- Final guidance recommends:
- Brigatinib for ALK-positive lung cancer after crizotinib.
- Pertuzumab for adjuvant treatment of HER2-positive early stage breast cancer.
- Increased risk of blood clots in lungs and death with higher dose of Xeljanz for rheumatoid arthritis reported.
- PRAC starts review on screening patients before treatment with fluorouracil, capecitabine, tegafur and flucytosine to decrease the risk of side effects.
- Medical device alert: risk of batteries overheating or igniting with some Pagewriter Cardiographs and Efficia Monitors.
- Company-led drug alert: Ozurdex implant recall.
- Updated safety advice: enFlow® IV fluid and blood warmer - risk of unsafe levels of aluminium leaking from the device.
- Change to DVLA management of cases for drivers with nystagmus.
- Report on tuberculosis in Europe 2019 shows it remains a major public health challenge despite an overall decline.
- New guidance published to accelerate progress of TB elimination.
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
BRIGATINIB RECOMMENDED FOR ALK-POSITIVE LUNG CANCER AFTER CRIZOTINIB
The National Institute for Health and Care Excellence (NICE) has published final guidance which recommends brigatinib (Alunbrig), within its marketing authorisation, for treating anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC) in adults who have already had crizotinib. It is recommended only if the company provides it according to the commercial arrangement. People with ALK-positive advanced NSCLC that has been treated with crizotinib are currently offered ceritinib as their next treatment. NICE says clinical evidence based on indirect comparisons of trials suggests that people having brigatinib live longer than those having ceritinib, and that they live longer before their condition worsens. Brigatinib may be more effective for brain metastases and better tolerated than existing treatments. NICE highlights that the cost-effectiveness estimates are uncertain, particularly because of whether brigatinib's treatment benefit continues after stopping treatment. The most plausible estimates for brigatinib compared with ceritinib are around the higher end of what NICE normally considers acceptable for an end-of-life treatment. But the population eligible for brigatinib is small and will decrease because crizotinib is no longer considered first-line treatment for ALK-positive NSCLC. Future treatments will be limited for those who have crizotinib. Taking these exceptional circumstances into account, brigatinib is recommended for ALK-positive advanced NSCLC in adults who have had crizotinib.
PERTUZUMAB RECOMMENDED FOR ADJUVANT TREATMENT OF HER2-POSITIVE EARLY STAGE BREAST CANCER
NICE has published final guidance which recommends pertuzumab (Perjeta), with intravenous trastuzumab and chemotherapy, for the adjuvant treatment of human epidermal growth factor receptor 2 (HER2)-positive early stage breast cancer in adults, only if:
- they have lymph node-positive disease
- the company provides it according to the commercial arrangement.
NICE says there is uncertainty about the size of the clinical benefit for pertuzumab in the adjuvant treatment of HER2‑positive early stage breast cancer at high risk of recurrence. Clinical trial evidence measuring invasive disease-free survival suggests that 1.7% fewer people with this type of cancer have invasive disease at four years with adjuvant pertuzumab. Evidence from people with lymph node-positive disease suggests more benefit in this population, with 3.2% fewer people having invasive disease at four years. However, it is not known whether this means that adjuvant pertuzumab increases the overall length of time people live. Due to the uncertainty in the clinical-effectiveness evidence, the cost-effectiveness estimates are very uncertain. NICE says that, given this uncertainty, an estimate above £20,000 per quality-adjusted life year (QALY) gained is not considered a cost-effective use of NHS resources. The company's final model includes only people with lymph node-positive disease, and incorporates NICE committee's preferred conservative estimates of how long treatment benefit with pertuzumab lasts after treatment is stopped. If the commercial discount to the price of pertuzumab, together with a weighted discount for biosimilar intravenous trastuzumab are taken into consideration, the cost-effectiveness estimate is comfortably below £20,000 per QALY gained. Therefore, adjuvant pertuzumab is recommended for HER2-positive early stage breast cancer in people with lymph node-positive disease.
