- Updated asthma guidance makes new recommendation on ICS use in children.
- Leg ulcer infection: antimicrobial prescribing guideline.
- Final guidance recommends:
- Sotagliflozin with insulin for treating type 1 diabetes
- Patiromer for hyperkalaemia.
- Acute coronary syndromes: draft guideline update makes series of new recommendations.
- Wireless device recommended for treating people with overactive bladder (draft).
- Pembrolizumab with axitinib not recommended for advanced renal cell carcinoma (draft).
- Draft quality standard: suspected neurological conditions.
- The following medicines have been accepted:
- Encorafenib in combination for unresectable or metastatic melanoma with a BRAF V600 mutation
- Teduglutide for the treatment of adult patients with short bowel syndrome
- Plerixafor in combination in children with lymphoma or solid malignant tumours
- Cemiplimab as monotherapy for metastatic or locally advanced cutaneous squamous cell carcinoma.
- Initial assessments completed for the following medicines:
- Burosumab for X-linked hypophosphataemia
- Voretigene neparvovec for vision loss due to inherited retinal dystrophy.
- Drug safety updates published:
- Nexplanon contraceptive implants: new insertion site to reduce rare risk of neurovascular injury and implant migration
- Lemtrada▼: updated restrictions and strengthened monitoring requirements following review of serious cardiovascular and immune-mediated reactions
- Picato▼: suspension of licence due to risk of skin malignancy.
- Self-expanding stents under MRI – various risks if MRI is operated outside the required conditions for these stents.
- Storage limit for frozen eggs, sperm and embryos to be reconsidered.
- New bill will give hospitals powers to develop personalised treatment.
- Guidelines published for the use of non-pharmaceutical measures to delay and mitigate the impact of 2019-nCoV.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
UPDATED ASTHMA GUIDANCE MAKES NEW RECOMMENDATION ON ICS USE IN CHILDREN
NICE has published an updated guideline which covers diagnosing, monitoring and managing asthma in adults, young people and children. The partial update is driven by evidence on inhaled corticosteroids (ICS) and replaces the 2017 recommendation which advised that children and young people whose asthma is not under control could increase their ICS dose to help manage symptoms.
The new recommendation emphasises the importance of regular use of ICS in children and young people with deteriorating asthma to help regain control of their symptoms, rather than increasing their dose. It notes that there is limited evidence of clinical benefit from increasing ICS doses in children aged 5-16 to regain asthma control.
The partial update also includes a second recommendation which states that the self-management plan for children and young people should contain advice to contact a healthcare professional for a review if their asthma control deteriorates.
LEG ULCER INFECTION: ANTIMICROBIAL PRESCRIBING GUIDELINE
NICE has published a guideline which sets out an antimicrobial prescribing strategy for adults with leg ulcer infection. It aims to optimise antibiotic use and reduce antibiotic resistance. NICE has also published a two-page visual summary of the recommendations, including tables to support prescribing decisions.
SOTAGLIFLOZIN WITH INSULIN RECOMMENDED FOR TREATING TYPE 1 DIABETES
NICE has published final guidance which recommends sotagliflozin with insulin as an option for treating type 1 diabetes in adults with a body mass index (BMI) of at least 27 kg/m2, when insulin alone does not provide adequate glycaemic control despite optimal insulin therapy, only if:
- sotagliflozin is given as one 200 mg tablet daily
- they are on insulin doses of 0.5 units/kg of body weight/day or more and
- they have completed a structured education programme that is evidence based, quality assured, delivered by trained educators and includes information about diabetic ketoacidosis, such as:
- how to recognise its risk factors, signs and symptoms
- how and when to monitor blood ketone levels
- what actions to take for elevated blood ketones and
- treatment is started and supervised by a consultant physician specialising in endocrinology and diabetes treatment, and HbA1c levels are assessed after six months and regularly after this.
NICE committee found that evidence from clinical trials run for one year in this population shows improvements in HbA1c and weight loss, and improvements in quality of life, with sotagliflozin plus insulin compared with people on placebo plus insulin. The company assumes that the improvement in HbA1c results in a lower risk of long-term complications over a person's lifetime. It's reasonable to assume some relationship between lowering HbA1c and reducing diabetic complications, and between lowering BMI and improving quality of life.
NICE says if sotagliflozin improves HbA1c for only two years, and no other physiological factors, the cost-effectiveness estimate for sotagliflozin plus insulin compared with insulin alone is within the range that NICE normally considers an acceptable use of NHS resources. However, due to the increased risk of diabetic ketoacidosis, sotagliflozin should be stopped if blood glucose control does not improve.
