A single-centre, observational, retrospective, real-life study evaluating adalimumab biosimilar ABP 501 in the treatment of plaque-type psoriasis and psoriatic arthritis in originator-naïve patients and in patients undergoing non-medical switch from originator.

BACKGROUND: ABP 501 is a biosimilar to the anti-tumor necrosis factor-alfa monoclonal antibody adalimumab and despite its effectiveness and safety in the treatment of psoriasis was demonstrated in randomized clinical trials, no real-life data are available, in particular in patients undergoing non-medical switch from originator to biosimilar. METHODS: We retrospectively searched our clinical records for all patients receiving ABP 501 between March 10, 2019 and September 7, 2019 at our Department. Therefore, we identified 94 patients, 46 patients underwent non-medical switch from adalimumab reference product to ABP 501. RESULTS: In originator-naïve patients, mean PASI significantly improved from baseline to week 24 (p < .0001) in both Pso and PsA cohorts. In these patients, mean DAS-28 ESR improved with no significant differences from baseline. In patients undergoing non-medical switch from adalimumab reference product to ABP 501, no significant difference in PASI or DAS-28 ESR were observed from week 16 before switch to week 24 after switch. CONCLUSIONS: AB- 501 is an effective treatment for plaque-type psoriasis and psoriatic arthritis regardless if patients are originator-naïve or if they were switched from the reference product.

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.

Certolizumab for the treatment of psoriasis and psoriatic arthritis: a real-world multicentre Italian study.

BACKGROUND: Certolizumab, a pegylated tumour necrosis factor-α inhibitor, reduced disease activity in randomized trials of patients with psoriasis and psoriatic arthritis. Real-life data are missing. OBJECTIVE: To confirm the effectiveness and safety of certolizumab in patients with psoriasis and psoriatic arthritis in routine clinical practice. METHODS: In this retrospective study involving 11 Italian sites, patients with psoriasis and psoriatic arthritis received subcutaneous certolizumab (400 mg loading dose at 0, 2 and 4 weeks, followed by 200 mg every 2 weeks) for up to 52 weeks. Primary outcomes included mean change from baseline in Psoriasis Area and Severity Index (PASI) and modified Nail Psoriasis Severity Index (mNAPSI) scores, and the proportion of patients achieving a 75%, 90% or 100% reduction in PASI score. Other endpoints included Disease Activity Score computed on 44 joints correlated with the erythrocyte sedimentation rate during the first hour (DAS44-ESR), Tender Joint Count (TJC), Swollen Joint Count (SJC), pain [visual analogue scale (VAS) score], inflammatory markers and quality of life (QOL). RESULTS: In the study were enrolled 153 patients (mean age: 55 years). Certolizumab reduced the mean PASI score from baseline by 4.45, 6.30 and 7.58 at weeks 12, 24 and 52, respectively (P < 0.001 for all). At weeks 24 and 52, 69.6% and 83.3% of patients had a PASI score ≤3. DAS44-ESR, TJC, SJC and mNAPSI scores, and pain VAS were also all significantly improved from baseline at each time point. C-reactive protein levels decreased during treatment, being significant at week 24. On multivariate analysis, psoriasis duration, baseline PASI, mNAPSI and pain VAS scores were found to be predictive of the improvement in PASI score at week 12. CONCLUSION: Certolizumab displayed also in the real-life encouraging results in both psoriasis and psoriatic arthritis patients.

Adalimumab in children and adolescents with severe plaque psoriasis: a safety evaluation.

