Real-world data from a single Greek centre on the use of secukinumab in plaque psoriasis: effectiveness, safety, drug survival, and identification of patients that sustain optimal response.

BACKGROUND: Few studies have investigated the long-term outcomes of secukinumab in real-life psoriasis treatment where diverse patient profiles require a personalized approach. OBJECTIVES: To determine long-term performance of secukinumab in moderate-to-severe plaque psoriasis, and identify potential clinical factors predictive of sustained optimal response under real-world conditions. METHODS: In this 78-week, single-centre, retrospective study, effectiveness, safety and drug survival of secukinumab were evaluated. Effectiveness data are reported as observed. Co-primary endpoints were absolute Psoriasis Area and Severity Index (PASI) ≤3 at week 4, 16, 52, 78, and clinical predictors of PASI ≤3 and PASI100 responses at week 52 and 78. RESULTS: A total of 85 patients (75.3% male; mean age 48.6 years) were included. Absolute PASI ≤3 was achieved in 73% and 83% of patients at week 52 and 78, respectively. PASI 75/90/100 responses at week 52 (71.6%, 50.8%, and 40.3%, respectively) were sustained at week 78 (73.6%, 64.2%, and 45.3%, respectively). Median absolute PASI remained low at week 52/78 (0.9/0.6, respectively), while mean absolute PGA also sustained low (0-1) values after 16-78 weeks. Investigator's Global Assessment 0/1 response rate was maintained by week 52/78 (72/83%, respectively). The drug survival rate of secukinumab at week 78 was 79.1%. Treatment was discontinued in 17.9% of patients after an average of 41.7 weeks, mainly due to loss of effectiveness (10.4%). A total of 27% experienced adverse events, without critical safety concerns. Based on multivariate analysis, advanced body mass index (BMI) and presence of ≥3 comorbidities decreased the chance of achieving PASI ≤3 at week 78 [OR (95% CI) 0.78 (0.64-0.97); P = 0.024, and OR (95% CI) 0.045 (0.002-0.83); P = 0.037, respectively]. CONCLUSIONS: Secukinumab showed consistently high effectiveness in this real-life cohort, with an acceptable safety profile. Over time, persistence of PASI ≤3 response appears to be lower in patients with high BMI or multiple comorbidities.

Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor.

Recent studies demonstrate roles for osteoprotegerin (OPG) in both skeletal and extra-skeletal tissues. Although its role in preventing osteoclast (OC) formation and activity is well documented, emerging evidence suggests a role of OPG in endothelial cell survival and the prevention of arterial calcification. In this communication, we show that vascular endothelial cells in situ, and human umbilical vein endothelial cells (HUVEC) in vitro, express abundant OPG. In HUVEC, OPG co-localizes with P-selectin and von Willebrand factor (vWF), within the Weibel-Palade bodies (WPB). Treatment of HUVEC with the pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha and IL-1beta, resulted in mobilization from the WPBs and subsequent secretion of OPG protein into the culture supernatant. Furthermore, TNF-alpha treatment of HUVEC resulted in a sustained increase in OPG mRNA levels and protein secretion over the 24-h treatment period. Reciprocal immunoprecipitation experiments revealed that while not associated with P-Selectin, OPG is physically complexed with vWF both within the WPB and following secretion from endothelial cells. Interestingly, this association was also identified in human peripheral blood plasma. In addition to its interaction with vWF, we show that OPG also binds with high avidity to the vWF reductase, thrombospondin (TSP-1), raising the intriguing possibility that OPG may provide a link between TSP-1 and vWF. In summary, the intracellular localization of OPG in HUVEC, in association with vWF, together with its rapid and sustained secretory response to inflammatory stimuli, strongly support a modulatory role in vascular injury, inflammation and hemostasis.

Actinic granuloma successfully treated with acitretin.

Actinic granuloma is a rare skin disorder that develops in an area of actinic elastosis. The pathogenesis of the disease is obscure but the most accepted hypothesis implicates the solar radiation as the triggering factor. Typically the disease presents in middle-aged individuals with significant past sun-exposure and involves mainly the sun-exposed skin. It manifests as asymptomatic annular patches with elevated borders and central atrophy and shows little tendency to regression. Several treatments have been tried with variable success. We present a 74-year-old male who consulted our department for annular atrophic plaques involving his forehead and nose, present for 8 months and insidiously spreading but otherwise asymptomatic. A biopsy confirmed the clinical suspicion of actinic granuloma and excluded other possibilities. Our patient was commenced on acitretin 25 mg/day and showed a remarkable improvement within a year; the lesions stopped spreading and almost disappeared.

Impetigo herpetiformis during the puerperium.

We report on a 29-year-old primigravida who developed impetigo herpetiformis 1 day after delivery. To our knowledge, this patient is the second reported case of impetigo herpetiformis presenting during the puerperium. The patient responded quickly to systemic administration of methotrexate and prednisolone.

Nuchal nevus flammeus as a skin marker of prognosis in alopecia areata.

In this work, the incidence of nuchal nevus flammeus was studied in 205 patients suffering from various forms of alopecia areata, as well as in a group of 555 volunteers without alopecia areata examined in our outpatient clinic. The incidence of nuchal nevus flammeus in the totalis-universalis form of alopecia areata was 58.2% (examined patients, n = 79), in ophiasis-extensive forms 22.8% (examined patients, n = 70) and in simple forms of alopecia areata 3.6% (examined patients, n = 56). In the group of 555 volunteers without alopecia areata the incidence of nuchal nevus flammeus was 4.5%. Our results show that nuchal nevus flammeus could be a valuable skin marker indicating a more severe course of alopecia areata.