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22nd June 2023
Use of a ceramide-containing cleanser and lotion significantly reduces the localised adverse effects of a retinoid-benzoyl peroxide gel used to treat acne, according to a recent randomised, placebo-controlled trial.
It was suggested in 1995 that an impaired water barrier function in the skin due to reduced amounts of ceramides may be responsible for the formation of acne lesions. Topical retinoids combined with benzoyl peroxide represent an effective treatment regime for acne. However, the combination is association with localised adverse effects characterised by burning, itching, tightness and dryness. Some evidence suggests that changes to the composition of the vehicle for acne medications, enhances tolerability.
Since a more tolerable vehicle might reduce skin irritation and possibly enhance treatment adherence, in the current study published in the Journal of Drugs in Dermatology, researchers performed a double-blind study was to measure the impact of acne treatment on skin barrier function when paired with a ceramide routine.
Participants using an adapalene and benzoyl peroxide (A/BPO) gel for the treatment of their acne, were recruited and randomised to an intervention or placebo group. The intervention group received a ceramide-containing foaming facial cleanser and facial lotion whereas the placebo group received basic foaming face wash, both of which were for twice-daily use. Participants applied the A/BPO gel once daily and self-reported measures of skin irritation. Both transepidermal water loss (TEWL) and the efficacy of A/BPO were also assessed.
A total of 91 participants completed the study, of whom 45 were in the ceramide arm.
Among those using the ceramide routine, TEWL was significantly lower after four weeks of treatment and remained so for all 12 weeks of the study (p < 0.05). Measures of skin dryness and scaling were significantly improved in the ceramide group after one week (p < 0.05), whereas erythema was only significantly improved at week four. Overall, a higher proportion of the intervention group reported having less skin dryness, tightness and that their skin felt more comfortable throughout the duration of the study.
The total mean count of inflammatory lesions was significantly lower after four weeks in the intervention group and this was maintained thereafter until week 12 (p < 0.05). However, there were no significant differences in the mean non-inflammatory lesion counts.
The authors concluded that while a topical A/BPO gel caused damage to the skin barrier, the associated symptoms such as irritation could be significantly reduced through the use of a ceramide routine.
An electronic prescribing (EP) system within an intensive care unit (ICU) requires a lower level of clinical pharmacist input compared to a paper-based system, according to a recent prospective, longitudinal UK study.
Although EP systems are designed to reduce medication errors, the quality of evidence on their effectiveness is variable. Nevertheless, within an ICU setting, the use of commercial computerised provider order entry systems led to an 85% reduction in medication prescribing error rates and a 12% reduction in ICU mortality rates. However, few studies have focused on whether EP systems optimise medication therapy, reduce costs, improve the quality of prescribing and patient outcomes.
In the current study, published in the International Journal of Medical Informatics, researchers compared the clinical significance of pharmacist contributions in two ICU departments to understand the impact of an EP system on the quality of patient care.
The team chose one department that used an EP system and compared the extent of pharmacist input with a second department using a paper-based prescribing (PBP) system. The primary outcome was the distribution of clinical significance levels of pharmacist contributions. This was assessed using a tool that assigned a clinical significance rating to pharmacists’ contributions based on the mitigation of risk or negative outcome for the patient and ranged from I (low level) to V (high level).
A total of 303 patients were included, with EP used in 171 patients. Overall, 1,658 contributions were analysed.
The median number of patient reviews in both groups was similar, as was the proportion of reviews with no change (49.3% vs 48.5%, PBP vs EP). In addition, there were 14.9% highly clinically significant pharmacist contributions (levels III and above) with EP compared to 44.6% with PBP.
The EP group had a lower odds for a higher clinical significance contribution compared to the PBP group (Odds ratio, OR = 0.05, 95% CI 0.02-0.12). However, over time, there was a lower odds of a higher level contribution from the PBP group (OR = 0.57, 95% CI 0.42 – 0.78, p < 0.001).
Based on these findings, the researchers concluded that the clinical significance of pharmacist contributions remained both low and stable in over time in the EP group. Moreover, while initially higher, pharmacists in an ICU using a PBP system actually reduced over time.
Taken together, the study suggests that the use of an EP system required significantly less pharmacist input to maintain patient safety, possibly because the EP system enables access to data to improve decision-making at the point of prescribing.
Perioperative pembrolizumab in patients with early-stage non-small cell lung cancer (NSCLC) leads to a significant improvement in event-free survival, but not overall survival, according to the findings of a recent randomised, placebo-controlled clinical trial.
