Biobank pilot to be launched by MHRA to better understand genetics and medicines safety

26th May 2023

A genetic ‘biobank’ will be launched on 1 June 2023 by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) to understand how a patient’s genetic make up can impact the safety of their medicines.

Known as the Yellow Card biobank, the biobank will contain genetic data and patient samples and be used by scientists to determine whether a side effect from a medicine was caused by a specific genetic trait.

A joint venture with Genomics England, the genetic research resource is the first of its kind to be launched by a drug safety regulator.

Operating alongside the MHRA’s existing Yellow Card reporting site for suspected side effects and adverse incidents involving medicines and medical devices, the new venture forms part of a long-term vision for more personalised medicine approaches.

Targeted prescriptions

By understanding the underlying mechanism of an adverse drug reaction (ADR), it is hoped that pharmacogenetic testing strategies could be developed so that ADRs could be prevented rather than requiring a reactive approach.

In turn, this will enable doctors to target prescriptions so UK patients will receive the safest medication for them, based on their genetic makeup.

‘We are excited by the upcoming launch of the Yellow Card biobank, which demonstrates that we are at the absolute forefront of innovation in the field of drug safety monitoring,’ said Dr June Raine, MHRA Chief Executive. ‘Almost a third of adverse reactions to medicines could be prevented with the introduction of genetic testing… This has the potential to transform our safety monitoring activities – enabling us to meet a real need by using high-quality patient data to reduce side effects of medicines.’

Participant recruitment

Recruitment for the biobank will commence on 1 September and participants will be visited at home by a nurse who will take a blood sample to be added to the biobank. The sequencing of participants’ genetic material will begin in spring 2024. Initial research findings are due to be published in 2025.

The pilot phase will start by looking at allopurinol and related rare, severe skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis. Other topics of focus for the pilot phase will be confirmed in due course.

Genomics England will support the MHRA with the sequencing and storage of genetic material through use of its well-established and secure infrastructure.

Commenting on the ‘transformative partnership’ with the MHRA, Professor Matt Brown, Chief Scientific Officer for Genomics England, added: ‘Many [severe ADRs] are influenced by underlying genetic risk factors, substantially heightening an individual’s vulnerability.

‘By joining forces with the MHRA, we are poised to gain greater understanding of these genetic influences – discoveries that will be vital if we are to move to harness the power of genomics to proactively protect patients from these harms.

‘Together, we hope that this is the first step towards redefining the future of drug safety.’

ADRs continue to be a significant burden on the NHS and account for one in 16 hospital admissions.

MRI-guided stereotactic radiotherapy superior to CT in prostate cancer

20th January 2023

MRI guided stereotactic radiotherapy is superior than that provided via CT guidance with respect to adverse effects for men with prostate cancer.

A randomised trial by Californian researchers has shown that magnetic resonance imaging (MRI)-guided stereotactic body radiation, significantly reduced grade 2 or higher acute physician-scored genitourinary and gastrointestinal toxic effects as well as patient self-reported prostate cancer symptom scores, compared to computed tomography (CT)-guided radiotherapy.

Stereotactic radiotherapy delivers treatment with high precision from a number of different angles around the body and is designed to reduce adverse effects on the tissue surrounding a tumour. Furthermore, results from several trials, indicate that this approach does not increase gastrointestinal or genitourinary acute toxicity.

While stereotactic radiotherapy has traditionally been delivered using linear accelerators and guided by computed tomography (CT) imaging, MRI-guided adaptive radiotherapy is seen as an emerging and alternative approach.

Moreover, it may also be possible using MRI to reduce the radiotherapy planning target volume (PTV) which encompasses the clinical target volume to account for possible uncertainties in beam alignment, patient positioning, organ motion, and organ deformation.

In the present study, the US researchers undertook a phase 3 study, with a view to demonstrating a reduced PTV with MRI compared to CT guidance, following stereotactic body radiotherapy for men with localised prostate cancer. Eligible men were randomised 1:1 to either MRI- or CT-guided stereotactic radiotherapy although neither the treating physician or patient were blinded to the treatment allocation.

