Drugs

BACKGROUND: Pharmacological treatment is common in practice and widely used for the management of insomnia. However, evidence comparing the relative effectiveness, safety, and certainty of evidence among drug classes and individual drugs for insomnia are still lacking. This study aimed to determine the relative effectiveness, safety, and tolerability of drugs for insomnia. METHODS: In this systematic review and network meta-analysis we systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, and ClinicalTrials...

BACKGROUND: Nutritional therapies are effective alternative treatments for male infertility or subfertility. These are cost-effective and easily implementable, unlike other advanced invasive treatments. Even moderate improvements in sperm quality could improve spontaneous pregnancy. OBJECTIVE: We aimed to compare the effectiveness of all nutritional therapies in male infertility/subfertility treatment and ranked their efficacy based on type and etiology. We intend to aid clinicians with an evidence-based approach to affordable and safer initial infertility treatment for those who mainly do not wish to have other advanced invasive treatments or could not afford or have access to them...

BACKGROUND: Berberine is a nutraceutical that can improve lipid metabolism. Berberine may also affect sex hormones and exert sex-specific lipid-modifying effects, which have been overlooked. This study aimed to comprehensively review the efficacy and safety of berberine in adults for the treatment of dyslipidemia with consideration of potential sex disparity. Data Sources We searched Medline, Embase, Wanfang, CNKI, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform from inception to 13 December 2022...

Weight loss has been associated with significant improvements in glycemic control, quality of life, and comorbidities in people with type 2 diabetes. Furthermore, achieving diabetes remission can reduce the risk of microvascular complications and mitigate the burden of diabetes on healthcare systems. However, preventing weight regain is challenging in the long term. Strict glycemic control, particularly in the early stages of the disease, can reduce the subsequent risk of microvascular complications and specific macrovascular endpoints in the long run; however, its impact on cardiovascular and all-cause mortality remains controversial...

Ublituximab (ublituximab-xiiy; BRIUMVI™ ) is a glycoengineered anti-CD20 monoclonal antibody developed by TG Therapeutics, Inc. for the treatment of multiple sclerosis (MS). The mechanism of action of ublituximab involves the depletion of B cells via antibody-dependent cellular cytotoxicity, as B cells have a key role in the pathogenesis of MS. Ublituximab is the first anti-CD20 treatment that is administered twice-yearly as one hour infusions, following the initial doses. In December 2022, ublituximab received its first global approval in the USA for the treatment of adults with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease...

Chronic unresolving inflammation is emerging as a key underlying pathological feature of many if not most diseases ranging from autoimmune conditions to cardiometabolic and neurological disorders. Dysregulated immune and inflammasome activation is thought to be the central driver of unresolving inflammation, which in some ways provides a unified theory of disease pathology and progression. Inflammasomes are a group of large cytosolic protein complexes that, in response to infection- or stress-associated stimuli, oligomerize and assemble to generate a platform for driving inflammation...

Worldwide, an estimated 296 million people are living with chronic hepatitis B virus (HBV) infection, with a significant risk of morbidity and mortality. Current therapy with pegylated interferon (Peg-IFN) and indefinite or finite therapy with nucleoside/nucleotide analogues (Nucs) are effective in HBV suppression, hepatitis resolution, and prevention of disease progression. However, few achieve hepatitis B surface antigen (HBsAg) loss (functional cure), and relapse often occurs after the end of therapy (EOT) because these agents have no direct effect on durable template: covalently closed circular DNA (cccDNA) and integrated HBV DNA...

Teplizumab (teplizumab-mzwv; TZIELD™) is a CD3-directed monoclonal antibody (humanized IgG1κ) that is being developed by Provention Bio, Inc. for the treatment of type 1 diabetes (T1D). In November 2022, teplizumab was approved in the USA to delay the onset of Stage 3 T1D in adults and pediatric patients 8 years of age and older with Stage 2 T1D, based on results of a clinical trial in high-risk relatives of individuals with T1D. This article summarizes the milestones in the development of teplizumab leading to this first approval in the treatment of T1D...

Bexagliflozin (BRENZAVVY™) is an orally administered potent inhibitor of sodium-glucose transporter 2 (SGLT-2). It is being developed by TheracosBio for the treatment of type 2 diabetes (T2D) and essential hypertension, and in January 2023 it received its first approval in the USA for use as an adjunct to diet and exercise to improve glycaemic control in adults with T2D. Bexagliflozin is contraindicated in patients receiving dialysis and is not recommended in patients with type 1 diabetes or in those with an estimated glomerular filtration rate of < 30 mL/min/1...

BACKGROUND: Many clinical trials have reported that low-dose aspirin decreases the risk of pre-eclampsia in women with prior pre-eclampsia. However, its impact in a real-world population has not been fully assessed. OBJECTIVES: To assess the rates of low-dose aspirin initiation during pregnancy in women with a history of pre-eclampsia, and to evaluate the impact of low-dose aspirin in prevention of pre-eclampsia recurrence in a real-world population. STUDY DESIGN: CONCEPTION is a French nationwide cohort study which uses data from the country's National Health Data System database...