Existing evidence points to an event-free survival benefit from using neoadjuvant durvalumab, an anti-programmed cell death-1 agent in resectable stage NSCLC. However, whether similar advantages would arise from the perioperative and adjuvant usage of pembrolizumab, a programmed cell death protein 1 inhibitor, in early stage NSCLC is uncertain.
Recently, an international research group published a randomised, placebo-controlled trial in the New England Journal of Medicine, to evaluate perioperative pembrolizumab in patients with early-stage NSCLC.
Eligible participants had resectable stage NSCLC and were randomised 1:1 to either perioperative pembrolizumab (200 mg) or placebo once every three weeks, with cisplatin-based chemotherapy. This was followed by surgery and then adjuvant pembrolizumab (200 mg) or placebo once every three weeks.
A dual primary endpoint of event-free survival and overall survival was used, with secondary endpoints of a major pathological response, pathological complete response and safety.
A total of 797 participants, of whom 397 were assigned to the pembrolizumab group, were included in the analysis.
The median time from randomisation to the data-cut-off date was 25.2 months. Event-free survival at 24 months was significantly higher in the pembrolizumab group compared to placebo (hazard ratio, HR, for progression, recurrence or death = 0.58, 95% CI 0.46 – 0.72, p < 0.001). In contrast, the estimated 24-month overall survival was not significantly different to placebo.
A major pathological response occurred in a significantly higher proportion of participants assigned to perioperative pembrolizumab (p < 0.0001). Similarly, there was a significantly higher pathological complete response (p = 0.0001).
Any treatment-related adverse events cross the treatment phases were reported in a similar proportion of patients (96.7% vs 95%, pembrolizumab vs placebo).
The use of biologics in women with psoriasis who are either pregnant or planning to conceive is not associated with an increased risk of miscarriage, abortion or congenital malformations, according to the findings of a recent study.
The available literature suggests that psoriasis improves during pregnancy although there is a slight risk of a disease flare following delivery. Although biologics are used for patients with moderate to severe psoriasis, the continued use of biologic therapy in pregnancy is a difficult decision to make because of the lack of safety data. Moreover, these decisions are further hampered by the fact that pregnant women are invariably excluded from clinical trials using biologics.
With uncertainty over the safety of biologics in pregnancy, in the current study, published in Journal of the European Academy of Dermatology and Venereology, Spanish researchers conducted a systematic review and meta-analysis to examine examine pregnancy outcomes in women with psoriasis exposed to biologics within three months before or during pregnancy. The team also included studies where women were planning to conceive and who were exposed to biologics.
A total of 51 observational studies in women with a mean age of 30.3 years and with 739 pregnancies exposed to approved biologics were included in the analysis. In most cases (70.4%) the biologics were administered during the first trimester, with the most common agent being ustekinumab (36.0%), followed by etanercept (19.3%). However, there were no studies with newer agents such as brodalumab, risankizumab or bimekizumab.
The estimated prevalence of miscarriage was 15.3% (95% CI 12.7 – 18.0) and elective abortions, 10.8% (95% CI 7.7 – 14.3). Congenital malformations occurred in about 3.0% (95% CI 1.6 – 4.8) of live births. These estimates were similar to those reported in the general population.
The researchers concluded that biologics used in psoriasis are safe and pose an acceptable risk to foetuses and neonates.
Colchicine has become the first anti-inflammatory agent to be approved by the US Food and Drug Administration (FDA) for the treatment of cardiovascular disease (CVD).
According to the Europe-based manufacturer, Agepha Pharma, the FDA has approved colchicine 0.5 mg as the first anti-inflammatory athero-protective cardiovascular treatment, for patients either with established CVD or with multiple risk factors for the disease.
While both inflammation and hypercholesterolaemia jointly contribute to atherothrombotic disease, an analysis published in The Lancet in 2023, found that in patients receiving statins, inflammation was a stronger predictor for risk of future cardiovascular events and death than cholesterol. Colchicine achieves a beneficial effect in CVD at the cellular level through several mechanisms that include inhibition of endothelial cell dysfunction and inflammation, smooth muscle cell proliferation and migration, macrophage chemotaxis, migration, adhesion and platelet activation.
Evidence that colchicine is effective in CVD comes from a large study published in the New England Journal of Medicine. Over 5,000 patients with chronic coronary disease were randomised to colchicine 0.5 mg daily or matching placebo. The primary endpoint for the trial was a composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischaemic stroke or ischaemia-driven coronary revascularisation.
