Ann Robinson reviews the latest research from the top medical journals
IL-6 anatgonists reduce covid-19 deaths at 28 days
Do interleukin-6 (IL-6) antagonists such as tocilizumab and sarilumab lower rates of mechanical ventilation and death from covid-19? Reports to date have been mixed, but this large prospective meta-analysis of 10 930 patients across 27 randomised clinical trials has found a greater chance of being discharged alive within 28 days of randomisation in those receiving IL-6 antagonists. Overall, 23% of patients died within 28 days, and the absolute risk for progression to intermittent mandatory ventilation (IMV) or death in patients who received corticosteroids plus IL-6 antagonists was 26% compared with an assumed risk of 33% for those reiving corticosteroids plus usual care or placebo. Unfortunately, all-cause mortality at 90 days didn’t show a sustained improvement, but data were limited. The heterogeneity of studies inevitably leads to limitations, and some of the included trials are still ongoing. Most (65.9%) of the data on tocilizumab came from the RECOVERY trial, and 71% of the sarilumab data came from the Regeneron trial, but these are mainly conducted in high income countries and may not translate to all healthcare settings. Most of the data will predate widespread vaccination, and they are a stark reminder of the high mortality from severe covid-19 that was the norm.
JAMA doi:10.1001/jama.2021.11330
Nudging towards lower antibiotic prescribing
How do you solve the problem of high antibiotic prescribing in primary care? An estimated 25-50% of all antibiotics initiated in primary care are said to be unnecessary and are often prescribed for longer than needed, especially by older doctors. A randomised clinical trial of 3500 primary care Canadian doctors found that a single mailed feedback letter to high prescribers telling them that their prescribing was in the highest quartile had limited impact (4.2% relative difference in overall prescribing). A letter about initiation of antibiotics had no impact on the doctors’ prescribing 12 months later, but a letter about duration of treatment corresponded to a modest but significant fall in prescribing (4.8% fewer prescriptions and relative 8.1% fewer prolonged duration prescriptions). A single letter may not be enough to effect change; only about a third of the doctors remembered having received the letter. And really, who reads letters now? Perhaps a text alert would be more persuasive. The effect size was modest, but it could be effective if rolled out on a national scale. It seems that telling doctors that they’re outliers compared with their peers is a potentially powerful way to change behaviour.
JAMA Intern Med doi:10.1001/jamainternmed.2021.2790
Options for psoriasis
Bimekizumab, a monoclonal antibody inhibitor of interleukin 17A and 17F, was more effective than the tumour necrosis factor inhibitor adalimumab in reducing symptoms and signs of moderate-severe plaque psoriasis, but it was associated with more side effects such as oral candidiasis and diarrhoea in this study. Longer, larger trials are needed to compare its safety and efficacy with other treatments; the 24 weeks of treatment with the active comparator in this study was too short given that psoriasis is a lifelong condition.
Another pharma funded and designed trial found that bimekizumab resulted in greater skin clearance than treatment with secukinumab, a selective interleukin 17A inhibitor, over 16 and 48 weeks. Again, bimekizumab resulted in more oral candidiasis. There was no placebo arm in this study, and the trial population was not diverse, but the two studies point to a hopeful addition to the range of options available to people living with psoriasis.
N Engl J Med doi:10.1056/NEJMoa2102388
N Engl J Med doi:10.1056/NEJMoa2102383
Levels of obesity in China: continued rise in rural areas
One in every five people on the planet is Chinese, so trends in China are of global significance. And this detailed analysis of six consecutive, nationally representative, health surveys between 2004 and 2018 found that an estimated 85 million adults aged 18-69 years in China were obese in 2018, which was three times as many as in 2004, although the rise in mean body mass index (BMI) has slowed down in urban areas since 2010, when national prevention programmes were rolled out. Women in rural areas and those with lower educational levels had higher mean BMIs, but the inverse was true among men. Further monitoring is needed to assess longer term trends, but this survey highlights the need for health policies to stop the continuing rise of obesity in China, especially in rural areas.
Lancet doi:10.1016/S0140-6736(21)00798-4
HIV outlook has improved, but mortality still slightly raised
This observational cohort study from 13 sites across the US found that 5-year, all-cause mortality among 82 766 participants starting HIV care between 1999 and 2017 was 10.6%, compared with a mortality of 2.9% in a matched US population. The difference got smaller over time, as the outlook for those living with HIV has improved (difference of 11.1 percentage points in 1999-2004 compared with only 2.7 percentage points in 2011-17). An important caveat is that differences in mortality may reflect sociodemographic factors rather than the consequences of HIV infection. But the headline finding is that mortality for people starting treatment for HIV infection in the US has decreased markedly, though it remains a bit higher than in the general population.
Ann Intern Med doi:10.7326/M21-0065
Ann Robinson is an NHS GP and health writer and broadcaster.