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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. [ABSTRACT FROM AUTHOR]

Summary: Background: Real‐world data on the persistence of apremilast vs. methotrexate are inconclusive. Objectives: To assess and compare the long‐term persistence of apremilast and methotrexate in a large cohort of patients with psoriasis. Methods: All adult patients with psoriasis registered in the French national health insurance database ('Système National des Données de Santé') between 2009 and 2017 were eligible for inclusion. The study population comprised apremilast‐ and methotrexate‐naive patients, defined as those with a first prescription of apremilast or methotrexate. Levels of persistence were compared using a Cox model with propensity‐score matching that included potential confounders (notably age, sex, psoriatic arthritis, comorbidities and previous exposure to topical and systemic treatments). Results: In this nationwide population‐based cohort, 14 147 adult patients with psoriasis (mean age 52·3 years, 55·2% male) were found to be naive to both apremilast and methotrexate. After propensity‐score matching, two subgroups of 4805 patients with similar baseline characteristics were included, of whom 3207 apremilast‐treated patients and 2736 methotrexate‐treated patients discontinued their treatment. Kaplan–Meier survival propensity‐score analyses revealed a discontinuation rate of 69% for apremilast and 59% for methotrexate in the first year of treatment. Apremilast‐treated patients had a higher risk of discontinuation than methotrexate‐treated patients when considering the study population as a whole (hazard ratio 1·28, 95% confidence interval 1·23–1·34) or in a propensity‐score‐matched analysis (hazard ratio 1·34, 95% confidence interval 1·27–1·41; P < 0·001). Conclusions: Our real‐world data suggest that in the first year of treatment, the discontinuation rate was significantly higher for apremilast‐treated patients than for methotrexate‐treated patients, regardless of the previous therapeutic lines received. What's already known about this topic? Psoriasis is a common chronic, relapse–remitting, inflammatory skin disease associated with severe psychosocial impact.Apremilast, a phosphodiesterase 4 inhibitor, is one of the most recently commercialized psoriasis drugs.Little is known about the long‐term clinical effectiveness of apremilast. What does this study add? The discontinuation rate at 1 year for apremilast was 69%, compared with 58% for methotrexate, in a nationwide population‐based cohort including 14 147 nonselected adult patients with psoriasis.Patients in the apremilast cohort had a higher risk of discontinuation than patients in the methotrexate cohort using propensity‐score matching, including potentially relevant individual risk factors such as age, sex, comorbidities and psoriatic arthritis, and regardless of the previous therapeutic lines received.In daily practice, physicians should take these results into account when choosing between methotrexate and apremilast as a first‐line systemic therapy. Linked Comment: Damiani. Br J Dermatol 2020; 182:534–535. [ABSTRACT FROM AUTHOR]

Dramatic reduction of clindamycin plasma concentration in hidradenitis suppurativa patients treated with the rifampin-clindamycin combination. Dear Editor, Hidradenitis suppurativa (HS) is a painful chronic inflammatory skin disease that impacts quality of life substantially. [Extracted from the article]

Treatment of erythema multiforme (EM) is not codified. We performed a systematic review of the effect of any topical or systemic treatment on time to healing and frequency of episodes with acute and chronic forms of EM in adults. Four databases (MEDLINE, CENTRAL, EMBASE and LILACS) and other sources were searched for articles published up to 20 March 2018. Randomized control trials (RCTs), observational studies and case series (n ≥ 10) were considered. From 1558 references, we included one RCT and six case series. The RCT (n = 20) showed a significant difference in complete remission of EM with continuous acyclovir vs. placebo over 6 months. One case series found a mean reduction in flare duration with thalidomide for recurrent EM (5.1 vs. 16.2 days; n = 20). Adverse events were poorly or not reported in included studies. Quality of life was never assessed. One limitation of our study is that we excluded the cases of isolated mucosal EM in order to prevent inclusion of Stevens‐Johnson syndrome cases. In conclusion, there is low‐level evidence for continuous acyclovir treatment for recurrent EM (one RCT). Evidence for other treatments is only based on retrospective case series. Results for thalidomide, in particular, encourage further research. Data concerning safety are insufficient. PROSPERO registration no. CRD42016053175. [ABSTRACT FROM AUTHOR]

Other biomarkers were identified as candidate biomarkers of psoriatic arthritis in psoriasis and also of type 2 diabetes in psoriasis. Br J Dermatol i 2022; [bjd.21627] The BIOMarkers in Atopic Dermatitis and Psoriasis (BIOMAP) is a European programme, which aims to identify biomarkers that predict disease progression and therapeutic response in order to achieve precision medicine.[1] Psoriasis is an immune-mediated disease, which manifests in chronic inflammatory effects on either the skin or joints. [Extracted from the article]

Between February 2011 and November 2018, we enrolled 25 patients including 13 women with PV (21) and GPP (4) at baseline, with a median age of 38 years, consulting for 31 flares with RTI symptoms. Overall, 21 of 25 patients had at least one positive multiplex PCR viral test, with I Rhinovirus i and I Coronavirus i as the most frequently detected pathogens, while only two of 25 bacterial swabs were positive (one each for I Staphylococcus aureus i and I Streptococcus dysgalactiae i ). All patients reported history of previous acute psoriasis flares following RTI, including two patients with GPP/DITRA sharing the homozygous c.80T>C; p.Leu27Pro severe mutation.[6] No genetic abnormality was detected in I IL36RN i , I CARD14 i and I AP1S3 i in other patients. [Extracted from the article]

Background Decision-making is a complex process. The aim of our study was to assess factors associated with the choice of the first biological treatment in patients with moderate-to-severe psoriasis. Methods Data on all patients included in the French prospective, observational, cohort, Psobioteq and initiating a first biologic prescription between July 2012 and July 2016 were analysed. Demographic information and clinical features were collected during routine clinical assessments by the dermatology team at the recruiting centres using a standardized case report form. The primary outcome was the nature of the first biologic treatment. Four groups were identified as follows: adalimumab, etanercept, ustekinumab and infliximab groups. Factors associated with the choice of the first biological agent were determined by a multinomial logistic regression model adjusted on year of inclusion. Results The study population included the 830 biological-naïve patients who initiated a first biological agent. The mean age was 46.6 years (± SD 13.9), and 318 patients (38.3%) were female. The most commonly prescribed biologic was adalimumab: 355 (42.8%) patients, then etanercept ( n = 247, 29.8%), ustekinumab ( n = 194, 23.4%) and infliximab ( n = 34, 4.0%). In the multinomial logistic regression analysis, patients were significantly more likely to receive adalimumab if they had a severe psoriasis as defined by baseline PASI or if they had psoriatic arthritis compared to etanercept ( aOR, 0.42; 95% CI, 0.16-1.07) and ustekinumab ( aOR, 0.15; 95% CI, 0.04-0.52). Patients were significantly more likely to receive ustekinumab ( aOR, 2.39; 95% CI, 1.04-5.50) if they had a positive screening for latent tuberculosis compared to adalimumab. Younger patients were also more likely to receive ustekinumab. Patients with chronic obstructive pulmonary disease were more likely to be prescribed ustekinumab or etanercept compared to adalimumab. There was a trend in favour of etanercept prescription in patients with cardiovascular comorbidities, metabolic syndrome and in patients with a history of cancer. Conclusion We identified patient- and disease-related factors that have important influence on the choice of the first biological agent in clinical practice. Clinicians appear to have a holistic approach to patient characteristics when choosing a biological agent in psoriasis. [ABSTRACT FROM AUTHOR]

The article discusses research that assessed the efficacy of anti-tumor necrosis factor (TNF)-alpha drugs in patients with hidradenitis suppurativa (HS). Topics covered include the initial characteristics of HS patients treated with an anti-TNF-alpha drug, factors associated with a complete or partial response to first-line anti-TNF-alpha therapy, and the modest and inconsistent efficacy of the therapy for moderate-to-severe HS.