After a median of 28.6 months, significantly fewer patients assigned to colchicine experienced a primary endpoint event (hazard ratio, HR = 0.69, 95% CI 0.57 – 0.83, p < 0.001). Other work has also revealed how colchicine is effective in patients with chronic coronary disease both prior to and following an acute coronary syndrome.
Commenting on the approval, Paul Ridker, a consultant for Agepha Pharma as well as professor of medicine at Harvard Medical School and director of the Centre for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, said: ‘Approval by the FDA of the first drug to target cardiovascular inflammation is an important step forward for the care of our patients.
‘To treat coronary disease effectively, cardiologists must aggressively reduce inflammation and cholesterol. For appropriate patients already taking a statin, adding the anti-inflammatory drug colchicine at a dose of 0.5 mg daily has been proven to significantly lower risks of recurrent heart attack and stroke.‘
Colchicine is formulated as a once-daily, continuous-use oral treatment for adults that can be used safely either alone or in combination with standard-of-care lipid-lowering medications to effectively reduce the risk of heart attack and stroke.
The manufacturer anticipates that it will be available for prescription in the US in the second half of 2023. Potential plans for gaining approval in the UK or EU are currently unknown.
Topical roflumilast is being increasingly trialled for a number of skin conditions but how effective is it, and will it take centre stage in the field of dermatology? Rod Tucker investigates.
Oral roflumilast is licensed for maintenance treatment in severe chronic obstructive pulmonary disease. Its mode of action relates to the suppression of inflammation, but this benefit extends far beyond respiratory diseases.
Roflumilast inhibits the enzyme phosphodiesterase 4 (PDE4), which hydrolyses cyclic adenosine monophosphate (cAMP), a secondary messenger within cells that is involved in many biological processes in the body. With research suggesting that higher levels of cAMP supress inflammation, PDE4 inhibitors effectively suppress the production of inflammatory markers.
PDE4 inhibitors have become a promising class of drugs with a potential role in a number of therapy areas such as pulmonary, dermatological and neurological diseases. To date, there are two further PDE inhibitors available: apremilast, which is an established oral therapy for psoriasis, and crisaborole, a topical agent used to treat atopic eczema.
But how effective is topical roflumilast in the management of skin diseases?
Topical roflumilast 0.3% has gained gained FDA approval for use in patients with plaque psoriasis. In the two trials leading to FDA approval, disease severity was assessed by a score of ‘clear’ or ‘almost clear’ and a two-point improvement on the Investigator Global Assessment (IGA) scale. This endpoint was achieved by 41.5% and 36.7% of patient treated with topical roflumilast compared to 5.8% and 7.1% with placebo.
In addition, roflumilast has also been found to significantly improve symptoms of scalp psoriasis. But, an added bonus for the drug, is that it is also effective and approved for psoriasis affecting intertriginous sites. Management of intertriginous, or inverse, psoriasis, is a therapeutic challenge, as noted by a recent systemic review which concluded that there is a lack of good quality evidence upon which to base treatment recommendations.
Although clinically distinct from psoriasis, seborrhoeic eczema is associated with an inflammatory milieu characterised by several cytokines. In a recent phase 2a, double-blind, vehicle-controlled trial, researchers investigated the efficacy of a roflumilast 0.3% foam in patients with the condition. Participants assigned to roflumilast saw significant improvements in the IGA score (73.8%) compared the the vehicle group (40.9%), and there were also signification reductions in pruritus.
PDE4 inhibition is also a potentially valuable target in atopic eczema, as demonstrated by crisaborole, which is a proven effective treatment. However, a recent turn of events has provided the manufacturer of topical roflumilast, Arcutis Biotherapeutics, with a distinct advantage in the topical treatment of atopic eczema, particularly in Europe.
In the UK, NICE has not provided a recommendation for the use of Pfizer’s crisaborole in atopic eczema, after the manufacturer withdrew its evidence submission. Similarly, in 2022, the marketing authorisation for crisaborole in the EU was withdrawn. As a result, the drug, is not recommended in the 2022 European guidelines on the management of atopic eczema.
Nevertheless, the position adopted by the UK and EU is in sharp contrast to the US, where the most recent iteration of the American Academy of Dermatology guidelines on atopic eczema do include a recommendation to use crisaborole.
