New results for acute myeloid leukaemia treatment
Results from AML-001, the phase III study of VIDAZA (azacitidine) compared with conventional care regimens (CCR) in elderly patients with newly-diagnosed acute myeloid leukaemia (AML - >30% blasts) were presented in a late-breaking abstract oral session at the 19th Congress of the European Hematology Association (EHA).
In the global, multi-centre, randomised, open-label pivotal study, patients at least 65 years old with newly diagnosed AML with >30% bone marrow blasts were pre-selected to receive one of three regimens from intensive chemotherapy (standard 7+3 regimen), low-dose Ara-C (20mg SC twice per day for 10 days of each 28-day cycle) or best supportive care only.
Patients were then randomised to receive either azacitidine (n=241) (75mg/m2/d SC for seven days of each 28-day cycle) or their predetermined CCR (n=247).
Median overall survival (OS), the primary endpoint of the study, was 10.4 months (range 8.0–12.7 months) for patients receiving azacitidine compared with 6.5 months (5.0–8.6) for patients receiving CCR (unstratified HR=0.84 [95% CI 0.69, 1.02], p=0.0829).
Additionally, a pre-specified sensitivity analysis for overall survival that censored patients at the start of subsequent AML therapy was conducted. Results of this analysis showed a significantly longer median overall survival for patients receiving azacitidine (median 12.1 months 95% CI, range 9.2–14.2 months) compared with patients receiving CCR (median 6.9 months 95% CI range 5.1–9.6 months) (stratified HR=0.76 [95% CI 0.60, 0.96], p=0.019). One-year survival was 47% for patients receiving azacitidine compared with 34% for patients receiving CCR.
Commenting on the results, Professor Jamie Cavenagh, Consultant Haematologist at Barts Health NHS Trust, London said “AML can affect people of any age but is more common in people over 65. While some patients over 60 are offered intensive chemotherapy to try to cure the leukaemia, not everyone is fit enough to go through this and the majority are given lower doses of chemotherapy instead, which means that the chances of going into remission are also lower. However, results from the AML-001 study showed that patients aged 65 and over, who received azacitidine, reached the longest median overall survival seen to date with a low-intensity therapy suggesting a potential future treatment option.”
Grade 3-4 anaemia, neutropenia, febrile neutropenia, and thrombocytopenia rates, respectively, were 16%, 26%, 28%, and 24% with azacitidine; 5%, 5%, 28%, 5% with best supportive care; 23%, 25%, 30%, 28% with low-dose Ara-C; and 14%, 33%, 31%, 21% with intensive chemotherapy.
RESONATE study: new data on ibrutinib
Patients with chronic lymphoid leukemia (CLL) or small lymphocytic lymphoma (SLL) who experience short response duration or adverse cytogenetics have poor outcomes. According to data from the RESONATE trial, presented at the EHA, ibrutinib is an effective new single agent therapy for CLL/SLL patients.
The efficacy of ibrutinib, the first-in covalent inhibitor of Bruton’s tyrosine kinase, in these difficult-to-treat patients was evaluated in the multicenter, international, phase 3 study RESONATE. This assessed daily ibrutinib monotherapy versus the anti-CD20 antibody of atumumab. Relapsed or refractory CLL/SLL patients (n=391) were randomised to receive ibrutinib or ofatumumab.
At a median follow-up of 9.4 months, ibrutinib significantly improved progression free survival (PFS); median PFS was not reached with ibrutinib and was 8.1 months with ofatumumab (hazard ratio [HR], 0.22; p<0.001). Ibrutinib also significantly improved overall survival (HR, 0.43; p=0.005).
This effect was observed despite cross over from ofatumumab to ibrutinib at progression as recommended by the data monitoring committee. Similar effects were observed regardless of del17p or purine analog-refractory disease.
The response rate by IRC was 63% for ibrutinib including 20% responses with lymphocytosis versus 4% with ofatumumab. Toxicities were manageable and did not frequently result in dose reduction or treatment discontinuation with 86.4% continuing ibrutinib at time of analysis.
In summary, ibrutinib significantly improved PFS, overall survival, and response rate compared to ofatumumab in previously treated CLL/SLL.
New data on abatacept, in combination with methotrexate, in RA
New data from a phase IIIb rheumatoid arthritis (RA) trial showing that the T-cell co-stimulation modulator, abatacept, in combination with methotrexate (MTX) achieved significantly higher rates of DAS-defined (DAS28 CRP <2.6) remission at 12 months than treatment with standard of care agent MTX (60.9% versus 45.2%, respectively) in biologic-naïve patients with early active RA.
Abatacept is indicated for use in combination with methotrexate (MTX) to treat moderate to severe active RA in adults who have had an inadequate response to
a disease-modifying anti-rheumatic drug (DMARD), including MTX or a tumour necrosis factor (TNF) antagonist (also known as an anti-TNF).
In this trial known as AVERT, a co-primary endpoint assessed maintenance of remission following the withdrawal of all RA drug therapy including abatacept, MTX and steroids. A small but statistically significantly higher number of patients treated with abatacept plus MTX, versus MTX alone, for 12 months maintained remission six months after all RA treatment was withdrawn. This investigational study was carried out in MTX-naïve patients with early RA, outside the current licence for abatacept.
