Impact of the first wave of the COVID-19 pandemic on the treatment of psoriasis with systemic therapies in France: results from the PSOBIOTEQ cohort

Background The nature of the COVID-19 pandemic led to concerns among patients and physicians about the potential impact of immunosuppressive treatments for chronic diseases such as psoriasis on the risk of severe COVID-19. Objectives To describe treatment modifications and determine the incidence of COVID-19 infection among psoriasis patients during the first wave of the pandemic, and identify the factors associated with these events. Methods Data from PSOBIOTEQ cohort relating to the first COVID-19 wave in France (March to June, 2020), as well as a patient-centred COVID-19 questionnaire, were used to evaluate the impact of lockdown on changes (discontinuations, delays or reductions) in systemic therapies, and to determine the incidence of COVID-19 cases among these patients. Logistic regression models were used to assess associated factors. Results Among the 1751 respondents (89.3%), 282 patients (16.9%) changed their systemic treatment for psoriasis, with 46.0% of these changes being initiated by the patients themselves. Patients were more likely to experience psoriasis flare-ups during the first wave if they changed their treatment during this period (58.7% vs 14.4%;P<0.0001). Changes to systemic therapies were less frequent among patients with cardiovascular diseases (P<0.001), and those aged ≥65 years (P=0.02). Overall, 45 patients (2.9%) reported having COVID-19, and eight (17.8%) required hospitalization. Risk factors for COVID-19 infection were close contact with a positive case (P<0.001) and living in a region with a high incidence of COVID-19 (P<0.001). Factors associated with a lower risk of COVID-19 were avoiding seeing a physician (P=0.002), systematically wearing a mask during outings (P=0.011) and being a current smoker (P=0.046). Conclusions Discontinuation of systemic psoriasis treatments during the first COVID-19 wave (16.9%) – mainly decided by patients themselves (46.0%) – was associated with a higher incidence of disease flares (58.7% vs 14.4%). This observation and factors associated with a higher risk of COVID-19 highlight the need to maintain and adapt patient–physician communication during health crises according to patient profiles, with the aim of avoiding unnecessary treatment discontinuations and ensuring that patients are informed about the risk of infection and the importance of complying with hygiene rules.

Impact of the first wave of the COVID-19 pandemic on the treatment of psoriasis with systemic therapies in France: Results from the PSOBIOTEQ cohort.

BACKGROUND: The nature of the COVID-19 pandemic led to concerns among patients and physicians about the potential impact of immunosuppressive treatments for chronic diseases such as psoriasis on the risk of severe COVID-19. OBJECTIVES: To describe treatment modifications and determine the incidence of COVID-19 infection among psoriasis patients during the first wave of the pandemic, and identify the factors associated with these events. METHODS: Data from PSOBIOTEQ cohort relating to the first COVID-19 wave in France (March to June, 2020), as well as a patient-centred COVID-19 questionnaire, were used to evaluate the impact of lockdown on changes (discontinuations, delays or reductions) in systemic therapies, and to determine the incidence of COVID-19 cases among these patients. Logistic regression models were used to assess associated factors. RESULTS: Among the 1751 respondents (89.3%), 282 patients (16.9%) changed their systemic treatment for psoriasis, with 46.0% of these changes being initiated by the patients themselves. Patients were more likely to experience psoriasis flare-ups during the first wave if they changed their treatment during this period (58.7% vs 14.4%; P < 0.0001). Changes to systemic therapies were less frequent among patients with cardiovascular diseases (P < 0.001), and those aged ≥ 65 years (P = 0.02). Overall, 45 patients (2.9%) reported having COVID-19, and eight (17.8%) required hospitalization. Risk factors for COVID-19 infection were close contact with a positive case (P < 0.001) and living in a region with a high incidence of COVID-19 (P < 0.001). Factors associated with a lower risk of COVID-19 were avoiding seeing a physician (P = 0.002), systematically wearing a mask during outings (P = 0.011) and being a current smoker (P = 0.046). CONCLUSIONS: Discontinuation of systemic psoriasis treatments during the first COVID-19 wave (16.9%) - mainly decided by patients themselves (46.0%) - was associated with a higher incidence of disease flares (58.7% vs 14.4%). This observation and factors associated with a higher risk of COVID-19 highlight the need to maintain and adapt patient-physician communication during health crises according to patient profiles, with the aim of avoiding unnecessary treatment discontinuations and ensuring that patients are informed about the risk of infection and the importance of complying with hygiene rules.