Sotagliflozin is not yet available in the NHS, but the company anticipates that it will be available to the NHS in England and Wales within 12 months of guidance publication. Therefore, the period of time the NHS has to comply with these recommendations has been extended.
PATIROMER RECOMMENDED FOR TREATING HYPERKALAEMIA
NICE has published final guidance which recommends patiromer (Veltassa) as an option for treating hyperkalaemia in adults only if used:
- in emergency care for acute life-threatening hyperkalaemia alongside standard care or
- for people with persistent hyperkalaemia and stages 3b to 5 chronic kidney disease or heart failure, if they:
- have a confirmed serum potassium level of at least 6.0 mmol/litre and
- are not taking, or are taking a reduced dosage of, a renin-angiotensin-aldosterone system (RAAS) inhibitor because of hyperkalaemia and
- are not on dialysis.
Treating acute life-threatening hyperkalaemia in emergency care is established clinical practice. Other potassium-lowering treatments are rarely used in this setting because they are poorly tolerated. Patiromer could therefore be a useful addition to emergency care, NICE says.
Clinical trials show that patiromer lowers serum potassium. But there is no clinical evidence that it extends life or improves quality of life. Patiromer may allow people to stay on RAAS inhibitors (drugs used to treat heart failure and kidney disease) for longer or at a higher dose. This may extend life and improve quality of life.
Considering the benefit from more people being able to stay on RAAS inhibitors, the cost-effectiveness estimates for patiromer suggest that it is a reasonable use of NHS resources.
ACUTE CORONARY SYNDROMES: DRAFT GUIDELINE UPDATE
NICE has published a draft guideline which updates and combines the recommendations from NICE’s existing guidelines on the early management of unstable angina and NSTEMI, the acute management of myocardial infarction with ST-segment elevation, and myocardial infarction: cardiac rehabilitation and prevention of further cardiovascular disease.
The updated guideline covers risk assessment, drug treatment, invasive management, cardiac rehabilitation and planning for discharge.
New recommendations include:
- Offering prasugrel or ticagrelor (rather than clopidogrel as currently recommended by NICE) as part of dual anti-platelet therapy with aspirin for people with unstable angina and NSTEMI having coronary angiography.
- Offering prasugrel as part of dual antiplatelet therapy with aspirin to people with acute STEMI intended for treatment with PCI (rather than the more commonly used ticagrelor or clopidogrel).
- Considering coronary angiography (with follow-on PCI if indicated) within 72 hours of first admission (rather than 96 hours NICE currently recommends) for people with unstable angina and NSTEMI who have an intermediate or higher risk of future adverse cardiovascular events.
- Offering a drug-eluting stent to people with unstable angina, NSTEMI and acute STEMI undergoing revascularisation by PCI.
- Offering complete revascularisation with PCI for people with acute STEMI and multivessel coronary artery disease without cardiogenic shock, either at the time of primary PCI or later during the same admission. For people with cardiogenic shock it recommends culprit vessel only revascularisation.
WIRELESS DEVICE RECOMMENDED FOR TREATING PEOPLE WITH OVERACTIVE BLADDER
People with an overactive bladder could have a rechargeable wireless device fitted to ease their condition, NICE has said in new draft guidance.
The Axonics sacral neuromodulation (SNM) simulates the sacral nerve with an electric current via an electrode. The electrode is attached to an implantable pulse generator which stimulates the nerves associated with bladder function. The aim of the stimulation is to make the bladder work in a more controllable way.
Based on current data it is thought the battery will last for around six years before it needs replacing although there is some evidence to suggest it could last as long as 15 years. Cost modelling by NICE suggests that six years is the point at which the device becomes cost saving compared with the current non-rechargeable system. NICE says Axonics SNS has potential to save the NHS around £6,200 per patient assuming a 15-year life span.
PEMBROLIZUMAB WITH AXITINIB NOT RECOMMENDED FOR UNTREATED ADVANCED RENAL CELL CARCINOMA
NICE has published draft guidance which does not recommend pembrolizumab (Keytruda) with axitinib (Inlyta) for untreated advanced renal cell carcinoma in adults.
NIC says although the evidence suggests pembrolizumab with axitinib would be welcomed by patients, there was uncertainty around the long-term benefit. Clinical and cost-effectiveness estimates were also above what NICE would normally consider as an acceptable use of NHS resources, and does not meet NICE’s criteria to be a life-extending treatment at the end of life.