Lecanemab (lecanemab-irmb; LEQEMBI™) is a humanized immunoglobulin gamma 1 (IgG1) against aggregated soluble and insoluble forms of amyloid-β peptide. It is being developed by Eisai, under a global licence from BioArctic (formerly BioArctic Neuroscience), and in collaboration with Biogen, for the treatment of Alzheimer's disease, and received its first approval for this indication on 6 January 2023 in the USA under the Accelerated Approval Pathway. According to the US prescribing information, treatment should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, and a confirmed presence of amyloid beta pathology (i...

Nadofaragene firadenovec (nadofaragene firadenovec-vncg; Adstiladrin® ) is a non-replicating adenoviral vector-based gene therapy developed by Ferring Pharmaceuticals for the treatment of high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC). Nadofaragene firadenovec constitutes vector DNA that encodes for interferon (IFN)-α2b and is the first approved gene therapy in bladder cancer. The production of IFN-α2b by transfected urothelial cells is associated with anticancer activity, including immunostimulatory, antiangiogenic and apoptotic effects...

Olutasidenib (REZLIDHIATM ), an isocitrate dehydrogenase-1 (IDH1) inhibitor, is being developed by Rigel Pharmaceuticals for the treatment of relapsed or refractory (R/R) acute myeloid leukaemia (AML). Olutasidenib was recently approved in the USA for the treatment of adults with R/R AML with a susceptible IDH1 mutation as detected by a US Food and Drug Administration-approved test. This article summarizes the milestones in the development of olutasidenib leading to this first approval for R/R AML.

Etranacogene dezaparvovec (etranacogene dezaparvovec-drlb; Hemgenix® ) is an adeno-associated virus vector-based gene therapy being developed by uniQure and CSL Behring for the treatment of haemophilia B. In November 2022, etranacogene dezaparvovec was approved in the USA for the treatment of haemophilia B [congenital factor IX (FIX) deficiency] in adults who are currently using FIX prophylaxis therapy, have current or historical life-threatening haemorrhage or have repeated, serious spontaneous bleeding episodes...

Adagrasib (KRAZATI™) is an orally available, potent, irreversible, small molecule inhibitor of KRAS G12C mutant isoform being developed by Mirati Therapeutics for the treatment of solid tumours harbouring KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). Adagrasib covalently binds to the mutant cysteine in KRAS G12C and locks the mutant KRAS protein in its inactive state, thereby preventing downstream signalling without affecting wild-type KRAS protein...

Systemic lupus erythematosus (SLE) is characterized by an aberrant immune response, leading to an extremely heterogeneous clinical presentation, potentially affecting different systems and organs. Despite the fact that SLE mortality has greatly decreased since the introduction of steroids, some forms of refractory/severe SLE still have the potential to result in permanent organ damage as well as increased mortality and morbidity. Furthermore, SLE patients with multiple comorbidities may face a clinical conundrum and have a bad prognosis...

Gene transfer with high doses of adeno-associated viral (AAV) vectors has resulted in serious adverse events and even death of the recipients. Toxicity could most likely be circumvented by repeated injections of lower and less toxic doses of vectors. This has not been pursued as AAV vectors induce potent neutralizing antibodies, which prevent cell transduction upon reinjection of the same vector. This review discusses different types of immune responses against AAV vectors and how they offer targets for the elimination or inhibition of vector-specific neutralizing antibodies...

Seizures and epilepsy can result from various aetiologies, yet the underlying cause of several epileptic syndromes remains unclear. In that regard, autoimmune-mediated pathophysiological mechanisms have been gaining attention in the past years and were included as one of the six aetiologies of seizures in the most recent classification of the International League Against Epilepsy. The increasing number of anti-neuronal antibodies identified in patients with encephalitic disorders has contributed to the establishment of an immune-mediated pathophysiology in many cases of unclear aetiology of epileptic syndromes...

OBJECTIVE: We aimed to investigate whether ibuprofen use, compared with other non-selective non-steroidal anti-inflammatory drugs (ns-NSAIDs), cyclooxygenase-2 inhibitors (COX-2i) or paracetamol, increases the risk of coronavirus disease 2019 (COVID-19) diagnosis or hospitalisation. DESIGN: A prevalent user and active comparator cohort study. SETTING: Two US claims databases (Open Claims and PharMetrics Plus) mapped to the Observational Medical Outcomes Partnership Common Data Model...

Mirvetuximab soravtansine (mirvetuximab soravtansine-gynx; Elahere™ ) is an antibody-drug conjugate (ADC), which is comprised of a folate receptor α (FRα) directed antibody conjugated to a microtubule inhibitor via a cleavable linker. The ADC is being developed by ImmunoGen for the treatment of FRα expressing cancers. In November 2022, mirvetuximab soravtansine was approved in the USA for the treatment of adult patients with FRα positive, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens...