Search

Objective: To evaluate the long-term effectiveness, safety, and tolerability of erenumab in a real-world migraine population, looking for putative predictors of responsiveness. Background: Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long-term extension studies of double-blind, placebo-controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures. Methods: A 48-week, multicenter, longitudinal cohort real-life study was conducted at 15headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high-frequency episodic migraine (HFEM) or CM aged 18–65years. Each patient was treated with erenumab 70mg, administered monthly. The dose was switched to 140mg in nonresponders and in responders who had become nonresponders for at least 4weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45–48 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a ≥50%, ≥75%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test-6 scores (HIT-6) during the same time interval. Results: A total of 242 patients with migraine received at least one dose of erenumab 70mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for ≥48weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with ≥3migraine-preventive medication classes. From baseline to Weeks 45–48, erenumab treatment reduced MMD by 4.3±5.3(mean±SD) in patients with HFEM, and MHD by 12.8±8.9 (mean±SD) in subjects with CM. VAS and HIT-6scores were decreased by 1.8±1.9 (mean±SD) and 12.3±11 (mean±SD) in HFEM, and by 3.0±2.2 (mean±SD) and 13.1±11.2 (mean±SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0–13.0) to 5 (IQR 2.0–8.0) in HFEM and from 20.0 (IQR 15.0–30.0) to 6.0 (IQR 3.8–10.0) in CM. The ≥50% responders were 56.1% (32/57) in HFEM and 75.6% (124/164) in CM; ≥75% responders were 31.6% (18/57) and 44.5% (73/164); and 100% responders were 8.8% (5/57) and 1.2% (2/164), respectively. At Week 48, 83.6% (137/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52–19.41; p=0.009) in HFEM. In patients with CM, ≥50% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03–8.7; p=0.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05–1.20; p=0.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15–0.87; p=0.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64–0.92; p=0.004). Conclusions: Long-term (48-week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real-life patients with HFEM or CM with ≥3 prior preventive treatment failures. The dose of 140mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM.

Listeria monocytogenes is the ubiquitous food-borne pathogen which causes listeriosis, a disease with a high mortality rate, mostly transmitted through contaminated ready-to-eat foods. To better understand the systemic response of L. monocytogenes exposed at 3 environmental factors (T, pH and NaCl), the proteome of L. monocytogenes strain NRG 1749-2016, isolated from a meat product, was investigated to identify differences in the protein patterns of such pathogen. Four different conditions were carried out as follows: A) T 37 °C, pH 7.0, NaCl 0.5%; B) T 37 °C, pH 5.5, NaCl 7%; C) T 12° pH 7, NaCl 0.5%; D) T 12 °C, pH 5.5, NaCl 7%. The proteins belonging to cytosol (C1) and vesicles (C2) were isolated and purified by CelLytic B Cell Lysis Reagent and CelLytic IB Inclusion Body Solubilization Reagent according manufacturer's instructions. The analysis were conducted by SDS PAGE and Immunoblotting techniques. The protein concentrations were evaluated by Pierce BCA Protein Assay Kit. From preliminary results, the protein banding patterns generated by 1D SDS PAGE were found to be different at visual observation for C1 and C2, in A, B, C and D conditions. The presence of specific antigen-antibody immunocomplexes (Ag-Ab ICs) was identified by Immunoblotting, in C1 at 100, 60, 55, 35 and 25 kDa for all incubated conditions with a positive serum to L. monocytogenes. As regards C2, Ag-Ab ICs at 110 kDa were observed in A and B, Ag-Ab ICs at 80 kDa in C and D, Ag-Ab ICs at 60 kDa in A and D, while Ag-Ab ICs at 40 and 30 kDa in all conditions. The analysis of the proteome profiles shows an intra-strain variation in the protein patterns produced by L. monocytogenes during the adaptation at different environmental conditions. Further analysis will be carried out to better understand the systemic response of L. monocytogenes, in particular in order to characterize the immunogenic proteins highlighted by Immunoblotting and their role in the virulence expression of such pathogen. Key messages Understand how L. monocytogenes adapts physiologically to different environmental factors. Development of new detection method of L. monocytogenes and prevention strategies for listeriosis outbreaks.

We aimed to evaluate the baseline characteristics, the reasons for prescription, and the effectiveness/safety profile of real-life apremilast for the treatment of psoriatic arthritis (PsA).PsA patients treated with apremilast were retrospectively extracted from an Italian multicentric cohort. Baseline population characteristics and reasons for apremilast prescription were analysed. Clinical response was defined as the proportion of patients achieving Disease Activity in PSoriatic Arthritis (DAPSA) remission/low disease activity (LDA), minimal disease activity (MDA), and very low disease activity (VLDA). Six-month retention rate was computed by the Kaplan-Meier method, with a detailed analysis of reasons for discontinuation. Univariate and multivariate models were developed to examine predictors of clinical response and persistence.The study population included 131 patients mainly with oligoarticular PsA (58%), carrying at least one comorbidity (64.1%, in particular history of malignancies [25.9%] and latent tuberculosis [16.3%]) treated with apremilast as first-line targeted therapy (47.7%) or in biologics failures (52.3%). Contraindication to biologics (60.3%) and lack of poor prognostic factors (27.5%) were the most frequent reason for apremilast prescription. The 6-month retention rate was 72.1%. Inefficacy (n=7), diarrhoea (n=10), nausea (n=3), and headache (n=7) were the most frequent reasons for discontinuation. At 3 months DAPSA LDA/remission, MDA, and VLDA were observed in 40.3, 6.7, and 5.6% of patients, respectively. Female sex was a negative predictor of both retention rate and clinical response.In our real-life analysis apremilast was mainly used in oligoarticular PsA carrying comorbidities leading to contraindications to biologics. Effectiveness and safety profiles were consistent with clinical trials.