Effectiveness of guselkumab in patients with facial and/or genital psoriasis: Interim analysis results at Week 12 from the GULLIVER study.

BACKGROUND: Facial (FP) and genital psoriasis (GP) significantly affect patients' quality of life. Despite the advances in treatments, limited data on efficacy and safety are available on these difficult-to-treat areas. Guselkumab is an interleukin (IL)-23 inhibitor which has been proven effective in treating patients with moderate-to-severe plaque psoriasis. OBJECTIVES: The aim of this interim analysis was to report the efficacy and safety of guselkumab in the treatment of patients with FP and/or GP. MATERIALS AND METHODS: GULLIVER is a 52-week Italian observational study to evaluate the effectiveness and safety of guselkumab in a real-life setting in patients with FP and/or GP. Adult patients with facial and/or genital moderate-to-severe psoriasis (sPGA score ≥ 3) were included. The primary endpoint of this analysis was the percentage of patients achieving a facial or genital sPGA score of 0 (clear) or 1 (almost clear), at Week 12. The change in the score of the facial or genital sPGA components in patients with a score ≥3 for each sPGA component was assessed. PASI score in patients with a baseline PASI above or below 10 was evaluated. RESULTS: Overall, 351 patients were included in the study; 83.3% of FP and 76.5% of GP patients achieved the primary endpoint. Similar response rates were observed for the facial or genital sPGA components in patients with a baseline facial or genital sPGA score ≥3 in each component. Among patients with a baseline PASI score >10, mean PASI score improved from 19.0 (SD 8.3) to 2.2 (SD 4.8). Forty-four AEs were observed in 32 patients; two mild and transient AEs (fatigue and nausea) were considered treatment related. No SAEs were observed. CONCLUSIONS: Guselkumab, showing to be effective and safe in treating FP and GP, may be a valid therapeutic option for patients with psoriasis localized in these difficult-to-treat areas.

Leukocytoclastic vasculitis (cutaneous small-vessel vasculitis) after COVID-19 vaccination.

Vaccinations may induce cutaneous adverse events, due to nonspecific inflammation or immuno-mediated reactions. Several types of vasculitis have been observed. We report on a 71-year-old woman who developed cutaneous small-vessel vasculitis after the second dose of Vaxzevria COVID-19 vaccination, showing leukocytoclastic vasculitis on histopathological examination of a skin biopsy. Cutaneous small-vessel vasculitis is a rare condition which can be idiopathic or secondary to underlying infections, connective tissue disorders, malignancy, and medications. The pathogenesis involves immune complex deposition in small blood vessels, leading to activation of the complement system and recruitment of leukocytes. Exacerbation of small-vessel vasculitis has been reported following the administration of various vaccines, particularly influenza vaccine. It is expected that SARS-CoV-2 vaccine results in the activation of B- and T-cells and antibody formation. We hypothesize that leukocytoclastic vasculitis caused by immune complex deposition within cutaneous small vessels could be a rare side effect of Vaxzevria COVID-19 vaccination.

Evidence for a 'window of opportunity' in hidradenitis suppurativa treated with adalimumab: a retrospective, real-life multicentre cohort study.

BACKGROUND: The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES: To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS: The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS: The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS: Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Brodalumab for the treatment of moderate-to-severe plaque-type psoriasis: a real-life, retrospective 24-week experience.

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.

Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials.

BACKGROUND: Baricitinib, an oral selective Janus kinase 1 and 2 inhibitor, effectively reduced atopic dermatitis (AD) severity in a phase II study with concomitant topical corticosteroids. OBJECTIVES: To evaluate the efficacy and safety of baricitinib in patients with moderate-to-severe AD who had an inadequate response to topical therapies. METHODS: In two independent, multicentre, double-blind, phase III monotherapy trials, BREEZE-AD1 and BREEZE-AD2, adults with moderate-to-severe AD were randomized 2 : 1 : 1 : 1 to once-daily placebo, baricitinib 1 mg, 2 mg, or 4 mg for 16 weeks. RESULTS: At week 16, more patients achieved the primary end point of Validated Investigator's Global Assessment of AD (0, 1) on baricitinib 4 mg and 2 mg compared with placebo in BREEZE-AD1 [N = 624; baricitinib 4 mg 16·8% (P < 0·001), 2 mg 11·4% (P < 0·05), 1 mg 11·8% (P < 0·05), placebo 4·8%], and BREEZE-AD2 [N = 615; baricitinib 4 mg 13·8% (P = 0·001), 2 mg 10·6% (P < 0·05), 1 mg 8·8% (P = 0·085), placebo 4·5%]. Improvement in itch was achieved as early as week 1 for 4 mg and week 2 for 2 mg. Improvements in night-time awakenings, skin pain and quality-of-life measures were observed by week 1 for both 4 mg and 2 mg (P ≤ 0·05, all comparisons). The most common adverse events in patients treated with baricitinib were nasopharyngitis and headache. No cardiovascular events, venous thromboembolism, gastrointestinal perforation, significant haematological changes, or death were observed with any baricitinib dosage. CONCLUSIONS: Baricitinib improved clinical signs and symptoms in patients with moderate-to-severe AD within 16 weeks of treatment and induced rapid reduction of itch. The safety profile remained consistent with prior findings from baricitinib clinical development in AD, with no new safety concerns.

