- Tildrakizumab and certolizumab pegol recommended for severe plaque psoriasis in final guidance.
- Inotersen now recommended for hereditary transthyretin-related amyloidosis following improved commercial agreement.
- Osimertinib not recommended for lung cancer in draft guidance.
- New and updated recommendations published for:
- Surgical site infections: prevention and treatment
- Ectopic pregnancy and miscarriage, including using ultrasound scans for diagnosis of tubal ectopic pregnancy.
- Draft guidelines published for:
- Diabetic foot infection: antimicrobial prescribing
- Cellulitis and erysipelas: antimicrobial prescribing
- Termination of pregnancy.
- Endoscopic ablation for pilonidal sinus and anal fistula recommended in interventional procedures guidance.
- Blinatumomab recommended for acute lymphoblastic leukaemia.
- Mepolizumab recommended for severe refractory eosinophilic asthma (restricted).
- Yellow fever vaccine (Stamaril) and fatal adverse reactions reported: extreme caution needed in people who may be immunosuppressed and those 60 years and older.
- Valproate medicines: new annual risk acknowledgement form and clinical guidance to support compliance with the Pregnancy Prevention Programme.
- Belimumab (Benlysta▼): increased risk of serious psychiatric events seen in clinical trials.
- Pregabalin and gabapentin: new scheduling requirements reminder.
- Elvitegravir boosted with cobicistat: avoid use in pregnancy due to risk of treatment failure and maternal-to-child transmission of HIV-1.
- Multiple sclerosis medicine Lemtrada restricted during ongoing EMA review.
- New review launched into risks of high-strength oestradiol-containing creams.
- Department for Health and Social Care confirms FMD is to blame for labetalol shortage.
- Updated guidance to protect people getting medicines online.
- GP scheme frees up half a million hours for patients.
- Digital tool introduced to help reduce avoidable lengthy stays in hospital.
- NHS staff to gain access to vital child health information through new service.
- WHO releases first guideline on digital health interventions.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
TILDRAKIZUMAB AND CERTOLIZUMAB PEGOL RECOMMENDED FOR SEVERE PLAQUE PSORIASIS
- the disease is severe, as defined by a total Psoriasis Area and Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10 and
- the disease has not responded to other systemic treatments, including ciclosporin, methotrexate and phototherapy, or these options are contraindicated or not tolerated
And, for certolizumab pegol, if the lowest maintenance dosage is used (200 mg every two weeks) after the loading dosage.
Tildrakizumab and certolizumab pegol are both proposed as an alternative to other biological treatments already recommended by NICE. Certolizumab pegol is also proposed as an alternative to systemic non-biological treatments such as methotrexate, ciclosporin and acitretin in adults who have not had systemic treatment.
NICE says clinical trial results show that tildrakizumab improves severe plaque psoriasis compared with placebo or etanercept. More improvement is usually seen at 28 weeks compared with 12 weeks of treatment. When compared indirectly, tildrakizumab appears to be as effective as adalimumab and ustekinumab but not as effective as other biological treatments. According to NICE, the most plausible cost-effectiveness estimates for tildrakizumab compared with most other available biological treatments show that it is generally cost effective.
For certolizumab pegol, NICE says clinical trial results show that it improves severe plaque psoriasis more than either placebo or etanercept. When compared indirectly, it appears to be as effective as other biological treatments for the condition, and also appears to be more effective than non-biological treatments.
INOTERSEN NOW RECOMMENDED TO TREAT HEREDITARY TRANSTHYRETIN-RELATED AMYLOIDOSIS IN FINAL DRAFT GUIDANCE
NICE has issued draft highly specialised technologies guidance which now recommends inotersen (Tegsedi) to treat the rare inherited condition hereditary transthyretin-related amyloidosis (hATTR). The positive recommendation follows an improved commercial agreement for inotersen from the company which addresses the uncertainties in the company’s economic model. NICE’s earlier draft guidance on inotersen concluded that it offers benefits for people with the condition in the short term by slowing progression of the disease and improving quality of life. However, it is uncertain whether these benefits are maintained in the longer-term. In addition, there were uncertainties in the economic modelling for the treatment. hATTR is an ultra-rare (in the UK it is thought to affect around 150 people), progressive condition that causes the liver to produce abnormal transthyretin protein. Deposits of transthyretin form in the tissues of the body (amyloidosis) and these can disrupt the structure and damage the function of the affected tissues. Over time, these deposits can cause pain, loss of sensation and weakness in the hands, arms, legs or feet, as well as chest pain, shortness of breath and fluid overload. In some cases, the autonomic nervous system, which controls involuntary body functions such as blood pressure, heart rate, and digestion, may also be affected by hATTR. There are no treatments available to treat the underlying cause of hATTR so current treatments are limited and mainly focus on symptom relief and supportive care including pain management, nutritional and mobility support and mitigation of the effects of the disease on other organs. Inotersen is a life-long treatment and works by suppressing the production of transthyretin. It can be self-administered once weekly by injection and costs £5,925 per 284 mg weekly dose. Commercial arrangements for the drug mean it is available at a discounted price.
