI 0.50-0.94). Conclusion In this international moderate-severe psoriasis case series, biologics use was associated with lower risk of COVID-19-related hospitalization than non-biologic systemic therapies, however further investigation is warranted due to potential selection bias and unmeasured confounding. Established risk factors (being older, male, non-white ethnicity, comorbidities) were associated with higher hospitalization rates. Clinical Implications We identify risk factors for COVID-19-related hospitalization in psoriasis patients, including older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated with lower hospitalization risk than non-biologic systemic therapies.

We identify risk factors for COVID-19-related hospitalization in psoriasis patients, including 188 older age, male sex, non-white ethnicity and comorbidities. Use of biologics was associated 189 with lower hospitalization risk than non-biologic systemic therapies. 190 191 192 Capsule summary 193 In this global registry-based study, risk factors for COVID-19-related hospitalization in 194 psoriasis patients were older age, male sex, non-white ethnicity and comorbidities. Use of 195 biologics was associated with lower hospitalization risk than non-biologic systemic 196 treatment. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS- 218 CoV-2), has led to unprecedented challenges for the international clinical and scientific 219 community (1) . Although most patients with COVID-19 experience mild symptoms, an 220 estimated 15% develop pneumonia and 5% progress to systemic hyperinflammation and 221 acute respiratory distress syndrome requiring critical care management, with risk of septic 222 shock, multi-organ failure and death (2). Reported mortality rates range from 2.3% to 7.2% 223 (2,3). Increased age, male sex and non-white ethnicity have emerged as risk factors of poor 224 COVID-19 outcome in the general population, in addition to comorbidities including 225 cardiovascular disease, diabetes and obesity (4-6). Since multimorbidity is prevalent in 226 psoriasis (7), there is an urgent need to understand the impact of COVID-19 in individuals 227 with this common lifelong immune-mediated skin disease. Psoriasis affects more than 60 228 million people worldwide (8) (18)). 277 The second data source was a separate online self-report patient-facing registry, 278 PsoProtectMe, which launched globally on 4 May 2020. The eligibility criterion was a (Table E1) . 

PsoProtect and PsoProtectMe data were extracted on 1 and 3 July 2020, respectively. 295 Incomplete, duplicate and erroneous entries were manually reviewed by the study team 296 and removed. All analysis was performed using the R statistical programming language (30). were summarized using descriptive statistics. Continuous variables were reported using 299 median and interquartile range (IQR), and categorical/dichotomous variables as number and 300 percentage. 301 We used clinician-reported registry data to investigate the demographic and disease-specific 302 factors associated with the primary outcome of hospitalization for COVID- 19 (Table E2 ). Small differences were observed in 323 proportions of men, white ethnicity, confirmed COVID-19 diagnosis and hospitalization. 324 Therefore, to maximise included data, the final regression models were based on 20 325 multiply imputed datasets generated with the Multivariate Imputation by Chained 326 Equations (MICE) R package (32). 327 Quadratic terms for age and sex covariates were considered but rejected due to lack of 328 improvement in model fit (likelihood ratio test). Minimally and fully adjusted odds ratios 329 (OR) and 95% confidence intervals (CI) were reported for each variable. Sensitivity analyses 330 were performed on the fully adjusted multivariable regression models. To assess the 331 association between biologic class and the primary outcome, a fully adjusted model was 332 fitted in which treatment type was further categorized by biologic class (TNF, IL-17 or IL-23 333 inhibitor). Improvement in fit relative to the original treatment type model was assessed 334 using a likelihood ratio test. The STROBE statement for cross-sectional studies was used as a 335 basis for reporting (33). Table E3 ). Demographic and clinical characteristics are summarized in Table   351 I. The median age was 50 years (IQR 41-58). There was a predominance of males (227, 61%) Table E4 , and split by confirmed and suspected COVID-19 in Table E5 . (Table II) Table E6 , and split by confirmed and suspected COVID-19 in Table E7 . ventilation (3%, versus 5% among those receiving non-biologics) and death (2%, versus 5%). 391 Compared to the reference group of biologic users, an age-and sex-adjusted model for 392 hospitalization rate estimated an odds ratio of 2.72 for non-biologic systemic users and a 393 95% CI that did not cross unity (1.37-5.40) (Table III) . 394 To account for potential confounding from a range of established COVID-19 risk factors, a 395 fully adjusted multivariable logistic regression model was fitted (Table III) 

