Comparison of injective related reactions following ofatumumab and ocrelizumab in patients with multiple sclerosis: data from the European spontaneous reporting system.

Introduction: In 2021 ofatumumab, a recombinant human anti-CD20 monoclonal antibody (mAb) already authorized for the treatment of chronic lymphocytic leukemia, received the marketing approval for the treatment of relapsing forms of multiple sclerosis (MS). Differently from ocrelizumab, that is administered intravenously, ofatumumab if the first anti-CD20 mAb to be administered subcutaneously without a premedication. Methods and objectives: In this study we aimed to describe and compare the main characteristics of Individual Case Safety Reports (ICSRs) describing the occurrence of Injective Related Reactions (IRRs) following the treatment with ocrelizumab and ofatumumab reported in the Eudravigilance (EV) database during years 2021-2023. Results: A total of 860 ICSRs with either ofatumumab and ocrelizumab as suspected drug were retrieved from Eudravigilance, of which 51% associated with ofatumumab and 49% with ocrelizumab. The majority of patients who experienced IRRs following ocrelizumab belonged to the age group of 18-64 years (73%), while the age-group was mostly not specified (55%) in ICSRs reporting ofatumumab as suspected. The distribution of gender was almost similar in the two groups, with the majority of ICSRs related to female patients. "Pyrexia" was the Preferred Term (PT) most reported for ofatumumab, while "Infusion related reaction" were more frequently reported with ocrelizumab. Premedication drugs were reported in 148 ICSRs. Out of 89 ICSRs for which the Time to Event (TTE) was calculated, 74 reported IRRs that occurred the same day of the drug administration. Discussion: Based on the results of this study, although a risk of ofatumumab-induced IRRs cannot be excluded, it should be considered as manageable considering that the drug seems to be mostly associated with the occurrence of fever. Thus, it is important to continue to closely monitor the use of these in clinical practice to improve the knowledge on their long-term safety.

Skin Toxicities Associated with Botulin Toxin Injection for Aesthetic Procedures: Data from the European Spontaneous Reporting System.

Botulinum toxin is a protein deriving from the bacteria Clostridium botulinum and it is widely used for the treatment of a variety of muscle hyperactivity syndromes and for cosmetic indications. Having a long-lasting effect, Botulinum toxin type A (BTA) is one of the most botulin toxin products used. Even if BTA has shown benefits in reducing the vertical lines between the eyebrows, Adverse Drug Reactions (ADRs) have been experienced as well, of which the most common ones are headache and drooping eyelids. In addition, since other local and systemic risks have been identified, a non-interventional post-authorization safety study (PASS) has been started. The aim of the present study was to report cases of skin toxicity associated with this drug, considering Individual Case Safety Reports (ICSRs) existing on the Eudravigilance website. Among 1464 ICSRs sent to the EV database, 718 ICSRs, including 5154 PTs, reported BTA as a suspected drug associated with cutaneous toxicity. The majority of patients experiencing BTA-induced skin toxicity were female (92.1%) belonging mostly to the age group of 18-64 years. The most serious criteria, when reported, were "Other Medically Important Condition" and "Caused/prolonged hospitalization", although the outcome was mainly reported as "Unknown". The most reported PTs, related to skin disorders, were: "Erythema", "Rash", "Pruritus", "Urticaria", "Swelling face", "Brow ptosis", "Eyelid ptosis", "Injection site pain", and "Angioedema". Considering that in most ICSRs, ADRs related to skin disorders were symptoms of hypersensitivity reactions which in some conditions could be life-threatening, further studies are required to better define the safety profile of BTA used for aesthetic procedures.

Hepatobiliary Adverse Reactions during Treatment with Cladribine: Analysis of Data from the European Spontaneous Reporting System.

BACKGROUND: Cladribine belongs to the group of disease-modifying therapies (DMTs) used to treat multiple sclerosis (MS). According to the highlights of a meeting held by the Pharmacovigilance Risk Assessment Committee (PRAC) on 14 January 2022, cladribine may be associated with the occurrence of liver injury, and thus liver function monitoring is recommended. OBJECTIVES AND METHODS: Using data from the European spontaneous reporting database (EudraVigilance-EV), we aimed to describe the main characteristics of Individual Case Safety Reports (ICSRs) reporting cases of hepatobiliary disorders related to cladribine. The reporting odds ratio (ROR) was calculated to provide the probability of reporting hepatobiliary ICSRs among DMTs used to treat MS. RESULTS: Overall, 118 ICSRs described the occurrence of cladribine-induced hepatobiliary ADRs. The majority of the ICSRs reported ADRs that were classified as serious (93%), and the outcome was mostly reported as "unknown" (50.8%). The most reported hepatobiliary disorders were drug-induced liver injury, abnormal hepatic function, ALT increases, liver disorders, hepatic failure, jaundice, lymphocyte count decreases, hepatotoxicity and hypertransaminasemia. The majority of cladribine-induced hepatic ADRs occurred in female patients belonging to the age group of 18-65 years. CONCLUSION: Considering the seriousness of cladribine-induced hepatic ADRs, a close monitoring of patients receiving this drug is highly recommended. In this context, further pharmacovigilance studies evaluating the hepatic safety profile of cladribine are strongly needed.

Immune-related adverse events and immune checkpoint inhibitors: a focus on neurotoxicity and clinical management.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) represent an innovative therapeutic approach of oncologic diseases. In Europe, this therapeutic class currently includes eight agents: ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab, durvalumab and dostarlimab. Despite their proved clinical benefits, they can induce immune-related adverse events (irADRs), that can also involve the nervous system. AREAS COVERED: Despite their rarity, neurological irADRs related to ICI-treatments can lead to serious and dangerous complications, highlighting the importance of a strict monitoring of patients. This review aims to summarize the safety profile of ICIs, focusing on their possible neurotoxicity and their management. EXPERT OPINION: Considering the clinical relevance of ICIs-induced irADRs and that the underlying mechanisms are still not completely understood, the use of ICIs requires extensive safety monitoring. Before to prescribe immunotherapy, oncologists should identify possible individual risk factors that may favor the onset of irADRs. Oncologists and general practitioners should inform and educate patients about the specific toxicities of immunological checkpoint inhibitors, including nervous ones. They should be carefully monitored at least 6 months after the end of treatment. ICIs-related nervous toxicities require a multidisciplinary management, in which neurologists and clinical pharmacologists should participate.