Introduction: Psoriasis is a chronic inflammatory systemic disease that affects 2% of the population and is associated with an important physical and physiological burden. About 0.5-2% of psoriatic cases onset during the pediatric age range, and often it's not diagnosed until adulthood. Adalimumab is an antitumor necrosis factor monoclonal antibody approved for use in children in 2008 and now it was used in several diseases in rheumatology, gastroenterology, and in dermatology.Areas covered: The purpose of this article was to summarize what has been described in the literature so far, about safety in the use of adalimumab in pediatric psoriasis. The presented data was extrapolated from a literature review from PubMed searches (using words 'pediatric psoriasis,' 'adalimumab children,' 'adalimumab safety,' 'pediatric psoriasis treatment,' 'adalimumab clinical trial'), treatment guidelines, and reports from European and United States regulatory agencies.Expert opinion: Actually there are some biologic agents for the treatment of pediatric psoriasis, but the lack of safety data from controlled trials is evident. The safety data on the use of adalimumab in pediatric psoriasis was taken from long-term studies in the adult population. These studies confirm the data on the safety of the drug as it is also supported by several works on real-life.

Robot-assisted radical cystectomy with totally intracorporeal urinary diversion: surgical and early functional outcomes through the learning curve in a single high-volume center.

The aim of the study is to report surgical and early functional outcomes of first 100 patients undergoing robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD) in a single center. The main surgeon (A.P.) attended a modular training program at a referring center mentored by a worldwide-recognized robotic surgeon (P.W.). The program consisted of: (a) 10 h of theoretical lessons; (b) video session (c) step-by-step in vivo modular training. Each procedure was performed as taught, without any technique variation. Demographics, intra-operative data and post-operative complications, along with early functional outcomes, were recorded for each patient. We retrospectively evaluated the first consecutive 100 patients submitted to RARC with totally ICUD from July 2015 to December 2018. Median age at surgery was 69 years (IQR 60-74). 52 (52%), 32 (32%), and 17 (17%) patients received orthotopic neobladder, ileal conduit and uretero-cutaneostomy, respectively. Median operative time was 410 min. A median number of lymph nodes retrieved were 27 and median estimated blood loss was 240 mL with median hospitalization time of 7 days. All procedures were completed successfully without open conversion. A statistically significant improvement was found in the late (30-90 post-operative days) post-operative complications (p = 0.02) and operative time for urinary derivation. At multivariate logistic regression model ASA score ≥ 3 (OR = 4.2, p = 0.002) and number of lymph nodes retrieved (OR = 1.16, p = 0.02) were found to be predictors of 90-day complications. An adequate modular training is paramount to obtain successful results and reduce the learning curve of RARC, as demonstrated by our experience.

The safety of anti-interleukins monoclonal antibodies for the treatment of psoriasis.

Introduction: Psoriasis is a chronic inflammatory disease and affects about 10% of the world's population. Psoriasis is associated with a number of comorbidities. Biologic therapies for the treatment of moderate-severe plaque psoriasis include tumor necrosis factor α inhibitors (TNFi), and newer molecules targeting IL-12 and 23, blocking p40 subunit, or targeting subunit p19 of IL-23 and other molecules blocking IL-17A, or directed against the IL-17 receptor. Areas covered: Anti-interleukin drugs show great improvement in disease control and on the other hand are not affected by important adverse reactions of older compounds. Approach to chronic disease affected patients, in particular, and to patients with multiple comorbidities is revolutionized by novel molecules that are safer and more manageable. Expert opinion: A recent work suggests that pro-fibrogenic cytokines, IL-17, might be important player of liver damage and even in regulation of obesity, diabetes, and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Choosing to interfere with IL-23/Il-17 axis, definitely, is like acting against psoriatic march and in a parallel way against its comorbidities.

Follicular occlusion tetrad in a male patient with pachyonychia congenita: clinical and genetic analysis.

The case of a 24-year-old male patient affected by follicular occlusion tetrad (acne conglobata, hidradenitis suppurativa, pilonidal cyst and dissecting cellulitis of the scalp) associated with clinical signs of pachyonychia congenita (PC)-2 (focal palmoplantar keratoderma, plantar pain, onycodystrophy and multiple cysts) is reported. The diagnosis was supported by genetic analysis that showed heterozygous mutation within the exon 1 of KRT17 gene. This case may reflect different expressions of a phenotypic spectrum induced by a common genetic alteration.

