key: cord-0923750-f0wmkbcq authors: Mahil, S. K.; Yates, M.; Yiu, Z. Z.; Langan, S. M.; Tsakok, T.; Dand, N.; Mason, K. J.; McAteer, H.; Meynall, F.; Coker, B.; Vincent, A.; Urmston, D.; Vesty, A.; Kelly, J.; Lancelot, C.; Moorhead, L.; Bachelez, H.; Capon, F.; Contreras, C. R.; De La Cruz, C.; Di Meglio, P.; Gisondi, P.; Jullien, D.; Lambert, J.; Naldi, L.; Norton, S.; Puig, L.; Spuls, P.; Torres, T.; Warren, R. B.; Waweru, H.; Weinman, J.; Brown, M. A.; Galloway, J. B.; Griffiths, C. M.; Barker, J. N.; Smith, C. H. title: Describing the burden of the COVID-19 pandemic in people with psoriasis: findings from a global cross-sectional study date: 2021-05-06 journal: nan DOI: 10.1101/2021.05.04.21256507 sha: b3b5788f1b9899dbcbdbbd9adbd4047ae0582650 doc_id: 923750 cord_uid: f0wmkbcq Background Indirect excess morbidity has emerged as a major concern in the COVID-19 pandemic. People with psoriasis may be particularly vulnerable to this because of prevalent anxiety and depression, multimorbidity and therapeutic use of immunosuppression. Objective Characterise the factors associated with worsening psoriasis in the COVID-19 pandemic, using mental health status (anxiety and depression) as the main exposure of interest. Methods Global cross-sectional study using a primary outcome of self-reported worsening of psoriasis. Individuals with psoriasis completed an online self-report questionnaire (PsoProtectMe; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection Me) between May 2020 and January 2021. Each individual completed a validated screen for anxiety (Generalized Anxiety Disorder-2) and depression (Patient Health Questionnaire-2). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. Results 4,043 people with psoriasis (without COVID-19) from 86 countries self-reported to PsoProtectMe (mean age 47.2 years [SD 15.1]; mean BMI 27.6kg/m2 [SD 6.0], 2,684 [66.4%] female and 3,016 [74.6%] of white European ethnicity). 1,728 (42.7%) participants (1322 [77%] female) reported worsening of their psoriasis in the pandemic. A positive screen for anxiety or depression associated with worsening psoriasis in age and gender adjusted (OR 2.04, 95% CI 1.77-2.36), and fully adjusted (OR 2.01, 95% CI 1.72-2.34) logistic regression models. Female sex, obesity, shielding behaviour and systemic immunosuppressant non-adherence also associated with worsening psoriasis. The commonest reason for non-adherence was concern regarding complications related to COVID-19. Conclusions These data indicate an association between poor mental health and worsening psoriasis in the pandemic. Access to holistic care including psychological support may mitigate potentially long-lasting effects of the pandemic on health outcomes in psoriasis. The study also highlights an urgent need to address patient concerns about immunosuppressant-related risks, which may be contributing to non-adherence. Indirect excess morbidity has emerged as a major concern in the COVID-19 pandemic. People with psoriasis may be particularly vulnerable to this because of prevalent anxiety and depression, multimorbidity and therapeutic use of immunosuppression. Characterise the factors associated with worsening psoriasis in the COVID-19 pandemic, using mental health status (anxiety and depression) as the main exposure of interest. Global cross-sectional study using a primary outcome of self-reported worsening of psoriasis. Individuals with psoriasis completed an online self-report questionnaire (PsoProtectMe; Psoriasis Patient Registry for Outcomes, Therapy and Epidemiology of COVID-19 Infection Me) between May 2020 and January 2021. Each individual completed a validated screen for anxiety (Generalized Anxiety Disorder-2) and depression (Patient Health Questionnaire-2). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression. CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. associated with worsening psoriasis. The commonest reason for non-adherence was concern regarding complications related to COVID-19. These data indicate an association between poor mental health and worsening psoriasis in the pandemic. Access to holistic care including psychological support may mitigate potentially long-lasting effects of the pandemic on health outcomes in psoriasis. The study also highlights an urgent need to address patient concerns about immunosuppressant-related risks, which may be contributing to nonadherence. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. The COVID-19 pandemic has led to high mortality and morbidity worldwide. Emerging data highlight an indirect excess morbidity related to public health riskmitigation efforts such as stay-at-home orders and the re-purposing of healthcare services 1 . Increased risks of mental health disorders and shortfalls in the care of common long-term conditions have been described [2] [3] [4] . Anxiety and depression are highly prevalent in psoriasis and impair quality of life 5,6 . They may also exacerbate cutaneous immune dysregulation in psoriasis through hypothalamic-pituitary-adrenal axis and sympathetic nervous system hyperactivity 7 . Psoriasis clinical guidelines thus recommend routinely screening for anxiety and depression and offering specialist psychological support 8, 9 . However, the current reduced access to healthcare services and established increased population mental health burden have led to rising concerns over the physical and psychological sequelae of the pandemic in people with psoriasis. This study thus sought to better understand the impact of the pandemic on people with psoriasis, to inform immediate priorities for clinical care. We used global selfreported cross-sectional data to characterise the factors associated with worsening psoriasis, with a particular emphasis on the impact of anxiety and depression. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) May 2020 and available in 9 languages, was disseminated via social media, patient organisations and clinical networks (Table S1) 11 . The eligibility criterion was any person reporting a clinician-confirmed diagnosis of psoriasis. Variables of interest and questionnaire design were developed and tested by a study group of clinicians, epidemiologists, health data researchers and patient representatives. Questions covered disease severity (whether psoriasis had worsened/improved/remained the same during the pandemic), mental health status (Generalized Anxiety Disorder 2-item scale and Patient Health Questionnaire-2 [PHQ-2] to screen for anxiety and depression, respectively), adherence (whether, and why, medication was stopped during the pandemic), shielding behaviour (defined as quarantine/staying home/strict distancing in the home/avoiding others), in addition to demographic, socio-economic, and clinical characteristics. Data were extracted on 15th January 2021 and analysed using Stata version 16. After excluding participants self-reporting COVID-19 (a confounding variable), the association between mental health status and worsening psoriasis was assessed using: (a) a minimally adjusted logistic regression model including age and sex covariates; and (b) a fully adjusted model including a consensus list of covariates selected a priori as potentially influential on psoriasis severity and anxiety/depression on the basis of expert opinion and existing evidence. In keeping with prior studies, . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 6, 2021. ; https://doi.org/10.1101/2021.05.04.21256507 doi: medRxiv preprint 8 mental health status (anxiety/depression) was defined as a binary variable: participants who scored >3 in either GAD-2 or PHQ-2 had a positive screen 12 . Combining GAD-2 and PHQ-2 generates the PHQ-4, a validated measure of mental health status 13, 14 . Country of residence was included as a cluster variable in the calculation of standard errors. The fully adjusted model was rerun following multiple imputation using chained equations (20 cycles) to account for missing covariate data. There were no adherence data for those not on systemic therapy, so a separate adjusted model was performed to include adherence. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted May 6, 2021. ; https://doi.org/10.1101/2021.05.04.21256507 doi: medRxiv preprint 9 An age and sex-adjusted regression model for worsening psoriasis estimated an odds ratio (OR) of 2.04 (95% CI 1.77-2.36) for those with a positive screen for anxiety or depression, compared to those without a positive screen (Table S2) (18.5%) reported non-adherence during the pandemic ( Table 1 ). The commonest reasons for non-adherence were concern regarding complications related to COVID-19 (n=217) and running out of supply (n=48). Therapy non-adherence was associated with worsening psoriasis (OR 2.90, 95% CI 2.31-3.63; Table S6 ), as estimated using a fully adjusted regression model. A positive screen for anxiety or depression was also more common in those who reported non-adherence compared to those who were adherent (42.8% vs 32.4%). . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. ; https://doi.org/10.1101/2021.05.04.21256507 doi: medRxiv preprint 10 These self-reported data from >4,000 individuals with psoriasis across 86 countries have immediate clinical relevance. In this population, worsening psoriasis is common and is associated with poor mental health. We also find that in the subset of individuals on systemic therapy, non-adherence is associated with worsening disease and is primarily driven by concerns about immunosuppressant-related risks of COVID-19. This is an important observation since current guidelines generally recommend continuing immunosuppression in people without COVID-19 to maintain disease control 15 . These guidelines are based on reassuring data on drug-related risks of poor COVID-19 outcomes 16 . While prior studies have investigated the course of COVID-19 and risk factors for severe disease in people with psoriasis 16, 17 , there is a paucity of data on patientreported outcomes in those without COVID-19 18 . Our findings build on data from the general population indicating an increased mental health burden during the pandemic, which is accentuated in females and in those with pre-existing health conditions 19,20 . People with psoriasis may be particularly vulnerable in the pandemic since they have a high prevalence of anxiety and depression compared to the general population, which is further elevated in females and in those with severe psoriasis 21 . There is evidence to suggest that poor mental health can contribute to worsening of psoriasis, and research into potential underlying inflammatory mechanisms is ongoing 7 . In the context of the pandemic, this association may be further compounded by poor access to healthcare. While causality cannot be inferred from the current study, exploration of the temporal relationship between poor mental health and worsening disease using longitudinal data will be informative (i.e. does . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. ; https://doi.org/10.1101/2021.05.04.21256507 doi: medRxiv preprint anxiety/depression precede worsening psoriasis and/or is it due, in part, to worsening disease). Our data also highlight gender inequalities in health outcomes in psoriasis. Although male gender is an established risk factor for severe COVID-19, females may be more susceptible to indirect excess morbidity from the pandemic. Taken together, this study indicates a considerable burden due to the COVID-19 pandemic in people with psoriasis. Our data underscore the importance of holistic models of care and indicate a need to provide access to psychological support 8,9 . In those with worsening disease, the possibility of non-adherence to systemic treatment should be explored. Evidence-based communication around medication-related COVID-19 risks and behavioural approaches for supporting adherence may help address potential fears, anxieties and confusion. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. ; https://doi.org/10.1101/2021.05.04.21256507 doi: medRxiv preprint 12 Attention given now to address these immediate priorities for clinical care may mitigate a long-lasting detrimental impact of the pandemic on health outcomes in people with psoriasis. We are very grateful to the patients who have contributed to PsoProtectMe. We would like to acknowledge the professional and patient organizations who supported or promoted PsoProtectMe (Table S1) Prof. Barker reports grants and personal fees from Abbvie, grants and personal fees from Novartis, grants and personal fees from Lilly, grants and personal fees from J&J, from null, during the conduct of the study. Prof. Griffiths reports grants and personal fees from AbbVie, grants from Amgen, grants from BMS, grants and personal fees from Janssen, grants from LEO, grants and personal fees from Novartis, grants from Pfizer, grants from Almirall, grants and personal fees from Lilly, grants and personal fees from UCB Pharma, outside the submitted work. Prof. Jullien reports personal fees and non-financial support from Abbvie, personal fees and non-financial support from Novartis, personal fees and non-financial support from Janssen-Cilag, personal fees and non-financial support from Lilly, personal fees and non-financial support from Leo-Pharma, personal fees and nonfinancial support from MEDAC, personal fees and non-financial support from Celgene, personal fees from Amgen, outside the submitted work. Dr. Capon reports consultancy fees from AnaptysBio, grants from Boheringer-Ingelheim, outside the submitted work. Prof. Bachelez reports personal fees from Abbvie, personal fees from Janssen, personal fees from LEO Pharma, personal fees from Novartis, personal fees from UCB, personal fees from Almirall, personal fees from Biocad, personal fees from Boehringer-Ingelheim, personal fees from Kyowa Kirin, personal fees from Pfizer, outside the submitted work. Prof. Gisondi reports personal fees from Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pierre Fabre, Sandoz, UCB, outside the submitted work. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. Ms. Moorhead reports personal fees from Abbvie, personal fees from Celgene, personal fees from Janssen, personal fees from LEO Pharma, personal fees from Novartis, personal fees from UCB, outside the submitted work. Dr. Puig reports grants and personal fees from AbbVie, grants and personal fees from Almirall, grants and personal fees from Amgen, grants and personal fees from Boehringer Ingelheim, personal fees from Bristol Myers Squibb, personal fees from Fresenius-Kabi, grants and personal fees from Janssen, grants and personal fees from Lilly, personal fees from Mylan, grants and personal fees from Novartis, personal fees from Pfizer, personal fees from Sandoz, personal fees from Sanofi, personal fees from Samsung-Bioepis, grants and personal fees from UCB, outside the submitted work. Dr. Mahil reports departmental income from Abbvie, Celgene, Eli Lilly, Janssen-Cilag, Novartis, Sanofi, UCB, outside the submitted work. Dr. Di Meglio reports grants and personal fees from UCB, personal fees from Novartis, personal fees from Janssen, outside the submitted work. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. ; https://doi.org/10.1101/2021.05.04.21256507 doi: medRxiv preprint Prof. Warren reports grants and personal fees from Abbvie, grants and personal fees from Celgene, grants and personal fees from Eli Lilly, grants and personal fees from Novartis, personal fees from Sanofi, grants and personal fees from UCB|, grants and personal fees from Almirall, grants and personal fees from Amgen, grants and personal fees from Janssen, grants and personal fees from Leo, grants and personal fees from Pfizer, personal fees from Arena, personal fees from Avillion, personal fees from Bristol Myers Squibb, personal fees from Boehringer Ingelheim, outside the submitted work. Prof. Smith reports grants from Abbvie, grants from Sanofi, grants from Novartis, grants from Pfizer, outside the submitted work. Mr. Urmston reports grants from Almirall, grants from Abbvie, grants from Amgen, grants from Celgene, grants from Dermal Laboratories, grants from Eli Lilly, grants from Janssen, grants from LEO Pharma, grants from T and R Derma, grants from UCB, outside the submitted work. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. https://www.nice.org.uk/guidance/cg153. Home -PsoProtect Me. https://psoprotectme.org/. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. Anxiety/depression is defined as those who screened positive for either anxiety or depression. Obesity is defined as a BMI greater than 30. is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted May 6, 2021. ; https://doi.org/10.1101/2021.05.04.21256507 doi: medRxiv preprint T a b l e 1 . P a t i e n t d e m o g r a p h i c s a n d c l i n i c a l c h a r a c t e r i s t i c s s t r a t i f i e d b y d i s e a s e s t a t e . . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 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