This website is intended for healthcare professionals only.
Take a look at a selection of our recent media coverage:
12th April 2024
Tisagenlecleucel (brand name Kymriah) has been recommended for routine rollout on the NHS by the National Institute for Health and Care Excellence (NICE), its manufacturer Novartis has announced.
Final draft guidance for the treatment, which has been available through the NHS Cancer Drugs Fund (CDF) since December 2018, recommends tisagenlecleucel for children and young adults up to and including 25 years of age who have B-cell acute lymphoblastic leukaemia (ALL) that is refractory, in relapse post-transplant or in second or later relapse.
A chimeric antigen receptor (CAR) T-cell therapy, tisagenlecleucel is administered as a one-off infusion into the blood stream.
Dr Sara Ghorashian, consultant in paediatric haematology at Great Ormond Street Hospital for Children NHS Foundation Trust, said: ‘During its time in the CDF, tisagenlecleucel has changed the way in which people with relapsed or refractory B-ALL have treatment.
‘It offers a chance of durable remissions and prolonged overall survival for people who often have no other option. The CDF has enabled us to build robust real-world evidence and I’m delighted that NICE has recommended that children and young adults should continue to have access to this treatment.’
The recommendation and final draft guidance from NICE for the routine rollout of this CAR T-cell therapy is based on data collected from its use in the NHS as well as additional clinical trial evidence from three studies.
Presented to NICE as a pooled dataset, the ELIANA, ENSIGN and B2101J trials showed people treated with tisagenlecleucel lived for longer and without experiencing relapse or progression, and improved overall survival for people compared with standard treatment.
For example, the median overall survival was 48 months, compared with a median overall survival for two other standard treatments of 7.5 months for blinatumomab and a median overall survival of three months for salvage chemotherapy.
Data collected from ELIANA have been published in the Journal of Clinical Oncology.
NHS use data found that the 24-month overall survival was 72% following treatment.
According to Novartis, tisagenlecleucel was used to treat 133 children and young adults while in the CDF between 2018 and September 2023.
Atogepant (brand name Aquipta), the first oral drug for chronic and episodic migraine prophylaxis where other treatments have failed should be available on the NHS, according to final draft guidance from NICE.
Up to 170,000 people could be eligible for atogepant, which is manufactured by AbbVie, under the recommendations.
This follows the approval of atogepant by the European Commission in August 2023 for chronic and episodic migraine prophylaxis in adults. The Scottish Medicines Consortium also accepted atogepant for restricted use in suitable patients in October 2023.
With this latest recommendation, it is expected that use of the drug, which works by blocking the calcitonin gene-related peptide receptor (CGRP), will be initially managed in secondary care, under a commercial agreement agreed with NICE.
But in the evidence provided to the appraisal process, drug manufacturer AbbVie noted there was potential for it to be monitored in primary care, and for follow-up appointments to be done by GPs.
Patient and professional organisations also told the committee that the availability of atogepant through GPs would improve access to treatment and reduce NHS costs.
The committee said that while atogepant would initially be prescribed and monitored in secondary care, ‘there would be interest in being able to use it in primary care’.
Under the recommendations outlined in the final draft guidance, the oral, once-daily atogepant will be an option for chronic and episodic migraine prophylaxis in adults who have had at least four migraine days per month.
To be eligible for the drug, patients must also have tried at least three previous preventive treatments.
Atogepant may be useful for those who cannot tolerate current fourth-line injectable treatments or who have contraindications to them, the guidance said.
The drug should be stopped after 12 weeks if the frequency of migraine attacks does not stop by at least 50% for episodic migraine and at least 30% for chronic migraine, NICE said.
It is also considered to be one of a range of suitable treatments and, after discussing the advantages and disadvantages of all the options, the least expensive should be used, NICE added.
Professor Peter Goadsby, honorary consultant neurologist, King’s College Hospital, said: ‘We know that people living with migraine may battle for years without an effective treatment to mitigate the daily struggles of living with this debilitating condition.
‘The decision by NICE should have a positive impact on patients who are eligible to receive atogepant as the treatment has been shown to reduce significantly the number of mean monthly migraine days in pivotal trials.
