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Background: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. Objective:We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort.Methods: Patients were included between March 2017 and April 2018. Efficacy outcomes were collected both at baseline and three months (M3), when available, including SCORAD (Scoring Atopic Dermatitis) and EASI (Eczema Area and Severity Index) scores. Adverse events (AE) were recorded at the follow-up. Results:We included 241 patients. The median follow-up time was 3.8±3.7 months. SCORAD75 and EASI75 were achieved in 27/163 (16.6%) and 40/82 (48.8%) patients, respectively. The median SCORAD and EASI at M3 were significantly lower compared with baseline (25±21 vs 56±27.4, p<10 -9 and 4.1±6.8 vs 17.9±15.4, p<10 -9 , respectively).Conjunctivitis was reported in 84/241 (38.2%) patients. The proportion of eosinophilia (>500/mm 3 ) during follow-up (57%) was higher than at baseline (33.7%) (n=172, p<10 -6 ).Dupilumab was stopped in 42 cases, 27 of which were due to an AE. Limitations:No control group, missing data. Conclusion:This real-life study demonstrated results similar to clinical trials, with regard to dupilumab effectiveness, but revealed a higher frequency of conjunctivitis and eosinophilia.

Objective Immune checkpoint inhibitors (ICIs) for cancer therapy frequently induce immune‐related adverse effects (IRAEs). Therefore, most patients with preexisting autoimmune diseases have been excluded from clinical trials of ICIs. This study was undertaken to evaluate the safety and efficacy of ICIs in patients with preexisting autoimmune disease and cancer. Methods A retrospective cohort study was conducted from January 2017 to January 2018 via 3 French national networks of experts in oncology and autoimmunity. Adults with preexisting autoimmune disease who were receiving ICIs were assessed for the occurrence of flare of preexisting autoimmune disease, other IRAEs, and cancer response. Results The study included 112 patients who were followed up for a median of 8 months. The most frequent preexisting autoimmune diseases were psoriasis (n = 31), rheumatoid arthritis (n = 20), and inflammatory bowel disease (n = 14). Twenty‐four patients (22%) were receiving immunosuppressive therapy at ICI initiation. Autoimmune disease flare and/or other IRAE(s) occurred in 79 patients (71%), including flare of preexisting autoimmune disease in 53 patients (47%) and/or other IRAE(s) in 47 patients (42%), with a need for immunosuppressive therapy in 48 patients (43%) and permanent discontinuation of ICI in 24 patients (21%). The median progression‐free survival was shorter in patients receiving immunosuppressive therapy at ICI initiation (3.8 months versus 12 months; P = 0.006), confirmed by multivariable analysis. The median progression‐free survival was shorter in patients who experienced a flare of preexisting autoimmune disease or other IRAE, with a trend toward better survival in the subgroup without immunosuppressant use or ICI discontinuation. Conclusion Our findings indicate that flares or IRAEs occur frequently but are mostly manageable without ICI discontinuation in patients with a preexisting autoimmune disease. Immunosuppressive therapy at baseline is associated with poorer outcomes.

SummaryBackground There is an unmet need to identify markers predictive of response to ipilimumab in patients with melanoma because the number of responders to ipilimumab is low and its cost is very high. An increase in absolute lymphocyte count (ALC) or low neutrophil/lymphocyte ratio (NLR) just before the third infusion has been reported to be associated with better overall survival (OS). Objectives Our aim was to determine whether NLR measured before the first infusion was associated with OS. Patients and methods Data were collected on a consecutive series of 58 patients treated with ipilimumab in four hospitals, including 51 at stage M1c and four at stage M1b. The influences of the NLR and other factors such as lactate dehydrogenase (LDH), performance status, ALC, absolute neutrophil count (ANC) and corticosteroids on survival were studied. We also assessed this association with NLR categorized as a binary variable. The cut-off value for the NLR was determined with time-dependent receiver operating characteristic (ROC) analysis. Univariate and multivariate analyses were performed using Cox regression models. Results High NLR (≥) 4, high ANC LDH levels (>2), performance status ≥2, symptomatic brain metastases, and corticosteroids before week 1 were associated with poorer survival on univariate analysis. Using multivariate analysis, a significant association between high NLR (continuous variable) and poorer survival was demonstrated and remained significant after adjustment on potential confounders [hazard ratio (HR) = 1Á21, 95% confidence interval (CI) 1Á07-1Á36]. NLR ≥4 was an independent prognostic factor (HR = 2Á2, 95% CI 1Á01-4Á78). Intake of corticosteroids before week 1 was not an independent prognostic factor (HR = 1Á28, 95% CI 0Á54-3Á06). Conclusions High NLR (≥4) before initiating ipilimumab treatment in patients with metastatic melanoma is an independent prognostic indicator of poor survival.

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This study highlights phenotypic features of psoriasis in elderly and in very late onset psoriasis. The management of these fragile patients remains poorly codified and needs further investigation.

Background Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. Objectives To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV.Methods This was an independently conducted post hoc analysis of the moderateto-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0Á5 or 1Á0 mg kg À1 per day prednisone tapered over 3 or 6 months, or 1Á0 or 1Á5 mg kg À1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24month efficacy and safety results were also reported.Results At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. Conclusions In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic?Rituximab in pemphigus vulgaris, D.M. Chen et al. 1113 CI, confidence interval; CRoff, complete remission off prednisone therapy; IQR, interquartile range; N/A, not applicable; CRmin, complete remission on minimal prednisone therapy (prednisone dose ≤ 10 mg per day). a No adjustment for multiplicity was made for any secondary end points and the P-values should be interpreted with caution. b 95% confidence interval (CI) calculated using the corrected Newcombe interval. c P-value calculated using Fisher's exact test with mid-P correction. d P-value calculated using Mann-Whitney U-test.