Background Malignant tumours of the salivary glands (MSGT) are rare and pleomorphic entities. Patients with advanced disease may benefit from targeted therapy; however, specific targets for optimising and personalising treatments are yet to be identified. Design Immunohistochemistry for C-KIT, EGFR, HER2, MUC1, phospho-mTOR, androgen/estrogens/progesterone receptors and Ki67 was carried out and evaluated in terms of progression-free and overall survival. High throughput molecular screening of key oncogenes was done in 107 patients using routine diagnostic methods and Sequenom technology. Results Several therapy leads were identified, including high levels of HER2 and androgen receptors in salivary duct carcinomas, C-KIT in myoepithelial carcinomas and EGFR in mucoepidermoid carcinomas. Recurrent mutations involving downstream elements of the EGFR pathway were found in HRAS, notably in tumours with a myoepithelial component, and in other key oncogenes (KRAS/NRAS/PI3KCA/BRAF/MAP2K). On the other hand, <1% of samples had EGFR or HER2 mutations. Conclusion Several tumour subtypes overexpressed targets of directed therapies suggesting potential therapy leads. Genotyping results suggest activation downstream of EGFR in 18 of the 107 samples that could be associated with low efficacy of EGFR inhibitors. Other molecules, such as PI3K/MEK or mTOR inhibitors, may have anti-tumour activity in this subgroup. The high mutation rate in HRAS highlights a novel key oncogenic event in MSGT. [ABSTRACT FROM PUBLISHER]

There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes. To systematically review the available literature on: (i) modalities of administration and prescription of oral retinoids as single agent or combined therapy for the treatment of plaque-type psoriasis (PV), nail psoriasis and localized and generalized pustular psoriasis : initial and optimal dosage; (ii) skeletal toxicity of retinoid for the treatment of psoriasis. A systematic literature search was carried out in MEDLINE, EMBASE, and Cochrane Library databases from 1975 to 2010 searching for randomized controlled trials and observational studies evaluating 1) various dosages of retinoid in psoriasis and 2) skeletal toxicity of retinoid in psoriasis. Articles were limited to human subjects and English/French languages. Efficacy of retinoids in psoriasis. Among 1348 identified references, 44 published studies were included. Starting daily dosages between 10 and 25 mg and stepwise escalation were associated with higher clinical efficacy and lower incidence of adverse events in comparison with higher doses and regimens rapidly reaching optimal dose. Retinoids as single agent therapy appeared to show limited efficacy in PV, while the good clinical efficacy reported in pustular forms should be cautiously considered, given the spontaneously remitting course of the disease. Combining retinoids with phototherapy appeared to be highly effective in patients with PV. Potential skeletal toxicity of retinoids. 15 published studies out of 105 identified references were included. There is no strong evidence of an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids. Acitretin appears to provide better efficacy in pustular psoriasis than in PV as a single agent treatment. There is no evidence for skeletal toxicity of retinoids in the setting of psoriasis, and accordingly monitoring this risk through X-ray is not warranted. [ABSTRACT FROM AUTHOR]

To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15-25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity. [ABSTRACT FROM AUTHOR]

Sbidian E, Feldmann D, Bengoa J, Fraitag S, Abadie V, de Prost Y, Bodemer C, Hadj-Rabia S. Germline mosaicism in keratitis–ichthyosis–deafness syndrome: pre-natal diagnosis in a familial lethal form. Keratitis–ichthyosis–deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin-26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre-natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non-consanguineous healthy parents lead to perform pre-natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study of the influence of steroid hormones on the development of subcutaneous neurofibromas (NFs), and the use of sex and pregnancy as proxies.

Linked Article: Gottlieb et al. Br J Dermatol 2021; 185:1124–1134. [ABSTRACT FROM AUTHOR]

Linked Article: Hsu et al. Br J Dermatol 2020; 182:880–888. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Bullous pemphigoid (BP) affects older patients with numerous comorbidities. The impact of BP on patient autonomy remains poorly understood.To assess the frequency and factors associated with functional decline (FD) in BP.In this retrospective monocentric study, we selected patients aged ≥75 years with BP diagnosed between 1 January 2015 and 31 December 2021 and followed for more than 3 months. We assessed activity limitation at diagnosis and included patients with no or mild activity limitation. We described FD and its associated factors at 6 weeks and 3 months. FD was qualified as moderate or severe. Age, comorbidities (CIRS‐G score), BP characteristics at diagnosis (including palms and soles involvement) and hospitalization were collected. Factors associated with FD were investigated through univariate and multivariate logistic regression models. Worsening of previous comorbidities or new comorbidities at Week 6 were collected.One hundred and thirty‐one patients were included (mean age 85 years), 75 (57.3%) had no activity limitation, and 56 (42.7%) a mild activity limitation at baseline. At Week 6, FD was observed in 44 (33.6%) patients, including 23 out of 75 (30.7%) with no activity limitation and 21 out of 56 (37.5%) with mild activity limitation at baseline. FD was moderate in 20 cases (45.5%) and severe in 24 (54.5%) and persisted at Month 3 in 37 (84%) patients. By multivariate analysis, factors associated with FD were a CIRS‐G score >7, palms and soles involvement and anti‐BP180 antibodies level. Fifty (38.2%) patients experienced a worsening of their pre‐existing comorbidities or a new one.FD is often observed in patients with BP, especially in those with severe symptoms, palms and soles involvement and comorbidities. A comprehensive, multidisciplinary approach involving geriatric assessments should be adopted to manage these patients. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on four case studies of neutrophilic cholangitis (NC) in patients suffering from psoriasis vulgaris (PV) and psoriatic arthritis (PsA).

The article comments on the research study "Population-based Clinical Practice Research Datalink study using algorithm modelling to identify the true burden of hidradenitis suppurativa," by J.R. Ingram et al., published in the journal. Ingram and colleagues estimated the prevalence of hidradenitis suppurativa, a chronic inflammatory skin disease typically characterized by recurrent painful, deep inflammatory nodules, at 0.8%.

Linked Article: Mason et al. Br J Dermatol 2019; 181:256–264. [ABSTRACT FROM AUTHOR]

The article presents several abstracts such as "Suicide and psoriasis: no longer an association," by A. Egeberg and colleagues and "Tyrosinase inhibitors from marine algae," by J. Y. Kwak and colleagues.

A letter to the editor is presented on the case of a woman diagnosed with pemphigoid gestationis.

