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.

Switches between biologics in patients with moderate-to-severe psoriasis: results from the French cohort PSOBIOTEQ.

BACKGROUND: Biologics are the cornerstone of treatment of patients with moderate-to-severe plaque psoriasis and switches between biologics are frequently needed to maintain clinical improvement over time. OBJECTIVES: The main purpose of this study was to describe precisely switches between biologics and how their pattern changed over time with the recent availability of new biologic agents. METHODS: We included patients receiving a first biologic agent in the Psobioteq multicenter cohort of adults with moderate-to-severe psoriasis receiving systemic treatment. We described switches between biologics with chronograms, Sankey and Sunburst diagrams, assessed cumulative incidence of first switch by competing risks survival analysis and reasons for switching. We assessed the factors associated with the type of switch (intra-class - i.e. within the same therapeutic class - vs. inter-class) in patients switching from a TNF-alpha inhibitor using multivariate logistic regression. RESULTS: A total of 2153 patients was included. The cumulative incidence of switches from first biologic was 34% at 3 years. Adalimumab and ustekinumab were the most prescribed biologic agents as first and second lines of treatment. The main reason for switching was loss of efficacy (72%), followed by adverse events (11%). Patients receiving a TNF-alpha inhibitor before 2016 mostly switched to ustekinumab, whereas those switching in 2016 or after mostly switched to an IL-17 inhibitor. Patients switching from a first-line TNF-alpha inhibitor before 2016 were more likely to switch to another TNF-alpha inhibitor compared with patients switching since 2018. Patients switching from etanercept were more likely to receive another TNF-alpha inhibitor rather than another therapeutic class of bDMARD compared with patients switching from adalimumab. CONCLUSION: This study described the switching patterns of biologic treatments and showed how they changed over time, due to the availability of the new biologic agents primarily IL-17 inhibitors.

Palmoplantar pustulosis and acrodermatitis continua of Hallopeau: demographic and clinical comparative study in a large multicentre cohort.

BACKGROUND: Acral pustular disease within the pustular psoriasis/psoriasis-like spectrum mainly includes palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH). Scarce data argue for a distinction between these two entities, but no study has compared the clinical and epidemiologic characteristics of ACH and PPP. OBJECTIVES: We aimed to perform a comparative description of the epidemiological and clinical characteristics of PPP and ACH in a multicentre retrospective cohort. METHODS: In this multicentre national retrospective cohort study, we compared the epidemiological characteristics, comorbidities and psoriasis characteristics of patients with PPP and ACH. RESULTS: A total of 234 patients were included: 203 (87%) with PPP, 18 (8%) with ACH and 13 (6%) with both, according to 2017 ERASPEN criteria. As compared with ACH, PPP was associated with female sex, smoking activity and higher median BMI (P = 0.01, P = 0.02 and P = 0.05 respectively). A family background of psoriasis was more frequent in PPP than ACH. Age of onset of palmoplantar disease was similar between PPP and ACH patients, median age 44 and 48 years respectively. Peripheral joint inflammatory involvement was the only rheumatic disease associated with ACH. The association with another psoriasis type was similar in PPP and ACH (57.6% and 61.1% respectively). CONCLUSION: Our study confirms in a large PPP cohort the predominance of females and a high prevalence of smoking and elevated body mass index but also shows an association of these features in PPP as compared with ACH. In addition, it highlights peripheral arthritis as the only arthritis endotype associated with ACH. Increased knowledge of the immunogenetic backgrounds underlying these two entities is warranted to better stratify pustular psoriasis or psoriasis-like entities for precision medicine.

CITY-PSO: Prescribing behaviour of French private-practice dermatologists in psoriasis management: An observational, multicentre, cross-sectional study.