Dermoscopic Analysis of 72 "Atypical" Seborrheic Keratoses. / Análisis dermatoscópico de 72 queratosis seborreicas «atípicas¼.

BACKGROUND: Seborrheic keratoses (SK) are easily recognizable by clinical and dermoscopic approach, nevertheless, some lesions act as a simulator of different skin conditions lacking typical clinical and dermoscopic criteria. OBJECTIVE: The aim of our study was to find specific dermoscopic features or a global pattern to improve diagnostic skills for challenging SK. MATERIALS AND METHODS: We examined 72 atypical SK excised from September 2014 up to September 2017 by using the 2-step algorithm modified by Malvehy (2002) and Argenziano (2003). RESULTS: In our study population, an average of 4.04 out of 15 dermoscopic specific criteria for SK was found (for example, multiple milia-like cysts). Additional criteria not included in 2-step algorithm were blue-whitish veil (found in 3 SK; 4.2%), polymorphous vessels (18 SK; 25%), blotch/globules (6 SK; 8.3%), shiny white streaks (3 lesions; 4.2%). The most represented global patterns were reticular (27 SK; 37.5%) and not specific (15 SK; 20.8%). All lesions exhibited peculiar findings of SK, furthermore elements suggestive for melanocytic lesion were found in 79.2% of all lesions. Comparing the literature and our results, we found 3 significant differences: a) the less prevalence of SK specific criteria in our study population; b) the description of findings usually not related to SK, among which blue-whitish veil, polymorphous vessels, blotch/globules and shiny white streaks, and c) 2 patterns not previously defined represented by "not specific pattern" (20.9% of all lesions examined) and "vascular pattern" (12.5% of all lesions examined) were also described. No specific feature or global pattern, statistically significant for dermoscopic diagnosis of difficult-to-diagnose SK have been found. CONCLUSION: Nevertheless the useful findings, no specific feature or global pattern statistically significant for dermoscopic diagnosis of challenging SK have been found. According to the 2-step algorithm and the dermatoscopic scoring system for melanocytic and not melanocytic lesion, SK with one or more dermatoscopic findings typical of melanocytic lesion should be removed surgically to exclude classic melanoma or melanoma mimicking SK.

Early screening for gestational diabetes mellitus is not associated with improved pregnancy outcomes: an observational study including 9795 women.

AIMS: In addition to screening for hyperglycaemia during pregnancy after 24 weeks of gestation (WG), the current guidelines also suggest screening in early pregnancy and referring women with early gestational diabetes mellitus (eGDM) or overt diabetes (OD) for immediate care. Our aim was to evaluate this strategy. METHODS: This study evaluated, at our hospital (2012-2016), whether the incidence of a predefined composite outcome (preeclampsia, large-for-gestational-age infant, shoulder dystocia) and secondary outcomes was different when women were screened only after 22WG ('late screening only') or before 22WG and treated for eGDM or OD if present, with repeat screening after 22WG if absent ('early ± late screening'). RESULTS: Early ± late screening (n = 4605, 47.0%) increased between 2012 and 2016 (P < 0.0001) and was associated with more risk factors for GDM than late screening only. Glycaemic status differed in both groups (early ± late screening: eGDM 10.3%, GDM 12.1%, OD 0.9% vs. late screening only: GDM 16.8%, OD 1.2%; P < 0.001), with a higher rate of insulin therapy (8.9% vs. 6.0%; P < 0.001) and less gestational weight gain (11.1 ± 5.4 kg vs. 11.4 ± 5.5 kg; P = 0.013) in the early ± late screening group. Rates of those meeting the composite criterion were similar in both groups [11.6% vs. 12.0%, respectively; odds ratio (OR): 1.040, 95% confidence interval (CI): 0.920-1.176; P = 0.53] and remained comparable after adjusting for Propensity Scores (OR: 1.046, 95% CI: 0.924-1.185; P = 0.4790). Rates for secondary outcomes were also similar in both groups. CONCLUSION: While a strategy including early measurement of fasting plasma glucose during pregnancy increases the incidence and care of hyperglycaemia during pregnancy, it may not significantly improve pregnancy outcomes.