OSIMERTINIB NOT RECOMMENDED FOR LUNG CANCER IN DRAFT GUIDANCE
NICE has published draft guidance which does not recommend osimertinib (Tagrisso), within its marketing authorisation, for untreated locally advanced or metastatic epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) in adults. Locally advanced or metastatic EGFR mutation-positive NSCLC is usually first treated with afatinib, erlotinib or gefitinib. According to NICE, evidence from a randomised controlled trial suggests that people who take osimertinib live longer than people who take erlotinib or gefitinib. They also live longer before their disease gets worse. But there is no direct evidence comparing osimertinib with afatinib, which may be more effective than erlotinib and gefitinib. Osimertinib does not meet NICE’s criteria to be considered a life-extending treatment at the end of life. The most plausible cost-effectiveness estimates are above what NICE normally considers an acceptable use of NHS resources. In addition, osimertinib does not meet NICE’s criteria to be included in the Cancer Drugs Fund because it does not have the potential to be cost effective at the price offered. Closing date for comments is 9 May 2019.
SURGICAL SITE INFECTIONS: PREVENTION AND TREATMENT GUIDELINE PUBLISHED
NICE has published a guideline which covers preventing and treating surgical site infections in adults, young people and children who are having a surgical procedure involving a cut through the skin. It focuses on methods used before, during and after surgery to minimise the risk of infection. This guideline updates and replaces NICE guideline CG74 (2008) and includes new and updated recommendations on:
- nasal decolonisation before surgery
- antiseptic skin preparation during surgery
- antiseptics and antibiotics before wound closure
- methods of wound closure
ECTOPIC PREGNANCY AND MISCARRIAGE: DIAGNOSIS AND INITIAL MANAGEMENT GUIDELINE PUBLISHED
NICE has published a guideline which covers diagnosing and managing ectopic pregnancy and miscarriage in women with complications, such as pain and bleeding, in early pregnancy (that is, up to 13 completed weeks of pregnancy). It aims to improve how early pregnancy loss is diagnosed, and the support women are given, to limit the psychological impact of their loss. This guideline updates and replaces NICE guideline CG154 (December 2012) and includes new and updated recommendations on:
DIABETIC FOOT INFECTION: ANTIMICROBIAL PRESCRIBING DRAFT GUIDELINE PUBLISHED
NICE has been developing an
antimicrobial prescribing guideline on diabetic foot infection. The diabetic foot infection recommendations for antimicrobial prescribing will update and replace the existing NICE guideline on diabetic foot problems: prevention and management (section on treating diabetic foot infection only - recommendations 1.6.6 -15). This guideline covers preventing and managing foot problems in children, young people and adults with diabetes. The guideline aims to reduce variation in practice. The update of the antimicrobial prescribing recommendations in the diabetic foot problems guideline is scheduled for publication on 11 October 2019.
CELLULITIS AND ERYSIPELAS: ANTIMICROBIAL PRESCRIBING DRAFT GUIDELINE PUBLISHED
NICE has published a draft guideline which sets out an antimicrobial prescribing strategy for cellulitis and erysipelas. These skin infections are usually caused by Streptococcus pyogenes or Staphylococcus aureus bacteria. The guideline aims to optimise antibiotic use and reduce antibiotic resistance. It does not cover diagnosis. Consultation closes on 10 May 2019.