Although roflumilast now has an advantage over crisaborole in the European market, initial findings for the drug in atopic eczema were disappointing. The results of a phase 2 proof-of-concept trial using two strengths of the drug (0.15% and 0.05%) found that neither strength improved Eczema Area and Severity Index (EASI) scores compared to the vehicle cream.
In contrast, the most recent data are more encouraging. In an abstract that combined two phase 3 trials in patients with atopic eczema, those assigned to roflumilast 0.15% cream achieved a significantly higher treatment success (p < 0.0001) compared to vehicle in both trials.
Arcutis Biotherapeutics appears to have great ambitions for its drug. Some work with the PDE4 inhibitor apremilast, demonstrated an ability to control the progression of vitiligo. Moreover, given that vitiligo is mediated via oxidative stress and that roflumilast is able to reduce oxidative stress, the drug may also be of value in this condition.
In preliminary work, it was shown that roflumilast enhanced melanin synthesis when combined with forskolin, a cAMP stimulator, but only exhibited a slight influence on melanogenesis when used alone. Although this indicates a potential role in vitiligo, which is reflected on the manufacturer’s website, this is not an active area of research.
Finally, with evidence from a trial demonstrating that apremilast improved disease severity in papulopustular rosacea, a trial of roflumilast in facial papulopustular rosacea is currently recruiting patients.
There is now mounting evidence to suggest that topical roflumilast has the potential to make an important impact on the treatment landscape of psoriasis, seborrhoeic and atopic eczema and possibly rosacea. But exactly where the drug might sit in the treatment ladder for these conditions is uncertain given the absence of studies with active comparators.
Nonetheless, any effective addition to the clinician’s therapeutic armamentarium in the fight against skin diseases is to be welcomed. With Arcutis Biotherapeutics having only just begun its journey with topical roflumilast, it remains to be seen whether the drug will ultimately achieve the status of a dermatological panacea.
19th June 2023
Tranexamic acid (TXA) use before admission to hospital in patients with major trauma and suspected trauma-induced coagulopathy, fails to improve survival and favourable outcomes after six months compared to placebo, according to the findings of a recent randomised trial.
Trauma-induced coagulopathy describes the abnormal blood clotting processes attributable to trauma and is an independent predictor of mortality. It has been suggested that antifibrinolytic drugs such as TXA could reduce mortality in trauma patients with bleeding. While some data support the use of early TXA to reduce risk of death in such patients, other works indicate no survival advantage for the drug.
In trying to provide more clarity on the potential value of early use of TXA, the current study, published in the New England Journal of Medicine, was a randomised, placebo-controlled trial of pre-admission TXA in trauma patients with suspected trauma-induced coagulopathy.
Participants were randomised to either an intravenous one gram bolus dose of TXA before hospital admission, with a second dose infused over eight hours once in hospital, or matching placebo. Eligible patients were adults with suspected severe traumatic injuries, assessed as being at a high-risk for trauma-induced coagulopathy and where the first dose of TXA or placebo could be administered within three hours of their injury prior to hospital admission.
The primary outcome was survival, with a favourable functional outcome six months after their injury. This was assessed using the Glasgow Outcome Scale-Extended (GOS-E), which ranges from one (death) to eight (no injury-related problems). Researchers defined a favourable outcome as a GOS-E score of five or more. Secondary outcomes included death from any cause within 28 days and within six months post-injury.
A total of 1,310 patients were included, of whom 661 were assigned to receive TXA.
There was no difference in the primary outcome. Survival with a favourable functional outcome at six months occurred in 53.7% in the tranexamic acid group and in 53.5% in the placebo group (risk ratio, RR = 1.00, 95% CI 0.90 – 1.12, p = 0.95). Some 28 days after their injury, significantly fewer patients given TXA had died (RR = 0.79, 95% CI 0.63 – 0.99). However, this difference became non-significant after six months (RR = 0.83, 95% CI 0.67 – 1.03). Furthermore, the number of serious adverse events did not differ meaningfully between the groups.
The researchers calculated that for every 100 patients treated with TXA rather than placebo, there were approximately four extra patients alive at six months but approximately four extra were also categorised as having severe disability.
The use of base-edited chimeric antigen receptor (CAR) T cells with a specificity for CD7 could become a therapeutic option for children with relapsed T-cell leukaemia, according to the interim findings of a recent phase 1 trial.
