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24th July 2023
A separate and dedicated older people’s emergency department (OPED) does not significantly lower the level of hospitalisations compared to the main ED but does reduce the time spent in the department, according to a new study.
Older patients seen at an emergency department (ED), especially those with frailty often have more complex health needs. Consequently, there is a need to examine ways to improve care for such patients within an ED, and one possible solution is the development of a dedicated OPED.
In a recent study published in the Journal of Emergency Medicine, a team based at Norfolk and Norwich University Hospital (NNUH) NHS Foundation Trust looked at patient flow in a dedicated OPED – the first in England – against that of the main ED.
The team retrospectively compared the outcomes for older patients attending the main ED in 2019 against those attending the newly formed dedicated OPED service in 2020.
The primary outcome was the proportion of patients admitted to hospital, but the researchers examined a range of other outcomes including the meeting of England’s four-hour national waiting time target, re-admissions, all-cause 30-day mortality, clinical frailty screening and discharge to the patient’s original place of residence. Multivariable logistic regression was performed to estimate adjusted odds ratios between the two emergency departments.
A total of 748 patients with a mean age of 87 years (58.7% female) were included in the retrospective analysis), of whom, 374 were assessed in the OPED.
Clinical assessment in the OPED did not significantly lower the proportion of patients subsequently hospitalised (adjusted odds ratio, aOR = 0.84, 95% CI 0.61 – 1.16). Despite this, there were no significant differences in 30-day mortality (aOR = 1.03, 95% CI 0.54 – 2.00) or in re-admissions within seven days of discharge (aOR = 2.06, 95% CI 0.88 – 4.86).
In contrast, patients seen in the OPED were more likely to meet the national four-hour target (aOR = 3.13, 95% CI 2.29 – 4.29) and for being discharged to their original place of residence (aOR = 1.57, 95% CI 1.02 – 2.41). In addition, patients in the OPED spent significantly less time in the emergency department and were seen more quickly by a clinician (p < 0.001 in both cases).
An OPED includes adaptations in staffing, physical infrastructure and care delivery interventions, all of which aims to combine multidisciplinary staffing and early frailty assessment within an environment tailored to benefit older frail patients.
Commenting on these findings, Dr Katharina Mattishent, consultant in older people’s medicine at NNUH and clinical lecturer at Norwich Medical School, UEA, said: ‘We have demonstrated that patients seen in our environmentally modified area of the ED, led by consultant geriatricians, were three times more likely to meet the four-hour national target compared with those seen in the main ED. This is an important finding, as increased wait times are associated with increased inpatient length of stay, mortality, hospital admissions, and functional decline in those with cognitive impairment.‘
20th July 2023
A flexibly dosed, twice-weekly subcutaneous injection of ketamine over four weeks led to higher levels of clinical remission compared to midazolam in patients with treatment-resistant depression, according to a new phase III trial.
The trial by Australian researchers, which was published in the British Journal of Psychiatry, compared racemic ketamine with midazolam in two patient cohorts: one with fixed dosing and a second with a more flexible regimen.
The trial was initially designed to compare twice-weekly subcutaneous racemic ketamine (0.5 mg/kg) or midazolam (0.025 mg/kg) for four weeks, with at least three days between treatments. Data for these findings were referred to in the study as cohort one.
The dosing schedule was revised after a Data Safety Monitoring Board recommendation to flexible-dose ketamine 0.5–0.9 mg/kg or midazolam 0.025–0.045 mg/kg, with response-guided dosing increments. Data for these findings were referred to in the study as cohort two.
The primary outcome was remission, characterised by a Montgomery-Åsberg Rating Scale for Depression score of less than 10, after four weeks of treatment.
The final analysis comprised 68 patients in the fixed-dose cohort one and 106 in the flexible-dose cohort two.
Ketamine was found to be significantly more efficacious than midazolam in cohort two at achieving remission (odds ratio, OR = 12.1, 95% CI 2.1 – 69.2, p = 0.005). However, there was no significant different between the two treatments when given as a fixed dose in cohort one (OR = 1.3, 95% CI 0.2 – 8.2, p = 0.76).
