Relapsing-remitting and primary progressive multiple sclerosis treated with ocrelizumab: A comparative study.

OBJECTIVES: To compare the clinical and radiological effectiveness of ocrelizumab in primary progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) in a clinical practice setting and describe its tolerability and adverse events. METHODS: A retrospective observational cohort study was conducted comparing clinical and magnetic resonance imaging (MRI) data of all patients with (pw)PPMS and RRMS who had received treatment with ocrelizumab at least one cycle and have been followed up for one year at minimum. RESULTS: 42 patients (27 women) treated with ocrelizumab: 29 had RRMS and 13 PPMS. The follow-up period was 26.4 ± 8.4 months. The proportion of pwRRMS with no evidence of disease activity (NEDA) in the first year was 69.2% and in the second was 80%. In the first year, radiological activity was reduced by 80.0% in pwRRMS and 91.7% in pwPPMS. In the second year, radiological activity was completely reduced in both groups. A statistically significant difference (p<0.05) was observed between the pre-ocrelizumab rate of disability progression vs. the first year rate of progression for pwRRMS and pwPPMS. However, an increase in the disability progression rate in the second year of treatment was found in pwPPMS. Ocrelizumab was mostly well tolerated and some adverse effects were reported: infusion-related reactions (IRRs) were the most frequent adverse event, followed by infections and hematological side effects. Discontinuations were due to infections, hematological complications, and perception of ineffectiveness. CONCLUSIONS: Ocrelizumab was very effective in reducing relapses and MRI activity. The rate of progression was slowed down; however, the effect was more evident for pwRRMS than for pwPPMS over time.

Diroximel Fumarate as a Novel Oral Immunomodulating Therapy for Relapsing Forms of Multiple Sclerosis: A Review on the Emerging Data.

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. Disease-modifying drugs (DMDs) and subsequent adherence are crucial for preventing reversible episodes of neurological dysfunction and delayed onset of progressive accumulation of irreversible deficits. Yet, side effects may limit their usage in clinical practice. Gastrointestinal (GI) side effects are a significant limitation of the use of dimethyl fumarate (DMF), the most frequently prescribed oral DMD in MS worldwide. Diroximel fumarate (DRF) is a second-generation oral fumaric acid ester (FAE) that was developed as a formulation with better GI tolerability. The improved tolerability is assumed to be related to a lower synthesis of gut-irritating methanol. Other explanations for DRF's lower extent of GI irritation include a more modest off-target activity due to its chemical structure. The superior GI tolerability of DRF compared to DMF could be proven in clinical trials and lead to approval of DRF for the treatment of relapsing forms of MS/relapsing-remitting MS (United States Food and Drug Administration and European Medicines Agency, respectively). Here, we summarize the mode of action of oral FAE and compare the chemical and physiological characteristics of DMF and DRF. Moreover, we discuss the adverse effects of FAE and introduce the emerging preclinical and trial data leading to the approval of DRF in MS. This article additionally reviews our current understanding of coronavirus disease 2019 (COVID-19) and the efficacy of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination in people treated with FAE.

Adverse effects associated with favipiravir in patients with COVID-19 pneumonia: a retrospective study.

BACKGROUND: Favipiravir is generally used in treating coronavirus disease 2019 (COVID-19) pneumonia in Turkey. OBJECTIVE: To determine the side effects of favipiravir and whether it is a good treatment option. DESIGN AND SETTING: Retrospective study conducted in Atatürk Chest Diseases and Chest Surgery Training and Research Hospital, Ankara, Turkey. METHODS: 357 patients who completed favipiravir treatment at the recommended dose were included. 37 patients with drug side effects and 320 patients without drug side effects were examined in two groups. RESULTS: Side effects were observed in 37 (10.36%) out of 357 patients using favipiravir. The most common side effect was liver dysfunction, in 26 (7.28%) of the patients. The following other side effects were also observed: diarrhea (1.4%), nausea (0.84%), abdominal pain (0.28%) and thrombocytopenia (0.28%). One patient (0.28%) presented both increased transaminases and nausea. CONCLUSION: In this study, it was determined that favipiravir may constitute an alternative for treating COVID-19 pneumonia given that its side effects are generally well tolerated and not serious.

Genetic Therapy and Molecular Targeted Therapy in Oncology: Safety, Pharmacovigilance, and Perspectives for Research and Clinical Practice.

The impressive advances in the knowledge of biomarkers and molecular targets has enabled significant progress in drug therapy for crucial diseases such as cancer. Specific areas of pharmacology have contributed to these therapeutic outcomes-mainly targeted therapy, immunomodulatory therapy, and gene therapy. This review focuses on the pharmacological profiles of these therapeutic classes and intends, on the one hand, to provide a systematic definition and, on the other, to highlight some aspects related to pharmacovigilance, namely the monitoring of safety and the identification of potential toxicities and adverse drug reactions. Although clinicians often consider pharmacovigilance a non-priority area, it highlights the risk/benefit ratio, an essential factor, especially for these advanced therapies, which represent the most innovative and promising horizon in oncology.

Intentional Hydroxychloroquine Overdose Treated with High-Dose Diazepam: an Increasing Concern in the COVID-19 Pandemic.

INTRODUCTION: Recent attention on the possible use of hydroxychloroquine and chloroquine to treat COVID-19 disease has potentially triggered a number of overdoses from hydroxychloroquine. Toxicity from hydroxychloroquine manifests with cardiac conduction abnormalities, seizure activity, and muscle weakness. Recognizing this toxidrome and unique management of this toxicity is important in the COVID-19 pandemic. CASE REPORT: A 27-year-old man with a history of rheumatoid arthritis presented to the emergency department 7 hours after an intentional overdose of hydroxychloroquine. Initial presentation demonstrated proximal muscle weakness. The patient was found to have a QRS complex of 134 ms and QTc of 710 ms. He was treated with early orotracheal intubation and intravenous diazepam boluses. Due to difficulties formulating continuous diazepam infusions, we opted to utilize an intermitted intravenous bolus strategy that achieved similar effects that a continuous infusion would. The patient recovered without residual side effects. DISCUSSION: Hydroxychloroquine toxicity is rare but projected to increase in frequency given its selection as a potential modality to treat COVID-19 disease. It is important for clinicians to recognize the unique effects of hydroxychloroquine poisoning and initiate appropriate emergency maneuvers to improve the outcomes in these patients.