TERMINATION OF PREGNANCY DRAFT GUIDELINE PUBLISHED
NICE has published a draft guideline which covers termination of pregnancy for women of any age. It aims to improve the organisation of services to make it easier for women to access a termination. Detailed recommendations on conducting terminations at different gestational stages are also included, to ensure that women get the most effective care possible. The consultation closes on 31 May 2019.
ENDOSCOPIC ABLATION RECOMMENDED FOR PILONIDAL SINUS AND ANAL FISTULA
NICE has published guidance saying that current evidence on endoscopic ablation for an anal fistula or for a pilonidal sinus raises no major safety concerns and the evidence on efficacy is adequate in quality and quantity for both procedures. These can therefore be can be used provided standard arrangements are in place for clinical governance, consent and audit.
ALL WALES MEDICINES STRATEGY GROUP
BLINATUMOMAB RECOMMENDED FOR ACUTE LYMPHOBLASTIC LEUKAEMIA
The All Wales Medicines Strategy Group (AWMSG) has recommended blinatumomab (Blincyto®) as an option for use within NHS Wales, under Patient Access Scheme (PAS), as monotherapy for the treatment of paediatric patients aged one year or older with Philadelphia chromosome negative CD19 positive B-cell precursor acute lymphoblastic leukaemia (ALL) which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic haematopoietic stem cell transplantation.
MEPOLIZUMAB RECOMMENDED FOR SEVERE REFRACTORY EOSINOPHILIC ASTHMA (RESTRICTED)
The AWMSG has recommended mepolizumab (Nucala®) as an option for restricted use within NHS Wales, under a PAS. Mepolizumab is licensed as an add-on treatment for severe refractory eosinophilic asthma in adolescents and children aged six years and older. Mepolizumab is restricted for use in a subpopulation of the licensed indication in line with the NICE recommendation for the restricted use of mepolizumab for treating severe refractory eosinophilic asthma in adults (TA431). Mepolizumab is not recommended for use within NHS Wales outside of this subpopulation.
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
YELLOW FEVER VACCINE (STAMARIL) AND FATAL ADVERSE REACTIONS REPORTED
The Medicines and Healthcare products Regulatory Agency (MHRA) has recently received two reports of fatal adverse reactions to the yellow fever vaccine Stamaril. Due to an increased risk of life-threatening reactions, the MHRA advises that the vaccine must not be given to anyone with a medical history of thymus dysfunction or who is immunosuppressed. In addition, extreme caution must be used and a careful risk assessment conducted before vaccination of people aged 60 years and older due to a substantially increased risk of such adverse reactions in this age group.
VALPROATE MEDICINES: NEW ANNUAL RISK ACKNOWLEDGEMENT FORM AND CLINICAL GUIDANCE
Ongoing patient survey data suggest that more effort is needed by clinicians to achieve full and timely compliance with the valproate Pregnancy Prevention Programme and meet the goal to rapidly reduce and eventually eliminate the harms of valproate in pregnancy in view of its serious teratogenicity. The MHRA has therefore updated the Annual Risk Acknowledgement Form, which should be used during annual specialist review of all women and girls of childbearing potential on valproate medicines (irrespective of indication). Specialists should comply with guidance given on the form if they consider the patient is not at risk of pregnancy, including the need for regular review in case her risk status changes.
BELIMUMAB (BENLYSTA▼): INCREASED RISK OF SERIOUS PSYCHIATRIC EVENTS SEEN IN CLINICAL TRIALS
The MHRA has reported that clinical trials, including interim findings from a randomised trial, show an increased risk of depression, suicidal ideation or behaviour, or self-injury in patients with systemic lupus erythematosus receiving belimumab compared with those receiving placebo in addition to standard therapy. The MHRA advises healthcare professionals to assess patients for these risks before the start of treatment with belimumab and to advise them to promptly seek medical attention if they develop new or worsening depression, suicidal ideation or thoughts about injuring themselves.
PREGABALIN AND GABAPENTIN: NEW SCHEDULING REQUIREMENTS REMINDER
The MHRA has issued a reminder that as of 1 April 2019, pregabalin and gabapentin are controlled under the Misuse of Drugs Act 1971 as Class C substances and scheduled under the Misuse of Drugs Regulations 2001 as Schedule 3. Healthcare professionals are advised to evaluate patients carefully for a history of drug abuse before prescribing pregabalin and gabapentin, to observe patients for development of signs of abuse and dependence; and ensure patients are aware of the risk of potentially fatal interactions with other medicines that cause CNS depression, particularly opioid medicines, and with alcohol.
