When IL-17 inhibitors fail : real-life evidence to switch from secukinumab to adalimumab or ustekinumab

Psoriasis is a chronic, systemic inflammatory disease that in the moderate to severe forms may benefit of biologics, namely TNF and IL-12/23 and IL-17 inhibitors. Loss of response, lack of response or discontinuation due to adverse events represent a concrete therapeutic challenge for dermatologists that have to switch patients to other treatments. Although some evidences already exist toward the switch from IL-12/23 and TNF inhibitors to IL-17 inhibitors, conversely nothing is present toward the switch from IL-17 inhibitors to IL-12/23 and TNF inhibitors. We performed a real-life study enrolling 50 patients randomly switched to adalimuamb, a TNF inhibitor, or ustekinumab, an IL-12/23 inhibitor. Our observational study suggests that switching from IL-17i to TNFi and IL-12/23i is a safe and effective therapeutic strategy

From randomized clinical trials to real life data. An Italian clinical experience with ixekizumab and its management

Interleukin(IL)-17 inhibitors display higher efficacy than both TNFi and IL-12/23i, which increased the goal psoriasis area severity index (PASI) from 75 to PASI 90 or even PASI 100. Ixekizumab, a recombinant, humanized IgG4 monoclonal antibody targeting IL-17A displayed a high efficacy and safety in RCTs, namely UNCOVER-2 and UNCOVER-3. However, few studies examined real-life data for these medications, and those which exist highlight discrepancies in efficacy and safety between RCTs and real-life data, likely due to the heterogeneity of patients treated outside of trials. Thus, we performed a single center large prospective observational study (RLSD) that enrolled 47 psoriatic patients followed for 20\u2009weeks and we compared the obtained data with the UNCOVER studies. At week 20 in RLSD versus UNCOVER-3 both PASI-90 and PASI-100 results were similar, whilst at week 12, the RLSD cohort obtained higher PASI 90 (76 vs 69,3%) and PASI-100 (55 vs 39%) than UNCOVER cohorts. Interestingly we also reported higher injection-site related pain that disappeared after week 12. In conclusion, real-life data together with RCTs contribute to enrich the information background available to dermatologists in daily practice

Sentinel lymph node biopsy in Merkel cell carcinoma : predictors of sentinel lymph node positivity and association with overall survival

Background: Merkel cell carcinoma (MCC) is a rare, aggressive malignancy with high rates of recurrence and metastasis. Objective: To evaluate predictors of sentinel lymph node (SLN) positivity in MCC using the National Cancer Database. Methods: The National Cancer Database, from 2012 to 2014, was used to identify 3048 patients with MCC, of whom 1174 received an SLN biopsy. Predictors of SLN positivity were evaluated using logistic regression. Overall survival was evaluated using a Cox proportional hazards model. Results: Of patients who underwent SLN biopsy, those with primary lesions on the trunk (odds ratio, 1.98; 95% confidence interval [CI], 1.23-3.17; P = .004), tumor-infiltrating lymphocytes (odds ratio, 1.58; 95% CI, 1.01-2.46; P = .04), or lymphovascular invasion (odds ratio, 3.45; 95% CI, 2.51-4.76; P < .001) were more likely to have positive SLNs on multivariate analysis. Overall survival was negatively affected by age 6575 years (hazard ratio [HR], 2.55; 95% CI, 1.36-4.77; P = .003), male sex (HR, 1.78; 95% CI, 1.09-2.91, P = .022), immunosuppression (HR, 3.51; 95% CI, 1.72-7.13; P = .001), and SLN positivity (HR, 3.15; 95% CI, 1.98-5.04; P < .001). Limitations: Lack of disease-specific survival and potential selection bias from a retrospective data set. Conclusions: Truncal MCC, tumor-infiltrating lymphocytes, and presence of lymphovascular invasion were independent predictors of positive SLNs. Overall survival was negatively affected by advancing age, male sex, immunosuppression, and SLN positivity

Predictors of sentinel lymph node positivity in thin melanoma using the National Cancer Database

Background: Sentinel lymph node biopsy (SLNB) specimens are often obtained from patients for further staging after these patients have undergone melanoma excision. Limited data regarding predictors of SLNB positivity in thin melanoma are available. Objective: We sought to evaluate predictors of SLNB positivity in thin melanoma. Methods: Patients with cutaneous melanoma with a Breslow thickness 641.00 mm who received a SLNB were identified from the National Cancer Database between 2004 and 2014 (n = 9186). Predictors of SLNB positivity were analyzed using logistic regression. Results: In a multivariate analysis, patients <60 years of age (P <.001) and Breslow thickness >0.8 mm (P =.03) were at increased risk for positive sentinel lymph node (SLN). Moreover, on multivariate analysis, the presence of dermal mitoses increased the odds of SLN positivity by 95% (odds ratio [OR] 1.95 [95% confidence interval {CI} 1.53-2.5], P <.001), ulceration by 63% (OR 1.63 [95% CI 1.21-2.18], P <.001), and Clark level IV to V by 48% (OR 1.48 [95% CI 1.19-1.85]). Patients without ulceration but with dermal mitoses had 92% (OR 1.92 [95% CI 1.5-2.48], P <.001) increased SLN positivity. Limitations: Limited survival data are available. Conclusions: Younger age, a Breslow thickness >0.8 mm, the presence of dermal mitoses, ulceration, and Clark level IV to V are positive predictors of positive SLN. While the new American Joint Committee on Cancer system has removed dermal mitotic rate from staging, continued evaluation of dermal mitotic rate could be valuable for guiding surgical decision making about SLNB

