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One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in two different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in WAG/Rij rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity. Our results have demonstrated that an early-long term treatment with fingolimod (1 mg/Kg/day), started before absence seizure onset, has both antiepileptogenic and antidepressant-like effects in the WAG/Rij rats. However, these effects were transitory, since 5 months after treatment discontinuation, both absence seizure and depressive like-behavior returned to control level.Furthermore, a temporary reduction of mTOR signaling pathway activity, indicated by reduced p-mTOR and p-p70S6k levels and by an increased p-AKT in WAG/Rij rats of 6 months of age accompanied the transitory antiepileptogenic fingolimod effects. Surprisingly, fingolimod has demonstrated longer-lasting positive effects on cognitive decline in this strain. This effect was accompanied by an increased acetylation of Lysine 8 of histone H4 (both 6 and 10 months of age). In conclusion, our results support the antiepileptogenic effects fingolimod. However, these antiepileptogenic effects were transitory. Moreover, fingolimod might also have a positive impact on animal behavior and particularly in protecting the development of memory decline.

Psoriasis is an inflammatory and chronic skin disorder associated with physical and psychological burden impairing patients’ quality of life. In the last decade, biologic drugs have widely changed treatment of moderate-severe psoriasis and their number is increasing overtime. To early identify expected/unexpected adverse events (AEs) with biologic treatments, pharmacovigilance programs are needed. We designed a post-marketing active pharmacovigilance program to monitor and analyse AEs and/or serious adverse events (SAEs) reports. All consecutive patients treated with one biologic drug during a two-years period and satisfying inclusion criteria have been enrolled in five Dermatology tertiary units. Demographic and clinical features of patients, type of treatment used, therapy discontinuation, failures, switch/swap to another biologic, and possible onset of AEs were collected. Overall, 512 patients with a diagnosis of psoriasis (286; 55.9%) or arthropathic psoriasis (226; 44.1%) have been enrolled. Eighty-two (16%) patients with AEs and 5 (1%) with SAEs have been identified. Further, 59 (11.5%) had a primary/secondary failure (mainly on infliximab and etanercept). The adverse events and SAEs were reported with golimumab (4/12), adalimumab (32/167), infliximab (9/48), etanercept (31/175) and ustekinumab (11/73), no adverse events have occurred with secukinumab (0/37). Infliximab and etanercept were significantly associated with primary/secondary failures, whereas no differences have been highlighted for AEs insurgence. On the other hand, ustekinumab seems to be associated with a low rate of AEs (p = 0.01) and no adverse events or failures have been reported with secukinumab (p = 0.04 and 0.03, respectively). Our study, even though limited by a small sample size and a brief follow-up period , provide useful data on widely used biologic drugs and their tolerability, discontinuation rate and the incurrence of severe adverse events. Further studies are necessary to include the recently approved biologic drugs and to increase the sample size for more detailed analysis.

Epilepsy is one of the world's oldest recognized and prevalent neurological diseases. It has a great negative impact on patients' quality of life (QOL) as a consequence of treatment resistant seizures in about 30% of patients together with drugs' side effects and comorbidities. Therefore, new drugs are needed and cannabinoids, above all cannabidiol, have recently gathered attention. Areas covered: This review summarizes the scientific data from human and animal studies on the major cannabinoids which have been of interest in the treatment of epilepsy, including drugs acting on the endocannabinoid system. Expert commentary: Despite the fact that cannabis has been used for many purposes over 4 millennia, the development of drugs based on cannabinoids has been very slow. Only recently, research has focused on their potential effects and CBD is the first treatment of this group with clinical evidence of efficacy in children with Dravet syndrome; moreover, other studies are currently ongoing to confirm its effectiveness in patients with epilepsy. On the other hand, it will be of interest to understand whether drugs acting on the endocannabinoid system will be able to reach the market and prove their known preclinical efficacy also in patients with epilepsy.

Post-marketing surveillance activities are essential to detect the risk/benefit profile of biologic disease-modifying antirheumatic drugs (bDMARDs) in inflammatory arthritis. The aim of this study was to evaluate adverse events (AEs) in patients treated with bDMARDs in rheumatology during a prospective pharmacovigilance study from 2016 to 2018. Descriptive statistical analyses were performed to evaluate bDMARDs-related variables of patients without AEs/failures vs patients with AEs and failures. The risk profile among biologics was assessed by comparing patients treated with each bDMARD to patients treated with etanercept. A total of 1155 patients were enrolled, mostly affected by rheumatoid arthritis (46.0%). AEs and failures were experienced by 8.7% and 23.3%, respectively. The number of comorbidities significantly influenced the onset of AEs, while anxiety-depressive, gastrointestinal disease, and fibromyalgia influenced onset of failures. The probability of developing an AE was significantly lower in patients treated with secukinumab, while the probability of developing treatment failure was significantly lower in patients treated with golimumab, secukinumab and tocilizumab. A total of 216 AEs were reported (25.5% serious), mostly regarding infections (21.8%), musculoskeletal (17.6%) and skin (16.2%) disorders. Serious AEs included neutropenia (12.7%), lymphocytosis (9.1%) and uveitis (7.3%). The obtained results revealed known AEs but real-world data should be endorsed for undetected safety concerns.

<b><i>Introduction:</i></b> Several studies in the adult population have shown that obesity is an independent risk factor for elevated intraocular pressure (IOP), whereas data in the paediatric population are sparse and controversial. The purpose of the present study is to investigate the relationship between body mass index (BMI), blood pressure (BP), and IOP in healthy school children. <b><i>Methods:</i></b> The survey was conducted among a random sample of 8-year-old Italian students. Data were collected on their health status and behaviours related to obesity (physical activity, food and drinking habits, etc.). Physical examinations, conducted at school, included measurements of height, weight, BP, and IOP. <b><i>Results:</i></b> Five hundred and seventy-six subjects were recruited (92.8% response rate); 42.4% were overweight or obese, 58.9% consumed inadequate daily servings of fruit and vegetables, and 87.5% were involved in sedentary activities. Elevated BP/hypertension (HTN) affected 3.6% and high IOP was revealed in 12.5% of the children. In the multivariate analysis, elevated BP/HTN was the only significant determinant of ocular HTN (OR 5.36, 95% CI 1.95–14.73, <i>p</i> = 0.001). <b><i>Conclusions:</i></b> Our results show that high IOP affects 12.5% of 8-year-old school children and appears to be associated with high BP related to a high BMI.

Background: This study aims to investigate the extent of the BNT162b2 mRNA vaccine-induced antibodies against SARS-CoV-2 in a large cohort of Italian subjects belonging to the early vaccinated cohort in Italy. Methods: A prospective study was conducted between December 2020 and May 2021. Three blood samples were collected for each participant: one at the time of the first vaccine dose (T0), one at the time of the second vaccine dose, (T1) and the third 30 days after this last dose (T2). Results: We enrolled 2591 fully vaccinated subjects; 16.5% were frail subjects, and 9.8% were over 80 years old. Overall, 98.1% of subjects were seropositive when tested at T2, and 76.3% developed an anti-S IgG titer ≥4160 AU/mL, which is adequate to develop viral neutralizing antibodies. Seronegative subjects at T1 were more likely to remain seronegative at T2 or to develop a low–intermediate anti-S IgG titer (51–4159 AU/mL). Conclusions: In summary, vaccination leads to detectable anti-S IgG titer in nearly all vaccine recipients. Stratification of the seroconversion level could be useful to promptly identify high-risk groups who may not develop a viral neutralizing response, even in the presence of seroconversion, and therefore may remain at higher risk of infection, despite vaccination.

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