Real-life effectiveness and safety of baricitinib in patients with severe alopecia areata: A 24-week Italian study.

BACKGROUND: Alopecia areata is an autoimmune condition characterized by rapid hair loss in the scalp, eyebrows and eyelashes, for which treatments are limited. Baricitinib, an oral inhibitor of Janus kinases 1 and 2, has been recently approved to treat alopecia areata. MATERIALS AND METHODS: We conducted a retrospective study involving 23 medical centres across Italy, enrolling patients affected by severe alopecia areata (SALT >50), for more than 6 months. Clinical and trichoscopic assessment was performed at each visit and impact on quality of life, anxiety and depression were evaluated using the Skindex-16 and the Hospital Anxiety and Depression Scale (HADS), respectively. RESULTS: A total of 118 patients were enrolled, with a mean age of 39 years and a mean SALT >95. The mean value of the SALT score decreased from an average of 96.6 (±8.23 sd) to 48 (±35.2 sd) after 24 weeks of treatment and 42.3% of patients achieved a SALT 30, 31.3% a SALT 20 and 20.3% a SALT 10 by Week 24. Trichoscopic signs showed fewer yellow dots and black dots significantly earlier than hair regrowth. Adverse events during the treatment period (mild laboratory test abnormalities) were reported in 12.7% patients. No drop-out were registered. CONCLUSION: Data on the effectiveness and safety of baricitinib are promising and support the use of this drug in severe forms of AA, also in the early stages. We also suggest performing trichoscopy in order to reveal early response to therapy.

Current treatment goals are achieved by the majority of patients with atopic dermatitis treated with tralokinumab: results from a multicentric, multinational, retrospective, cohort study.

BACKGROUND: Tralokinumab is a human monoclonal antibody targeting interleukin-13 that is approved for the treatment of moderate-severe atopic dermatitis. Studies analyzing the efficacy and safety of tralokinumab in a real-world setting are scarce. RESEARCH DESIGN AND METHODS: A European, multicentric, real-world, retrospective cohort study was defined to assess the effectiveness and safeness profile of tralokinumab, investigating the achievement of pre-specified treatment goals; and to detect potential differences in terms of effectiveness and safeness across some selected patient subcohorts. RESULTS: A total of 194 adult patients were included in this study. A significant improvement in physician-assessed disease severity was detected at each follow-up visit as compared with baseline and similar trend was observed for patient-reported outcomes and quality of life. No meaningful difference in effectiveness was found when considering patient age (<65 versus ≥65 years), neither dissecting patient cohort in dupilumab-naive vs dupilumab-treated subjects. Among tralokinumab-treated patients, 88% achieved at least one currently identified real-world therapeutic goal at week 16. CONCLUSIONS: This retrospective multicenter study confirmed the effectiveness and safeness of tralokinumab throughout 32 weeks of observation, showing the achievement of therapeutic goals identified in both trial and real-world settings in a large proportion of tralokinumab-treated patients.

The Combination of Dupilumab with Other Monoclonal Antibodies.

INTRODUCTION: Dupilumab is an interleukin-4 (IL-4) receptor alpha antagonist indicated for the treatment of moderate-to-severe atopic dermatitis (AD), which could be associated with atopic and non-atopic comorbidities for which concomitant administration of targeted pharmacotherapy including monoclonal antibodies could be required. However, the safety of combining dupilumab with other monoclonal antibodies for different therapeutic indication may be debated. METHODS: We conducted an extensive search in MEDLINE via PubMed for original articles published from January 1, 2017 to October 22, 2022, reporting clinical cases in which dupilumab has been associated with other monoclonal antibodies. RESULTS: Four small case series were identified reporting data on a total of 16 patients. To them, we have added other patients (n = 8) derived from our clinical practice, achieving a total of 24 cases followed for a period of 2-22 months. Patients were receiving dupilumab mainly because of AD (except one patient for bullous pemphigoid and one for asthma) and other monoclonal antibodies for psoriasis treated with guselkumab (n = 7) and secukinumab (n = 1), asthma with omalizumab or benralizumab (n = 3), Crohn's disease with adalimumab (n = 3), chronic spontaneous urticaria with omalizumab (n = 3), primary familial hypercholesterolemia with evolocumab (n = 2), hidradenitis suppurativa with adalimumab (n = 1), psoriatic arthritis with secukinumab (n = 1), rheumatoid arthritis with abatacept (n = 1), ankylosing spondylitis with secukinumab (n = 1) and colorectal carcinoma with cetuximab (n = 1). No adverse events related to the combination of the two monoclonal antibodies were reported except for a mild injection site reaction (n = 1) and arthralgia, which resolved spontaneously within a few weeks (n = 1). CONCLUSIONS: Because the evidence is modest, the question remains open as to whether dupilumab can be safely combined with other monoclonal antibodies. Dupilumab does not exert immunosuppressive effects and does not impair the activity of cytochrome P450 isozymes.

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

Risk of non-alcoholic fatty liver disease in patients with chronic plaque psoriasis: an updated systematic review and meta-analysis of observational studies.

PURPOSE: Chronic plaque psoriasis is associated with the presence of non-alcoholic fatty liver disease (NAFLD), but the magnitude of this association remains currently uncertain. We aimed to investigate the magnitude of the association between psoriasis and the risk of prevalent and incident NAFLD, and to assess whether psoriasis severity and/or psoriatic arthritis are associated with a greater risk of NAFLD. METHODS: A systematic review and meta-analysis of observational studies evaluating the association between psoriasis and NAFLD, as diagnosed by imaging or International Classification of Diseases codes was performed. Literature search on PubMed, Scopus and Web of Science on May 3, 2021 was undertaken. Studies using liver biopsy were not available. For the meta-analysis, the random-effects modelling was adopted. RESULTS: We identified 15 observational (case-control and cross-sectional) studies for a total of 249,933 patients with psoriasis (49% with NAFLD) and 1,491,402 controls (36% with NAFLD). Psoriasis was associated with prevalent NAFLD (n = 11 studies; pooled random-effects odds ratio [OR] 1.96, 95% CI 1.70-2.26; I2 = 97%, p < 0.01). Psoriatic patients with NAFLD had a higher mean psoriasis area and severity index (PASI) than their counterparts without NAFLD (n = 8 studies, pooled weighted mean difference: 3.93, 95% CI 2.01-5.84; I2 = 88%, p < 0.01). The risk of NAFLD was marginally higher in patients with psoriatic arthritis than in those with psoriasis alone (n = 5 studies, pooled random-effects OR 1.83, 95% CI 0.98-3.43; I2 = 64%, p = 0.03). Sensitivity analyses did not alter these findings. Funnel plot did not show any significant publication bias. A major limitation of the study was the high degree of heterogeneity across studies. CONCLUSION: Psoriasis is associated with prevalent NAFLD and this risk parallels the severity of psoriasis.

Acquired perforating dermatoses show increased levels of cutaneous advanced glycation end-products.

BACKGROUND: Acquired perforating dermatoses (APDs) are characterized by transepidermal elimination of skin materials. Altered glycation of dermal components may be involved in pathogenesis. AIM: To assess whether patients affected by APDs have increased levels of cutaneous advanced glycation end-products (AGEs). METHODS: A cross-sectional controlled study involving a total of 109 patients was conducted, enrolling 29 patients consecutively diagnosed with primary APDs [reactive perforating collagenosis (RPC), elastosis perforans serpiginosa (EPS), perforating folliculitis (PF) and Kyrle disease (KD)], 40 age- and sex-matched healthy controls (HCs) and 40 patients with mild atopic dermatitis (AD). The levels of cutaneous AGEs were measured using a validated fluorescence technique. RESULTS: The median skin autofluorescence value in patients with APDs was significantly higher [2.7 arbitrary units (AU), interquartile range (IQR) 1.9-3.9 AU] compared with HCs (1.8 AU, IQR 1.6-2.3 AU; P < 0.001) and patients with AD (2.1 AU, IQR 1.9-2.3 AU; P = 0.01). Median values were 3.5 AU (IQR 2.7-4.6 AU) for RPC, 1.83.5 AU (1.4-2.4 AU) for EPS, 3.1 AU (2.4-4.4 AU) for PF and 2.6 AU (2.3-3.1 AU) for KD. CONCLUSIONS: Our results may suggest a possible physiopathological role of AGEs in the transepidermal elimination mechanisms involved in certain APDs.