ABSTRACT
BACKGROUND: Brodalumab was efficacious and safe in moderate-to-severe plaque-type psoriasis in the AMAGINE trials; published reports under real-life conditions are limited. OBJECTIVES: To evaluate the effectiveness and safety of brodalumab in patients with moderate-to-severe plaque-type psoriasis in a real-world setting. METHODS: This observational, retrospective study enrolled adult patients (≥18 years) with moderate-to-severe plaque-type psoriasis who underwent 24 weeks of treatment with brodalumab at 17 Italian dermatological centres. Baseline data included demographics, comorbidities, age of onset and duration of psoriasis and previous treatments. Psoriasis Area and Severity Index (PASI), Physician Global Assessment (PGA), static PGA of Genitalia, Dermatology Life Quality Index and patient satisfaction were assessed at weeks 0, 4, 12 and 24; adverse events were recorded. RESULTS: Seventy-eight patients (mean age 47.9 years, 71.8% male, average disease duration 16.8 years) were enrolled. A rapid and significant reduction in mean PASI score was observed after 4 weeks of treatment, decreasing further at weeks 12 and 24 (all P < 0.0001 vs. baseline). A higher number of cardiometabolic comorbidities and previous therapies were negatively associated with the achievement of PASI 90 at all assessments. Brodalumab was effective in bio-experienced patients, including those who had failed on anti-interleukin (IL)-17 therapies. Quality of life and patient satisfaction increased significantly during treatment (P < 0.0001 and P < 0.01 vs. baseline, respectively). Treatment was interrupted in 9 (11.5%) patients due to adverse events (n = 4), lack of efficacy (n = 3), lost to follow-up (n = 1) and surgical procedure (n = 1). CONCLUSIONS: Brodalumab is effective and safe in the treatment of moderate-to-severe psoriasis in a real-world setting, including in patients with failure to anti-IL17 therapies.
Subject(s)
Psoriasis , Quality of Life , Adult , Antibodies, Monoclonal , Antibodies, Monoclonal, Humanized , Female , Humans , Male , Middle Aged , Psoriasis/drug therapy , Retrospective Studies , Severity of Illness Index , Treatment OutcomeABSTRACT
Annual dermatologic examination is required in all transplant recipients because of the high risk of skin cancers. Nevertheless, if the transplant recipient is merely advised to have a dermatologic consultation, the adherence usually appears to be poor. We analyzed our population of liver transplant recipients in 2 periods: in 2014 (group 1) and in 2016 (group 2), when we had organized the presence of a dermatologist at scheduled intervals to annually examine the entire liver transplant population we actively follow-up. The adherence to dermatologic screening during period 1 was significantly lower (50/179; 28% of patients) than during period 2 (198/200; 99% of patients) (P < .0001). In group 1 and 2, respectively, we found cutaneous lesions in 3 of 50 (6%) and in 13 of 198 (7%) examined patients and in 3 of 179 (1.7%) and in 13 of 200 (6.5%) of the whole groups of patients in follow-up (P = .02). The type of neoplastic lesions found at dermatologic visits were similar in group 1 (1 squamous cell carcinoma, 1 basal cell carcinoma) and group 2 (2 squamous cell carcinoma, 3 basal cell carcinoma) (P = .45), but with this intensive protocol of surveillance we discovered more preneoplastic lesions (1 leukoplakia in group 1 vs 7 actinic keratosis and 1 dysplastic nevus in group 2; P = .03). These results suggest that the planned presence of a dermatologist is mandatory among the many aspects of a well-organized transplant follow-up team.
Subject(s)
Liver Transplantation/adverse effects , Mass Screening/methods , Patient Compliance , Skin Neoplasms/diagnosis , Skin Neoplasms/etiology , Transplant Recipients , Adult , Female , Follow-Up Studies , Humans , Male , Middle AgedABSTRACT
The p63 gene belongs to the p53 gene family and encodes for sequence-specific transcription factors. p63 has been characterized primarily in the context of epidermis where is implicated in the establishment of keratinocyte cell fate and in maintenance of epithelial self-renewal. DeltaNp63 isoform has been showed to be involved in several kinds of human tumors of epidermal origin, even nonmalignant, for the neoplastic and proliferative potential. Here, we report the differential expression and the cellular localization of the DeltaNp63 isoform in fibroblasts isolated from human keloids and hypertrophic scars compared to normal skin. Differently from hypertrophic scar, our results show that DeltaNp63 has a nuclear localization and is overexpressed only in keloid fibroblasts, suggesting an essential role of DeltaNp63 in vivo in human keloids. Consistent with our results, we hypothesize that DeltaNp63 overexpression may be oncogenic because of its ability to block the activity of p53 since p53 is underexpressed in fibroblasts from keloids.
Subject(s)
Cicatrix, Hypertrophic/metabolism , Fibroblasts/metabolism , Keloid/metabolism , Membrane Proteins/metabolism , Tumor Suppressor Protein p53/metabolism , Blotting, Western , Cells, Cultured , Cicatrix, Hypertrophic/pathology , Fibroblasts/cytology , Fluoroimmunoassay , Humans , Keloid/pathology , Membrane Proteins/genetics , Protein Isoforms/genetics , Protein Isoforms/metabolism , RNA/biosynthesis , Sequence Deletion/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
Keloids are benign skin tumors that develop following wounding. A cDNA product from human keloid specimens was identified using the differential display technique. The full-length cDNA was cloned by RT-PCR using human keloid mRNA as template. The predicted product of the cDNA was found to be 99% identical to the DeltaN-p63 gamma isotype of p63, a transcription factor that belongs to the family that includes the structurally related tumor suppressor p53 and p73. The DeltaN-p63 isotype lacks the acidic N terminal region corresponding to the transactivation domain of p53. Since this can potentially block p53-mediated target gene transactivation, it may serve as a dominant-negative isoform. Real-Time RT-PCR analysis of RNAs from normal skin tissue and keloids showed that the DeltaN-p63 isotype is specifically expressed in keloids, but is virtually undetectable in normal skin. Immunostaining of p63 in normal skin revealed that only basal cells of the epithelium expressed the protein, while in keloid tissues the antigen was detected in the nuclei of cells scattered through all layers of the epithelium and in fibroblast-like cells in the dermis. These results may indicate that aberrant p63 expression plays a role not only in malignant tumors but also in benign skin diseases that show hyperproliferation of epidermal cells in vivo. Moreover, this isoform of p63 could serve as a specific molecular marker for this human disease.
