Management of Patients Affected by Moderate-to-Severe Atopic Dermatitis with JAK Inhibitors in Real-World Clinical Practice: An Italian Delphi Consensus.

INTRODUCTION: Several systemic therapies have been approved for the treatment of severe AD. In particular, Janus kinase inhibitors (JAKi), including abrocitinib, baricitinib, and upadacitinib, recently received approval for the treatment of patients with severe AD after being evaluated in several clinical trials. However, a few concerns have been raised regarding their long-term safety and the management of these drugs in real-world clinical practice. In this article we described the results of a Delphi consensus aimed at describing the knowledge on JAKi and focusing, in particular, on providing clinical recommendations for dermatologists in daily practice regarding the use of these drugs. METHODS: Twelve Italian dermatologists reviewed the most recent literature regarding the efficacy and safety profiles of JAKi and proposed 24 statements. RESULTS: Agreement was reached for statements focusing on three main topics: (1) place in therapy of JAKi in patients with moderate-to-severe AD; (2) effectiveness and safety of JAK inhibitors in different phenotypes; (3) different approaches to the management of patients treated with JAKi in clinical practice. The panel proposed several recommendations regarding all the statements. CONCLUSION: Given the wide use of JAKi in clinical practice, it is crucial to establish a specific follow-up for each patient's phenotype in order to achieve the best possible clinical outcome and minimize potential adverse events.

Treatment adherence with diclofenac 3% gel among patients with multiple actinic keratoses: an integrated low-intensity intervention program versus standard-of-care.

BACKGROUND: Diclofenac 3% gel is a widely used topical treatment with proven efficacy in reducing the burden of actinic keratosis (AK); however, clinical benefit might not fully translate in clinical practice as nonadherence is substantial for prolonged treatment regimens. We evaluated the efficacy of an integrated low-intensity intervention program versus standard-of-care on treatment adherence among patients with multiple AK receiving diclofenac in hyaluronic acid gel 3%. METHODS: We designed an open label, randomized, parallel group, interventional, multicenter, longitudinal cohort study including patients with multiple, grade I/II AKs. Visits were scheduled for end of treatment (T4), follow-up 1 (T5) and follow-up 2 (T6) at 90, 180 and 365 days from baseline, respectively. Patients in the intervention group received additional visits at 30 and 60 days from baseline, a brief health education intervention, an enhanced patient-physician communication, a weekly SMS reminder to medication prescriptions. RESULTS: Patients were equally allocated between intervention (intervention group [IG], N.=86) and control group ([CG] N.=86); at baseline, both groups had similar socio-demographic and clinical characteristics. Change scores from baseline showed a slight increment in quality of life related to AK in both groups (CG: ΔT4-T1=-0.079; IG: ΔT4-T1=-0.006; P=0.39) and in quality of physician-patient interaction reported by IG (ΔT3-T2=0.18; P<0.0001). Adherence rate was not statistically different between IG and CG (28.4% vs. 40.7%; P=0.11). Patients reported similar satisfaction for effectiveness, convenience and side effects of treatment. Clinical conditions improved over time and results did not differ between groups; complete clearance rate at 1 year was 18% and 29% for CG and IG, respectively. CONCLUSIONS: Our findings showed no difference in adherence rate between the two groups, suggesting that enhanced follow-up interventions and health care education may not be sufficient drivers to promote adherence among this clinical population. Further studies are needed to explore barriers to adherence with treatments for AKs.

Antibodies against antigens related to scleroderma in a cohort of patients with morphea.

BACKGROUND: Morphea is a rare fibrosing skin disorder. Antinuclear antibodies (ANA), anti-histone and rheumatoid factor are detected in high rate of morphea cases. Scleroderma-related antibodies are usually absent. METHODS: Twenty-one adult patients affected by morphea were examined at the time of enrollment and after 6 months with the assessment of clinical outcome measures of disease severity and damage. Healthy subjects were considered as normal controls while patients affected by systemic sclerosis and other connective tissue diseases (CTD) were considered as pathological controls. Serum samples from all the patients and controls were analyzed for the detection of ANA, anti-nucleosome antibodies, anti-dsDNA and anti-extractable nuclear antigen. Scleroderma-related autoantibodies were searched using a line-blot test. RESULTS: We enrolled 21 patients affected by morphea. ANA were found in 12 patients (57%). Anti-DNA and anti-nucleosome antibodies were negative in all cases. Systemic sclerosis-specific antibodies were found in 11 morphea patients (52.4%) and one healthy control (6.25%). In patients affected by systemic sclerosis (100%) and different CTD (%), scleroderma-related autoantibodies were more frequently detected than in morphea (52.4%). In morphea, anti-TRIM21/Ro52 antibodies were found in 4 patients (36.4%) and resulted to be the most frequently detected antibodies also in two groups of SSC and CTD. CONCLUSIONS: The high prevalence of ANA and the identification of some antagonists of systemic sclerosis-related autoantibodies, confirm the idea of a significant activation of autoimmune system in morphea.

Serum levels of tumor necrosis factor-alpha in patients with psoriasis before, during and after narrow-band UVB phototherapy.

BACKGROUND: Narrow-band UVB (NB-UVB) phototherapy is widely used worldwide for moderate and severe psoriasis, which is a chronic autoimmune inflammatory disease characterized by skin infiltrates of Th1-, Th17- and Th22-cells releasing locally pro-inflammatory cytokines. We investigate serum levels of tumor necrosis factor-α (TNF-α) in psoriatic patients before and after NB-UVB phototherapy. METHODS: Twenty-eight subjects with moderate/severe plaque type psoriasis were enrolled. The severity of skin involvement was rated according to the Psoriasis Area and Severity Index (PASI) score at baseline (T0) and after 4 (T1) and 12 (T2) weeks of NB-UVB treatment. At the same time points, blood samples were taken for evaluation of TNF-α levels. NB-UVB phototherapy was administered twice weekly on non-consecutive days until 12 weeks. RESULTS: The median PASI score significantly decreased from 12.0 at baseline (T0), to 6.9 after 4 weeks (T1, P<0.001) and to 0 after 12 weeks (T2, P<0.001). TNF-a serum levels significantly increased in respect to the baseline after 12 weeks of therapy. CONCLUSIONS: NB-UVB phototherapy is highly effective against psoriasis but, as it increases the TNF-α serum level, it seems unlikely that it can decrease the chronic inflammatory state that is thought to be responsible of the systemic co-morbidities of psoriasis.