T helper cell

Dupilumab in Persistent Asthma with Elevated Eosinophil Levels.

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BACKGROUND

Moderate-to-severe asthma remains poorly treated. We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.

METHODS

We enrolled patients with persistent, moderate-to-severe asthma and a blood eosinophil count of at least 300 cells per microliter or a sputum eosinophil level of at least 3% who used medium-dose to high-dose inhaled glucocorticoids plus long-acting beta-agonists (LABAs). We administered dupilumab (300 mg) or placebo subcutaneously once weekly. Patients were instructed to discontinue LABAs at week 4 and to taper and discontinue inhaled glucocorticoids during weeks 6 through 9. Patients received the study drug for 12 weeks or until a protocol-defined asthma exacerbation occurred. The primary end point was the occurrence of an asthma exacerbation; secondary end points included a range of measures of asthma control. Effects on various type 2 helper T-cell (Th2)–associated biomarkers and safety and tolerability were also evaluated.

RESULTS

A total of 52 patients were assigned to the dupilumab group, and 52 patients were assigned to the placebo group. Baseline characteristics were similar in the two groups. Three patients had an asthma exacerbation with dupilumab (6%) versus 23 with placebo (44%), corresponding to an 87% reduction with dupilumab (odds ratio, 0.08; 95% confidence interval, 0.02 to 0.28; P<0.001). Significant improvements were observed for most measures of lung function and asthma control. Dupilumab reduced biomarkers associated with Th2-driven inflammation. Injection-site reactions, nasopharyngitis, nausea, and headache occurred more frequently with dupilumab than with placebo.

CONCLUSIONS

In patients with persistent, moderate-to-severe asthma and elevated eosinophil levels who used inhaled glucocorticoids and LABAs, dupilumab therapy, as compared with placebo, was associated with fewer asthma exacerbations when LABAs and inhaled glucocorticoids were withdrawn, with improved lung function and reduced levels of Th2-associated inflammatory markers.

Source: NEJM

 

 

 

 

 

30 years of HIV: where next?.

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Kuala Lumpur will host the 2013 International AIDS Society (IAS) meeting from June 30—July 3. This issue of The Lancet will be there too, with its content rich in the diverse diaspora that characterises global efforts to prevent, treat, and ultimately cure the disease that today affects 34 million people worldwide.

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The emergence of antiretroviral therapy (ART) in 1996 heralded a new era in HIV treatment that continues to this day. The scale-up of ART in the past few years is testament to the extraordinary international public health response to the epidemic. In 2011, for the first time, more than half of people eligible for ART in low-income and middle-income countries were receiving it (54%): the glass is just over half full. But accessibility to ART is only the start of the so-called treatment cascade, where individuals with HIV and country programmes have to be prepared for the reality of first-line treatment failure and the commitment to switch therapy, and to adhere to it. An Article by Mark Boyd and colleagues offers a welcome new therapeutic option after first-line treatment failure.

HIV prevention efforts remain key, yet a vaccine remains frustratingly elusive, with the failure of the latest trial, HVTN-505, announced in April. However, a new scientific movement is emerging, illustrated by a 2 day symposium attached to IAS 2013 that will discuss new approaches in basic science under an arresting banner: towards an HIV cure. A Review by Rafick Sekaly outlines the molecular barriers that currently stand in the way of this goal, and sets out future strategies for ultimately conquering the virus, including the initiation of ART at higher CD4 cell counts, and gene therapy. But as Sharon Lewin rightly articulates in a Comment, expectations must not run away from reality. Although the ultimate goal must be a world free of HIV for all people, rich or poor, our efforts of the past three decades must be sustained to prevent and treat a disease for which a cure, tantalising though that sounds, almost certainly remains years away.

Source: Lancet