Clinical Presentation and Prognostic Features in Patients with Immunotherapy-Induced Vitiligo-like Depigmentation: A Monocentric Prospective Observational Study.

Vitiligo-like depigmentation (VLD) is an immune-related adverse event (irAE) of checkpoint-inhibitor (CPI) treatment, which has previously been associated with a favourable outcome. The aim of this study was to explore clinical, biological and prognostic features of melanoma patients with VLD under CPI-treatment and to explore whether they exhibit a characteristic immune response profile in peripheral blood. Melanoma patients developing VLD under CPI were included in a prospective observational single-center cohort study. We collected and analysed clinical parameters, photographs and serum from 28 VLD patients. They received pembrolizumab (36%), nivolumab (11%), ipilimumab/nivolumab (32%) or clinical trial medications (21%). We performed a high-throughput proteomics assay (Olink), in which we identified a distinct proteomic signature in VLD patients in comparison to non-VLD CPI patients. Our clinical assessments revealed that VLD lesions had a predominantly symmetrical distribution pattern, with mostly smaller "freckle-like" macules and a preferential distribution in UV-exposed areas. Patients with previous targeted therapy showed a significantly longer time lapse between CPI initiation and VLD onset compared to non-pre-treated patients (12.5 vs. 6.25 months). Therapy responders exhibited a distinct proteomic profile when compared with non-responders in VLD such as upregulation of EDAR and downregulation of LAG3. ITGA11 was elevated in the VLD-group when compared to non-VLD-CPI-treated melanoma patients. Our findings demonstrate that on a proteomic level, VLD is characterized by a distinct immune signature when compared to CPI-treated patients without VLD and that therapy responsiveness is reflected by a characteristic immune profile. The pathomechanisms underlying these findings and how they could relate to the antitumoral response in melanoma remain to be elucidated.

Effectiveness of methotrexate in moderate to severe psoriasis patients: real-world registry data from the Swiss Dermatology Network for Targeted Therapies (SDNTT).

Methotrexate (MTX) is a frequently used anti-psoriatic drug that is commonly recommended in international psoriasis guidelines. It is effective in treating skin lesions, nail changes and psoriatic arthritis. In 2017 a prospective, multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, commonly known as the METOP trial, was published assessing the effectiveness and safety of subcutaneous administration of methotrexate. Because trial data do not always relate to real-life data with unselected patient populations, we wanted to determine whether the data obtained in the METOP-trial correspond to real-life registry data from our Swiss Dermatology Network for Targeted Therapies (SDNTT). Data of 449 patients with moderate to severe psoriasis who participated in the SDNTT registry between 2011 and 1st of July 2017 were analyzed. Only patients receiving methotrexate s.c. were included. 66 patients under MTX were included into this study. Baseline PASI was 6.3 ± 3.8 (SDNTT) compared to 15.9 ± 5.9 in the METOP trial. In our cohort, only 18% of all patients reached PASI 75 after 12 weeks, 6% showed a complete remission (PASI 100) compared to 41% and 4% in the METOP trial after 16 weeks. 22.7% of all patients showed increased liver enzymes in either study and nausea was seen in 15% (SDNTT) versus 22% (METOP) of patients. No severe adverse events were observed in our cohort. Compared to the METOP-trial, the response rates seen our real-world cohort were distinctly lower.

Successful intra-class switching among IL-17 antagonists: a multicentre, multinational, retrospective study.

IL-17 blockers are among the newer anti-psoriatic treatment options and little is known about the interclass switching. We have thus initiated a multi-center, multi-national, retrospective study to assess the treatment response of patients who were switched from one IL-17 blocker to another. Analysis consisted of data from patients with moderate-to-severe psoriasis who did not respond satisfactorily to one of the available IL-17 blockers (secukinumab, ixekizumab, brodalumab) and were subsequently switched to another drug of this class. After 12 weeks of treatment, patients' PASIs were evaluated. Treatment success was defined as reaching PASI 75 after 12 weeks. Topical treatment was allowed and used in all patients. 26 patients were included (13 male, 13 female) and 29 switches were evaluated. Overall, 29 switches in 21 patients were evaluated. 18 patients changed their therapy from secukinumab to ixekizumab, or in 7 cases to brodalumab. Brodalumab was used in 3 cases after failure of treatment with ixekizumab. Only in one case, non-response of brodalumab resulted in a therapy switch to secukinumab. In 15 (52%) cases, PASI 75 was reached. In 6 (20%) patients, the switch led to a PASI 50 response. No success of treatment was seen among 8 (28%) participants. When patients fail to respond or do not tolerate an IL-17 blocker, switching to another anti-IL-17A/RA is a promising viable option. Larger studies are needed to confirm our results.