Histopathology of the skin in rheumatic diseases.

Rheumatological systemic autoimmune diseases, such as connective tissue diseases, rheumatoid arthritis or spondyloarthritis, are characterized by the presence of joint involvement associated with extra-articular manifestations. Among them, cutaneous diseases are often the most relevant and representative clinical manifestation, as in psoriatic arthritis, scleroderma or systemic lupus erythematosus. In this context, it is useful for rheumatologists to understand better skin diseases and their histopathological features. Evaluation of skin biopsy specimens can be helpful not only to confirm the diagnosis in both classic and clinically atypical variants, but also to improve further our knowledge of the pathogenetic mechanisms and the close link between skin and articular diseases. In this review, we discuss the clinical features, diagnostic evaluation and the histopathological features of skin manifestation of the most relevant rheumatological autoimmune diseases.

Dose adjustment of biologic therapies for psoriasis in dermatological practice: a retrospective study.

INTRODUCTION: Despite the large routine use of biologic drugs in psoriasis treatment, the majority of studies do not take into consideration dose-adjustment practice in 'real-life' dermatological setting. In routine clinical practice, the disease management may include a large number of conditions requiring non-standard dosage regimens, including dose escalation, dose reduction and/or off-label treatment interruption. OBJECTIVE: The ONDA (Outcome of non-standard dosing regimen in Psoriasis and Psoriatic Arthritis) study aim was to retrospectively analyse dose-adjustment strategies among biologic therapies for psoriasis in dermatological practice during a 3-year period. RESULTS: This retrospective, observational, multicentre study was carried out in 350 patients (68% male, 32% female) affected by plaque-type psoriasis (Pso) with a coexistence of psoriatic arthritis in 164 patients (46.9%). At baseline mean PASI score was 14.9 (SD 7.2). Dose adjustment was demonstrated to be a common practice with 70/350 patients (20%) who needed a dose variation during the treatment time, in particular a dose increase in 20/70 patients (28.6%) and a dose reduction in 50/70 patients (71.4%). Dose increase was due to inefficacy on Pso parameters in 60% of cases and to inefficacy of PsA parameters in 40% of cases, while dose reduction (or temporary off-label treatment interruption) was due to prolonged remission in 54% of cases, other reason in 18% of cases, patient choice or request in 14% of cases, occurrence of concomitant event in 12% of cases. CONCLUSION: Dose adjustment is a common clinical practice, consisting of frequent dose reduction when a disease prolonged remission is obtained or dose increase to improve efficacy on Pso and PsA disease parameters.

Safety evaluation of apremilast for the treatment of psoriasis.

INTRODUCTION: Psoriasis (PSo) is a chronic inflammatory skin disease associated with co-morbidities such as hypertension, diabetes, dyslipidemia and metabolic syndrome. It is a typothypical Th1/Th17 disease that affects from 2 to 3% of the world population. Numerous are the drugs that can be used in our clinical practice; the choice of these drugs depends on the characteristics of the patient. Areas covered: Apremilast is the first oral small molecules to receive FDA approval for the treatment of adults with active psoriasis and psoriatic arthritis. It is a small-molecule that specifically inhibits the activity of cyclic AMP phosphodiesterase-4 (PDE4). Several analyses have been performed on data from phase III studies to assess apremilast safety and efficacy on psoriasis and psoriatic arthritis (PsA). Apremilast could also represent a treatment opportunity for those patients unresponsive to both systemic and biological agents or whose treatment was contraindicated. Expert opinion: For its safety profile and easy route of administration, apremilast may offer an oral treatment option for those patients that discontinue treatments because of ineffectiveness, intolerability or ineligibility to the currently available drugs.