In terms of safety, serious adverse events were rare and most were unrelated to the study drug. For instance, in cohort one, there were two serious adverse events in the midazolam group – a suicide attempt and mood deterioration – but both unrelated to the study medications. There were no serious adverse events in the ketamine group.
Among those in cohort two, there were three serious adverse events in the midazolam group: a suicide attempt, increased suicidal ideation and a wrist injury, which, again, were unrelated to the study treatments. In contrast, there were two serious adverse events in the ketamine group: one major dissociative episode and auditory hallucination, both of which were deemed to be related to treatment. No deaths were reported throughout the study.
Failing to respond to an adequate course of two or more treatments is referred to as treatment-resistant depression, and ketamine is a novel highly effective and rapidly acting treatment. It is available as an intravenous infusion of a racemic mixture and as a commercially developed single enantiomeric intranasal spray containing S-ketamine.
Immune checkpoint inhibitors have transformed the management of non-small cell lung cancer, but how long should treatment be continued for optimal survival? Clinical writer Rod Tucker takes a closer look at the evidence.
It has long been recognised that a hallmark of cancer is immune evasion and that the immune system is held back by inhibitory immune checkpoint receptors and ligands. The discovery that immune checkpoint inhibitors (ICIs) could interrupt these immune checkpoints and thereby provide an anti-tumour effect, leading to cancer regression, was a major therapeutic advance in oncology.
The first ICI to receive FDA approval was ipilimumab in 2011 and, since then, there have been several other agents approved by regulatory authorities across the world.
Lung cancer is the leading cause of global cancer incidence and mortality and it accounts for an estimated two million diagnoses and 1.8 million deaths worldwide, with non-small cell lung cancer (NSCLC) responsible for more than 80% of cases.
ICIs have been deployed in the management of NSCLC and drugs such as nivolumab have proved to be very effective treatments. Nevertheless, an important and practical consideration is how long to continue with the therapy. Guidance on the use of ICIs, such as the advice in the UK from NICE for pembrolizumab in NSCLC, recommends that treatment is halted after two years. However, in its guidance, the clinical experts at NICE accept that the optimal treatment duration is unknown and they acknowledge that extended duration treatment courses are likely to be burdensome for patients, hence the restriction.
But is this somewhat arbitrary limit of two years sufficient to derive an optimal survival response, or should it be longer? In the absence of objective evidence, clinicians are left to ponder whether adhering to this duration best serves the interests of their patients. Although some evidence indicates a prolonged survival with ICIs after treatment has ceased, there is clearly a need for more definitive data.
CheckMate 153 was the first randomised trial to examine the optimal duration of ICI therapy in patients with NSCLC. The trial compared a fixed one-year treatment regimen with nivolumab to a continuous one with exploratory analyses examining the incidence of adverse events, progression-free survival and overall survival. The results suggested a significant progression-free survival advantage favouring continuous treatment (hazard ratio, HR = 0.56, 95% CI 0.37 to 0.84).
The longest safety and efficacy data for patients with advanced NSCLC comes from the phase Ib KEYNOTE-001 study using pembrolizumab and included both previously treated and treatment naive patients. The findings, published in 2019, offered an insight of the five-year survival in those with advanced disease and the results were impressive. After 60.6 months, among previously treated patients, the median overall survival was 10.5 months in previously treated patients compared to 22.3 months in treatment-naive cohort.
Nivolumab also appears to provide impressive five-year survival data. In a study of previously treated patients with advanced NSCLC given nivolumab, the estimated five-year overall survival rate (after 96 weeks of therapy) was 16%.
Although these findings make clear that ICIs do improve survival in the longer term following cessation of treatment, there still remains the unanswered question as to how long is enough to derive these survival benefits.
The findings of a recent retrospective analysis could furnish clinicians with the answer they have been looking for.