DRAFT QUALITY STANDARD: SUSPECTED NEUROLOGICAL CONDITIONS
NICE has published a draft quality standard, which covers the assessment and referral of children and adults who have symptoms or signs associated with neurological conditions. It describes high-quality care in priority areas for improvement, including:
- Adults with transient rotational vertigo on head movement are assessed using the Hallpike manoeuvre
- Children under 12 years with headache and 'red flag' symptoms are referred immediately for neurological assessment
- Children under four years with suspected abnormal head size or shape have their head circumference assessed using a standardised growth chart.
SCOTTISH MEDICINES CONSORTIUM
ENCORAFENIB ACCEPTED IN COMBINATION FOR UNRESECTABLE OR METASTATIC MELANOMA WITH A BRAF V600 MUTATION
Following a resubmission assessed under the end-of-life and orphan medicine process, the Scottish Medicines Consortium (SMC) has accepted encorafenib (Braftovi®), under a Patient Access Scheme (PAS), for use within NHS Scotland, in combination with binimetinib for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.
Progression-free survival was significantly longer in the encorafenib plus binimetinib group compared with BRAF inhibitor monotherapy in a phase III study of patients with unresectable or metastatic BRAF V600 melanoma.
TEDUGLUTIDE ACCEPTED FOR THE TREATMENT OF ADULT PATIENTS WITH SHORT BOWEL SYNDROME
The SMC has accepted teduglutide (Revestive®), under a PAS, for use within NHS Scotland, for the treatment of adult patients with short bowel syndrome. The SMC advises patients should be stable following a period of intestinal adaptation after surgery.
The SMC notes that in a phase III randomised study in adults, significantly more patients achieved at least a 20% reduction in parenteral support volume at weeks 20 and 24 when treated with teduglutide compared with placebo.
The SMC has previously accepted teduglutide for restricted use for initiation in paediatric patients (aged 1-17 years).
PLERIXAFOR ACCEPTED IN COMBINATION IN CHILDREN WITH LYMPHOMA OR SOLID MALIGNANT TUMOURS
Following an abbreviated submission, the SMC has accepted plerixafor (Mozobil®) for use within NHS Scotland, in combination with granulocyte-colony stimulating factor (G-CSF) to enhance mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in children aged one year to <18 years with lymphoma or solid malignant tumours, either:
- pre-emptively, when circulating stem cell count on the predicted day of collection after adequate mobilisation with G-CSF (with or without chemotherapy) is expected to be insufficient with regards to desired hematopoietic stem cells yield, or
- who previously failed to collect sufficient haematopoietic stem cells.
The SMC has previously accepted plerixafor for use in adults, in combination with G-CSF to enhance mobilisation of haematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with lymphoma and multiple myeloma whose cells mobilise poorly.
CEMIPLIMAB ACCEPTED AS MONOTHERAPY FOR METASTATIC OR LOCALLY ADVANCED CUTANEOUS SQUAMOUS CELL CARCINOMA
The SMC has accepted cemiplimab (Libtayo®), under a PAS, for use within NHS Scotland on an interim basis subject to ongoing evaluation and future reassessment, as monotherapy for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma (CSCC) who are not candidates for curative surgery or curative radiation.
The SMC notes that in a phase II study of cemiplimab in patients with metastatic or locally advanced CSCC the objective response rate was 44%.
TWO INITIAL ASSESSMENTS COMPLETED UNDER THE ULTRA-ORPHAN FRAMEWORK
The SMC has completed its initial assessment of the evidence for:
- burosumab (Crysvita), for the treatment of X-linked hypophosphataemia with radiographic evidence of bone disease in children one year of age and older and adolescents with growing skeletons.
- voretigene neparvovec (Luxturna), for the treatment of adult and paediatric patients with vision loss due to inherited retinal dystrophy caused by confirmed biallelic RPE65 mutations and who have sufficient viable retinal cells.
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
NEXPLANON CONTRACEPTIVE IMPLANTS: NEW INSERTION SITE TO REDUCE RARE RISK OF NEUROVASCULAR INJURY AND IMPLANT MIGRATION
The Medicines and Healthcare products Regulatory Agency (MHRA) has published a drug safety update for Nexplanon contraceptive implants in order to reduce the rare risk of neurovascular injury and implant migration. Healthcare professionals are advised to:
- Ensure the correct insertion of the implant is carried out by an appropriately trained and accredited professional – correct insertion of the implant just under the skin is essential to reduce the risk of neurovascular injury and the implant migrating through the vasculature.