Les anti-TNF-alpha ont considérablement amélioré la prise en charge des maladies inflammatoires chroniques. Plusieurs produits biosimilaires ont été commercialisés à l'expiration des brevets de référence, réduisant le coût de ces traitements. L'équivalence entre biosimilaire et produit de référence est démontrée lors d'un essai randomisé de phase 3 dans une indication de la molécule, puis une extrapolation des données sur les autres indications est réalisée. Nous avons comparé la persistance et la sécurité du produit de référence à celles des biosimilaires de l'infliximab (IFX), de l'etanercept (ETA) et de l'adalimumab (ADA) chez les initiateurs de traitement dans chacune des indications de ces molécules. Nous avons utilisé les données du Système national des données de santé pour identifier les initiateurs d'IFX, ETA et ADA à partir de la date de commercialisation en France du premier biosimilaire de chacune des molécules (respectivement 01/2015, 05/2016 et 10/2018) et jusqu'au 30 juin 2021. Les patients ont ensuite été suivis pendant un an. Nous avons comparé la persistance (durée sans arrêt ni modification de traitement) et la sécurité (infection sévère, hospitalisation toute cause, décès) du traitement entre les utilisateurs du produit de référence et des biosimilaires par régressions de Cox pondérées sur l'inverse du score de propension de traitement par produit de référence ou biosimilaire. Les analyses ont été réalisées par molécule, selon la pathologie traitée et selon le biosimilaire utilisé. Au total, 86 776 patients ont été inclus dans l'étude : respectivement 22 670, 24 442 et 39 664 initiateurs d'IFX, ETA et ADA ; 49 752 (53 %) étaient initiateurs d'un produit biosimilaire ; 28 % étaient atteints de spondylarthrite ankylosante, 21 % de polyarthrite rhumatoïde, 5 % de rhumatisme psoriasique, 24 % de maladie de Crohn, 13 % de rectocolite hémorragique, 8 % de psoriasis, et moins de 1 % d'hidradénite suppurée ou d'uvéite. Les caractéristiques des sujets à l'inclusion étaient très proches entre utilisateurs de produits de référence et biosimilaires. Nous n'avons pas identifié de surrisque de non-persistance (les hazard ratios étaient proches de 1, ici toute pathologie et tout produit confondus : IFX 0,86 [0,80–0,93], ETA 0,84 [0,80–0,88], et ADA 0,97 [0,92–1,01]) ou d'événement indésirable (infection : IFX 1,01 [0,85–1,20], ETA 1,08 [0,86–1,36], et ADA 0,95 [0,81–1,11] ; hospitalisation : IFX 1,10 [1,00–1,21], ETA 0,97 [0,87–1,08], et ADA 0,90 [0,83–0,98]) associé à l'utilisation de biosimilaire comparée à l'utilisation de produit de référence. Notre étude est la première à comparer de façon exhaustive et systématique biosimilaires et produits de référence de l'IFX, l'ETA et l'ADA, dans toutes les pathologies indiquées et produit par produit, en termes d'efficacité et de sécurité sur divers événements indésirables. La principale limite de l'étude est la nature médico-aadministrative de notre base de données, qui ne contient pas toutes les informations cliniques des patients. Les résultats de notre étude sont rassurants quant à la persistance des biosimilaires en comparaison au produit de référence des anti-TNF alpha dans toutes les indications de ces molécules. [ABSTRACT FROM AUTHOR]

Le rhumatisme psoriasique (RhPso) semble affecter différemment les patients masculins et féminins, ce qui se traduit par des variations dans la présentation clinique, l'évolution de la maladie, et il semblerait dans la réponse au traitement sans que l'on sache s'il s'agit d'un effet « thérapie ciblée » ou un effet classe. Cette étude visait à évaluer l'influence du sexe sur la persistance à long terme de chacune des classes de thérapies ciblées disponibles. Nous avons mené une étude de cohorte à partir des données du Système National des Données de Santé (SNDS) rassemblant les informations de remboursement de 99 % des résidents français. Nous avons inclus tous les adultes atteints de RhPso (CIM-10 M07), nouveaux utilisateurs de thérapies ciblées (n'en ayant reçu aucune dans l'année précédant la date index) entre 2015 et 2021 et étudié toutes les lignes de traitements au cours de cette période. La persistance thérapeutique a été définie comme la durée séparant l'initiation d'une thérapie ciblée de son arrêt et a été estimée en utilisant la méthode de Kaplan-Meier. Les comparaisons des persistances thérapeutiques en fonction du sexe ont été réalisées à l'aide de modèles de fragilité multivariés et ajustés sur les csDMARDs et la prednisone comme variables dépendantes du temps. Des analyses de sensibilité (ne considérant que la première ligne thérapeutique, analyses après modification des définitions des séquences thérapeutiques, de l'évènement et des nouveaux utilisateurs) ont été menées. Nous avons inclus 14 778 patients atteints de RhPso, nouveaux utilisateurs de thérapies ciblées : 8475 (57 %) femmes (15 831 lignes étudiées : 60 % de TNFi, 24 % d'IL17i, 10 % d'IL12/23i, 2 % d'IL23i et 4 % de JAKi) et 6303 (43 %) hommes (10 488 lignes étudiées : 59 % de TNFi, 23 % d'IL17i, 11 % d'IL12/23i, 4 % d'IL23i et 3 % de JAKi). En moyenne, chaque patient avait eu 1,8 ± 1,1 lignes thérapeutiques avec une durée moyenne de 1,6 ± 1,5 ans. À l'inclusion, on observait plus d'exposition aux csDMARD, aux AINS, à la prednisone, aux antalgiques de palier 2 et 3 et aux infiltrations cortisoniques chez les femmes que chez les hommes. La persistance globale à 1 an était de 52 % chez les femmes et de 62 % pour les hommes, et chutait respectivement à 27 % et à 39 % à 3 ans. Après ajustement, la persistance était significativement plus faible chez les femmes que chez les hommes sous TNFi (HRa 1,4, IC 99 % 1,3–1,5) et IL17i (HRa 1,2, IC 99 % 1,1–1,3) mais pas sous IL12/23i (HRa 1,1, IC 99 % 0,9–1,3), IL23i (HRa 1,1, IC 99 % 0,7–1,5) et JAKi (HRa 1,2, IC 99 % 0,9–1,6). Les résultats ne différaient pas selon les différentes analyses de sensibilité. Outre la confirmation d'une persistance plus faible des TNFi chez les femmes que chez les hommes dans le RhPso, nous avons constaté que cette différence concernait également les IL17i mais n'était pas significative pour l'IL12/23i, les IL23i et les JAKi. Cela souligne la nécessité d'études basées sur le sexe et le genre pour mieux comprendre les mécanismes sous-jacents, mais aussi d'études en face-à-face avec des analyses stratifiées par sexe afin d'optimiser la prise en charge des patients atteints de RhPso et d'atteindre l'objectif ambitieux de médecine personnalisée dans les années à venir. [ABSTRACT FROM AUTHOR]