Cognisant that most ICI trials continued for up to two years, researchers from the University of Pennsylvania evaluated the association between duration of therapy with overall survival. Publishing their findings in the journal JAMA Oncology, the team compared overall survival in those who had received ICI treatment for two years and those whose therapy continued for longer.
Survival outcomes were dichotomised as either between 700 and 760 days (i.e. two years, fixed duration) or greater than 760 days (i.e. an indefinite duration). After various adjustments for potential confounders, survival was found to be 79% in the two-year fixed-duration group and 81% for the indefinite-duration group. The hazard ratio for death associated with fixed-duration ICI therapy compared with the indefinite-duration group was non-significant (HR = 1.33, 95% CI 0.78 – 2.25, p = 0.29).
While there are recognised limitations from retrospective analyses, these findings do suggest that up to two years of ICI therapy is sufficient and that a longer duration – which is more costly and burdensome for patients – offers no survival benefit.
While guidance restricting the use of ICI therapy in NSCLC to no longer than two years might appear somewhat random, the latest evidence, although prefaced by important caveats, does appear to support that premise. Furthermore, the latest data should also offer reassurance to clinicians that these current restrictions are unlikely to affect their ability to deliver optimal care for patients with NSCLC.
19th July 2023
Using two cutting edge heart scanning techniques to scan patients with hypertrophic cardiomyopathy (HCM) has enabled the identification of microstructural and microvascular disease changes that can serve as early-phenotype biomarkers for the condition.
Patients with HCM are at an elevated risk of heart failure and sudden death, highlighting the need to identify those with the condition early. Fortunately, this has now become a step closer following the publication of a study by a team from Barts Health NHS Trust in the journal Circulation.
Both myocyte disarray and microvascular disease (MVD) have already been implicated in adverse events in patients with HCM. As a result, the Barts team measured myocardial microstructure and MVD in three groups of HCM patients: those with overt HCM; those who were genotype-positive (G+LVH+) or genotype-negative (G-LVH+) for HCM and subclinical (G+LVH-) HCM. The researchers also included a group of healthy, match controlled patients.
All individuals underwent a 12-lead ECG, plus cardiac MRI perfusion (perfusion CMR) to measure myocardial blood flow, perfusion reserve and perfusion defects, and cardiac diffusion tensor imaging (cDTI) measuring fractional anisotropy for which lower values were expected with more disarray.
The analysis included 206 subjects: 101 patients with overt HCM (51 G+LVH+ and 50 G-LVH+), 77 with G+LVH- and 28 matched healthy volunteers.
When compared against health volunteers, those with overt HCM had evidence of significantly altered microstructure, including lower fractional anisotropy, higher mean diffusivity and higher second eigenvector angle and for which p < 0.001 in each comparison.
Similarly, overt HCM patients had significant changes in microvascular parameters (again all p < 0.001), including lower stress myocardial blood flow and myocardial perfusion reserve.
Patients with G-LVH+ were similar to those with G+LVH+ but had elevated second eigenvector angle (p <0.001 after adjustment for left ventricular hypertrophy and fibrosis). In overt disease, perfusion defects were found in all G+ but not all G- patients.
In those with G+LVH- compared with healthy volunteers, there were similar alterations in the microstructure, although to a lesser extent, and MVD changes with perfusion defects in 28% versus 0 healthy volunteers.
In fact, disarray and MVD were independently associated with pathological electrocardiographic abnormalities in both overt and subclinical disease after adjustment for fibrosis and left ventricular hypertrophy.
The researched suggested that microstructural alteration and MVD occur in overt hypertrophic cardiomyopathy but are different in G+ and G- patients. Measurable changes in myocardial microstructure and microvascular function are early-phenotype biomarkers in the emerging era of disease-modifying therapy, they added.
Commenting on the research, lead author Dr George Joy, a clinical research fellow at Barts Heart Centre and University College London, said: ‘The ability to detect early signs of HCM could be crucial in trials testing treatments aimed at preventing early disease from progressing or correcting genetic mutations. The scans could also enable treatment to start earlier than we previously thought possible.
