- Final guidance published recommends:
- Lenalidomide plus dexamethasone for previously untreated multiple myeloma
- Lenalidomide plus dexamethasone for multiple myeloma post bortezomib
- Cardiac contractility modulation device implantation for heart failure (research only)
- Reinforcement of a permanent stoma with synthetic or biological mesh to prevent parastomal hernia (special arrangements)
- Valve-in-valve TAVI for aortic bioprosthetic valve dysfunction (standard arrangements).
- Draft antimicrobial prescribing guidance on leg ulcer infections published.
- Guidelines published:
- Hypertension in pregnancy: diagnosis and management
- Depression in children and young people: identification and management.
- Rufinamide recommended as adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (restricted).
- Medical device alert issued for various Dialog+ haemodialysis machines with software versions 9.xx: software and hardware upgrade required.
- Company-led drug alert: Docetaxel Injection 160mg /16ml and Docetaxel Injection 20mg / 2ml.
- Positive EAMs scientific opinion published:
- Polatuzumab vedotin in combination with bendamustine and rituximab for relapsed/refractory diffuse large B-cell lymphoma
- Renewal for idebenone for respiratory function decline in patients with Duchenne Muscular Dystrophy
- Atezolizumab for lung cancer, in combination with carboplatin and etoposide
- Atezolizumab as first-line treatment for triple-negative breast cancer
- Dupilumab for severe atopic dermatitis for whom systemic therapies are unsuitable
- Tafamidis of transthyretin amyloidosis with wild type or hereditary cardiomyopathy to reduce all-cause mortality and cardiovascular-related hospitalization.
- Shortage Notice: Disopyramide 100mg/150mg capsules.
- Supply Status Update: EpiPen® 0.3mg and 0.15mg Adrenaline Auto-Injectors.
- NHS to launch young people’s gambling addiction service.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
LENALIDOMIDE PLUS DEXAMETHASONE FOR PREVIOUSLY UNTREATED MULTIPLE MYELOMA
NICE has published final guidance which recommends lenalidomide (Revlimid) plus dexamethasone as an option for previously untreated multiple myeloma in adults who are not eligible for a stem cell transplant, only if:
- thalidomide is contraindicated (including for pre-existing conditions that it may aggravate) or
- the person cannot tolerate thalidomide, and
- the company provides lenalidomide according to the commercial arrangement.
Previously untreated multiple myeloma is normally treated with thalidomide-based therapy. If people cannot take thalidomide, bortezomib-based therapy is used. There is a high unmet need for new treatment options for people who cannot take thalidomide. Evidence from an indirect comparison suggests that lenalidomide plus dexamethasone substantially improves the length of time people live compared with bortezomib-based therapy.
However, lenalidomide plus dexamethasone cannot be recommended for untreated multiple myeloma in people who could take thalidomide because this would not be cost effective. Because the definition of thalidomide intolerance in clinical practice varies, it is appropriate that NHS England clearly defines who would be eligible for treatment with lenalidomide plus dexamethasone (see section 3.2).
LENALIDOMIDE PLUS DEXAMETHASONE FOR MULTIPLE MYELOMA POST BORTEZOMIB
NICE has also published final guidance which recommends lenalidomide (Revlimid) plus dexamethasone as an option for treating multiple myeloma in adults only if:
- they have had only one previous therapy, which included bortezomib, and
- the company provides it according to the commercial arrangement.
For people who have had bortezomib as a first treatment, the second treatment would be with cytotoxic chemotherapy. However, clinical evidence shows that lenalidomide plus dexamethasone is more effective than cytotoxic chemotherapy. The most plausible cost-effectiveness estimate for lenalidomide plus dexamethasone may be above the range that NICE normally considers to be a cost-effective use of NHS resources. However, lenalidomide has been recommended for use as a first treatment (for which it is cost effective). Therefore, the need for lenalidomide as a second treatment will likely decrease because people are more likely to have it as a first treatment in the future. However, some people who are currently taking bortezomib as a first treatment will value access to lenalidomide as an effective next treatment option.