BACKGROUND: Information regarding the prescribing behaviour of French private-practice dermatologists (PPDs) is scarce. OBJECTIVES: First, to describe the population of PPDs involved in psoriasis management. Second, to describe the population of adult patients treated for psoriasis and their management. METHODS: We published a call for participation targeting PPDs; we first asked respondents to complete a form regarding their prescribing behaviour, and then to include consecutive patients consulting for psoriasis during a one-month study period and to collect patient data. RESULTS: The 94 participating PPDs included 1022 patients of mean age 52.9±17.9 years. The average body mass index was 28, and 25% had vascular comorbidities. Two thirds of patients had chronic psoriasis, for which 45% had consulted at least 5 times. Psoriasis was mostly with plaques (70.8%) and 11.4% of patients had psoriatic arthritis. The average body surface area (BSA) affected was 10.1%. Among the 679 patients without initial systemic treatment, 159 were started on systemic treatment. The main agents initiated were phototherapy (n=63), methotrexate (n=40), acitretin (n=30) and apremilast (n=20). In multivariate analysis, a higher BSA [Odds Ratio (OR) 1.10, 95% Confidence Interval (CI): 1.07-1.13; P<10-4] and Dermatology Life Quality Index (DLQI) [OR 1.09, 95% CI: 1.03-1.15; P=0.04] were associated with prescription of systemic therapy at the end of the consultation. CONCLUSION: The main limitation of our study was that participating PPDs were strongly involved in psoriasis management, which accounts for the high proportion of moderate-to-severe psoriasis and prescription of systemic treatments. Such committed PPDs and the development of psoriasis networks are key factors for improving the quality of care provided to psoriasis patients.

Identification of three clinical neurofibromatosis 1 subtypes: Latent class analysis of a series of 1351 patients.

BACKGROUND: Neurofibromatosis 1 (NF1) is one of the most common inherited disorders characterized by mutations in the tumour suppressor gene NF1. Its clinical manifestations are highly variable and unpredictable. A specific NF1 mutation does not predict the severity or complications of the disease. OBJECTIVE: The objective of this study was to build an empirical classification scheme without any a priori hypotheses to identify the underlying NF1 subtypes that best explain the observed heterogeneity. METHODS: We performed latent class analysis (LCA) of 1351 consecutive NF1 patients aged >17 years seen between 2002 and 2014. Data and phenotypic features were collected prospectively on a standardized form. RESULTS: The median age was 36.8 (17-81) years. A three-class model showed the best fit: 706 (52%) belonged to the LC1 'Cutaneous neurofibromas' class having preferentially cutaneous neurofibromas (99%), plexiform neurofibromas (63%) and blue-red macules (29%); 593 (44%) belonged to the LC2 'Subcutaneous neurofibromas' class characterized by the presence of at least 10 subcutaneous neurofibromas (21%) and a familial form (77%) and 52 (4%) belonged to the LC3 'Dysmorphic phenotype' class characterized by dysmorphic features (78%) and learning difficulties (87%). Patients in LC1 had a higher likelihood of developing scoliosis (RR = 1.7, 95% confidence interval (CI) [1.2-2.4]). Patients in LC2 were more likely to be men (RR = 1.4, 95% CI [1.1-1.7]). Patients in LC3 were at higher risk of having an optic pathway glioma (RR = 4.8, 95% CI [1.9-11.8]) and epilepsy (RR = 4.5, 95% CI [1.8-11.6]). CONCLUSION: Our findings invite the performance of a larger cohort study to test whether the various latent classes reflect different underlying genetic modifiers of these phenotypic traits.

Psoriasis-related treatment exposure and hospitalization or in-hospital mortality due to COVID-19 during the first and second wave of the pandemic: cohort study of 1 326 312 patients in France.

BACKGROUND: Data on treatment exposures for psoriasis and poor COVID-19 outcomes are limited. OBJECTIVES: To assess the risk of hospitalization or in-hospital mortality due to COVID-19 by treatment exposure in patients with psoriasis. METHODS: All adults with psoriasis registered in the French national health-insurance (Système National des Données de Santé, SNDS) database between 2008 and 2019 were eligible. Two study periods were considered: 15 February to 30 June 2020 and 1 October 2020 to 31 January 2021, the first and second waves of the COVID-19 pandemic in France, respectively. Patients were classified according to their baseline treatment: biologics, nonbiologics, topicals or no treatment. The primary endpoint was hospitalization for COVID-19 using Cox models with inverse probability of treatment weighting. The secondary endpoint was in-hospital mortality due to COVID-19. RESULTS: We identified 1 326 312 patients with psoriasis (mean age 59 years; males, 48%). During the first study period, 3871 patients were hospitalized for COVID-19 and 759 (20%) died; during the second period 3603 were hospitalized for COVID-19 and 686 (19%) died. In the propensity score-weighted Cox models, risk of hospitalization for COVID-19 was associated with exposure to topicals or nonbiologics [hazard ratio (95% confidence interval): 1·11 (1·04-1·20) and 1·27 (1·09-1·48), respectively] during the first period, and with all exposure types, during the second period. None of the exposure types was associated with in-hospital mortality due to COVID-19. CONCLUSIONS: Systemic treatments for psoriasis (including biologics) were not associated with increased risk of in-hospital mortality due to COVID-19. These results support maintaining systemic treatment for psoriasis during the pandemic.

