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Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.

An anti–SARS-CoV-2 antibody cocktail was given to patients within 3 days after PCR confirmation of Covid-19. In patients who were antibody-negative at baseline, treatment was associated with rapid viral clearance and potentially with a less frequent need for medical attention. The effect was less marked among patients who were antibody-positive at baseline.

In a phase 2 trial, outpatients with Covid-19 who received a single infusion of a 2800-mg dose of the neutralizing antibody LY-CoV555 had a greater reduction from baseline in viral load than those who received placebo. Hospitalization was less frequent among antibody-treated patients (1.6% vs. 6.3%).

In two trials involving patients with relapsing multiple sclerosis, the anti-CD20+ monoclonal antibody ocrelizumab was associated with lower annualized relapse rates, lower risk of disability progression, and better MRI features than interferon beta-1a. Despite the availability of several disease-modifying treatments for relapsing forms of multiple sclerosis, patients often continue to have clinical and subclinical disease activity, and neurologic disability continues to accrue. Thus, there is a need for more effective treatments with acceptable safety profiles. 1 – 3 B cells are thought to influence the underlying pathogenesis of multiple sclerosis by means of antigen presentation, 4 autoantibody production, 5 , 6 cytokine regulation, 4 and the formation of ectopic lymphoid aggregates in the meninges, which possibly contribute to cortical demyelination and neurodegeneration. 7 , 8 Ocrelizumab is a humanized monoclonal antibody that selectively targets CD20, a cell-surface antigen that is expressed . . .

Among participants with eosinophilic granulomatosis with polyangiitis, 32% had remission at weeks 36 and 48 when treated with mepolizumab, an anti–interleukin-5 monoclonal antibody, as compared with 3% of the participants in the placebo group. Eosinophilic granulomatosis with polyangiitis (formerly known as the Churg–Strauss syndrome) is characterized by asthma, sinusitis, pulmonary infiltrates, neuropathy, and eosinophilic vasculitis of one or more end-organs. 1 – 4 Eosinophils are thought to induce pathogenic effects in patients with eosinophilic granulomatosis with polyangiitis by means of tissue and vascular infiltration and inflammation through a variety of mediators. 5 , 6 Although systemic glucocorticoids form the cornerstone of treatment for eosinophilic granulomatosis with polyangiitis, 7 – 9 most patients remain dependent on glucocorticoid therapy, and relapses are common. 10 – 13 Furthermore, some patients do not have a sufficient response to glucocorticoids. Because recurrent relapses place the patient at . . .

Summary In the past 20 years the treatment scenario of multiple sclerosis has radically changed. The increasing availability of effective disease-modifying therapies has shifted the aim of therapeutic interventions from a reduction in relapses and disability accrual, to the absence of any sign of clinical or MRI activity. The choice for therapy is increasingly complex and should be driven by an appropriate knowledge of the mechanisms of action of the different drugs and of their risk-benefit profile. Because the relapsing phase of the disease is characterised by inflammation, treatment should be started as early as possible and aim to re-establish the normal complex interactions in the immune system. Before starting a treatment, neurologists should carefully consider the state of the disease, its prognostic factors and comorbidities, the patient's response to previous treatments, and whether the patient is likely to accept treatment-related risks in order to maximise benefits and minimise risks. Early detection of suboptimum responders, thanks to accurate clinical monitoring, will allow clinicians to redesign treatment strategies where necessary.

Obinutuzumab is an anti-CD20 antibody engineered to elicit killing mechanisms distinct from rituximab. In a trial of chemotherapy plus obinutuzumab or rituximab that used the antibody as maintenance therapy for 2 years, obinutuzumab prolonged progression-free survival.

In a large randomized trial that compares regimens in which brentuximab vedotin replaced bleomycin, the group receiving the brentuximab had a 4.9 percentage-point improvement in modified progression-free survival, less pulmonary toxicity, and more myelotoxicity and neurotoxicity.