CARDIAC CONTRACTILITY MODULATION DEVICE IMPLANTATION FOR HEART FAILURE (RESEARCH ONLY)
NICE has published evidence-based recommendations on cardiac contractility modulation device implantation for heart failure in adults, which involves placing a device under the skin of the chest, which delivers electrical pulses to make the heart contract more strongly. NICE finds that the evidence on cardiac contractility modulation device implantation for heart failure raises no major safety concerns. However, the evidence on efficacy is inadequate in quantity and quality. Therefore, NICE recommends that this procedure should only be used in the context of research, and that further research should ideally be in the form of randomised controlled trials. These should report details of patient selection, duration and timing of stimulation, and duration of effect of stimulation. Outcomes should include ejection fraction, oxygen consumption, New York Heart Association classification and patient-reported outcomes, including quality of life.
REINFORCEMENT OF A PERMANENT STOMA WITH A SYNTHETIC OR BIOLOGICAL MESH TO PREVENT A PARASTOMAL HERNIA (SPECIAL ARRANGEMENTS)
NICE has published evidence-based recommendations on reinforcement of a permanent stoma with a synthetic or biological mesh to prevent a parastomal hernia, which involves inserting a piece of mesh to strengthen the abdominal wall. NICE finds that the evidence on the safety of the procedure shows there are serious but well-recognised complications. Furthermore, the evidence on efficacy is limited in quantity and quality. Therefore, NICE advises that this procedure should not be used unless special arrangements are in place for clinical governance, consent, and audit or research. Clinicians wishing to do reinforcement of a permanent stoma with a synthetic or biological mesh to prevent a parastomal hernia should:
- Inform the clinical governance leads in their NHS trusts.
- Ensure that patients understand the procedure's safety and efficacy, as well as any uncertainties about these. Provide them with clear written information to support shared decision making. In addition, the use of NICE's information for the public is recommended.
- Audit and review clinical outcomes of all patients having the procedure. NICE has identified relevant audit criteria and has developed an audit tool (which is for use at local discretion).
In addition, all adverse events involving the medical devices (including the synthetic or biological mesh) used in this procedure should be reported to the Medicines and Healthcare products Regulatory Agency. NICE also recommends that further research could be in the form of randomised controlled trials, observational studies and analysis of registry data. It should report details of patient selection, the type of synthetic or biological mesh used, mesh-associated complications and long-term outcomes (at least three years). In participating centres, clinicians should encourage patients to take part in the National Institute for Health Research CIPHER study.
VALVE-IN-VALVE TAVI FOR AORTIC BIOPROSTHETIC VALVE DYSFUNCTION (STANDARD ARRANGEMENTS)
NICE has published final guidance on valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) for aortic bioprosthetic valve dysfunction in adults. This involves placing a new bioprosthetic valve inside a failing bioprosthetic valve. NICE says that the current evidence on the safety and efficacy of ViV‑TAVI for aortic bioprosthetic dysfunction is adequate to support the use of this procedure provided that standard arrangements are in place for clinical governance, consent and audit. NICE says the details of all patients should be entered into the UK TAVI registry, and any device-related adverse events should be reported to the Medicines and Healthcare products Regulatory Agency.
DRAFT ANTIMICROBIAL PRESCRIBING GUIDANCE ON LEG ULCER INFECTIONS IN ADULTS PUBLISHED
NICE has issued draft antimicrobial prescribing guidance on leg ulcer infections in adults. NICE advises that health professionals need to be aware of the multiple causes of leg ulcers and although many ulcers are commonly colonised with bacteria, most leg ulcers are not infected. NICE says it is important to note that antibiotics do not promote healing if a leg ulcer is not infected. If symptoms do not improve, however, a sample from deep within the ulcer should be sent for microbiological testing. General wound swabs are not likely to indicate an infection as bacterial colonisation is common in all sores. However, the Levine technique may be used to detect infection-causing organisms. Antibiotics should only be offered when there are clear signs and symptoms of infection. Initially, oral antibiotics should be given, if the person is able to take them. If intravenous antibiotics are given, their use should be reviewed after 48 hours taking into consideration any microbiological results, worsening of symptoms and/or patient response to treatment. Flucloxacillin is the first choice of oral antibiotic and should be administered at 500mg four times a day for seven days. The NICE antimicrobial prescribing suite of guidelines focus on a variety of common bacterial infections and make recommendations on appropriate antibiotic choice and use.