‘We now want to see if we can use these scans to identify which patients without symptoms or heart muscle thickening are most at risk of developing severe HCM and its life-changing complications. The information provided from scans could therefore help doctors make better decisions on how best to care for each patient.‘
Repeating liver stiffness measurements (LSM) allows for an individual and updated risk assessment for decompensation and mortality in patients with advanced chronic liver disease (CLD), a study has found.
LSM provide an opportunity for clinicians to non-invasively monitor liver disease progression and even regression. But is there a prognostic value in measurement of liver stiffness dynamics over time for liver-related events and death in patients with CLD?
This was the question posed in a recent retrospective study, published in the journal Gastroenterology by a team of researchers from the Department of Internal Medicine III at the Medical University of Vienna and University Hospital Vienna in Austria. They showed that the dynamics of LSM are directly linked to either an increased or decreased risk for hepatic decompensation in compensated and decompensated advanced CLD.
Researchers focused on patients with CLD undergoing more than two reliable LSM at least 180 days apart. For the purposes of the analysis, patients were categorised as having non-advanced CDL (nonACLD), compensated advanced CLD (cACLD) and decompensated advanced CLD (dACLD).
The primary objective to assess the association of longitudinal changes in LSM with clinical events of hepatic decompensation in nonACLD and cACLD patients. A range of secondary objectives included a comparison of LSM dynamics between different disease severity groups and an exploratory analysis of the impact of dynamics of LSM on liver-related mortality in dACLD.
A total of 2,508 patients with 8,561 reliable LSM (a median of three per patient) were included in the analysis. This comprised 65.7% with non-ACLD, 30.2% with cACLD and 4.1% with dACLD. In addition, 83 patients with cACLD developed hepatic decompensation after a median follow-up of 71 months.
The researchers found that a 20% increase in LSM at any time was associated with an increased risk for hepatic decompensation (Hazard ratio, HR = 1.58, 95% CI 1.41 – 1.79, p < 0.001) as well as hepatic-related mortality (HR = 1.45, 95% CI 1.28 – 1.68, p < 0.001) in cACLD patients.
In addition, LSM dynamics yielded a high accuracy to predict hepatic decompensation in the following 12 months (area under the curve, AUC = 0.933). This performance was numerically superior to dynamics in FIB-4 (AUC = 0.873), MELD (AUC = 0.835) and single time-point LSM.
Any LSM decrease to less than 20 kPa identified cACLD patients with a substantially lower risk of hepatic decompensation (HR = 0.13, 95% CI 0.07 – 0.24).
Commenting on these findings, the study’s principal investigator Thomas Reiberger said: ‘An understanding of the individual patient’s personal risk profile means that it is possible to initiate optimised, personalised treatment.‘
Indeed, taken together, the findings of the study reveal how regular measurements of liver stiffness indicate a personalised patient risk profile, which enables the initiation of individualised treatment strategies.
A series of points to consider to help define the clinical and imaging features of people with psoriasis who transition to psoriatic arthritis (PsA) have been developed by the European Alliance of Associations for Rheumatology (EULAR) in order to identify those who might benefit from a therapeutic intervention.
The fact that psoriasis typically develops some 10 years before PsA, provides an opportunity for clinicians to investigate risk factors and predictors for PsA in those with the skin disease. Now, with the help of both dermatologists and rheumatologists, a EULAR multidisciplinary taskforce of 30 members and from 13 European countries has produced five overarching principles and a total of 10 points to consider.
Published in the Annals of the Rheumatic Diseases, these principles acknowledge that not everyone with psoriasis will go on to develop PsA, and even among those who do develop the arthritis, this can occur at different times. The taskforce also stress the importance of being able to identify specific risk factors for PsA and how these could influence the choice of treatment, which is crucial given that some systemic psoriasis treatments might reduce the risk of transitioning to PsA.
The 10 points highlight that arthralgia, together with abnormalities seen on ultrasound or magnetic resonance imaging scans, represent key elements of subclinical PsA that could serve as short-term predictors. Additionally, the more traditional risk factors for PsA – such as psoriasis severity, obesity and nail involvement – can be seen as more long-term disease predictors.