‘This welcome news increases the treatment options available that clinicians can offer to suitable patients, providing them with access to an additional preventive treatment that is now available on the NHS in England and Wales.‘
The NICE recommendation is supported by data from three pivotal Phase 3 clinical studies evaluating atogepant 60 mg once-daily in adults living with episodic (ADVANCE and ELEVATE) and chronic (PROGRESS) migraine.
In the three trials, the treatment met the primary endpoint of a change from baseline in mean monthly migraine days across 12 weeks versus placebo. Additionally, the treatments achieved significant reductions from baseline in several secondary efficacy endpoints compared to placebo: mean monthly headache days and mean monthly acute medication days, along with an additional achievement of ≥50% reduction in three-month average of monthly migraine days in the ELEVATE study.
Atogepant was also found to be generally well tolerated.
The most commonly reported adverse reactions in the ADVANCE and PROGRESS trials were nausea (7%), constipation (7%) and fatigue/somnolence (5%).
For the ELEVATE study, treatment-emergent adverse events were reported by 81 participants (52%) in the atogepant group (n=156). The most common (≥5%) were constipation (10%), Covid-19 (8%), nausea (7%), and nasopharyngitis (5%).
NICE director of medicines evaluation Helen Knight said: ‘[The] final draft guidance demonstrates our commitment to focusing on what matters most and getting the best care to people while ensuring value for the taxpayer.
‘Currently, the most effective options for people with chronic migraines who have already tried three preventative treatments are drugs that need to be injected.
‘The committee heard from patient experts that some people cannot have injectable treatments, for example because they have an allergy or phobia of needles. So, some people with chronic migraines would welcome an oral treatment. Atogepant also offers more choice for people with episodic migraine.’
Rob Music, chief executive of the Migraine Trust, added: ‘A migraine attack can be incredibly debilitating. Symptoms can include intense head pain, loss of or changes to senses and lack of ability to carry out day to day life.
‘It is positive to see even more therapies emerging for people with migraine after many still rely on treatments developed for other conditions. We now need to ensure access to the newer treatments is swift, so that migraine patients can benefit from them.‘
If there are no appeals, the final NICE guidance is expected to be published on 15 May 2024.
Last year, NICE recommended rimegepant as the first oral treatment for episodic migraine and acute migraine, in draft guidance published in June and September, respectively.
14th March 2024
Etrasimod (brand name Velsipity) has been approved by the Medicines and Healthcare products Regulatory Agency (MHRA) and recommended by the National Institute for Health and Care Excellence (NICE) for treating eligible patients with ulcerative colitis (UC).
It is approved for patients aged 16 years and older with moderately to severely active UC who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biological agent.
The recommended dose of etrasimod is one 2 mg tablet taken once daily with food for the first three days. After this, it can be taken each day with or without food.
The approval of etrasimod in the UK follows its marketing authorisation by the European Commission in February 2024 for the same indication.
This was the first time an oral advanced UC therapy had been approved for use in older adolescents.
Commenting on the recommendation, Helen Knight, director of medicines evaluation at NICE, said: ‘Severe ulcerative colitis is a debilitating lifelong condition; etrasimod provides a new convenient and effective treatment option that will make a positive difference for thousands of people.
‘I’m very pleased we have been able to publish our final guidance recommending the treatment on the day the MHRA granted it a licence. We are determined to continue getting the best care to patients fast.’
NICE has noted that just over 25,000 people in England are now eligible to receive the new treatment, which was evaluated using a simpler technology appraisal process.
As a result, the full final NICE guidance was available up to eight weeks faster than would have been the case under standard process.
The MHRA and NICE approvals of etrasimod were based on results from the phase 3 ELEVATE UC 52 and ELEVATE UC 12 trials.
These randomised, double-blind, placebo-controlled trials involved 743 patients aged 16 years and over for whom standard treatment or other treatments did not work well enough or could not be used.
They evaluated the safety and efficacy of etrasimod 2 mg once daily on clinical remission.
The coprimary endpoints in ELEVATE UC 52 were the proportion of patients who achieved clinical remission at Week 12 (induction period) and Week 52 (maintenance period).
The primary endpoint for ELEVATE UC 12 was the proportion of patients in clinical remission at the end of the 12-week induction period.
Taken together, the results from the studies showed that, after 12 weeks of treatment, 26% (129/496) of those who received etrasimod had achieved clinical remission compared with 11% (27/247) of those who received the placebo.