Facteurs prédictifs d'une poussée de psoriasis après une infection par le SARS-CoV-2 chez l'enfant

Introduction: La pandémie à SARS-CoV-2 a été source de nombreuses questions quant à l'impact de l'infection sur les dermatoses inflammatoires chroniques, et de l'impact des traitements de ces dermatoses sur la sévérité de l'infection. Le registre international Chi-PsoCov (enfants psoriasique souffrant de psoriasis et ayant développé une infection à SARS-CoV-2) a permis de montrer que les biothérapies n'augmentaient pas le risque de formes sévères de COVID-19 chez les enfants atteints de psoriasis. Par ailleurs, il était montré que le COVID-19 était responsable du développement de psoriasis de novo ou de l'aggravation d'un psoriasis connu chez certains enfants.Dans cette partie du travail nous nous sommes concentrés sur les enfants ayant développé une poussée de psoriasis après l'infection : aspects phénotypiques des poussées, et recherche de facteurs de risque liés à la maladie, au psoriasis, ou aux traitements, associés à l'aggravation du psoriasis après l'infection. Matériel et méthodes: Les données ont été collectées de février 2021 à mai 2022 en provenance de 14 pays. Les enfants étaient inclus s'ils avaient moins de 18 ans, un antécédent de psoriasis ou psoriasis apparu dans le moins suivant l'infection COVID-19, et avaient été infectés par le SARS-CoV-2 avec ou sans symptômes. Les enfants ayant développé un psoriasis de novo étaient exclus de cette étude. Résultats: Sur les 152 inclusions du registre Chi-PsoCov, dix enfants ont développé un psoriasis dans le mois suivant l'infection et n'ont pas été retenus dans ce travail. L'analyse a porté sur 135 enfants ayant développé 142 COVID-19. Le psoriasis était stable dans 120 cas (84,5 %) et s'aggravait dans le mois suivant l'infection dans 22 cas (15,5 %).Dans 20 cas, lors de la poussée, le phénotype était inchangé, et dans 2 cas, il y avait un changement de phénotype : psoriasis en plaques en psoriasis en gouttes (n = 1) ou inversé (n = 1).Ni les caractéristiques démographiques, ni les aspects du psoriasis (notamment psoriasis actif vs en rémission), ni la sévérité de l'infection à SARS-CoV-2 n'étaient associés à des poussées de psoriasis. Seule l'utilisation de traitements systémiques du psoriasis, conventionnels ou biothérapies, lors de l'infection semblait protectrice de la survenue de poussées (50,0 % dans le groupe stable vs 27,3 % dans le groupe poussées, p = 0,049). Discussion: L'infection à SARS-CoV-2 est responsable dans environ 15 % des cas de poussées de psoriasis. Dans la grande majorité des cas, le phénotype précédent l'infection est conservé. Ces poussées ne sont pas associées à la sévérité du psoriasis, de l'infection ou autres paramètre cliniques. Seuls les traitements systémiques semblent réduire ce risque, probablement en « contrôlant » la poussée. Il est possible qu'une susceptibilité d'ordre génétique, non explorée ici, explique aussi cette susceptibilité à l'infection.