Summary: Background: Epidermal necrolysis is a rare and severe cutaneous adverse reaction to drugs with long‐term somatic consequences and potentially underrecognized psychological complications. Objectives: To assess the prevalence and risk factors of post‐traumatic stress disorder (PTSD) in Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing psychiatric evaluation. Methods: In this prospective study, we included adult patients admitted at the acute phase of SJS/TEN to our dermatology department from June 2009 to February 2013. The main objective was to assess the prevalence of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist score > 44. Secondary objectives were to investigate risk factors of PTSD in the medical history of patients and characteristics of the disease at the acute phase by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and Peritraumatic Distress Inventory (PDI) and the degree of impairment on the Sheehan Disability Scale. Results: We initially included 32 of 80 patients admitted during the study period. At 6 months, seven of 30 still followed up had a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%) patients had a hydroxyzine prescription at the acute phase. The main risk factors associated with PTSD at 6 months were psychological results at the acute phase. Conclusions: Despite frequent prescription of hydroxyzine at the acute phase, almost one‐quarter of patients with SJS/TEN had PTSD at 6 months. A systematic psychiatric evaluation should be offered regularly for at least 1 year after the acute disease phase. What's already known about this topic? Epidermal necrolysis, comprising Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), is a rare and severe cutaneous adverse reaction with long‐term somatic consequences and still underrecognized psychological complications. What does this study add? We conducted a prospective study including 31 (32 initially) adults with SJS/TEN and found a 23% prevalence of post‐traumatic stress disorder at 6 months after the acute disease phase.Risk factors were high scores of peritraumatic emotional reaction and dissociation at the acute phase but not age, sex or initial severity of the disease. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Summary: Background: Genital psoriasis is often under‐recognized. Objectives: To assess the instantaneous prevalence of genital psoriasis and describe its clinical features, association with a particular subtype of psoriasis and its impact on general and sexual quality of life (QoL). Methods: GENIPSO is a prospective study conducted by private and hospital‐based dermatologists. This study featured the consecutive inclusion of patients consulting for extragenital psoriasis. The clinical features of psoriasis and genital psoriasis were recorded and QoL and sexual health questionnaires were distributed to patients. Results: Overall, 335 of 776 patients (43·2%) included in the study had genital involvement. All were aware that they had genital lesions but only 135 patients (40%) declared that they had been previously examined. Genital lesions were associated with male sex, severity of psoriasis, age of onset > 20 years, inverse psoriasis and involvement of scalp, nail and external auditory canal, but were not associated with obesity, psoriatic arthritis and active sex life. Itching was the main symptom. Genital psoriasis was associated with impairment of QoL and sexual health according to the Dermatology Life Quality Index and the Female Sexual Function Index. Conclusions: Genital psoriasis has a high prevalence in patients consulting for extragenital psoriasis, which affects QoL, and should be taken into account by dermatologists in order to optimize global care. What's already known about this topic? Genital psoriasis is frequent but under‐recognized. What does this study add? The instantaneous prevalence of genital psoriasis in patients consulting for extragenital psoriasis was 43·2%.All patients were aware of their genital psoriasis but only 40% declared having had a previous examination of the genital area by a dermatologist. What are the clinical implications of this work? Owing to its frequency and impact on general and sexual quality of life, genital psoriasis should be screened in all patients, including those already receiving treatment for psoriasis. Respond to this article Linked Comment:Ryan. Br J Dermatol 2019; 180:460–461. Plain language summary available online [ABSTRACT FROM AUTHOR]

Les inhibiteurs du TNF alpha ont révolutionné la prise en charge thérapeutique des maladies inflammatoires chroniques. Plusieurs produits biosimilaires ont été commercialisés à l'expiration de leur brevet, réduisant le coût de ces traitements. L'objectif de notre étude était d'évaluer le taux de pénétration des biosimilaires de l'infliximab (IFX), de l'etanercept (ETA) et de l'adalimumab (ADA) chez les nouveaux utilisateurs et les patients en cours de traitement depuis le début de la commercialisation des biosimilaires, globalement et selon la pathologie traitée, la spécialité du médecin et les caractéristiques des patients. Nous avons utilisé l'ensemble des données du Système National de Données de Santé pour identifier les initiateurs et les utilisateurs en cours de traitement d'IFX, d'ETA et d'ADA à partir de la date de commercialisation en France du 1er biosimilaire de chacune des molécules (respectivement 01/2015, 05/2016 et 10/2018). Les patients ont ensuite été suivis jusqu'au 30 septembre 2021. Les caractéristiques sociodémographiques des patients, les pathologies traitées et les parcours d'utilisations des produits de référence ou biosimilaires ont été analysés de façon descriptive. Au total, 207 118 patients ont été inclus dans l'étude. Respectivement 25 950, 27 727, 48 768 patients avaient initié un traitement par IFX, ETA et ADA. Après la date de commercialisation de chaque biosimilaire, les biosimilaires représentaient 78 % (IFX), 46 % (ETA) et 53 % (ADA) de l'ensemble des initiations de ces molécules, et 94 % (IFX), 66 % (ETA) et 60 % (ADA) au cours de la dernière année de suivi. Respectivement 20 254, 31 038, 53 381 utilisaient le produit de référence de l'IFX, de l'ETA et de l'ADA au moment de la commercialisation de leur premier biosimilaire. Au total, 46 % (IFX), 19 % (ETA) et 17 % (ADA) étaient passés sur un produit biosimilaire au moins une fois à la fin de l'étude. Le taux de pénétration des biosimilaires était beaucoup plus élevé pour l'IFX que pour ses homologues. L'initiation par un biosimilaire et le passage du produit de référence au produit biosimilaire ont davantage été observés en rhumatologie qu'en dermatologie, gastro-entérologie ou ophtalmologie. L'utilisation des biosimilaires était similaire quelles que soient les caractéristiques sociodémographiques des patients. Le taux d'initiation des biosimilaires a augmenté rapidement à partir de la date de commercialisation. Le passage du produit de référence au biosimilaire est resté limité. Dans l'ensemble, l'utilisation des biosimilaires dépendait principalement de la molécule considérée (délivrance en milieu hospitalier de l'IFX) et de la spécialité du prescripteur (l'adoption des biosimilaires était plus rapide pour les rhumatologues). Les disparités d'utilisation des biosimilaires des anti-TNF alpha mises en évidence dans cette étude soulignent la nécessité et l'utilité de politiques d'incitations à la prescription de biosimilaires et d'un suivi régulier de leur utilisation. [ABSTRACT FROM AUTHOR]