EULAR suggests standard naming to define the three distinct stages relevant to the prevention of PsA: people with psoriasis at higher risk of PsA, subclinical PsA and clinical PsA. This, the EULAR group felt, was important because in other inflammatory rheumatic musculoskeletal diseases, such as rheumatoid arthritis, the clinical onset is usually preceded by a preclinical phase encompassing arthralgia and immunological or imaging abnormalities, but without a clinical diagnosis.
A definition for early psoriatic arthritis was proposed by EULAR based on the development of joint swelling as a clinical outcome measure for trials of PsA prevention.
EULAR believes that the points to consider will help to define the clinical and imaging features of those with psoriasis that raise the index of suspicion for progression to PsA. Furthermore, these points could be used to identify people who could benefit from a therapeutic intervention to delay or prevent PsA.
An additional and important practice issue, is that clinicians inform patients with psoriasis about the risk of developing PsA and encourage them to report any joint-related symptoms to facilitate early diagnosis. Previous studies have shown that even a diagnostic delay as short as six months can lead to significantly more severe radiographic joint damage, worse physical function and decrease the changes of therapeutic success
18th July 2023
The assumption that pathogen populations within a host are clonal and therefore antimicrobial resistance (AMR) will occur through the emergence of de novo variants has been challenged by a new study offering insight into the mechanism through which AMR is generated.
Published in the journal Nature Communications, the study showed how mixed strain infections within the host play a key role in shaping the emergence of resistance in response to treatment.
Using Pseudomonas aeruginosa – an opportunistic pathogen that is an important cause of hospital-acquired infection – as an example, they studied changes in the genetic diversity and antibiotic resistance of Pseudomonas aeruginosa collected from lower respiratory tract samples from intensive care unit (ICU) patients before and after antibiotic treatment.
The patients were part of the ASPIRE-ICU observational trial of Pseudomonas infection across European hospitals. They were screened for Pseudomonas soon after admission to ICU and at regular intervals thereafter.
Pseudomonas isolates were sampled in an unbiased manner – without a consideration of resistance phenotypes – and up to 12 randomly chosen isolates were collected from all patient samples containing Pseudomonas. These samples were analysed using a combination of phenotypic assays, looking at resistant organisms and genomic analyses to quantify within-patient diversity and antibiotic resistance.
In total, 441 isolates were collected to characterise the diversity of Pseudomonas aeruginosa using lower respiratory tract samples from 35 ICU patients in 12 different hospitals.
The researchers found that while 23 of the 35 patients were colonised with a single strain, roughly a third (12 patients) displayed multiple strains and this strain diversity tended to be high.
Antimicrobial resistance evolved rapidly in patients colonised by diverse Pseudomonas aeruginosa populations, and this occurred through selection of pre-existing resistant strains, showing a clear link between within-host diversity and resistance.
The researchers suggested that this underscored the importance of within-host bacterial diversity as a means for understanding antimicrobial resistance.
They also felt that in future, measuring the diversity of pathogen populations could make it possible to more accurately predict the likelihood of treatment failure for individual patients.
Eblasakimab is the first biologic treatment for moderate to severe atopic dermatitis to show a competitive efficacy profile when given as a once-monthly dose, according to data released by the manufacturer, Aslan pharmaceuticals.
The novel monoclonal antibody targets the interleukin-13 (IL-13) receptor subunit of the Type 2 receptor, that is a key pathway in several allergic inflammatory diseases, including atopic dermatitis.
The findings, while yet to be published, relate to the phase 2b TREK-AD study, which randomised patients to one of five eblasakimab dosing arms for a total of 16 weeks: 300 mg every two weeks, 400 mg every two weeks, 400 mg every four weeks, 600 mg every four weeks or a placebo.
The study’s primary endpoint was the percentage change from baseline in the Eczema Area and Severity Index (EASI) score at week 16 versus placebo. The study also included a validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) score of 0/1 (i.e. clear or almost clear).