COVID-19 et psoriasis de l'enfant : facteurs associés à une évolution défavorable de la COVID-19 et impact de l'infection sur le psoriasis. Registre Chi-PsoCov

Introduction: La pandémie à SARS-CoV-2 a soulevé de nombreuses questions sur la prise en charge des maladies chroniques et leurs traitements. Les données concernant l'utilisation des biothérapies chez les adultes atteints de psoriasis sont rassurantes, mais manquent chez l'enfant. Par ailleurs, l'infection à SARS-CoV-2 pourrait influencer l'évolution du psoriasis chez l'enfant. L'objectif de cette étude était d'évaluer l'impact de l'infection à SARS-CoV-2 sur le psoriasis, et la sévérité de l'infection selon le traitement systémique reçu. Matériel et méthodes: Les données ont été collectées de février 2021 à février 2022 en provenance de 14 pays. Les enfants étaient inclus s'ils avaient moins de 18 ans, un antécédent de psoriasis ou apparu dans le moins suivant l'infection COVID-19, et avaient été infectés par le SARS-CoV-2 avec ou sans symptômes. Résultats: Au total, 117 enfants ont été inclus (filles : 49,6 %, âge moyen : 12,4 ans) avec 120 infections) SARS-CoV-2. La principale forme de psoriasis était le psoriasis en plaques (69,4 %) ;le psoriasis était actif avant l'infection dans 70,1 % des cas. La majorité des enfants ne prenaient pas de traitement systémique au moment de l'infection (54,2 %), 33 enfants (28,3 %) étaient sous biothérapie (principalement anti-TNF alpha et ustékinumab), et 24 (20,0 %) sous traitement systémique conventionnel (principalement méthotrexate). L'infection était confirmée chez 106 enfants (88,3 %) et 3 ont eu la maladie 2 fois (1 enfant asymptomatique sous ustékinumab et 2 enfants symptomatiques sans traitement systémique). L'infection était symptomatique chez 75 enfants (62,5 %) avec une durée moyenne des symptômes de 6,5 jours, significativement plus longue chez les enfants sous traitement systémique conventionnel (p = 0,002) ou sans traitement systémique (p = 0,006) par rapport aux enfants traités par biothérapies. Six enfants ont nécessité une hospitalisation, dont un enfant en réanimation ;ils étaient plus fréquemment sous traitements systémiques conventionnels par rapport aux autres enfants (p = 0,01), et principalement sous méthotrexate (p = 0,03). Aucun enfant sous biothérapie n'a été hospitalisé, et aucun décès n'a été rapporté.Après l'infection, le psoriasis s'est aggravé dans 17 cas (15,2 %), sans modification du phénotype sauf pour un enfant avec un psoriasis initialement en plaques qui a eu suite à l'infection une poussée de psoriasis en gouttes. Neuf enfants (8,0 %) ont développé un psoriasis de novo dans le mois qui a suivi l'infection, plus souvent un psoriasis en gouttes (p = 0,01) par rapport aux enfants ayant un antécédent connu de psoriasis. Ces enfants avaient un antécédent familial de psoriasis dans 75,0 % des cas. Discussion: L'utilisation des biothérapies semble rassurante sans augmentation du risque de forme sévère de COVID-19 chez les enfants atteints de psoriasis. L'infection à SARS-CoV-2 était responsable du développement de psoriasis de novo ou de l'aggravation d'un psoriasis connu chez certains enfants.

Long-term safety of risankizumab in patients with psoriatic disease: Findings from integrated analyses of 17 clinical trials in psoriasis and 4 in psoriatic arthritis