A potential problem with CAR T cell therapy is that since both the CAR T cells and the malignant T cells share the same antigen target, there is a risk of fratricide or self-killing of the CAR T cells. One solution is to use base-edited universal and hence ‘off-the-shelf’ CAR T cells. The base-editing process involves making changes to single letters of DNA code, which stop genes being expressed without having to make a cut to the chromosomes.
In the current study, published in the New England Journal of Medicine, researchers investigated the safety of these edited cells. They used base editing to inactivate three genes encoding for CD52 and CD7 receptors, as well as the β chain of the αβ T-cell receptor. Next, they added a CAR, which recognised the CD7 T-cell receptor on leukaemic T cells. The final base-edited CD7-targeted CAR (BE-CAR7) T cells were then given to three children as an infusion.
The first patient receiving the BE-CAR7 T cells was a 13-year-old girl with relapsed T-cell acute lymphoblastic leukaemia. After 28 days, it was found that BE-CAR7 T cells were the major circulating mononuclear cells. She then received a reduced-intensity (non-myeloablative) allogeneic stem cell transplant from her original donor, with successful immunologic reconstitution and ongoing leukaemic remission.
The other two patients receiving BE-CAR7 T cells had less successful results. One died of a fatal fungal infection-related complication, whereas the other patient underwent allogeneic stem cell transplantation while in remission.
The researchers suggested that these interim results support further investigation of base-edited T cells for patients with relapsed T cell leukaemia and are aiming to recruit 10 children for the initial cohort.
With increasing evidence that cannabis use is associated with adverse cardiovascular effects, questions are undoubtedly being asked about the safety of the drug for medical uses. Rod Tucker investigates.
Cannabis was one of the first plants cultivated by man, and its first use can be traced to ancient China where evidence suggests it was used for medical purposes from around 2,700 BC and for textiles and other uses as early as 4,000 BC.
Although the plant contains hundreds of compounds, the two most well studied are tetrahydrocannabinol (THC) and cannabidiol (CBD). In the late 1980s and early 1990s, the site of action for cannabis was identified with the discovery of two major cannabinoid receptors, CB1 and CB2, and their endogenous ligands, which form part of the endocannabinoid system.
While THC is the main psychoactive compound in cannabis that produces the euphoric ‘high’ sensation, over the last decade it has become increasingly clear that it is CBD that has a number of therapeutic benefits. Recognition of this fact has given rise to the terms ‘medical cannabis’ or ‘medical marijuana’.
In a 2021 meta-analysis published in the BMJ, researchers concluded that there was moderate- to high-certainty evidence that medical cannabis or cannabinoids results in a small to very small improvement in pain relief, physical functioning and sleep quality in patients with both chronic, non-cancer pain and cancer-related pain.
Although medical cannabis use is associated with some adverse effects such as cognitive impairment, vomiting, drowsiness and impaired attention, there has been little attention paid to any potential adverse cardiovascular (CV) sequelae. One likely explanation is that there remains some uncertainty over the magnitude of these effects and therefore whether such risks should be highlighted.
In fact, in a statement on the use of cannabis and its CV effects, the American Heart Association (AHA) states that ‘overall, evidence is still inconclusive for cannabis use and adverse cardiovascular outcomes’ and it called for carefully designed prospective studies to examine this issue in more detail.
Since the publication of the AHA statement, more evidence has come to light, which suggests that the use of cannabis has several adverse effect on the CV system.
For several states in the US and many other countries such as Canada, use of recreational cannabis has been legalised although this has had some unintended consequences, such as an increase cannabis and alcohol poly use, in addition to adverse cardiovascular effects.
In a recent abstract in the Journal of the Society for Cardiovascular Angiography and Interventions, researchers found that cannabis users were at a more than three times greater risk of developing peripheral artery disease than non-users (Odds ratio, OR = 3.68, p<0.001). Fortunately, however, there was no increased risk for any subsequent intervention or mortality from their peripheral ischaemia.
Despite this, a further abstract revealed that cannabis users were at a statistically significant higher risk of having a myocardial infarction (OR = 3.33, p < 0.001) and an increased likelihood of requiring a percutaneous coronary intervention during hospitalisation (OR = 1.76, p <0.001). Furthermore, users were also at a markedly increased risk of all-cause mortality during hospitalisation (OR = 14.77, p < 0.001).
Cannabis use also increases the risk of arrhythmias and in particular, atrial fibrillation (AF) as well as myocardial injury in those without pre-existing cardiovascular disease. While these studies are concerning, a 2020 systematic review on the cardiac effects of cannabis use concluded that while there is an increased risk of cardiac dysrhythmia, which can be life-threatening, this is rare.