Summary Background The calcitonin gene-related peptide (CGRP) pathway is a promising target for preventive therapies in patients with migraine. We assessed the safety and efficacy of AMG 334, a fully human monoclonal antibody against the CGRP receptor, for migraine prevention. Methods In this multicentre, randomised, double-blind, placebo-controlled, phase 2 trial, patients aged 18–60 years with 4 to 14 migraine days per month were enrolled at 59 headache and clinical research centres in North America and Europe, and randomly assigned in a 3:2:2:2 ratio to monthly subcutaneous placebo, AMG 334 7 mg, AMG 334 21 mg, or AMG 334 70 mg using a sponsor-generated randomisation sequence centrally executed by an interactive voice response or interactive web response system. Study site personnel, patients, and the sponsor study personnel were masked to the treatment assignment. The primary endpoint was the change in monthly migraine days from baseline to the last 4 weeks of the 12-week double-blind treatment phase. The primary endpoint was calculated using the least squares mean at each timepoint from a generalised linear mixed-effect model for repeated measures. Safety endpoints were adverse events, clinical laboratory values, vital signs, and anti-AMG 334 antibodies. The study is registered with ClinicalTrials.gov , number NCT01952574 . An open-label extension phase of up to 256 weeks is ongoing and will assess the long-term safety of AMG 334. Findings From Aug 6, 2013, to June 30, 2014, 483 patients were randomly assigned to placebo (n=160), AMG 334 7 mg (n=108), AMG 334 21 mg (n=108), or AMG 334 70 mg (n=107). The mean change in monthly migraine days at week 12 was −3·4 (SE 0·4) days with AMG 334 70 mg versus −2·3 (0·3) days with placebo (difference −1·1 days [95% CI −2·1 to −0·2], p=0·021). The mean reductions in monthly migraine days with the 7 mg (−2·2 [SE 0·4]) and the 21 mg (−2·4 [0·4]) doses were not significantly different from that with placebo. Adverse events were recorded in 82 (54%) patients who received placebo, 54 (50%) patients in the AMG 334 7 mg group, 54 (51%) patients in the AMG 334 21 mg group, and 57 (54%) patients in the AMG 334 70 mg group. The most frequently reported adverse events were nasopharyngitis, fatigue, and headache. Serious adverse events were reported for one patient in the AMG 334 7 mg group (ruptured ovarian cyst) and one patient in the AMG 334 70 mg group (migraine and vertigo); these events were judged to be unrelated to AMG 334 treatment. Nine (3%) of 317 patients had neutralising antibodies. No apparent association was recorded between patients with positive anti-AMG 334 antibodies and adverse events. No clinically significant vital signs, laboratory, or electrocardiogram findings were recorded. Interpretation These results suggest that AMG 334 70 mg might be a potential therapy for migraine prevention in patients with episodic migraine and support further investigation of AMG 334 in larger phase 3 trials. Funding Amgen.

This study of ANCA-associated vasculitis compared a single course of rituximab with conventional immunosuppression with cyclophosphamide followed by azathioprine and showed similar results for the primary outcome of complete remission by 6 months, maintained through 18 months. Granulomatosis with polyangiitis (previously termed Wegener's granulomatosis) and microscopic polyangiitis are called antineutrophil cytoplasmic antibody (ANCA)–associated vasculitides because they are frequently accompanied by autoantibodies against proteinase 3 or myeloperoxidase. 1 , 2 For nearly four decades, cyclophosphamide and glucocorticoids have been the standard therapy for the induction of remission. However, the primary results of the Rituximab in ANCA-Associated Vasculitis (RAVE) trial 3 and results from a European trial 4 showed that rituximab was as effective as cyclophosphamide for the induction of remission in patients with severe disease. Moreover, the rituximab-based regimen was superior in patients who had relapsing disease at 6 months. 3 Rituximab has . . .