Ustekinumab to guselkumab transitions: A series of 54 patients emulating the navigate trial in real life.

NAVIGATE clinical trial demonstrated a higher rate of Psoriasis Assesment Severity Index (PASI)90 response in patients treated with guselkumab when compared to ustekinumab and an improved response in those who switched from ustekinumab to guselkumab due to partial response. The objective of the study is to describe ustekinumab to guselkumab switching in clinical practice. Observational, multicentric, descriptive study including 54 psoriasis patients who switched to guselkumab after treatment with ustekinumab from March 2019 to February 2021. Mean basal PASI with ustekinumab (16.7) was higher than with guselkumab (7.2). Up to 49.01% of patients were able to reach PASI90 with ustekinumab and up to 21.56% had a less frequent dosage regime vs. summary of product characteristics. Main reason to start guselkumab was a loss of ustekinumab cutaneous or articular response (82.36%) but up to 17.64% were switched in order to increase dosage regime efficiency. Six months after starting guselkumab, the absolute PASI was lower than 2 in 72% of patients and 38.5% of them were treated with a reduced dosage regime. Guselkumab doses used by our cohort were 19.5% lower than the expected according to the summary of product characteristics. No adverse events reported. There is no real-world evidence regarding patients who switched from ustekinumab to guselkumab. A short paragraph in the article by Fougerousse et al, reported 63 patients with a mean basal PASI of 5.3 and similar efficacy rate at week 16 to NAVIGATE. Our study adds practical information regarding efficacy, safety and efficiency through dose optimization in a real-world cohort.

A retrospective, observational multicenter study of 141 patients treated with ustekinumab 90 mg.

A change of pricing policy in Spain have made both doses of ustekinumab (UST), 45 and 90 mg, recently available at the same price. Our primary objective was to evaluate effectiveness of UST 90 mg at 52 and 104 weeks in psoriasis patients in clinical practice; secondary objectives were to study the reasons for using this dose and to delineate its efficacy in patients previously treated with anti-IL17 drugs. 91.8% of the 141 patients treated with UST 90 started with 45 mg and later increased their dose. Clinicians changed dose due to weight over 100 kg in 20.6% of the cases and all the other dose changes were off-label to improve partial cutaneous or articular response or due to a previous failure of anti-IL17 therapy. After 12 months of UST 90 treatment, absolute PASI was lower than 3 in 87.5% of patients and lower than 1 in 72.2%. Efficacy data were even better for patients with body mass index (BMI) <25. UST 90 can be effective in patients with previous use of anti-IL17 drugs. It appears to be an alternative treatment option not only for high BMI patients, but also to increase the cutaneous or articular efficacy of the drug in patients with normal BMI.

High-Frequency Color Doppler Sonography of Bullous Pemphigoid: Correlation With Histologic Findings.

Bullous pemphigoid is the most frequent autoimmune-mediated blistering skin disease, belonging to the group of subepidermal bullae. We performed high-frequency color Doppler sonography in 3 cases of bullous pemphigoid, in bullous and adjacent non-bullous skin, which showed homogeneous sonographic findings. Subepidermal cystic structures with dermal hypoechogenicity were observed in bullous skin. In nonbullous skin, the dermis showed hypoechogenicity compared to normal skin. Color Doppler signals were increased in both areas. These findings correlate histologically with subepidermal bullae and dermal inflammatory infiltrates.

PLCG1 mutations in cutaneous T-cell lymphomas.

Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of primary cutaneous T-cell lymphoproliferative processes, mainly composed of mycosis fungoides and Sézary syndrome, the aggressive forms of which lack an effective treatment. The molecular pathogenesis of CTCL is largely unknown, although neoplastic cells show increased signaling from T-cell receptors (TCRs). DNAs from 11 patients with CTCL, both normal and tumoral, were target-enriched and sequenced by massive parallel sequencing for a selection of 524 TCR-signaling-related genes. Identified variants were validated by capillary sequencing. Multiple mutations were found that affected several signaling pathways, such as TCRs, nuclear factor κB, or Janus kinase/signal transducer and activator of transcription, but PLCG1 was found to be mutated in 3 samples, 2 of which featured a redundant mutation (c.1034T>C, S345F) in exon 11 that affects the PLCx protein catalytic domain. This mutation was further analyzed by quantitative polymerase chain reaction genotyping in a new cohort of 42 patients with CTCL, where it was found in 19% of samples. Immunohistochemical analysis for nuclear factor of activated T cells (NFAT) showed that PLCG1-mutated cases exhibited strong NFAT nuclear immunostaining. Functional studies demonstrated that PLCG1 mutants elicited increased downstream signaling toward NFAT activation, and inhibition of this pathway resulted in reduced CTCL cell proliferation and cell viability. Thus, increased proliferative and survival mechanisms in CTCL may partially depend on the acquisition of somatic mutations in PLCG1 and other genes that are essential for normal T-cell differentiation.