Secukinumab shows high efficacy irrespective of HLA-Cw6 status in patients with moderate-to-severe plaque-type psoriasis: SUPREME study.

BACKGROUND: Understanding genetic variations is important in predicting treatment response and forms the basis for identifying new pharmacogenetic and pharmacogenomic targets for psoriasis treatment. There are limited data on the efficacy of secukinumab in relation to genetic markers. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg in HLA-Cw6-positive (Cw6-POS) and HLA-Cw6-negative (Cw6-NEG) patients with moderate-to-severe chronic plaque-type psoriasis. METHODS: SUPREME was a 24-week, phase IIIb study with an extension period up to 72 weeks. Primary end point was Psoriasis Area Severity Index (PASI) 90 response rate after 16 weeks. RESULTS: In total, 434 patients were recruited: 185 (42·6%) were Cw6-POS and 246 (56·7%) were Cw6-NEG (three not assessed). Mean ± SD age was 45·2 ± 13·2 years (Cw6-POS 42·7 ± 13·1; Cw6-NEG 47·2 ± 12·9). The baseline PASI score was comparable between the cohorts [Cw6-POS 20·7 ± 8·99; Cw6-NEG 21·5 ± 9·99 (P = 0·777)]. At week 16, PASI 90 was achieved in 80·4% of Cw6-POS and 79·7% of Cw6-NEG patients (difference 0·76; 95% confidence interval -7·04 to 8·23). No differences in absolute PASI at week 16 (Cw6-POS 1·36 ± 3·58; Cw6-NEG 1·18 ± 2·29) were observed. The overall safety profile of secukinumab was consistent with that previously reported. No statistically significant difference was detected in the rate of treatment-emergent adverse events [Cw6-POS 42·7%; Cw6-NEG 49·6% (P = 0·295)]. A high PASI 90 response was achieved with secukinumab with a fast reduction in absolute PASI. CONCLUSIONS: Determination of HLA-Cw6 status for secukinumab therapy is unnecessary, as it is highly effective regardless of HLA-Cw6 status.

Clinical similarity of the biosimilar ABP 501 compared with adalimumab after single transition: long-term results from a randomized controlled, double-blind, 52-week, phase III trial in patients with moderate-to-severe plaque psoriasis.

BACKGROUND: ABP 501, a U.S.A. Food and Drug Administration- and European Medicines Agency-approved biosimilar, is highly similar to adalimumab in structure, function and pharmacokinetics. OBJECTIVES: To demonstrate similarity in efficacy, safety and immunogenicity of ABP 501 vs. adalimumab for moderate-to-severe plaque psoriasis (clinical trial: NCT01970488). METHODS: Patients were randomized (1 : 1) to receive ABP 501 or adalimumab 40 mg every 2 weeks for 16 weeks. At week 16, patients with ≥ 50% improvement from baseline in Psoriasis Area and Severity Index (PASI) score were eligible to continue to week 52. Patients receiving ABP 501 continued; adalimumab patients were rerandomized (1 : 1) to continue adalimumab or undergo a single transition to ABP 501. Key efficacy assessments included percentage PASI improvement from baseline, PASI responders and mean change in affected body surface area from baseline to weeks 16, 32 and 50. Safety was monitored via adverse events (AEs) and antidrug antibodies (ADAs) were assessed. RESULTS: A total of 308 patients were rerandomized at week 16 (ABP 501/ABP 501, n = 152; adalimumab/adalimumab, n = 79; adalimumab/ABP 501, n = 77). PASI percentage improvements from baseline were similar across groups for weeks 16, 32 and 50 (range: 85·8-88·2%), with no significant differences detected across groups in percentages of PASI 50, 75, 90 and 100 responders. Changes from baseline in percentage body surface area affected were similar across groups and time points. No new safety signals were detected. AEs were balanced between groups. Percentages of patients with binding and neutralizing ADAs were similar across treatments. CONCLUSIONS: ABP 501 and adalimumab have similar clinical efficacy, safety and immunogenicity profiles over 52 weeks, including after single transition, in this patient population.