The primary outcome was set as the incidence of acute (defined by occurring less than 90 days after stereotactic therapy) grade 2 or higher genitourinary (GU) toxic effects, whereas secondary outcomes included gastrointestinal toxic effects.

Other measures assessed included changes in the international prostate symptom score (IPSS) and for which increases of 15 points or more are considered to be clinically relevant.

MRI-guided stereotactic therapy and GU toxicity

A total of 156 men with a mean age of 71 years were randomised to the MRI arm (77) or the CT arm.

The proportion of GU toxic effects of grade 2 or higher was significantly lower among those receiving MRI-guided stereotactic therapy (24.4% vs 43.4%, p = 0.01). There were no reported gastrointestinal toxic effects at grade 2 or higher compared to 10.5% in the CT-guided group (p = 0.003).

The researchers also observed a significantly lower proportion of men with an IPSS score increase of 15 points or more after 4 weeks (6.8% vs 19.4%, p = 0.01).

The authors concluded that MRI-guided stereotactic radiotherapy reduced physician-reported toxic GU and gastrointestinal adverse effects than CT-guided stereotactic radiotherapy and called for future studies to examine the sustainability of these benefits.

Citation
Kishan AU et al. Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial. JAMA Oncol 2023

Influenza vaccination protects against adverse outcomes in COVID-19 patients

7th August 2021

A large retrospective study has revealed a reduction in adverse outcomes in COVID-19 patients previously vaccinated against influenza.

The influenza vaccination has an effectiveness ranging from 30 to 60% for the three different influenza strains. However, over the course of the COVID-19 pandemic, there have been emerging data that suggests influenza vaccination confers some level of protection against COVID-19. For example, one US study found that among those who had not received an influenza vaccination, there was a two-fold higher risk of hospitalisation because of COVID-19. A further study appeared to confirm that having received a flu vaccination, reduced the risk of testing positive for COVID-19. Part of the reason for a potentially protective effect after influenza vaccination is related to the presence of MF59, an oil-in-water immunogenic adjuvant which appears to induce higher levels of antigen-specific antibody levels and ultimately, better protection.

While some preliminary data would suggest that receipt of an influenza vaccine protects against infection with COVID-19, no studies have examined whether vaccination mitigates any of the adverse outcomes associated with COID-19 infection. Using a retrospective design, a team from the Division of Plastic and Reconstructive Surgery, University of Miami, Florida, US, used propensity matching to compare the incidence of adverse outcomes between influenza vaccinated and unvaccinated individuals who had tested positive for COVID-19. They used a de-identified database and focused on individuals who had either received a flu vaccination six months and two weeks prior to the onset of symptoms or not. The two-week period was included because this is the length of time required to acquire immunity after an influenza vaccination. Additional data collected included demographics and co-morbidities and used these to propensity-match the two cohorts. Adverse outcomes were assessed within 30, 60, 90 and 120 days after a positive COVID-19 test result.

Findings
Two propensity matched cohorts of 37,377 patients with a median age of 52.5 years (58% female) were included in the analysis. Compared with unvaccinated individuals 60 days after testing positive, COVID-19 patients who received the influenza vaccine experienced significantly less sepsis (risk ratio, RR = 1.38, 95% CI 1.17–1.63, p < 0.01) and stroke (RR = 1.45), admission to an intensive care unit (RR = 1.16) and deep vein thrombosis (RR = 1.53). Furthermore, there was an overall lower number of emergency department visits at 120 days after infection (RR = 1.28). However, mortality did not differ at any of the time points between the two cohorts.
In their conclusion, while accepting the limitation imposed by a retrospective design and the potential for errors in data coding, the authors called for this potential protective effect of influenza vaccination against adverse outcomes in those testing positive for COVID-19, to be validated in further studies.

Citation

Taghioff SM et al. Examining the potential benefits of the influenza vaccine against SARS-CoV-2: A retrospective cohort analysis of 74,754 patients. PloS ONE 2021