HYPERTENSION IN PREGNANCY: DIAGNOSIS AND MANAGEMENT GUIDELINE PUBLISHED
NICE has published a guideline which covers diagnosing and managing hypertension, including pre-eclampsia, during pregnancy, labour and birth. It also includes advice for women with hypertension who wish to conceive and women who have had a pregnancy complicated by hypertension. This guideline includes new and updated recommendations on:
- assessing proteinuria
- managing chronic hypertension in pregnancy and gestational hypertension
- managing pre-eclampsia, including severe pre-eclampsia in critical care settings
- treatment during the postnatal period (including breastfeeding)
- advice and follow-up in community care
It also includes recommendations on:
- reducing the risk of hypertension in pregnancy
- fetal monitoring and care of women during labour and birth
This guideline updates and replaces NICE guideline CG107 (August 2010).
DEPRESSION IN CHILDREN AND YOUNG PEOPLE: IDENTIFICATION AND MANAGEMENT GUIDELINE PUBLISHED
NICE has published a guideline which covers guideline covers identifying and managing depression in children and young people aged five to 18 years. Based on the stepped-care model, it aims to improve recognition and assessment and promote effective treatments for mild and moderate to severe depression. The guideline includes new and updated recommendations on:
- psychological therapies for mild depression
- psychological therapies for moderate to severe depression
These supplement the existing recommendations on:
- care for all children and young people with depression
- stepped care
- detection, risk profiling and referral
- transfer to adult services
This guideline updates and replaces NICE guideline CG28 (September 2005).
ALL WALES MEDICINES STRATEGY GROUP
RUFINAMIDE RECOMMENDED AS ADJUNCTIVE THERAPY FOR SEIZURES ASSOCIATED WITH LENNOX-GASTAUT SYNDROME (RESTRICTED)
The All Wales Medicines Strategy Group recommends Rufinamide (Inovelon®) as an option for restricted use within NHS Wales. Rufinamide is licensed as adjunctive therapy in the treatment of seizures associated with Lennox-Gastaut syndrome in patients one years of age and older. Rufinami is restricted for use where other adjunctive treatments have proved sub-optimal or have not been tolerated. Rufinamide is not recommended for use within NHS Wales outside of this subpopulation.
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
VARIOUS DIALOG+ HAEMODIALYSIS MACHINES WITH SOFTWARE VERSIONS 9.XX- SOFTWARE AND HARDWARE UPGRADE REQUIRED
The Medicines and Healthcare products Regulatory (MHRA) has issued a medical device alert for Dialog+ haemodialysis machines with software versions 9.xx (excluding versions 9.18, 9.1A, 9.1B) as there is a software and hardware upgrade required (MDA/2019/024). Manufactured by B. Braun Avitum AG, the company reports that a malfunction of the temperature sensor can result in the temperature of the dialysis fluid to be more than ±1°C outside the programmed values, which can lead to inadequate treatment. Healthcare professionals are advised to:
- Identify affected machines
- Contact the manufacturer to obtain service kit SW 9.1B or to schedule machines for a service upgrade.
- Ensure this upgrade is scheduled at the next planned service, prioritising patients who use this machine at home.
- Whilst waiting for the scheduled upgrade:
- be aware of the potential for incorrect dialysis fluid temperatures whilst patients are undergoing treatment. The machine will alarm and stop treatment if the temperature goes outside the range 33 to 42 °C.
- consider adding a check for dialysis fluid temperature if a patient complains about unexpectedly feeling warmer or cooler than usual during treatment.
