Tacrolimus 0.1% versus ciclopiroxolamine 1% for maintenance therapy in patients with severe facial seborrheic dermatitis: A multicenter, double-blind, randomized controlled study.

BACKGROUND: No long-term maintenance therapy has been tested in patients with seborrheic dermatitis (SD). OBJECTIVE: We sought to compare the efficacy and tolerance of tacrolimus 0.1% ointment versus ciclopiroxolamine 1% cream as maintenance therapy for severe SD. METHODS: This double-blind randomized controlled study was conducted from 2014 to 2017 in 5 Dermatology Departments and 15 dermatology practices in France. Consecutive patients with severe and chronic facial SD were included. Patients were initially treated with desonide 0.05% cream twice daily for 7 days. Patients cleared after this open phase were randomized to receive tacrolimus 0.1% or ciclopiroxolamine 1% cream 2 times a week 24 weeks. The primary endpoint was disease-free-duration, defined as the time from randomization to first relapse. RESULTS: One hundred fourteen patients were randomized (tacrolimus, n = 57; ciclopiroxolamine, n = 57). Twelve patients relapsed in the tacrolimus group after a median delay of 91.5 days (range 15-195 days) versus 23 patients in the ciclopiroxolamine group (median delay, 27 days [range 13-201 days]). Comparison of disease-free duration curves showed that patients in the tacrolimus group had a longer duration of complete remission than those in the ciclopiroxolamine group (P = .018), corresponding to a hazard ratio of relapse of 0.44 (95% confidence interval 0.22-0.89; P = .022). LIMITATIONS: The theoretical sample size was not reached. CONCLUSION: Tacrolimus 0.1% is more effective than ciclopiroxolamine 1% as maintenance therapy for patients with facial SD.

Study of metastatic kinetics in metastatic melanoma treated with B-RAF inhibitors: Introducing mathematical modelling of kinetics into the therapeutic decision.

BACKGROUND: Evolution of metastatic melanoma (MM) under B-RAF inhibitors (BRAFi) is unpredictable, but anticipation is crucial for therapeutic decision. Kinetics changes in metastatic growth are driven by molecular and immune events, and thus we hypothesized that they convey relevant information for decision making. PATIENTS AND METHODS: We used a retrospective cohort of 37 MM patients treated by BRAFi only with at least 2 close CT-scans available before BRAFi, as a model to study kinetics of metastatic growth before, under and after BRAFi. All metastases (mets) were individually measured at each CT-scan. From these measurements, different measures of growth kinetics of each met and total tumor volume were computed at different time points. A historical cohort permitted to build a reference model for the expected spontaneous disease kinetics without BRAFi. All variables were included in Cox and multistate regression models for survival, to select best candidates for predicting overall survival. RESULTS: Before starting BRAFi, fast kinetics and moreover a wide range of kinetics (fast and slow growing mets in a same patient) were pejorative markers. At the first assessment after BRAFi introduction, high heterogeneity of kinetics predicted short survival, and added independent information over RECIST progression in multivariate analysis. Metastatic growth rates after BRAFi discontinuation was usually not faster than before BRAFi introduction, but they were often more heterogeneous than before. CONCLUSIONS: Monitoring kinetics of different mets before and under BRAFi by repeated CT-scan provides information for predictive mathematical modelling. Disease kinetics deserves more interest.

Risk factors for relapse in patients with bullous pemphigoid in clinical remission: a multicenter, prospective, cohort study.

OBJECTIVE: To identify prognostic factors for relapse in the first year after cessation of therapy in bullous pemphigoid (BP). DESIGN: Prospective, multicenter, cohort study (January 1, 2000, through December 31, 2006). SETTING: Fifteen French dermatology departments. Patients Patients with BP in remission under low doses of topical or systemic corticosteroids. Interventions Cessation of corticosteroid treatment (day 0) followed by a systematic clinical and immunologic follow-up. MAIN OUTCOME MEASURES: The end point was clinical relapse within the first year after cessation of therapy. Associations of clinical, biological, and immunologic (including direct immunofluorescence, serum anti-basement membrane zone autoantibodies, and serum BP180 autoantibodies by enzyme-linked immunosorbent assay [ELISA] on day 0) variables with clinical relapse were assessed by means of univariate and multivariate analyses. RESULTS: On day 0, 30 of 114 patients (26.3%) still had a positive result of direct immunofluorescence, 63 of 112 (56.3%) had circulating anti-basement membrane zone autoantibodies, and 34 of 57 (60%) had anti-BP180 antibodies by ELISA. At month 12, 22 patients were dead (n = 11) or lost to follow-up (n = 11), 51 were in remission, and 45 had had relapses (mean interval to relapse, 3.2 months). Factors predictive of relapse within 12 months after cessation of therapy were a positive result of direct immunofluorescence microscopy (P = .02), a greater age (P = .01), and high-titer ELISA scores (P = .02) on day 0. In multivariate analysis, the only factor independently predictive of relapse was a high-titer ELISA score on day 0 (odds ratio, 11.00; 95% confidence interval, 1.29-93.76). CONCLUSIONS: High-titer anti-BP180 ELISA score and, to a lesser degree, a positive direct immunofluorescence finding are good indicators of further relapse of BP. At least 1 of these tests should be performed before therapy is discontinued.

Onset of psoriatic arthritis in patients treated with efalizumab for moderate to severe psoriasis.

OBJECTIVE: To investigate the nature of polyarthritis in patients with moderate to severe psoriasis undergoing treatment with efalizumab, a humanized anti-CD11a monoclonal antibody. METHODS: In a multicenter study, we retrospectively analyzed patients who developed arthritis during treatment with efalizumab. The relationship between joint manifestations and psoriatic disease was addressed by using different classification criteria for psoriatic arthritis (PsA). The course of arthritis and its response to treatment were also investigated. RESULTS: Sixteen patients developed de novo inflammatory rheumatic disease, with a mean delay of 15 weeks following the start of treatment, and with exclusive asymmetric peripheral monarthritis or oligoarthritis (8 patients), inflammatory spinal disease (1 patient), or both (7 patients), associated in some cases with enthesitis and dactylitis. All patients fulfilled at least 2 different sets of classification criteria for PsA. In most of them, an improvement in skin lesions was observed at the onset of PsA, as measured using the Psoriasis Area and Severity Index (mean score 24.88 before efalizumab versus 18.78 at the time of arthritis). Efalizumab treatment was stopped in 11 patients and was followed by the elimination of rheumatologic symptoms in 1 patient, while 8 patients required treatment with nonsteroidal antiinflammatory drugs with or without methotrexate, with 2 later being switched to tumor necrosis factor alpha inhibitors. Reintroduction of efalizumab (2 patients) was followed by a relapse of PsA. CONCLUSION: This study questions the role of efalizumab in the induction of PsA. It also emphasizes the discrepancy between the courses of psoriatic skin and joint manifestations under treatment. Prospective case-control studies are needed to accurately investigate the impact of efalizumab on PsA.