ELVITEGRAVIR BOOSTED WITH COBICISTAT: AVOID USE IN PREGNANCY DUE TO RISK OF TREATMENT FAILURE AND MATERNAL-TO-CHILD TRANSMISSION OF HIV-1
The MHRA has reported that pharmacokinetic data shows that exposure of elvitegravir boosted with cobicistat (Genvoya▼, Stribild) is lower during the second and third trimesters of pregnancy than postpartum. Low elvitegravir exposure may be associated with an increased risk of treatment failure and an increased risk of HIV-1 transmission to the unborn child, and therefore elvitegravir/cobicistat should not be used during pregnancy. Healthcare professionals are advised to switch women who are pregnant and taking elvitegravir/cobicistat to an alternative regimen.
EUROPEAN MEDICINES AGENCY
MULTIPLE SCLEROSIS MEDICINE LEMTRADA RESTRICTED DURING ONGOING EMA REVIEW
The European Medicines Agency (EMA) has started a review of the multiple sclerosis (MS) medicine Lemtrada (alemtuzumab) following new reports of immune-mediated conditions and problems with the heart and blood vessels with the medicine, including fatal cases. As a temporary measure while the review is ongoing, Lemtrada should only be started in adults with relapsing-remitting MS that is highly active despite treatment with at least two disease-modifying therapies or where other disease-modifying therapies cannot be used. Patients being treated with Lemtrada who are benefitting from it may continue treatment in consultation with their doctor. In addition to the restriction, the EMA’s safety committee (PRAC) has recommended an update of the product information for Lemtrada to inform patients and healthcare professionals about cases of:
- immune-mediated conditions, including autoimmune hepatitis (with damage to the liver) and haemophagocytic lymphohistiocytosis (overactivation of the immune system which may affect different parts of the body);
- problems with the heart and blood vessels occurring within 1–3 days of receiving the medicine, including bleeding in the lungs, heart attack, stroke, cervicocephalic arterial dissection;
- severe neutropenia.
Healthcare professionals should consider stopping treatment in patients who develop signs of these conditions and patients should immediately seek medical help if they experience symptoms. The EMA will evaluate all available data on the safety concerns with the medicine and consider any additional measures necessary to protect patients and whether there should be changes in the authorised use.
NEW REVIEW INTO RISKS OF HIGH-STRENGTH OESTRADIOL-CONTAINING CREAMS LAUNCHED
The PRAC has started a new review of high-strength oestradiol containing creams (100 micrograms of oestradiol present per gram of cream) that are used for treating women with vaginal atrophy who have been through menopause. The Committee will assess the risk of oestradiol being absorbed systemically (throughout the body) from these creams, which may result in side effects that include venous thromboembolism (formation of blood clots in the veins), stroke and endometrial cancer. In 2014, the EMA completed a review of the risk of systemic absorption with high-strength oestradiol creams and recommended measures to minimise it. However, in March 2019 the EU Court of Justice partially annulled the conclusions of the review on procedural grounds. Although the Court of Justice did not question the scientific conclusions, the partial annulment means that some of the measures taken to minimise the risk has been invalidated. The European Commission has therefore initiated a review at EU level. The PRAC will therefore review all available data and recommend measures that should be implemented to protect patients.
DISPENSING DOCTORS’ ASSOCIATION
DEPARTMENT FOR HEALTH AND SOCIAL CARE CONFIRMS FMD IS TO BLAME FOR LABETALOL SHORTAGE
The Dispensing Doctors’ Association (DDA) reports that the Department for Health and Social Care (DHSC) has confirmed that the Falsified Medicines Directive (FMD) is one of the factors causing the current labetalol shortages. According to the DDA, in a supply update, the DHSC stated that the supplier Mylan expects delays in resupply until early-mid May due to delays in the serialisation of FMD packs. In addition, the supplier Recipharm has reported a problem with sourcing the active pharmaceutical ingredient and therefore cannot provide a resupply date. The DHSC has advised prescribers not to commence new patients on labetalol during this time, and to consider alternative treatments. However, some unlicensed stock is available for import, with lead times of between seven and 21 days.