- Report suspected or actual adverse events involving these devices through the local incident reporting system and/or national incident reporting authority as appropriate: England, Scotland, Northern Ireland, Wales. Report directly to manufacturers if the local or national systems do not.
COMPANY-LED DRUG ALERT – DOCETAXEL INJECTION 160MG /16ML AND DOCETAXEL INJECTION 20MG / 2ML
The MHRA has issued a company-led drug alert for Docetaxel Injection 160mg /16ml and Docetaxel Injection 20mg / 2ml. Pfizer UK Limited is recalling batches as routine stability testing has identified that levels of a known impurity, 10-oxo-docetaxel, may exceed the acceptable level at end of shelf-life.
POSITIVE EAMS SCIENTIFIC OPINION RECOMMENDS POLATUZUMAB VEDOTIN WITH BENDAMUSTINE AND RITUXIMAB FOR LYMPHOMA
The MHRA has issued a positive Early Access to Medicines Scheme (EAMS) scientific opinion for polatuzumab vedotin in combination with bendamustine and rituximab in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in adult patients who are not eligible for hematopoietic stem cell transplant. DLBCL is an aggressive form of lymphoma with limited treatment options when it is refractory to or relapses after standard therapy. The Public Assessment report states that in patients who cannot undergo high-dose chemotherapy and stem cell transplantation, the addition of polatuzumab vedotin to bendamustine and rituximab has been shown to notably slow the progression of cancer and prolong patient survival despite some increase in side effects.
RENEWAL OF POSITIVE EAMS SCIENTIFIC OPINION ISSUED FOR IDEBENONE FOR DUCHENNE MUSCULAR DYSTROPHY
The MHRA has issued a renewal of the positive EAMS scientific opinion for idebenone (Raxone) to treat the decline of respiratory function in patients with Duchenne Muscular Dystrophy (DMD). Patients with DMD who have progressed to the stage of respiratory decline, and who are not receiving glucocorticoids, have no treatment options available to them, other than supportive care. Although Translarna (ataluren) is available for the treatment of DMD patients with a so-called nonsense mutation in the dystrophin gene, it is restricted to those patients who are ambulatory. DMD patients who are in respiratory decline will be largely unable to walk and will therefore not be eligible to receive ataluren. In a small study of DMD patients treated with idebenone for 12 months there was evidence of benefit on lung function that might, over the longer term, help to delay the onset of serious respiratory complications. MHRA notes that with any small study, there is always uncertainty whether the benefit and risks will be replicated more widely in the proposed target population, however, to address this uncertainty the Company conducted a variety of analyses to test the robustness of the data within the limitations of a small study and there was no evidence that the small sample had been non-representative of a larger population. No serious safety concerns have emerged.
ATEZOLIZUMAB FOR LUNG CANCER, IN COMBINATION WITH CARBOPLATIN AND ETOPOSIDE
A positive EAMS scientific opinion has been given to atezolizumab in the first line treatment of adult patients with extensive-stage small cell lung cancer, in combination with carboplatin and etoposide. Atezolizumab is a monoclonal antibody and has been designed to attach to and block the activity of a protein called PD-L1, which is found on the surface of tumour and immune cells. By blocking PD-L1, atezolizumab restores the capacity of immune cells to fight cancer cells. The Public Assessment report states that in patients with extensive stage small cell lung cancer, the addition of atezolizumab to carboplatin and etoposide chemotherapy has been shown to slow the progression of cancer and increase patient survival.
ATEZOLIZUMAB AS FIRST-LINE TREATMENT FOR TRIPLE-NEGATIVE BREAST CANCER
Another positive EAMS scientific opinion has been issued for atezolizumab as first-line treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumours have PD-L1 expression ≥ 1%. The Public Assessment Report states that in patients with triple-negative breast cancer that has progressed to advanced stage disease, where it is locally inoperable or has spread to other parts of the body, the cancer is usually poorly responsive to chemotherapy and patient survival is a matter of months. The addition of atezolizumab to nab-paclitaxel chemotherapy has been shown to notably slow the progression of cancer and increase patient survival despite worse tolerability than chemotherapy alone.