Objective: To report long-term risankizumab safety in patients with psoriatic disease. Method: Risankizumab safety data to March 25, 2021 were pooled from 17 phase 1–3 clinical trials in plaque psoriasis (PsO) and 4 phase 2/3 trials in psoriatic arthritis (PsA). Adverse events (AEs) of safety interest were reported for patients receiving ≥1 dose risankizumab. Results: Among 3197 patients with PsO (9982.6 patient years’ [PY] exposure;median (range) treatment duration, 3.7 years [1 day–6.9 years]) and 1542 patients with PsA (1594.9 PY;1.0 year [84 days–2.0 years]), rates of treatment-emergent AEs (158.3 and 160.8 events (E)/100PY), serious AEs (7.6 and 8.4 E/100PY) and AEs leading to discontinuation (1.9 and 2.3 E/100PY) were similar. Nasopharyngitis (PsO 14.5 E/100PY, PsA 7.9 E/100PY) and upper respiratory infection (PsO 7.8 E/100PY, PsA 5.6 E/100PY) were the most common infections;sepsis and pneumonia for PsO (0.1 E/100PY each) and COVID-19 for PsA (0.4 E/100PY) were the most common serious infections. Rates of opportunistic fungal infections were <0.1 and 0.1 E/100PY in PsO/PsA patients. Rates of nonmelanoma skin cancer (NMSC) were 0.7 and 0.4 E/100PY, and malignant tumors excluding NMSC were 0.6 and 0.3 E/100PY in PsO/PsA patients. Rates of major adverse cardiovascular events were 0.5 and 0.4 E/100PY in PsO/PsA patients. Conclusion: Rates of AEs of safety interest remained low in this largest and longest safety reporting for risankizumab to date, supporting the safety of risankizumab for the long-term treatment of patients with psoriatic disease.

LONG-TERM SAFETY of RISANKIZUMAB in PATIENTS with PSORIATIC DISEASE: FINDINGS from INTEGRATED ANALYSES of 17 CLINICAL TRIALS in PSORIASIS and 4 in PSORIATIC ARTHRITIS

Background: Risankizumab, an interleukin-23 inhibitor, was efficacious and well tolerated in phase 2 and 3 clinical studies in patients with psoriatic disease. Objectives: To report long-term risankizumab safety in patients with psoriatic disease. Methods: Risankizumab safety data to March 25, 2021 were pooled from 17 phase 1-3 clinical trials in plaque psoriasis (PsO) and 4 phase 2/3 trials in pso-riatic arthritis (PsA). Adverse events (AEs) of safety interest were reported for patients receiving ≥1 dose risankizumab. Results: Among 3197 patients with PsO (9982.6 patient years' [PY] exposure;median (range) treatment duration, 3.7 years [1 day-6.9 years]) and 1542 patients with PsA (1594.9 PY;1. 0 year [84 days-2.0 years]), rates of treatment-emergent AEs (158.3 and 160.8 events (E)/100PY), serious AEs (7.6 and 8.4 E/100PY) and AEs leading to discontinuation (1.9 and 2.3 E/100PY) were similar. Nasopharyn-gitis (PsO 14.5 E/100PY, PsA 7. 9 E/100PY) and upper respiratory infection (PsO 7. 8 E/100PY, PsA 5.6 E/100PY) were the most common infections;sepsis and pneumonia for PsO (0.1 E/100PY each) and COVID-19 for PsA (0.4 E/100PY) were the most common serious infections. Rates of opportunistic fungal infections were <0.1 and 0.1 E/100PY in PsO/PsA patients. Rates of non-melanoma skin cancer (NMSC) were 0.7 and 0.4 E/100PY, and malignant tumors excluding NMSC were 0.6 and 0.3 E/100PY in PsO/PsA patients. Rates of major adverse cardiovascular events were 0.5 and 0.4 E/100PY in PsO/PsA patients. Conclusion: Rates of AEs of safety interest remained low in this largest and longest safety reporting for risankizumab to date, supporting the safety of risankizumab for the long-term treatment of patients with psoriatic disease.

Children with psoriasis and COVID-19: factors associated with an unfavourable COVID-19 course, and the impact of infection on disease progression (Chi-PsoCov registry).