GENERAL PHARMACEUTICAL COUNCIL
UPDATED GUIDANCE TO PROTECT PEOPLE GETTING MEDICINES ONLINE
The General Pharmaceutical Council (GPhC) has published updated guidance to protect people getting medicines online. After considering feedback from the sector and patients and the public to proposals published last year, the GPhC has introduced further safeguards for patients and the public in the following key areas:
- Ensuring medicines are clinically appropriate for patients – online pharmacies will have to make sure there are robust processes in place to carry out identity checks on people obtaining medicines;
- The pharmacy team can identify requests for medicines that are inappropriate, including by being able to identify multiple orders to the same address or orders using the same payment details;
- The pharmacy websites do not allow a patient to choose a prescription-only medicine and its quantity before there has been an appropriate consultation with a prescriber;
- Further safeguards for certain categories of prescription only medicines including:
- Medicines liable to abuse, overuse or misuse, or where there is a risk of addiction such as opiates, sedatives, laxatives, pregabalin and gabapentin.
- Medicines that require ongoing monitoring or management. For example, those used to treat diabetes, asthma, epilepsy and mental health conditions.
- Non-surgical cosmetic medicinal products, such as Botox.
GP SCHEME FREES UP HALF A MILLION HOURS FOR PATIENTS
NHS England has reported that the Time for Care scheme has seen GP practices free up more than half a million hours of time for patients in the last year (see OnMedica article). NHS England said the Time for Care scheme, which has been undergoing trials since 2016, should be in place in three-quarters of GP practices by 2022. The scheme encourages practices to try innovations to cut bureaucracy. In 2018, 205,157 clinical hours - equivalent to GPs having 1.2 million more appointment slots - were freed up by the scheme. NHS England said that represents close to £40 million in time saved, as the average cost of an appointment is £30. The scheme also saved 330,096 administration hours in the past year.
DIGITAL TOOL INTRODUCED TO HELP REDUCE AVOIDABLE LENGTHY STAYS IN HOSPITAL
NHS England has announced that a new digital portal is being introduced by the NHS and councils which allows health and social care staff to see how many vacancies there are in local care homes, saving hours of time phoning around to check availability and helping people to get the right care or return home as quickly as possible. People who need a care home placement will be supported to get out of hospital sooner, as the new technology will be rolled out to care homes, councils and hospitals across the country by NHS England as part of its Long Term Plan for the health service. The digital portal is accessible on any device and takes care homes just 30 seconds to upload details of their available beds, helping health and social care staff to find the right services for individual patients, including those with dementia or a learning disability. Over 6,250 care homes have already signed up to the system, piloted in the North, Devon and Berkshire last year, and now thousands more can sign up to use it.
NHS STAFF TO GAIN ACCESS TO VITAL CHILD HEALTH INFORMATION THROUGH NEW SERVICE
NHS Digital and NHS England have announced the launch of a new service that will help to make important child health information available to health professionals and parents at the point of care. The service has initially launched in North East London in partnership with North East London Foundation Trust (NELFT) and their health visiting and child health services. The service shows which preventative interventions a child has received; improving the speed of diagnosis and treatment by giving health visitors and parents access to the same information sources at the same time. It implements a near real-time message exchange sending birth notifications, change of address and change of GP practice details. Data is also forwarded to a digital red book offered to mothers as an alternative to the current paper red book.
WORLD HEALTH ORGANIZATION
WHO RELEASES FIRST GUIDELINE ON DIGITAL HEALTH INTERVENTIONS
The World Health Organisation (WHO) has released new recommendations on 10 ways that countries can use digital health technology, accessible via mobile phones, tablets and computers, to improve people’s health and essential services. One digital intervention already having positive effects in some areas is sending reminders to pregnant women to attend antenatal care appointments and having children return for vaccinations. Other digital approaches reviewed include decision-support tools to guide health workers as they provide care; and enabling individuals and health workers to communicate and consult on health issues from across different locations. The guideline also makes recommendations about telemedicine, which allows people living in remote locations to obtain health services by using mobile phones, web portals, or other digital tools. WHO points out that this is a valuable complement to face-to-face-interactions, but it cannot replace them entirely. It is also important that consultations are conducted by qualified health workers and that the privacy of individuals’ health information is maintained. The guideline also emphasises the importance of reaching vulnerable populations, and ensuring that digital health does not endanger them in any way.