Omalizumab in Chronic Urticaria : an Italian Survey

Omalizumab is approved for use in chronic spontaneous urticaria (CSU); however, it is not approved for chronic inducible urticaria (CIndU). The aim of the present study was to assess the effectiveness of omalizumab in treating CSU and CIndU in Italy. This is a multicentre prospective observational real-life study involving patients with severe urticaria capable of undergoing omalizumab therapy. We enrolled 127 patients (59.1% females), ranging in age from 15 to 83 years, 69.3% had CSU alone, 26.8% had CSU and CIndU, and 3.9% had only CIndU (30.8% delayed pressure, 35.9% dermographic, 15.3% cholinergic, 12.8% cold, 5.1% aquagenic). After the first cycle of omalizumab (300 mg every 4 weeks for 24 weeks), 16 CSU patients and 10 patients (20.5%) with CIndU with or without CSU did not require a second cycle of omalizumab (300 mg every 4 weeks for 20 weeks). The patient with aquagenic urticaria achieved remission after the first cycle. None showed a lack of response to the second cycle of omalizumab. Omalizumab is a promising drug for both spontaneous and inducible chronic urticaria. Current evidence indicates that omalizumab may be approved also for CIndU

Predicting secukinumab fast-responder profile in psoriatic patients : advanced application of artificial-neural-networks (ANNs)

Background: Drug resistance to biologics in psoriasis therapy can occur \u2013 it may be acquired during a treatment or else present itself from the beginning. To date, no biomarkers are known that may reliably guide clinicians in predicting responsiveness to biologics. Biologics may pose a substantial economic burden. Secukinumab efficiently targets IL-17 in the treatment of psoriasis. Objective: To assess the \u201cfast responder\u201d patient profile, predicting it from the preliminary complete blood count (CBC) and clinical examination. Materials and methods: From November 2016 to May 2017 we performed a multicenter prospective open label pilot study in three Italian reference centers enrolling bio-naive plaque psoriasis patients, undergoing the initiation phase secukinumab treatment (300mg subcutaneous at week 0,1,2,3,4). We define fast responders as patients having achieved at least PASI 75 at the end of secukinumab induction phase. Clinical and CBC data at week 0 and at week 4 were analyzed with linear statistics, principal component analysis, and artificial neural networks (ANNs), also known as deep learning. Two different ANNs were employed: Auto Contractive Map (Auto-CM), an unsupervised ANNs, to study how this variables cluster and a supervised ANNs, Training with Input Selection and Testing (TWIST), to build the predictive model. Results: We enrolled 23 plaque psoriasis patients: 19 patients were responders and 4 were non-responders. 30 attributes were examined by Auto-CM, creating a semantic map for three main profiles: responders, non-responders and an intermediate profile. The algorithm yielded 5 of the 30 attributes to describe the 3 profiles. This allowed us to set up the predictive model. It displayed after training testing protocol an overall accuracy of 91.88% (90% for responders and 93,75% for non-responders). Conclusions: The present study is possibly the first approach employing ANNs to predict drug efficacy in dermatology; a wider use of ANNs may be conducive to useful both theoretical and clinical insight

Psoriatic and psoriatic arthritis patients with and without jet-lag: does it matter for disease severity scores? Insights and implications from a pilot, prospective study

Background: Jet-lag may affect air-travelers crossing at least two time-zones and has several health-care implications. It occurs when the human biological rhythms are out of synch with respect to the day-night cycle at the country destination. Its effect in psoriasis is missing. We aimed to evaluate the effect of Jet-lag in psoriatic patients\u2019 management. Methods: This is a prospective observational study that enrolled psoriatic patients that underwent a flight: patients who experienced jet-lag were compared to patients who did not experience jet-lag. Before the flight, a dermatologist recorded clinical and demographical data with particular attention to Psoriasis Area Severity Index (PASI) and Disease Activity in Psoriatic Arthritis (DAPSA). Patients performed Self-Administered Psoriasis Area Severity Index (SAPASI), the Dermatology Life Quality Index (DLQI) and the pruritus Visual Analog Scale (VAS) scores. After the flight, patients completed the SAPASI, DLQI and pruritus-VAS scores. Results: The sample recruited comprised of 70 psoriatic patients aged 42.4 \ub1 9.7 years (median 42.5 years). Thirty (42.9%) were males, mean BMI was 25.5 \ub1 2.2 kg/m2. Average disease duration was 15.2 \ub1 7.1 years, and 20 (28.6%) subjects had developed PsA. Average hours of flight were 5.4 \ub1 3.5 (median 3.5 h), with 34 (48.6%) subjects reporting jet-lag. At the multivariate regression analysis, the change in the SAPASI score resulted correlated with jet-lag (regression coefficient 1.63, p =.0092), as well the change in the DLQI score (regression coefficient = 1.73, p =.0009), but no change on the pruritus VAS scale was found. Conclusions: The present study suggests that jet-lag may influence disease severity and DLQI scores, but not itch in psoriatic patients