- Review the updated guidance for how to correctly insert the implant, including an amended diagram that illustrates:
- the new insertion site
- the correct position of the arm for insertion (flexed at the elbow with the woman’s hand underneath her head
- how to view the needle (by sitting and viewing it from the side) to avoid deep insertion
- show the woman how to locate the implant and advise her to do this occasionally; if she has any concerns, she should return promptly to the clinic for advice
- localise any implant that cannot be palpated (for example, by imaging the arm) and remove it at the earliest opportunity – perform chest imaging if it cannot be located in the arm
- implants inserted at the previous site that can be palpated should not pose a risk and do not need to be moved to the new site; only replace implants if you have concerns regarding their location or if routine replacement is due
LEMTRADA▼: UPDATED RESTRICTIONS AND STRENGTHENED MONITORING REQUIREMENTS FOLLOWING REVIEW
A review of the benefits and risks of alemtuzumab (including fatal reactions) in the treatment of multiple sclerosis has now concluded and has recommended a revised indication, additional contraindications, and strengthened monitoring requirements before, during and after treatment. Patients offered alemtuzumab should be alerted to the early risks of cardiovascular events and thrombocytopenia around the time of infusion and to the delayed risk of immune-mediated reactions. Healthcare professionals should inform patients what to do if they develop any symptoms of these disorders.
PICATO▼: SUSPENSION OF THE LICENCE DUE TO RISK OF SKIN MALIGNANCY
The licence of Picato (ingenol mebutate gel) has been suspended as a precautionary measure while the European Medicine’s Agency continues to investigate an increased incidence of benign and malignant skin tumours in several clinical studies (see previous Drug Safety Update, October 2019). Healthcare professionals are therefore advised to stop prescribing Picato; to consider other treatment options for actinic keratosis; and to advise patients who have been treated with Picato to continue to be vigilant for new skin lesions within the treatment area and to seek medical advice immediately should any occur.
SELF-EXPANDING STENTS UNDER MRI – VARIOUS RISKS IF MRI IS OPERATED OUTSIDE THE REQUIRED CONDITIONS FOR THESE STENTS
The MHRA has published a medical device alert for self-expanding stents (S.M.A.R.T. and PRECISE) under MRI due to the various risks if MRI is operated outside the required conditions for the stents. Healthcare professionals should be provided with a copy of this FSN, which contains the updated MRI compatibility information.
DEPARTMENT OF HEALTH AND SOCIAL CARE
STORAGE LIMIT FOR FROZEN EGGS, SPERM AND EMBRYOS TO BE RECONSIDERED
The government has called for views on whether the current law to store frozen eggs, sperm and embryos for a maximum of 10 years should change - only those stored for medical reasons, such as cancer treatment and premature infertility, can be preserved for longer (up to 55 years in total).
The consultation will consider:
- whether the limit should be extended in line with significant improvements in freezing technologies
- whether women are disproportionately affected by the current time limit
- the safety and quality issues related to prolonged storage
- the additional demand for storage facilities that will arise if the statutory time limit is increased.
NEW BILL WILL GIVE HOSPITALS POWERS TO DEVELOP PERSONALISED TREATMENT
NHS hospitals will be able to use develop personalised medicines for unique cancers and diseases, following the introduction of the Medicines and Medical Devices Bill, the Department for Health and Social Care (DHSC) has announced (see OnMedica article).
The bill will also:
- increase the range of professions able to prescribe medicines in low-risk circumstances, thus reducing GP appointments
- introduce new regulations on medical devices, such as pacemakers, breast implants and ultrasound imagers, to ensure patient safety
The new bill means hospitals can use patient tissue and DNA samples to tailor treatments to individual patients when other medicines have failed, or to develop drugs that have a short shelf-life and would otherwise be unavailable to patients.
The DHSC emphasises there will be safeguards and limits on what medications are eligible. The government will work with the NHS and stakeholders to determine what medicines could be eligible and in what circumstances.
Companies will need to register medical devices with the Medicines and Healthcare products Regulatory Agency (MHRA), ensuring suppliers follow strict safety checks.
EUROPEAN CENTRE FOR DISEASE PREVENTION AND CONTROL
GUIDELINES FOR THE USE OF NON-PHARMACEUTICAL MEASURES TO DELAY AND MITIGATE THE IMPACT OF 2019-NCOV
The European Centre for Disease Prevention and Control (ECDC) has published guidance on the application of non-pharmaceutical countermeasures to minimise the spread of the 2019 novel coronavirus (2019-nCoV) in the population. Some of the measures proposed refer specifically to certain phases of the epidemic (containment or mitigation phases), and can be adapted depending on the assessed severity/impact of the infection. Other measures are valid for all phases of an epidemic.
The guidance is based on the current knowledge of the 2019-nCoV and evidence available on other viral respiratory pathogens, mainly the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), the Middle East Respiratory Syndrome-related coronavirus (MERS-CoV) and seasonal or pandemic influenza viruses.
The ECDC will update the guidance as and when new relevant information becomes available or as required by the epidemiological situation.