Role of the HLA-C*06 allele in clinical response to ustekinumab: evidence from real life in a large cohort of European patients.

BACKGROUND: Little is known about the role of the HLA-C*06 allele in the response to psoriasis treatments. OBJECTIVES: To confirm the role of HLA-C*06 as a pharmacogenetic marker of response to ustekinumab in a new, large cohort of patients involving four European centres. METHODS: In this retrospective multicentre study we reviewed data of 255 patients with psoriasis genotyped for HLA-C*06 who started ustekinumab treatment between January 2014 and March 2015. The severity of psoriasis and response to treatment were evaluated using the Psoriasis Area and Severity Index (PASI) score at baseline and then at follow-up visits on weeks 4, 12, 28, 40 and 52. The primary end point was the proportion of patients achieving ≥ 50% reduction in PASI score (PASI 50) at week 4. A ≥ 75% reduction in PASI score (PASI 75) and a ≥ 90% reduction in the PASI score (PASI 90) after 12 weeks were secondary end points. RESULTS: At week 4, PASI 50 was seen in 71·7% of HLA-C*06-positive (C*06POS) and 35·2% of HLA-C*06-negative (C*06NEG) patients. At week 12, PASI 75 was reached by 69.1% of C*06POS patients and 40·5% of C*06NEG patients. After 52 weeks, PASI 75 was reached by 83.7% of C*06POS patients and 58.8% of C*06NEG patients. CONCLUSIONS: The results from our new, large cohort of European patients treated with ustekinumab in daily clinical practice confirm the role of HLA-C*06 as a potential predictor of response to ustekinumab.

Italian guidelines on the systemic treatments of moderate-to-severe plaque psoriasis.

Psoriasis is a common disease, which has a considerable impact on the healthcare system. Therefore, appropriate use of therapeutic resources is very important. Management of psoriasis in daily clinical practice is highly variable because many issues are still debated and not definitely addressed by the evidence-based medicine. Moreover, the different availability and reimbursability of drugs in each country justifies national guidelines. Expert consensus can provide helpful guidelines for optimizing patient care. A total of 20 dermatologists from different areas of Italy and with large experience in the treatment of psoriasis agreed to participate in the guidelines expert panel who aimed to reach consensus on the factors influencing psoriasis severity, the indications for systemic treatments, the parameters to be considered in the choice of treatment, and the factors to be considered in the choice of biological treatment. The recommendations for the use, screening and monitoring of systemic therapies were based on the 2015 S3 European Dermatology Forum/European Academy of Dermatology and Venereology psoriasis guidelines. Recommendations on the treatment of psoriasis in special patient populations were also agreed. The final document was discussed in a meeting moderated by a facilitator with participation of the entire group and adopting a nominal group technique to reach consensus. A statement was regarded as consented when agreement was achieved by at least 75% of the voting experts according to the Delphi procedure.

Dietary effect of dried bay leaves (Laurus nobilis) meal on some biochemical parameters and on plasma oxidative status in New Zealand white growing rabbit.

Effects of dietary supplementation of Laurus nobilis on selected biochemical parameters and plasma oxidative status in growing rabbits, fed with and without enriched-fat diet, integrated with and without dried bay leaves meal, were investigated. In the test, 120 New Zealand white 35-day-old male rabbits were divided into four homogeneous groups of 30 animals each. A negative control group (CON) received a feed that met the animal nutrient requirement; a positive control group (CG) receiving a supplement of 2.5% pig fat in feed; an experimental group (GA) feeding an integration of 2.5% pig fat and 1 g/kg of dried bay leaves (Laurus nobilis) in feed; an experimental group (CA) with dried bay leaves at the rate of 1 g/kg in feed. The dietary integration with dried bay leaves meal have resulted in a significant decrease in the blood lipid profile, glycemic profile and liver enzymes, with reduced levels of ALT and AST, glucose, total cholesterol, LDL cholesterol, triglycerides and increased HDL cholesterol. Plasma oxidative status markers have statistically improved with an increase in blood total phenols, SOD, ORAC, the FRAP and lipo-vitamin concentration, together with a significant reduction in ROMs and the MDA values. The results of present research underline that the dietary treatment with bay leaves meal, in the extend of 1 g/kg feed, confirms the lowering cholesterol activity and the epato-protective and ipo-glycemic effect in enrich-fat diet, controlling the oxidative status of plasma markers.