Abatacept in combination with methotrexate (MTX) was well tolerated in the study patients. In particular, serious adverse events, serious infection events and discontinuation due to serious adverse events were comparable to patients treated with MTX.
“Remission of both clinical symptoms and radiographic joint damage is an important and achievable goal in the management of rheumatoid arthritis, particularly in the early disease phase,” said Professor Paul Emery, Arthritis Research UK, Professor of Rheumatology and Head of the Academic Division of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds. “Data from the AVERT trial show that patients taking a combination of abatacept plus methotrexate achieved
higher rates of remission than treating them with methotrexate alone. Interestingly, this benefit was maintained in some patients even after all RA treatment had been withdrawn.”
Obesity and osteoarthritis
For all obese patients with osteoarthritis (OA), weight loss should be advocated as a first-line management approach, and packages of support should be put in place based on assessments of need that are personalised to the individual and holistic.
This is according to a Briefing Note for policy makers from Arthritis Care launched recently at the House of Commons.
It also stated that healthcare practitioners should routinely check obese patients for signs of OA and refer them to lifestyle weight management programmes that conform to NICE public health guidance. Also GPs should signpost patients to local support groups and national patient bodies such as Arthritis Care, who can offer information, advice and support with OA and weight loss.
Obesity is a large and growing health problem. It has been estimated that if the increase in obesity continues 60% of the UK population will be overweight or obese by 2050, with one in two of today’s children set to be obese in middle age by 2030. The wider social costs of overweight and obesity were estimated at a staggering £15.8 billion in 2007 and could reach £50 billion by 2050. The direct cost to the NHS alone of the obesity increase will be £1.9 billion by 2020.
Osteoarthritis is a significant health risk associated with obesity; the majority of people with OA are overweight or obese. Compared to someone of normal weight, an obese person is 14 times more likely to develop knee osteoarthritis. Even in comparison to other health risks associated with obesity, OA stands out in its prevalence: recent research indicates that obesity confers an increased chance of developing OA of the knee four times greater than the risk associated with high blood pressure or type-2 diabetes.
Even modest weight gain speeds up the breakdown of cartilage, particularly in the knee, and increases susceptibility to OA. Additionally, poor gait and posture are more common in obese people, further predisposing the joints to OA. Every 5kg of weight gain confers a 36% increase in the risk of knee OA and once entrenched, OA is likely to have the effect of bringing about a vicious circle of reduced activity, a more sedentary lifestyle and so further weight gain.
Around 160,000 knee and hip operations are carried out annually in England and Wales alone. Procedures can cost from £4,000 to £12,000, and could total around £1.6bn. But there is evidence that heavier people fare less well in the short term after knee and hip replacement, with complications such as infection.
Weight loss and exercise combined have even been shown to achieve the same level of symptom relief as joint replacement surgery. Not only can exercise facilitate weight maintenance, it can increase muscle strength and aerobic capacity. The most appropriate forms of exercise are low-impact aerobic exercise programmes such as walking, bike riding or swimming. It is important—especially in elderly OA patients to tailor the exercise programmes according to patient mobility, comorbidities and patient preferences.
However, many people with OA will struggle to maintain weight loss and exercise regimes, in part because of the potential adverse effects of exercise on the joints during training, but also because they require long lasting changes to lifestyle that typically require substantial and ongoing support with and for people with arthritis, empowering them to take control of their arthritis and their lives.
New data on liraglutide in type 2 diabetes
Data from a new phase 3 study (LIRA-RENAL) demonstrated that once-daily Victoza (liraglutide)provided greater glycaemic control versus placebo with no worsening of renal function in adults who have type 2 diabetes coupled with moderate renal impairment (stage 3 chronic kidney disease).
The data were presented today at the 74th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco. Renal impairment is one of the more challenging and common long-term complications of diabetes and limits the use of available antidiabetic treatment options.
In the UK, the risk of developing chronic kidney disease stages 3b–5 among people with diabetes appears to be eight times higher in women and over 12 times higher in men compared to those without diabetes.
The 26-week, double-blind, randomised, controlled LIRA-RENAL study investigated the efficacy and safety of liraglutide compared with placebo when added to pre-existing oral antidiabetic treatment, insulin or a combination thereof. The study showed that adults with type 2 diabetes and moderate renal impairment, defined as those with stage 3 chronic kidney disease (eGFR 30-59 mL/min/1.73 m2; MDRD), treated with liraglutide had significantly greater improvements in mean HbA1c (a measure of blood glucose levels), were more likely to achieve target HbA1c <7%, and experienced significantly greater weight loss from baseline versus placebo. No worsening of renal function and a lower incidence of hypoglycaemia with treatment of liraglutide compared with placebo were observed in the study.
“About a third of people with diabetes also have chronic kidney disease. It can be a particular problem, especially in the over 65s, limiting diabetes treatment options and increasing the risk of hypoglycaemia,” said Steve Bain, Professor of Medicine at Swansea University and Clinical Lead for the Diabetes Research Network, Wales. “It is reassuring to see that liraglutide was found to be effective in lowering HbA1c in this patient population, with a lower incidence of hypoglycaemia compared to placebo, no unexpected tolerability issues, and no deterioration in renal function.”