DUPILUMAB FOR SEVERE ATOPIC DERMATITIS FOR WHOM SYSTEMIC THERAPIES ARE UNSUITABLE
A positive EAMS scientific opinion has been given to dupilumab (Dupixent) as a treatment of adolescent patients between 12 and 18 years of age with severe atopic dermatitis for whom the available systemic therapies are not suitable. Dupilumab works by attaching to a molecule called the IL-4 receptor alpha subunit which sits primarily on the surface of cells of the immune system. This interferes with messages of two molecules, IL4 and IL13 that trigger the inflammation in the skin. Eczema patients have an overactive chronic inflammatory response and dupilumab works by dampening this down. The Public Assessment Report states that dupilumab results in meaningful improvement in the extent and severity of eczema as well as in the symptom of itch and in some patients the improvement may be marked. The risks associated with Dupixent can be managed and do not outweigh the benefits.
TAFAMIDIS OF TRANSTHYRETIN AMYLOIDOSIS WITH WILD TYPE OR HEREDITARY CARDIOMYOPATHY
A positive EAMS scientific opinion has been issued for tafamidis (Vyndaqel) for the treatment of transthyretin amyloidosis in adult patients with wild type or hereditary cardiomyopathy to reduce all-cause mortality and cardiovascular-related hospitalization. Tafamidis binds to transthyretin (TTR) and stabilises it, preventing breakdown of the active substance of Vyndaqel used to prevent the breakdown TTR into harmful fibrils called amyloid. By interfering with this essential step in the disease, tafamidis can prevent harmful amyloid fibrils from forming and depositing on the heart. By preventing the breakdown of TTR, tafamidis can slow the progression of transthyretin amyloid cardiomyopathy.
PHARMACEUTICAL SERVICES NEGOTIATING COMMITTEE
SHORTAGE NOTICE: DISOPYRAMIDE 100MG/150MG CAPSULES
The Pharmaceutical Services Negotiating Committee (PSNC) has reported that Sanofi and Mylan, the manufacturers of Disopyramide 100mg and 150mg capsules, are currently experiencing temporary disruptions. Sanofi and Mylan will be out of stock of Disopyramide 100mg capsules from approximately mid-June 2019 to late-July 2019. Mylan will be out of stock of the Disopyramide 150mg capsules from approximately mid-August 2019 till mid-September 2019. Supplies are available from specialist importers on an ‘unlicensed’ basis.
SUPPLY STATUS UPDATE: EPIPEN® 0.3MG AND 0.15MG ADRENALINE AUTO-INJECTORS
The PSNC has reported Mylan’s manufacturing partner Meridian Medical Technologies, a subsidiary of Pfizer that manufactures EpiPen®, recently experienced manufacturing issues resulting in interruptions in the production of EpiPen 0.3mg and EpiPen Jr 0.15mg Adrenaline Auto-Injectors (AAIs). To help manage stock availability until a steady supply resumes, Mylan has put in place a prescription-only process for EpiPen 0.3mg, meaning patients can obtain up to a maximum of two EpiPen 0.3mg AAIs per prescription.
NHS TO LAUNCH YOUNG PEOPLE’S GAMBLING ADDICTION SERVICE
NHS England has announced that the first NHS gambling clinic for children will open this year as part of a new network of services for addicts (see OnMedica article). The move comes amid growing concern that the scourge of problem gambling is being fuelled by online gaming sites and targeted adverts, NHS England say. The number of children classed as having a gambling problem is 55,000, according to the Gambling Commission. The Commission also found that 450,000 are gambling regularly, more than those who have taken drugs, drunk alcohol or smoked. Specialist face-to-face NHS treatment for gambling addiction has only been available in London but is being made available across the country. Up to 14 new NHS clinics are being opened – starting with the NHS Northern Gambling Service in Leeds this summer, followed by Manchester and Sunderland. The National Problem Gambling Clinic in London will also offer specialist help for children and young people aged 13 to 25 as part of an expansion which will also ramp up treatment for adults.