A total of 289 patients were randomised and treated in the intent-to-treat (ITT) population across the five dosing arms. Patients treated with eblasakimab 600mg, 400mg and 300mg, all saw a rapid onset of action in the first few weeks of treatment, with a statistically significant improvement in EASI score by Week 4.
When assessed at Week 16, some 62.7% of eblasakimab patients given 600 mg monthly achieved a reduction of at least 75% from baseline (EASI-75) compared to 30.7% given the placebo (p = 0.0041).
In addition, 34.1% of eblasakimab patients receiving the 600 mg dose, achieved an EASI90, compared to only 10.1% on the placebo (p = 0.0088).
Finally, 31.2% of these patients achieved vIGA-AD score of 0 or 1 compared to 15.1% with the placebo (p = 0.0502).
No new safety signals were seen in the study, and the frequency of adverse events was comparable between the active eblasakimab treatment and placebo arms, with the most frequently observed adverse events being nasopharyngitis (13.4% vs 8.8% for placebo), atopic dermatitis (8.6% vs 7.0% for placebo), headache (6.9% vs 7.0% for placebo) and upper respiratory tract infection (6.5% vs 5.3% for placebo).
Commenting on these findings, Eric L. Simpson, lead investigator in the TREK-AD study and Frances J. Storrs Professor of Medical Dermatology at the Oregon Health and Science University, said: ‘This is the first time we’ve seen a once-a-month treatment option deliver competitive efficacy data, which would be a game-changer for patients with atopic dermatitis.
‘We haven’t seen much in the way of advancement since the launch of dupilumab, and there remains a huge unmet burden of disease experienced by patients. These results support eblasakimab’s potential to be a leading therapy for the treatment of atopic dermatitis, if approved.‘
Use of a direct oral penicillin challenge in patients with a low-risk of penicillin allergy has been shown to be non-inferior to the standard-of-care skin testing in the recent PALACE randomised trial.
Removing the label of being allergic to penicillin involves intra-dermal skin testing followed by an oral penicillin challenge. Now, an international research group has shown that a direct oral penicillin challenge in those with a low-risk penicillin allergy is equally as safe as the current standard-of-care assessment.
In the parallel, two-arm, non-inferiority, open-label, randomised trial, patients with a PEN-FAST score below three, were randomly allocated to either the intervention group who had a direct oral challenge with penicillin, or the control group who received the standard of care.
The primary outcome of interest was a physician-verified positive immune-mediated oral penicillin challenge within one hour after the intervention. Researchers set the non-inferiority margin as a risk difference of less than five on a one-sided 95% confidence interval.
The trial recruited a total of 382 adults who were randomised, although only 377 patients with a median age of 51 years (65.5% female) were included in the final analysis. Among these, 187 were allocated to the intervention group. Most patients had a PEN-FAST score of 0 or 1.
The primary outcome occurred in only a single patient in both groups, giving a risk difference of 0.0084, which was below the non-inferiority margin.
In the five days following the oral penicillin challenge, a total of nine immune-mediated adverse events were recorded in the intervention group and 10 in the control group. None of these were deemed to be serious.
Dr Ana-Maria Copaescu, first author of the study and associate investigator in the Infectious Diseases and Immunity in Global Health Program at the Research Institute of the McGill University Health Centre in Quebec, said: ‘The biggest takeaway from the PALACE study is that patients with a low-risk penicillin allergy, like a childhood rash, can safely have a test dose of penicillin to determine if they are still allergic.
‘This will change the way doctors test for penicillin allergy in the future. Millions of patients worldwide… will be able to have their penicillin allergy disproved by a safe single oral test dose following a carefully risk-validated risk assessment.‘
Antibiotics such as penicillin are widely used in clinical practice although a true allergy to these drugs is rare with an estimated frequency of anaphylaxis at one to five per 10,000 cases. Hypersensitivity reactions are significantly more common, resulting in symptoms such as nausea, vomiting, pruritus, urticaria and wheezing.