To assess potential differences in COVID-19 hospitalization risk between classes of biologics, 421 a multiple logistic regression model was fitted in which biologics were split into TNF, IL-23 422 and IL-17 inhibitor groups (n = 98, 89 and 78, respectively) (Table E10) . Hospitalization was 423 observed more frequently in patients receiving IL-23 inhibitors (23%) than those on TNF 424 (14%) or IL-17 inhibitors (13%); a fully adjusted odds ratio of 1.65 for the IL-23 inhibitor 425 group was estimated relative to the TNF inhibitor group. However, the 95% confidence 426 interval was wide (0.64-4.25) and the split by biologic type did not significantly improve 427 model fit (P = 0.48). 428 The limited numbers of patients using combination therapy or any individual agent 429 precluded analysing their association with hospitalization. Our case series is dominated by patients with moderate-severe psoriasis, therefore our 579 findings may not be generalisable to those with milder psoriasis. The majority of clinician-580 reported cases were receiving biologics, which contrasts with our patient-reported data. If 581 this represents a different propensity for clinicians to report patients on different treatment 582 types, then together with a higher likelihood of hospitalized cases being reported, this could 583 lead to inflated effect size estimates due to selection bias. In contrast to clinician-reported 584 data, a potential limitation of the self-report dataset is exposure misclassification, but it is 585 reassuring that the overall baseline characteristics of both registries are comparable. 586 Although not an objective of this study, the clinical course of COVID-19 in individuals with 587 and without psoriasis cannot be compared due to the lack of a matched control group from 588 the general population. COVID-19 outcomes in those receiving biologics in our study also 589 cannot be directly compared to studies of the general population due to fundamental (2) Plaque psoriasis phenotype includes 1 patient with erythroderma and 3 with plaque and erythroderma. Pustular psoriasis phenotype includes 3 with plaque and/or erythroderma also present. 13 records imported directly from the AAD COVID-19 registry were assumed to have plaque psoriasis. For patients on multiple systemic therapies, time on treatment was measured from the latest date (i.e. start of co-therapy) For patients on multiple systemic therapies, treatment stoppage was taken as stopping any of the treatments. 'Obesity' combines patients for whom obesity is selected as a comorbidity with those having BMI >30. It may therefore miss some of the 73 patients for whom BMI is not available. J o u r n a l P r e -p r o o f Table footnotes 2 participants excluded from treatment groups due to unknown drug (clinical trial) 'Biologics' category includes participants reporting co-therapy with conventional systemic or steroids (61), small molecule inhibitor (2) or both (3) 'Non-biologic systemic therapy' category includes participants reporting conventional systemic or steroids (229), small molecule inhibitor (39) or both (6) Time on treatment and adherence data were excluded for participants reporting multiple biologics (5), multiple conventional systemics or steroids (10) or multiple small molecule inhibitors (0) For participants reporting systemic treatments in more than one category, time on treatment was measured from the latest date (i.e. start of co-therapy) Obesity combines participants selecting obesity as a comorbidity with those having BMI >30. It may therefore miss some of the 114 participants for whom BMI is not available.

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Non-biologic systemic therapy' category includes participants reporting conventional systemic or steroids (39), small molecule inhibitor (26) or both (2) 4 patients with unresolved COVID-19 are excluded from COVID-19 outcome summaries (treated as missing) Symptom of 'unspecified cough

 621 We are very grateful to the healthcare professionals who have reported cases to the 622 PsoProtect registry* and to the patients who have contributed to PsoProtectMe. We would

like to acknowledge the professional and patient organizations who supported or promoted 624 the PsoProtect and PsoProtectMe registries (Table E1)