Le rituximab (RTX) est un anticorps monoclonal utilisé en hématologie ou dans certaines maladies inflammatoires. Des produits bio-similaires du RTX sont arrivés sur le marché en octobre 2017. Depuis 2019, les centres régionaux de pharmacovigilance ont commencé à remonter des cas d'hypersensibilité sévère suite à des injections de bio-similaire du RTX, notamment au moment du switch princeps vers bio-similaire. La présente étude avait pour objectif de déterminer si l'utilisation de bio-similaires du RTX présentait un surrisque de chocs anaphylactiques ou réactions sériques par rapport au produit de référence, à l'initiation du traitement, au switch , et au cours du temps. Nous avons utilisé les données du Système national de données de santé pour identifier les utilisateurs de RTX entre le 1er octobre 2017 et le 31 décembre 2021. Une première cohorte était constituée de patients ayant initié leur traitement par RTX ; une seconde cohorte était constituée de patients switcheurs, appariés à 1 ou 2 patients toujours sous produit de référence sur l'âge, le sexe, le nombre d'injections passées et la pathologie. L'événement d'intérêt a été défini comme une hospitalisation pour un choc anaphylactique ou une réaction sérique à la suite d'une injection de RTX. Nous avons estimé le surrisque éventuel dû à l'utilisation d'un bio-similaire au moment de la première injection (initiation ou injection du switch) par une régression logistique multivariée, et au cours du temps par un modèle de Cox avec exposition dépendante du temps. Au total, 91 894 initiateurs ont été inclus dans la première cohorte, dont 17 605 (19 %) avec le produit de référence et 74 289 (81 %) avec un bio-similaire. À l'initiation, 86 (0,49 %) et 339 (0,46 %) cas d'hypersensibilité ont été identifiés respectivement dans le groupe princeps et le groupe bio-similaire. L' odds ratio ajusté (ORa) de l'exposition au bio-similaire associé à l'événement d'intérêt était de 1,04 [0,80–1,34]. Le Hazard ratio ajusté (HRa) entre l'exposition au cours du temps au bio-similaire versus le produit de référence était de 1,15 [0,93–1,42]. Au total, 17 123 switcheurs ont pu être appariés à 24 659 non-switcheurs. Au switch , 28 (0,11 %) et 14 (0,08 %) cas d'hypersensibilité ont été identifiés respectivement dans le groupe non- switch et le groupe switch. L'ORa de l'exposition au bio-similaire associé à l'événement d'intérêt était de 0,74 [0,39–1,42]. Le HRa entre l'exposition au cours du temps au bio-similaire versus le produit de référence était de 1,06 [0,70–1,62]. Nous avons retrouvé un effet protecteur de la prise de corticoïdes en amont de l'injection, un surrisque chez les patients ayant des antécédents d'événement et les patients jeunes, et une diminution du risque d'événement avec le nombre d'injections précédentes. Les résultats des analyses de sensibilité étaient cohérents avec l'analyse principale. Notre étude portant sur la quasi-exhaustivité de la population française ne permet pas de conclure à une association entre exposition aux bio-similaires du RTX et hospitalisation pour choc anaphylactique ou réaction sérique à la suite de l'injection, aussi bien à l'initiation, au switch , et au cours du temps. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Inherited epidermolysis bullosa (EB) comprises a highly heterogeneous group of rare diseases characterized by exacerbated skin and/or mucosal fragility and blister formation after minor mechanical trauma. Level of cleavage in the skin, clinical features with immunofluorescence antigen mapping and/or electron microscopy examination of a skin biopsy and/or gene involved, type(s) of mutation present and sometimes specific mutation(s), allow to define the EB type and subtype. This family of genodermatoses exposes patients to several complications, cutaneous squamous cell carcinoma (cSCC) being the most severe of them.Objective: The aim of this systematic review was to document patients with EB who developed cSCC.Methods: A systematic literature search was performed, from inception to March 2014, using Medline, Embase, Cochrane and ClinicalTrials.gov databases. Only articles published in English and French were selected. The diagnosis of EB had to be confirmed by EM and/or IFM and/or mutation analysis, while cSCC had to be confirmed by histological analysis.Results: Of 167 references in the original search, 69 relevant articles were identified, representing 117 cases. cSCCs were identified in all types of EB, though predominantly in recessive dystrophic EB (RDEB) forms (81 cases (69.2 %)). The median age at diagnosis was 36 years old (interquartile range (IQR), 27-48 years and range, 6-71 years) for all forms. Of those with measurements in the literature (88 cases (75.2 %)), tumor size was greater than 2 centimeters in 52 cases (59.1 %). The histopathological characteristics were specified in 88 cases (75.2 %) and well-differentiated forms predominated (73.9 %). No conclusion could be drawn on the choice of surgical treatment or the management in advanced forms.Limitations: This study was retrospective and statistical analysis was not included due to various biases. This study design did not allow to infer prevalence, nor EB subtype risk for cSCC occurrence.Conclusions: Our study correlated with historical data shows that most of the cSCCs occurred in subjects with the RDEB subtype, however reports also show that cSCCs can present in any patients with EB. The first signs of cSCC developed at a younger age in EB patients than in non-EB patients. Interestingly, the cSCC duration, before its diagnosis, was shorter in individuals with RDEB than with junctional EB (JEB) and dominant dystrophic EB (DDEB). This study further emphasizes the importance of regular monitoring of EB patients, particularly with the RDEB subtype as they developed cSCC at a younger age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Negative tests for SARS-CoV-2 infection do not rule out its responsibility for chilblains: reply from the authors Dear Editor, With great interest, we read the comment by Battesti and Descamps1 on our recently published study in the I BJD i .2 Their comment is based on their findings that histological and immunostaining of skin biopsies of seven cases of "epidemic chilblains" with negative SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing and repeated serology was similar to those of a historical series of 11 cases of chilblains lupus, notably for high expression of CD123 and MxA [a type-I interferon (IFN-I)-induced protein] in both groups.3 Thus, they hypothesized that chilblains observed during the COVID-19 outbreak are linked to a high IFN response to SARS-CoV-2, leading to both negative RT-PCR and serology due to this effective antiviral response and that development of chilblains is due to IFN production. Secondly, their hypothesis warranted further exploration, notably to confirm the high IFN production in patients with chilblains and negative serology and PCR. [Extracted from the article]

Summary: 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. Whatis already known about this topic? Almost all chronic diseases have emerged as risk factors for hospitalization for COVID‐19 and poor COVID‐19 outcomes.Multimorbidity is frequent in psoriasis. In France, psoriasis was found to be associated with increased risk of hospitalization for COVID‐19 but not in‐hospital mortality due to COVID‐19.Biologics are associated with an increased risk of infection. Few data have been published on the course of COVID‐19 in patients with psoriasis receiving biologics. Whatdoes this study add? Systemic treatments for psoriasis (including nonbiologics and biologics) were not associated with an increased risk of in‐hospital mortality due to COVID‐19.Our results did not support a prophylactic effect of long‐term use of biologics on risk of hospitalization for COVID‐19 or in‐hospital mortality.These results provide evidence supporting the continuity of care for psoriasis and maintaining systemic treatment for psoriasis during the pandemic. Linked Comment: S. Cazzaniga and L. Naldi. Br J Dermatol 2022; 186:7–8. Plain language summary available online [ABSTRACT FROM AUTHOR]

Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non-plaque psoriasis. To prepare for evidence-based recommendations concerning the practical use of CyA in psoriasis, we performed a systematic review to better define treatment strategy, risk of kidney toxicity and evidence for use in non-plaque psoriasis. A systematic search was performed on PubMed, Cochrane and Embase databases, using the key-words 'psoriasis', 'CyA', 'nephrotoxicity' during the period from 1980 to June 2010. The initial literature search identified 428 articles. The final selection included 16 randomized controlled trials (RCT) for treatment strategy, 25 articles (histological studies and RCT) for risk of kidney toxicity and 10 articles (RCT, prospective studies and case series) for use in non-plaque psoriasis. Higher doses of CyA of 5 mg/kg produced Psoriasis Area Severity Index (PASI) 75 response in between 50 and 97% of patients, whereas lower doses of 2.5 mg/kg yielded PASI 75 in between 28 and 85%. CyA could maintain remission at doses of at least 3 mg/kg/day. Low calory diet in obese patients was shown to improve CyA efficacy. More than 50% of the patients treated with CyA may have an increase in serum creatinin value over 30% of baseline if treatment is prolonged for 2 years. CyA at a dose of 2.5 mg/kg/day was effective for 89% of patients with palmoplantar pustulosis. More than 50% of the patients with erythrodermic psoriasis obtained a significant improvement at doses between 3 and 5 mg/kg/day at 2-4 months. CyA was more effective than etretinate on nail psoriasis. Oral CyA is indicated for patients with plaque psoriasis, pustular psoriasis or erythrodermic psoriasis. The starting dose of 5 mg/kg is associated with a higher degree of clearance. The benefit-risk appears to be better for patients without risk factors for nephrotoxicity: non-obese patients without hypertension and aged below 60. Although CyA is ideally suited for crisis intervention, continuous maintenance treatment with CyA may be envisaged in some patients provided serum creatinin is regularly monitored and the cumulative treatment duration is preferably limited to 2 years or less. [ABSTRACT FROM AUTHOR]

Les options thérapeutiques dans le rhumatisme psoriasique (RhPso) et le psoriasis (Pso) se sont multipliées depuis l'ère des thérapeutiques biologiques. Les essais cliniques (vs placebo pendant 12 à 16 semaines) ne permettent pas d'évaluer l'efficacité au long cours des thérapeutiques entre elles et sont le plus souvent incomplets et inadéquats sur la tolérance. La persistance d'un traitement est un indicateur pertinent, reflétant l'intérêt du patient pour le traitement en intégrant les dimensions d'efficacité (traitement perçu comme inefficace non poursuivi) et de tolérance (traitement mal toléré moins poursuivi). L'objectif de cette étude était de comparer la persistance des différentes classes thérapeutiques dans une cohorte de patients RhPso et une cohorte de patients Pso. Nous avons mené une étude de cohorte à partir des données du Système National des Données de Santé (SNDS) rassemblant les informations de remboursement de 99 % des résidents français. Les adultes identifiés RhPso (CIM-10 M07), d'une part, et ceux Pso (délivrance d'au moins 2 dérivés topiques de la vitamine D), d'autre part, nouveaux utilisateurs d'un biomédicament (n'en ayant reçu aucun dans l'année précédant la date index) entre le 01/01/2015 et le 31/12/2019 ont été inclus. Ceux ayant été hospitalisés pour Pso, dans la cohorte RhPso, et pour RhPso, dans la cohorte Pso, dans l'année précédant l'initiation du biomédicament ont été exclus. La persistance thérapeutique a été définie comme la durée séparant l'initiation d'un biomédicament de son arrêt, après exclusion de ceux n'ayant pas maintenu la 1ère ligne au moins 6 mois, et a été estimée en utilisant la méthode de Kaplan-Meier. Les comparaisons des persistances selon les classes thérapeutiques ont été réalisées à l'aide de modèles de Cox pondérés par un score de propension (IPTW) puis ajustées sur les traitements conventionnels et la prednisone (variables dépendantes du temps). Un total de 6531/66 456 patients RhPso initiant un biomédicament ont été identifiés (49 ± 13 ans, 45 % d'hommes) dont 4974 (76 %) initiant un anti-TNF, 803 (12 %) l'anti-IL12/23 et 754 (12 %) un anti-IL17. Un total de 20 814/1 330 592 patients Pso initiant un biomédicament (53 ± 17 ans, 50 % d'hommes) ont été inclus ; 13 232 (63 %) initiant un anti-TNF,4785 (23 %) l'anti-IL12/23, et 2797 (14 %) un anti-IL17. Les taux de persistance globale à 3 ans des biomédicaments étaient de 36 % et 42 % pour le RhPso et le Pso, respectivement. Après IPTW et ajustement sur les variables dépendantes du temps, les anti-IL17 étaient associés à une meilleure persistance que les anti-TNF pour le RhPso et le Pso (RhPso : HRp 0,86, IC95 % 0,76-0,96 ; Pso : HRp 0,85, IC95 % 0,80-0,91) et une meilleure persistance que l'anti-IL12/23 pour le RhPso (HRp 0,82, IC95 % 0,71-0,95). Aucune différence n'était observée entre les anti-IL17 et l'anti IL12/23 pour le Pso. L'anti-IL12/23 avait une meilleure persistance que les anti-TNF pour le Pso (HRp 0,81, IC95 % 0,77-0,85), aucune différence n'était observée dans le RhPso. Cette étude en vie réelle confirme une meilleure persistance des anti-IL17 comparativement aux anti-TNF chez les patients RhPso et Pso avec une excellente extrapolabilité des résultats (étude en population générale et effectifs de grande taille). Les anti-IL17 ont également une meilleure persistance que l'anti-IL12/23 dans le RhPso, sans différence observée dans le Pso. Cependant, les taux de persistance des 3 classes thérapeutiques restent globalement faibles à 3 ans. [ABSTRACT FROM AUTHOR]

Linked article: C. Marasca et al. J Eur Acad Dermatol Venereol 2020;34: e413–e414. https://doi.org/10.1111/jdv.16361. [ABSTRACT FROM AUTHOR]

Summary: 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. What is already known about this topic?Palmoplantar pustulosis is a chronic inflammatory dermatosis that affects the hands and feet, and has a major impact on patients' quality of life.A Cochrane review published in 2006 concluded that there is no effective treatment and suggested that the standards of study design and reporting need to be improved to allow patients and clinicians to assess the effectiveness of treatments available. What does this study add?Evidence is still lacking for commonly used treatments such as topical corticosteroids, phototherapy, acitretin, methotrexate and ciclosporin.A topical vitamin D derivative may be more effective than placebo in achieving clearance in the short term (low‐certainty evidence).Secukinumab and guselkumab may be superior to placebo in reducing severity (moderate‐certainty evidence) than placebo but not ustekinumab (moderate‐certainty evidence). Linked Comment: Feldman and Huang. Br J Dermatol 2021; 184:990. [ABSTRACT FROM AUTHOR]

Summary: 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. What is already known about this topic? Systematic reviews and meta‐analyses assessing the safety of biologic treatments for plaque‐type psoriasis in randomized controlled trials concluded that the proportion of serious adverse events (SAEs) was not significantly different between biologic and placebo groups. What does this study add?On excluding cases of worsening psoriasis, the risk of occurrence of SAEs is higher in the biologic group than in the placebo group, especially for anti‐tumour necrosis factor‐α treatments.Given the rare events, we could not highlight whether this higher risk of SAEs was related to adverse events of special interest. Linked Comment: Dávila?Seijo. Br J Dermatol 2021; 184:385. Plain language summary available online [ABSTRACT FROM AUTHOR]