Epidemiologic study in a real-world analysis of patients with treatment for psoriasis in the French national health insurance database.

BACKGROUND: Psoriasis is one of the most frequent chronic inflammatory dermatoses in the world. Data on the prevalence of psoriasis in adults differ depending on the study. OBJECTIVE: To estimate the prevalence of patients with treatment for psoriasis in France and to identify and characterize patients receiving systemic treatments. METHODS: This was a French, nationwide cohort study based on health administrative data from the French national health insurance scheme linked to the national hospital discharge database (SNDS-PMSI). All adults with psoriasis registered in the SNDS between 1 January 2008 and 31 December 2016 were eligible for inclusion. All patients with a new prescription for a systemic treatment for psoriasis were included. RESULTS: A total of 874 549 patients were identified as having psoriasis (mean ± SD age 53.8 ± 17 years; 52.4% males); 112 969 (13%) had filled at least one prescription for a systemic medication used to treat psoriasis. The prevalence of patients with treatment for psoriasis was estimated at 1.3%. Overall, 73 168 and 16 545 were new users of conventional systemic treatments and biologics, respectively. The most frequent comorbidities associated with psoriasis were hypertension, dyslipidaemia, diabetes and chronic obstructive pulmonary disease. CONCLUSION: The prevalence of psoriasis we found was lower than in other studies. It was probably underestimated because we identified only patients with treatment for psoriasis. Our results concerning comorbidities associated with psoriasis patients requiring systemic treatment were similar to those from other published studies using other data sources, highlighting our ability to catch moderate-to-severe psoriasis. This study highlights the usefulness and reliability of the use of insurance databases in studies, because they allow for a better application to the general population.

Meta-analysis results do not reflect the real safety of biologics in psoriasis.

BACKGROUND: In reported systematic reviews and meta-analyses of randomized controlled trials (RCTs) assessing treatments for psoriasis, the proportion of serious adverse events (SAEs) did not differ between treatments and placebo. Including cases of psoriasis worsening as SAEs may explain the lack of difference. OBJECTIVES: This systematic review and meta-analysis aimed to explore this possibility. METHODS: Among the 140 RCTs included in the Living Network Cochrane Review (last search on 8 May 2019), we selected those comparing a biologic treatment against placebo. The primary outcome was the numbers of SAEs in the treatment and placebo arms after excluding cases of psoriasis worsening. Secondary outcomes were the number of adverse events (AEs) of special interest. The trial was registered on PROSPERO (CRD42019124495). RESULTS: We analysed 51 RCTs. Of these, 21 included at least one anti-tumour necrosis factor (TNF)-α arm, 15 one anti-interleukin (IL)-17 arm, 11 one anti-IL-23 arm and nine one anti-IL-12/23 arm. With cases of psoriasis worsening included, the risk of occurrence of SAEs between biologic treatments and placebo did not differ: risk ratio (RR) 1·09, 95% confidence interval (CI) 0·88-1·36. After excluding cases of psoriasis worsening, the RR became significant (RR 1·30, 95% CI 1·02-1·65). By drug class, the RRs were for anti-TNF-α, 1·68 (95% CI 1·11-2·54; no missing data); anti-IL-17, 1·28 (95% CI 0·88-1·85; no missing data); anti-IL-23, 0·95 (95% CI 0·59-1·52; no missing data) and anti-IL-12/23, 1·18 (95% CI 0·72-1·94; no missing data). We were unable to examine potential differences in AEs of special interest between biologic treatments and placebo arms because of the small number of events. CONCLUSIONS: On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic than in the placebo arm. Given the rare events, we could not highlight whether this higher risk of SAEs was related to AEs of special interest. Reporting of SAEs in clinical trials has to be changed to provide more transparency through the separate reporting of disease flares leading to hospital admission and other SAEs.

