Despite the success of immune modulation in the treatment of relapsing multiple sclerosis, disability progression is a major problem driven by multiple mechanisms. Comorbidities (eg, vascular risk) and ageing are thought to augment these neurodegenerative pathologies. In the phase 2b MS-STAT trial of simvastatin (80 mg) versus placebo in secondary progressive multiple sclerosis (SPMS), the adjusted difference in brain atrophy rate between groups was -0·254% per year: a 43% reduction. In this phase 3 MS-STAT2 trial, we aimed to assess the efficacy of simvastatin versus placebo in slowing the progression of disability in SPMS.

An estimated 3-10% of patients with asthma are unable to reach full control with currently available inhaled therapies. In a large proportion of these patients, asthma can be driven in whole or in part by type 2 (T2) inflammation, which is usually initiated by an immunological response to stimulation at mucosal surfaces. The introduction of monoclonal antibodies, which target T2 inflammatory processes, provides important options for this population. In the past decade, five anticytokine biologics (ACBs) that block specific T2 inflammatory cytokines have been introduced. Three biologics, mepolizumab, reslizumab, and benralizumab, inhibit the IL-5 or IL-5 receptor pathway; dupilumab blocks IL-4 and IL-13 through its activity on the IL-4 receptor-alpha; and tezepelumab prevents activation of the thymic stromal lymphopoietin cytokine production cascade. These drugs reduce exacerbations and improve lung function and patient-reported asthma quality of life in individuals with a history of asthma exacerbations and evidence of T2 inflammation. Some also allow oral corticosteroid reduction or elimination in patients dependent on these therapies for asthma control. The effect of ACBs varies by the degree of T2 inflammation, which is most easily assessed by blood eosinophil counts and exhaled nitric oxide. The use of ACBs guided by these biomarkers and phenotypic characteristics of patients with severe asthma allows a personalised medicine approach that increases the likelihood of improvement.

Combination inhaled corticosteroid-formoterol reliever monotherapy reduces the rate of asthma attacks compared to short-acting β2-agonist (SABA) reliever monotherapy in adults. Its comparative efficacy in children has not been established.

Antimicrobial resistance is a global health threat. Many children with acute illness in ambulatory care are unnecessarily prescribed antibiotics. We assessed the clinical effectiveness of a clinical decision tool for these children, including a validated decision tree, guided point-of-care C-reactive protein testing (POCT of CRP), and safety-netting advice.

C3 glomerulopathy is an ultra-rare, severe form of glomerulonephritis caused by overactivation of the alternative complement pathway. We aimed to assess efficacy and safety of iptacopan (LNP023), an oral, proximal complement inhibitor that targets factor B to selectively inhibit the alternative pathway of the complement cascade.