I Editor, i Basic treatment of atopic dermatitis (AD) associates topical corticosteroids (TCS) during flares and daily moisturizing to restore epidermal barrier. The TOPICOP® questionnaire measuring fear, beliefs and reluctance to TCS use showed an average level of TCS phobia of 44% (35-58%).1 Therapeutic patient education (TPE) did not affect fear suggesting a possible role of caregivers in TCS phobia.2 We focused on the risk factors for parental TCS phobia. Study population was divided into 3 groups of TCS phobia with the TOPICOP®100 score in tertiles, ranging from minimum to maximum TCS phobia; tertile 1: TOPICOP®100 score <= 23 (low TCS phobia); tertile 2: score of 24-50 (moderate TCS phobia); and tertile 3: score over than> 50 (high TCS phobia). [Extracted from the article]

Summary: 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. 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. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. Objectives: To evaluate the real‐life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. Methods: A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results: Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1–82.7), P = 0.04 and 0.1 (0.01–0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3–28.6), P = 0.02 and 4.7 (1.0–22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7–52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1–29.4), P = 0.04]. Conclusions: We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis. [ABSTRACT FROM AUTHOR]

A commonly used assessment is the Psoriasis Area and Severity Index (PASI), with an absolute value of 10 or more indicating severe disease.1 How patients perceive the severity of psoriasis and physicians' evaluations may be discordant, especially when lesions involve visible areas or are associated with itching. [Extracted from the article]

Summary: Background: Necrotizing soft‐tissue infections (NSTIs) are life threatening, requiring broad‐spectrum antibiotics. Their aetiological diagnosis can be limited by poor performance of cultures and administration of antibiotics before surgery. Objectives: We aimed (i) to compare 16S‐targeted metagenomics (TM) and unbiased semiquantitative panmicroorganism DNA‐ and RNA‐based shotgun metagenomics (SM) with cultures, (ii) to identify patients who would best benefit from metagenomics approaches and (iii) to detect the microbial pathogens in surrounding non‐necrotic 'healthy' tissues by SM‐based methods. Methods: A prospective observational study was performed to assess the analytical performance of standard cultures, TM and SM on tissues from 34 patients with NSTIs. Pathogen identification obtained with these three methods was compared. Results: Thirty‐four necrotic and 10 healthy tissues were collected from 34 patients. The performance of TM was inferior to that of the other methods (P < 0·05), whereas SM performed better than standard culture, although the result was not statistically significant (P = 0·08). SM was significantly more sensitive than TM for the detection of all bacteria (P = 0·02) and more sensitive than standard culture for the detection of anaerobic bacteria (P < 0·01). There was a strong correlation (r = 0·71, Spearman correlation coefficient) between the semiquantitative abundance of bacteria in the culture and the bacteria‐to‐human sequence ratio in SM. Low amounts of bacterial DNA were found in healthy tissues, suggesting a bacterial continuum between macroscopically 'healthy' and necrotic tissue. Conclusions: SM showed a significantly better ability to detect a broader range of pathogens than TM and identify strict anaerobes than standard culture. Patients with diabetes with NSTIs appeared to benefit most from SM. Finally, our results suggest a bacterial continuum between macroscopically 'healthy' non‐necrotic areas and necrotic tissues. What's already known about this topic? Necrotizing soft‐tissue infections (NSTIs) are characterized by rapidly progressive necrosis of subcutaneous tissues and high mortality, despite surgical debridement combined with broad‐spectrum antibiotics.The spectrum of potentially involved pathogens is very large, and identification is often limited by the poor performance of standard cultures, which may be impaired by previous antibiotic intake.Metagenomics‐based approaches show promise for better identification of the pathogens that cause these infections, but they have not been evaluated in this medical context. What does this study add? Shotgun metagenomics (SM) showed higher sensitivity than 16S rRNA gene sequencing and a better ability than culture to detect anaerobic bacteria. As a result, a significant proportion of infections with bacteria, such as Pasteurella multocida or Clostridium perfringens, were detected only by SM.SM bacterial quantification enabled better detection of low amounts of bacterial DNA from macroscopically 'healthy' tissue, suggesting a subclinical infectious extension. What is the translational message? The high analytical performance of SM shown in this study should allow its future implementation for the diagnosis of necrotizing fasciitis, complementing or replacing routine methods.The large amount of data, including additional information on antimicrobial resistance, virulence profiles and metabolic adaptation of the pathogens, will improve microbiological documentation.Our results will improve our understanding of infectious pathophysiology in the future, leading to potentially better medical care. Linked Comment: Moitinho‐Silva et al. Br J Dermatol 2020; 183:10. Plain language summary available online Respond to this article [ABSTRACT FROM AUTHOR]

Topical steroids represent the main treatment for psoriasis and are often maintained in patients receiving a systemic treatment.[[1]] The objective of this study was to evaluate the consumption of topical steroids before and after the initiation of systemic treatment in psoriatic patients. Overall, 73 168 patients (mean age 52.1 years; males 59.1%) and 16 545 patients (mean age 48.6 years; males 57.3%) had a new prescription for conventional systemic treatments and biologics. Persistence of treatment with biologics for patients with psoriasis: a real-world analysis of 16 545 biologic-naive patients from the French National Health Insurance database (SNIIRAM). [Extracted from the article]

Background: Surgery is a radical treatment for hidradenitis suppurativa (HS) and may be considered as the only one potentially curative. Objectives: To characterize HS recurrence in patients after surgery and assess the risk factors of recurrence. Methods: We conducted a monocentric retrospective cohort study. All consecutive patients who had surgery (January 1, 2012 to March 31, 2017) were included. We estimated the rate of recurrence of HS lesions after surgery (<1 cm from the scar), and recurrence‐associated factors were analysed by univariate then multivariate logistic regression, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 75 patients [median age 31.4 years (range 16–71); 36 females], corresponding to 115 interventions were included. The Hurley score at surgery was III for 70 (60%) patients. In total, 61/115 (53%) interventions involved wide excision and 50 (43%) limited local excision. The localizations were axillary folds (n = 46; 40%), buttocks (n = 15, 13%), genital area (n = 13; 11%), perineal area (n = 12; 10%) and inguinal folds (n = 18; 16%). We observed 11 (10%) complications and 40 (35%) recurrences. On multivariate analysis, probability of recurrence was associated with only one‐stage surgical closure [OR 3.2 (95% CI 1.4–7.3), P = 0.005]. Overall, 44 (52%) patients were completely satisfied and 22 (26%) partially satisfied, and most (81%) considered the surgery the best treatment. Conclusions: Hidradenitis suppurativa recurrence in our study was 35% and associated with one‐stage surgical closures, but two‐thirds of patients were satisfied with surgical treatment and would recommend surgery. [ABSTRACT FROM AUTHOR]