Donanemab has been found to slow the progression of early symptomatic Alzheimer’s disease after 76 weeks of treatment, according to the findings of a phase 3 randomised trial.
The monoclonal antibody donanemab, which targets the insoluble, modified, N-terminal truncated form of β-amyloid present only in brain amyloid plaques, was given to patients with early symptomatic Alzheimer disease with amyloid and tau pathology. Nearly half of those given the drug showed no signs of disease progression after 12 months.
Commenting on the research, Dr Richard Oakley, associate director of research and innovation at the Alzheimer’s Society, said: ‘This is truly a turning point in the fight against Alzheimer’s and science is proving that it is possible to slow down the disease. Treatments like donanemab are the first steps towards a future where Alzheimer’s disease could be considered a long-term condition alongside diabetes or asthma.‘
Published in the Journal of the American Medical Association, participants of the TRAILBLAZER-ALZ 2 trial were categorised as having either low/medium or high tau pathology and randomised 1:1 ratio to receive donanemab or a placebo intravenously every four weeks for 72 weeks.
The primary outcome of interest was the change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks. There were a number of secondary outcomes, one of which was the change in the sum of boxes of the Clinical Dementia Rating Scale (CDR-SB) score.
A total of 1,736 participants (57.4% women) with a mean age of 73.0 years were recruited. Some 68.1% had low/medium tau pathology and 76% completed the trial.
The least-squares mean (LSM) change in iADRS score at 76 weeks was −10.2 with donanemab and −13.1 with placebo (difference = 2.92, p < 0.001) for the combined population. In addition, the LSM change in CDR-SB score at 76 weeks was 1.72 with donanemab and 2.42 with placebo (difference = −0.7 p <0 .001) in the combined population.
Furthermore, an estimated 47% of participants receiving donanemab had no change in the CDR-SB at one year (i.e. no disease progression) compared with 29% of participants receiving the placebo.
The trial also revealed how donanemab treatment significantly reduced brain amyloid plaque at all time points assessed, with 80% (low/medium tau population) and 76% (combined population) of participants achieving amyloid clearance at week 76.
The level of clearance beyond 76 weeks, as well as levels of Alzheimer disease biomarkers, are currently being studied in an ongoing extension phase.
In subgroup analysis, among participants with mild cognitive impairment, donanemab slowed decline by 60% on iADRS and 46% on CDR-SB. Additionally, in an analysis based on participant’s age, in those under 75 years, donanemab slowed decline by 48% on iADRS and 45% on CDR-SB, whereas the drug slowed decline by 25% on iADRS and 29% on CDR-SB in those over 75 years.
Liana Apostolova, distinguished professor in Alzheimer’s Disease research and professor in neurology, radiology, medical and molecular genetics at Indiana University School of Medicine, said: ‘These results demonstrate that diagnosing and treating people earlier in the course of Alzheimer’s disease may lead to greater clinical benefit. The delay of disease progression over the course of the trial is significant and will give people more time to do such things that are meaningful to them.‘
Dr Oakley added: ‘It’s also important to note that side effects did occur, although serious side effects only occurred in 1.6% of people receiving the drug. Regulators will need to balance these side effects against the benefits of the drug.
‘We should also note that the majority of people who took part in this trial were white – it’s crucial that in future trials we see more diversity to prove that new drug treatments have similar effects for everyone living with Alzheimer’s disease.‘
Highlighting the ‘defining moment for dementia research‘, Kate Lee, Alzheimer’s Society CEO, added: ‘New treatments could mean nothing if we don’t fix dementia diagnosis. We estimate around 720,000 people in the UK could potentially benefit from these emerging new Alzheimer’s disease treatments if they’re approved for use here. But the NHS is simply not ready to deliver them.
‘Everyone living with dementia deserves access to a speedy, accurate diagnosis to get the support and treatments they need, now and in the future.‘
This comes shortly after news that diagnosing Alzheimer’s disease through the use of blood biomarkers could transform care for patients after new proposed guidelines were presented at the International Alzheimer’s Congress in Amsterdam.
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