A more recent meta-analysis of observational studies published in 2023 in the journal Toxicology Reports, indicated that cannabis use does increase the risk of an acute myocardial infarction, stroke and any adverse cardiovascular event. Nevertheless, while the pooled odds ratio estimates for each event were non-significant there was also a high degree of heterogeneity among studies.
With a clear body of evidence implicating the development of adverse CV outcomes among cannabis users, a limitation of the data is that it is derived from self-reported, recreational use. Furthermore, the focus of research has been on the adverse cardiovascular effects of THC, whereas medical cannabis is predominately based on CBD.
So, is there evidence that CBD-based medical cannabis is harmful to the heart? While there is currently a paucity of data on the CV effects of medicinal cannabis, the available information is somewhat reassuring.
One review highlighted the anti-inflammatory and anti-oxidant effects of CBD and suggested that it appears to have positive effect on the CV system. Further evidence to support the beneficial impact of CBD on the CV system comes from studies in patients with hypertension.
For instance, a study of medicinal cannabis use in older hypertensives published in the European Journal of Internal Medicine, found that after only three-months use of mainly cannabis oil, there was a signification drop in blood pressure. Interestingly, the researchers were unable to detect any adverse changes to participant’s ECGs and no new sustained arrhythmias developed, even though the median daily intake of THC and CBD was roughly the same (21 mg). Similar blood pressure reducing effects were seen in a recent randomised, placebo-controlled, cross-over trial in hypertensive patients using an oral CBD product.
Additionally, repeated CBD dosing has been shown to reduce arterial stiffness and improve endothelial function, revealing a potentially valuable role for those with vascular diseases. Whilst studies to date are largely positive and do not suggest harmful effects on the heart, a recent analysis by Danish researchers sounded a note of caution. Using a national registry, the team examined the potential adverse cardiac effects of CBD when used for the management of chronic pain. Their findings revealed a 64% increased risk of arrhythmias among CBD users compared to non-users.
While it has become recognised that the recreational use of cannabis is associated with deleterious effects on the cardiovascular system, this seems to be less likely with medical cannabis. Nonetheless, research to more clearly delineate the cardiovascular risks associated with medicinal cannabis use is urgently required. In the meantime, clinicians need to remain wary, because the jury is still out on whether or not medical cannabis and the cardiovascular system represents a dangerous combination.
15th June 2023
Vorasidenib improves progression-free survival in patients with residual or recurrent grade 2 glioma, according to a recent double-blind, placebo-controlled trial.
Diffuse gliomas represent 75% of all primary malignant brain tumours in adults and are both locally aggressive and currently incurable. Moreover, mutations in the isocitrate dehydrogenases (IDHs) encoded by IDH1 and IDH2 are present in the majority of malignant gliomas. Vorasidenib is a novel dual inhibitor of mutant IDH1 and IDH2 enzymes with the potential to treat low grade glioma.
With a Phase 1 trial showing that vorasidenib was effective, the current Phase 3 trial, published in the New England Journal of Medicine, examined the value of the drug in patients with residual or recurrent grade 2 IDH-mutant glioma.
Eligible participants had residual or recurrent histologically established grade 2 oligodendroglioma or astrocytoma and confirmed IDH1 and IDH2 mutation status. Individuals were randomised to receive vorasidenib 40 mg daily or matching placebo in continuous 28-day cycles. The primary endpoint was imaging-based progression-free survival (PFS). An important secondary outcome was the time to the next anticancer intervention.
The study included 331 patients who were assigned to receive either vorasidenib (168 patients) or a placebo. The median follow-up was 14.0 months in the vorasidenib group and 14.3 months in the placebo group.
The median imaging-based PFS was significantly longer in the drug group compared to placebo (27.7 months vs 11.1 months), representing a 61% lower risk of progression or death with the drug (hazard ratio, HR = 0.39, 95% CI, 0.27 – 0.56, p <0.001).
The time to the next intervention was also significantly improved with vorasidenib compared to placebo (HR = 0.26, 95% CI 0.15 – 0.43, p < 0.001). Both the PFS and delay in the time to next treatment advantages of the drug were seen across most of the subgroups studied.
Adverse events of grade 3 or above were higher with vorasidenib compared to the placebo (22.8% vs 13.5%). An increased alanine aminotransferase level of grade 3 or above was seen in 9.6% of vorasidenib and in none of the placebo patients.
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