Summary: Background: Epidermal necrolysis (EN) is a rare and life‐threatening condition. Objectives: To assess whether admitting hospital characteristics and interhospital transfer are associated with mortality due to EN. Methods: We studied the French nationwide hospital discharge database (retrospective national cohort). All patients admitted during 2012–2016 with a code for EN in the International Classification of Diseases, 10th Revision, were eligible. We extracted data on the patients (age, sex, intensive care unit admission, comorbidities) and hospitals (private proprietary vs. public, nonteaching or teaching; and number of admissions for EN as a proxy for experience). Multivariable analysis was used to identify independent predictors of in‐hospital mortality with mixed logistic regression. Results: We identified 991 patients (467 male; mean age 52·7 ± 23 years). They were admitted to 300 different hospitals, including teaching hospitals (25% of hospitals) for around half of the patients. Overall, 597 patients (60%) had a diagnosis of Stevens–Johnson syndrome (SJS), 171 (17%) had SJS/toxic epidermal necrolysis (TEN) overlap and 223 (23%) had TEN. In total, 109 (11%) patients died: nine (2%) with SJS, 26 (15%) with SJS/TEN overlap and 74 (33%) with TEN. The in‐hospital mortality rate was lower in centres with vs. without substantial EN experience – odds ratio for one supplemental EN admission in a department 0·5 (95% confidence interval 0·3–1·0); P = 0·05 – even after adjusting for potentially relevant individual risk factors. We found no significant association between mortality and interhospital transfer. Conclusions: Our findings highlight increased survival of patients with EN in centres with a high volume of EN procedures. If confirmed in other settings, these findings reinforce the importance of expertise in early diagnosis and management of this condition. What's already known about this topic? Epidermal necrolysis (EN) is a rare and life‐threatening condition.At the individual level, risk factors for in‐hospital mortality have been identified.Few studies have examined the association between hospital characteristics and EN mortality, with special attention to referral hospitals. What does this study add? Short‐term mortality rates were lower for patients in centres with EN experience than in centres without EN experience, after adjusting for known risk factors.We found no association between interhospital transfer and survival.If confirmed in other settings, these findings support the early transfer of patients with suspected or diagnosed EN to centres with experience, where a multidisciplinary approach can be implemented by experienced healthcare professionals, to maximize short‐term survival. Respond to this article Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. Methods: In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab – REVEAL, ustekinumab – PHOENIX, brodalumab – AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. Results: A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non‐plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9–9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non‐eligible patients [0.78 (95% CI 0.62–0.97) (P = 0.03)]. Conclusion: The majority of patients treated with biologics in the PsoBioTeq real‐life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events. [ABSTRACT FROM AUTHOR]

Dear Editor, Hidradenitis suppurativa (HS) (also known as suppurative hidradenitis) is a chronic inflammatory disease of skin appendages, commonly associating with other conditions including spondyloarthritis,[[1]] and is a major component of severe cutaneo-articular autoinflammatory syndromes (AIS), called PAPASH [Pyogenic Arthritis, Pyoderma gangrenosum, Acne, Suppurative Hidradenitis], PsAPASH (PSoriatic Arthritis, Pyoderma gangrenosum, Acne, Suppurative Hidradenitis) and PASS (Pyoderma gangrenosum, Acne, Suppurative hidradenitis and ankylosing Spondylitis).[[1], [3]] The clinical phenotypes of these AIS are ill-defined, and unlike PASH (Pyoderma gangrenosum, Acne, Suppurative Hidradenitis) or PAPA (Pyogenic Arthritis, Pyoderma gangrenosum, Acne) syndromes, still lack any biological or genetic marker. Moreover, their optimal therapeutic management remains unclear.[[4]] We report an in-depth description of the clinicopathological, radiological, immunobiological features and treatment outcomes in a series of nine patients diagnosed with PAPASH (n = 2), PsAPASH (n = 1) or PASS (n = 6), in three tertiary care centres between 2014 and 2016. Most patients had high CRP (mean: 68 mg L SP -1 sp ; normal < 5 mg L SP -1 sp ), which correlated with increased serum amyloid A levels in four of six patients analysed, and five showed polyclonal hypergammaglobulinaemia. [Extracted from the article]

Les inhibiteurs de janus kinases (anti-JAK) sont des thérapies ciblées utilisées dans le traitement de pathologies auto-inflammatoires. Ils bloquent la signalisation intracellulaire de plusieurs cytokines, dont l'interleukine 6, impliquée dans la réparation de l'épithélium digestif. Ces anti-JAK pourraient ainsi être associés au risque de perforation gastro-intestinale, un évènement rare mais grave rapporté lors des essais cliniques. L'objectif de cette étude était de comparer le risque de survenue d'une perforation gastro-intestinale pour les patients initiant un anti-JAK par rapport aux patients initiant l'adalimumab, dans une population de patients en vie réelle, atteints de rhumatismes inflammatoires chroniques (RIC). Dans cette étude de cohorte exposés/non exposés, les données provenaient du système national des données de santé (SNDS) français. Le groupe des exposés comportaient les patients ayant initié un anti-JAK (tofacitinib, baricitinib, upadacitinib, filgotinib) et le groupe des non-exposés ceux ayant initié l'adalimumab entre 01/07/2017 et le 31/12/2021. Les patients étaient atteints de RIC : polyarthrite rhumatoïde (PR), rhumatisme psoriasique (RhPso), spondyloarthrite axiale (axSPA). La survenue d'une perforation gastro-intestinale (GI) était identifiée par une hospitalisation au cours du suivi. Les hazard ratio pondérés (HRp) ont été estimés par la méthode de pondération par l'inverse du score de propension afin de prendre en compte les facteurs de confusion : âge, sexe, comorbidités, antécédents de pathologies digestives et délivrances de traitements, notamment les inhibiteurs de la pompe à protons, les traitements des RIC et les anticoagulants et antiagrégants plaquettaires. Des analyses en sous-groupes ont été réalisées, selon les anti-JAK, les RIC, la prise de traitements à risque de perforation GI (corticothérapie, anti-IL6), l'antécédent de pathologies digestives. La cohorte incluait 39 783 patients : 12 349 et 27 434 dans les groupes anti-JAK et adalimumab respectivement (âge moyen 58,2 et 47,3 ans, sexe féminin 76 % et 58 %, PR 85 % et 27 %, RhPso/axSPA 15 % et 73 %). Au cours du suivi, 38 et 42 perforations GI sont survenues dans les groupes anti-JAK et adalimumab. Le risque de perforations GI n'était pas significativement augmenté : HRp 1,2 [IC 95 % 0,8–2,0] (p = 0,40). Les résultats étaient non significatifs dans les analyses en sous-groupes, selon les anti-JAK et le rhumatisme inflammatoire chronique. Les principales limites de cette étude comportent le biais de confusion résiduel en l'absence de certaines informations cliniques dans la base de données médico-administratives et le manque de puissance dans certains sous-groupes. Toutefois, cette étude est une étude de cohorte nationale à partir d'une base de données exhaustive, limitant le biais de sélection. L'identification des évènements lors d'une hospitalisation est une méthode fiable. Cette étude montre que le risque de perforation gastro-intestinale n'est pas significativement augmenté chez les patients initiant un anti-JAK par rapport à l'adalimumab parmi des patients atteints de rhumatismes inflammatoires chroniques. D'autres études demeurent nécessaires, en comparaison aux autres traitements disponibles afin de guider les choix thérapeutiques. [ABSTRACT FROM AUTHOR]