EUROPEAN MEDICINES AGENCY
INCREASED RISK OF BLOOD CLOTS IN LUNGS AND DEATH WITH HIGHER DOSE OF XELJANZ FOR RHEUMATOID ARTHRITIS REPORTED
The EMA is advising healthcare professionals and patients not to exceed the recommended dose of Xeljanz (tofacitinib) when treating rheumatoid arthritis. The advice follows early results from an ongoing study in patients with rheumatoid arthritis which showed an increased risk of blood clots in the lungs and death when the normal dose of 5 mg twice daily was doubled. In the EU, 5 mg twice daily is the authorised dose for rheumatoid arthritis and psoriatic arthritis. The higher dose of 10 mg twice daily is approved for the initial treatment of patients with ulcerative colitis. The EMA is assessing the early results and will consider if any regulatory action is needed. While full results are awaited, the EMA is recommending that healthcare professionals monitor patients for signs and symptoms of blood clots in the lungs. Patients should not stop or change their dose of Xeljanz without talking to their doctor. Patients should seek medical attention immediately if they experience symptoms such as difficulty breathing, pain in the chest or upper back and coughing up blood. Healthcare professionals are being informed in writing of the preliminary results of the study and the current treatment recommendations.
PRAC STARTS REVIEW ON SCREENING PATIENTS BEFORE TREATMENT WITH FLUOROURACIL, CAPECITABINE, TEGAFUR AND FLUCYTOSINE TO DECREASE THE RISK OF SIDE EFFECTS
The European Medicine Agency’s (EMA) safety committee (PRAC) announced that it has started a review of medicines containing fluorouracil (also known as 5-fluorouracil or 5-FU) and the related medicines capecitabine, tegafur and flucytosine, which can be converted to fluorouracil in the body. Fluorouracil (given by injection), capecitabine and tegafur are cancer medicines, whereas topical fluorouracil is used for various skin conditions; flucytosine is a medicine used in severe fungal infections. The review will examine existing screening methods and their value in identifying patients with low levels or complete lack of dihydropyrimidine dehydrogenase (DPD), an enzyme necessary to break down fluorouracil, as these patients are at an increased risk of severe side effects.
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY
MEDICAL DEVICE ALERT – RISK OF BATTERIES OVERHEATING OR IGNITING WITH SOME PAGEWRITER CARDIOGRAPHS AND EFFICIA MONITORS
The Medicines and Healthcare products Regulatory Agency has issued a medical device alert (MDA) for Philips Pagewriter Cardiographs (TC20/30/50/70) manufactured before 20 November 2018 and Efficia Monitors (CM10/12/100/120/150) manufactured before 25 October 2018 – due the risk of batteries overheating or igniting. This problem affects lithium ion batteries that have exceeded their specified replacement interval or number of charging cycles. Healthcare professionals are advised to:
- Identify all affected devices using the manufacturer's Field Safety Notices (FSNs) for the TC Cardiograph and the Efficia monitor.
- Contact Philips to confirm receipt of each FSN using their response form.
For TC Cardiographs:
- Check if the battery has exceeded 300 charge-discharge cycles or if the battery state of health is less than 80%. If necessary, replace the battery in accordance with the instructions in the FSN. Contact Philips to order replacement batteries
- Ensure that systems are in place to routinely assess battery condition. Philips are developing a software update that will assist in battery management and will contact you once this is available
- For Efficia Monitors:
- Report adverse events involving these devices through your local incident reporting system and/or your national incident reporting authority as appropriate: England, Scotland, Northern Ireland, Wales. You should also report directly to manufacturers if your local or national systems do not.
A previous MDA was published for the same issue in Philips Suresigns VS and VM patient monitors and viewing stations manufactured before the 03 May 2018. Healthcare professionals are reminded to ensure that the actions described in that MDA have been completed.