Interventions for chronic palmoplantar pustulosis: abridged Cochrane systematic review and GRADE assessments.

BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease in which sterile and relapsing pustules appear on the palms and soles. OBJECTIVES: To assess the effects of interventions for chronic PPP to induce and maintain complete remission. METHODS: We searched for randomized controlled trials (RCTs), including people with PPP or chronic palmoplantar pustular psoriasis, in the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and eight trials registers up to July 2020. Study selection, data extraction and risk-of-bias assessment were carried out independently by two review authors. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. RESULTS: We included 37 RCTs (1663 participants, 76% women, mean age 50 years). Mean treatment duration was 11 weeks. Topical vitamin D derivative may be more effective than placebo in achieving clearance [risk ratio (RR) 7·83, 95% confidence interval (CI) 1·85-33·12; low-certainty evidence from two trials]. Concerning biological therapies, there was little or no difference between etanercept and placebo in achieving clearance (low-certainty evidence from one trial), ustekinumab is less effective than placebo in reducing severity (low-certainty evidence from one trial), and guselkumab (RR 2·88, 95% CI 1·24-6·69) and secukinumab (RR 1·55, 95% CI 1·02-2·35) are probably better in reducing disease severity (moderate-certainty evidence from two and one trial(s), respectively) but may cause more serious adverse events than placebo. CONCLUSIONS: Evidence is lacking for or against major chronic PPP treatments. Risk of bias and imprecision limit our confidence in the results.

Most chilblains observed during the COVID-19 outbreak occur in patients who are negative for COVID-19 on polymerase chain reaction and serology testing.

BACKGROUND: Acral lesions, mainly chilblains, are the most frequently reported cutaneous lesions associated with COVID-19. In more than 80% of patients tested, nasopharyngeal swabs were negative on reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2 when performed, and serology was generally not performed. METHODS: A national survey was launched on 30 March 2020 by the French Society of Dermatology asking physicians to report cases of skin manifestations in patients with suspected or confirmed COVID-19 by using a standardized questionnaire. We report the results for acral manifestations. RESULTS: We collected 311 cases of acral manifestations [58.5% women, median age 25.7 years (range 18-39)]. The most frequent clinical presentation (65%) was typical chilblains. In total, 93 cases (30%) showed clinical suspicion of COVID-19, 67 (22%) had only less specific infectious symptoms and 151 (49%) had no clinical signs preceding or during the course of acral lesions. Histology of skin biopsies was consistent with chilblains. Overall, 12 patients showed significant immunological abnormalities. Of the 150 (48%) patients who were tested, 10 patients were positive. Seven of 121 (6%) RT-PCR-tested patients were positive for SARS-CoV-2, and five of 75 (7%) serology-tested patients had IgG anti-SARS-CoV-2. Tested/untested patients or those with/without confirmed COVID-19 did not differ in age, sex, history or acral lesion clinical characteristics. CONCLUSIONS: The results of this survey do not rule out that SARS-CoV-2 could be directly responsible for some cases of chilblains, but we found no evidence of SARS-CoV-2 infection in the large majority of patients with acral lesions during the COVID-19 lockdown period in France. What is already known about this topic? About 1000 cases of acral lesions, mainly chilblains, were reported during the COVID-19 outbreak. Chilblains were reported to occur in young people within 2 weeks of infectious signs, which were mild when present. Most cases did not have COVID-19 confirmed by reverse transcription polymerase chain reaction (RT-PCR), and few serology results were available. What does this study add? Among 311 patients with acral lesions, mainly chilblains, during the COVID-19 lockdown period in France, the majority of patients tested had no evidence of SARS-CoV-2 infection. Overall, 70 of 75 patients were seronegative for SARS-Cov-2 serology and 114 of 121 patients were negative for SARS-CoV-2 RT-PCR.