BACKGROUND: The COVID-19 pandemic has raised questions regarding the management of chronic skin diseases, especially in patients on systemic treatments. Data concerning the use of biologics in adults with psoriasis are reassuring, but data specific to children are missing. Moreover, COVID-19 could impact the course of psoriasis in children. OBJECTIVES: The aim of this study was therefore to assess the impact of COVID-19 on the psoriasis of children, and the severity of the infection in relation to systemic treatments. METHODS: We set up an international registry of paediatric psoriasis patients. Children were included if they were under 18 years of age, had a history of psoriasis, or developed it within 1 month of COVID-19 and had COVID-19 with or without symptoms. RESULTS: One hundred and twenty episodes of COVID-19 in 117 children (mean age: 12.4 years) were reported. The main clinical form of psoriasis was plaque type (69.4%). Most children were without systemic treatment (54.2%); 33 (28.3%) were on biologic therapies, and 24 (20%) on non-biologic systemic drugs. COVID-19 was confirmed in 106 children (88.3%) and 3 children had two COVID-19 infections each. COVID-19 was symptomatic for 75 children (62.5%) with a mean duration of 6.5 days, significantly longer for children on non-biologic systemic treatments (P = 0.02) and without systemic treatment (P = 0.006) when compared with children on biologics. The six children who required hospitalization were more frequently under non-biologic systemic treatment when compared with the other children (P = 0.01), and particularly under methotrexate (P = 0.03). After COVID-19, the psoriasis worsened in 17 cases (15.2%). Nine children (8%) developed a psoriasis in the month following COVID-19, mainly a guttate form (P = 0.01). DISCUSSION: Biologics appear to be safe with no increased risk of severe form of COVID-19 in children with psoriasis. COVID-19 was responsible for the development of psoriasis or the worsening of a known psoriasis for some children.

Type I interferon response and vascular alteration in chilblain-like lesions during the COVID-19 outbreak.

BACKGROUND: The outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear. OBJECTIVES: To study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus. METHODS: This observational study was conducted during 9-16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included. RESULTS: Histological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic-natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL. CONCLUSIONS: Our findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.

Risk-mitigating behaviours in people with inflammatory skin and joint disease during the COVID-19 pandemic differ by treatment type: a cross-sectional patient survey.

BACKGROUND: Registry data suggest that people with immune-mediated inflammatory diseases (IMIDs) receiving targeted systemic therapies have fewer adverse coronavirus disease 2019 (COVID-19) outcomes compared with patients receiving no systemic treatments. OBJECTIVES: We used international patient survey data to explore the hypothesis that greater risk-mitigating behaviour in those receiving targeted therapies may account, at least in part, for this observation. METHODS: Online surveys were completed by individuals with psoriasis (globally) or rheumatic and musculoskeletal diseases (RMDs) (UK only) between 4 May and 7 September 2020. We used multiple logistic regression to assess the association between treatment type and risk-mitigating behaviour, adjusting for clinical and demographic characteristics. We characterized international variation in a mixed-effects model. RESULTS: Of 3720 participants (2869 psoriasis, 851 RMDs) from 74 countries, 2262 (60·8%) reported the most stringent risk-mitigating behaviour (classified here under the umbrella term 'shielding'). A greater proportion of those receiving targeted therapies (biologics and Janus Kinase inhibitors) reported shielding compared with those receiving no systemic therapy [adjusted odds ratio (OR) 1·63, 95% confidence interval (CI) 1·35-1·97]. The association between targeted therapy and shielding was preserved when standard systemic therapy was used as the reference group (OR 1·39, 95% CI 1·23-1·56). Shielding was associated with established risk factors for severe COVID-19 [male sex (OR 1·14, 95% CI 1·05-1·24), obesity (OR 1·37, 95% CI 1·23-1·54), comorbidity burden (OR 1·43, 95% CI 1·15-1·78)], a primary indication of RMDs (OR 1·37, 95% CI 1·27-1·48) and a positive anxiety or depression screen (OR 1·57, 95% CI 1·36-1·80). Modest differences in the proportion shielding were observed across nations. CONCLUSIONS: Greater risk-mitigating behaviour among people with IMIDs receiving targeted therapies may contribute to the reported lower risk of adverse COVID-19 outcomes. The behaviour variation across treatment groups, IMIDs and nations reinforces the need for clear evidence-based patient communication on risk-mitigation strategies and may help inform updated public health guidelines as the pandemic continues.