COMPANY-LED DRUG ALERT - OZURDEX IMPLANT RECALL
Allergan Pharmaceuticals Ireland is further recalling batches of Ozurdex 700 micrograms intravitreal implant in applicator (Dexamethasone) due to the possibility that a single loose silicone particle of approximately 300 microns in diameter may become detached. In October 2018, Allergan recalled certain batches of OZURDEX® product due to the potential for a silicone particle from the needle sleeve to be implanted into the eye during product administration. At the time of the initial recall, there were some unexpired batches on the UK market where additional testing had not identified the defect but it could not be ruled out. These batches were not recalled. Since sufficient replacement stock is now available, these batches (see MHRA website for batch numbers) are now being recalled by Allergan as agreed. A copy of the Dear Healthcare Professional Communication issued by Allergan on 28 February 2019 can be found here.
ENFLOW® IV FLUID AND BLOOD WARMER - RISK OF UNSAFE LEVELS OF ALUMINIUM LEAKING FROM THE DEVICE – UPDATED SAFETY ADVICE FROM MANUFACTURER
The manufacturer – Vyaire – has provided the Medicines and Healthcare products Regulatory Agency with additional evidence that suggests using the enFlow system with lactated Ringer’s, platelets, plasma, whole blood, packed red blood cells and Sterofundin may lead to a risk of administering potentially harmful concentrations of aluminium. Healthcare professionals (HCPs) are advised to:
- Use an alternative fluid warming device if available.
- If alternatives are available, follow the instructions in the manufacturer’s updated Field Safety Notice.
- In the short term, if no alternative is available, carry out and document a local risk assessment based on a clinical risk-benefit analysis before using this fluid warmer. Overriding clinical need for fluid warming should take precedence over considerations of risk of aluminum release.
- Put measures in place to source alternative fluid warming systems.
- 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. HCPs should report directly to manufacturers if local or national systems do not.
THE ROYAL COLLEGE OF OPHTHALMOLOGISTS
CHANGE TO DVLA MANAGEMENT OF CASES FOR DRIVERS WITH NYSTAGMUS
The Royal College of Ophthalmologists has reported that the secretary of state for transport’s honorary medical advisory panel on driving and visual disorders has advised that it is the visual problems associated with nystagmus that are relevant when assessing fitness to drive, not nystagmus itself. On this basis, it has been decided that the DVLA doesn’t need to be notified of nystagmus if the visual acuity and visual field standards for driving are met and providing any associated medical condition is declared. The visual acuity standard requires drivers to have a measured acuity of at least 6/12 (decimal 0.5) and be able to read a number plate from 20 metres. Details of the visual field standards can be found here. While drivers no longer need to notify of nystagmus, they must still notify DVLA if they are unable to meet the vision standards or they have any associated vision problem, for example, diplopia.
EUROPEAN CENTRE FOR DISEASE PREVENTION AND CONTROL
REPORT ON TUBERCULOSIS IN EUROPE 2019 SHOWS IT REMAINS A MAJOR PUBLIC HEALTH CHALLENGE DESPITE AN OVERALL DECLINE
The latest European Centre for Disease Prevention and Control - World Health Organisation report on Tuberculosis (TB) surveillance and monitoring in Europe 2019 (2017 data) shows that despite an overall decline in numbers of people suffering from TB, the disease remains a major public health challenge in the Region. Of the 275, 000 new diagnoses and relapses, an estimated 77, 000 people are suffering from difficult-to-treat multidrug-resistant TB (MDR-TB). The European Union and European Economic Area (EU/EEA) countries fare better, with only 1,041 people reported to have MDR-TB. However, the report found that most countries in the Region, including many in the EU/EEA, struggle to treat patients successfully.
WORLD HEALTH ORGANISATION
NEW GUIDANCE PUBLISHED TO ACCELERATE PROGRESS OF TB ELIMINATION
The World Health Organisation (WHO) has issued new guidance which aims to improve the treatment of multidrug resistant TB (MDR-TB). WHO is recommending shifting to fully oral regimens to treat people with MDR-TB. This new treatment course is found to be more effective and less likely to provoke adverse side effects. In addition, WHO also recommends backing up treatment with active monitoring of drug safety and providing counselling support to help patients complete their course of treatment.