ELEVATE UC 52 also found that 32% (88/274) of people taking etrasimod achieved clinical remission after 52 weeks compared with 7% (9/135) for those receiving the placebo.
Both studies also achieved all key secondary efficacy endpoints, with a favourable safety profile consistent with previous studies of etrasimod.
The most common side effects of the were found to be bradycardia, hypertension, urinary tract infection and lower respiratory tract infection.
NICE also noted that indirect comparisons suggest etrasimod is likely to work better than adalimumab and may be similarly effective to other usual treatments for moderately to severely active UC.
The monoclonal antibody dostarlimab (brand name Jemperli) has been recommended by the National Institute for Health and Care Excellence (NICE) for use in combination with platinum-based chemotherapy for eligible patients with endometrial cancer.
The final draft guidance recommends dostarlimab for the treatment of primary advanced or recurrent endometrial cancer with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR) in adults who are candidates for systemic therapy.
Dostarlimab is already approved by NICE for previously treated advanced or recurrent endometrial cancer with MSI-H or dMMR. This new approval moves dostarlimab to an earlier line of therapy, so the drug can be given in combination with chemotherapy instead of after disease progression following first-line treatment.
As MSI-H or dMMR endometrial cancer is more likely to respond to immunotherapy treatment than chemotherapy, offering this treatment earlier in the pathway will help to reduce the risk of reoccurrence, NICE said.
Clinical trials show that dostarlimab improves life expectancy and delays worsening of endometrial cancer in the short-term. Until research shows its long-term benefits, the treatment will be offered via managed access through the Cancer Drugs Fund (CDF) to NHS patients with recurrent or advanced endometrial cancer only. It is not recommended for routine use in the NHS.
Dostarlimab is delivered by intravenous infusion in hospital over 30 minutes and it is thought that it the decision by NICE will affect 540 patients in the UK.
The treatment was granted marketing authorisation in the EU in December 2023 for the same indication and was authorised by the Medicines and Healthcare products Regulatory Agency’s global partnership Project Orbis in October 2023.
Commenting on the decision, Helen Knight, director of medicines evaluation at NICE, said: ‘Advanced or recurrent womb cancer has a devastating effect on quality of life and there are limited treatment options available.
We are focused on delivering what matters most and getting care to those who need it fast, so I am delighted this treatment option will be made quickly available through the CDF, enabling people with this type of cancer to enjoy more precious time with their families and loved ones’.
NICE’s approval represents the fourth treatment option or indication for endometrial cancer available via NHS commissioning or through the CDF since the organisation’s inception in 1999.
Publication of the final guidance is expected on 3 April 2024.
27th February 2024
The Janus kinase (JAK) inhibitor ritlecitinib has been recommended by NICE for the treatment of severe alopecia areata in adults and children aged 12 and over.
Treatment with ritlecitinib is a one-a-day capsule that has been shown in clinical trials to reduce inflammation and hair loss at the follicle for up to two years, the final draft guidance says.
The NHS approval of the treatment for people aged 12 years and older comes after an initial rejection by the committee in September.
NICE said the position had changed after a public consultation, additional information from the drug manufacturer Pfizer and an improved discount on the cost of the medicine.
The list price of the drug is £949.41 per pack of 30 capsules but the details of the commercial agreement with the NHS is confidential.
In discussions, the committee noted there is no standard treatment for severe alopecia areata, and access to treatment varies widely. Hair loss can cause severe psychological distress.
Another JAK inhibitor, baricitinib, is licensed for severe alopecia areata in Great Britain but is not available for severe alopecia areata on the NHS, NICE said.
It is thought that up to 14,000 people with alopecia areata could benefit from the drug after the NICE recommendation.
Helen Knight, director of medicines evaluation at NICE, said: ‘Our committee heard how severe alopecia areata can have a significant impact on people’s health and quality of life.
‘I’m delighted that we are now able to recommend this innovative treatment, the first time a medicine for severe alopecia areata has been recommended by NICE for use in the NHS.
‘It is especially pleasing that we have been able to recommend ritlecitinib just 16 weeks after it was granted a licence by the Medicines and Healthcare products Regulatory Authority, demonstrating NICE’s commitment to getting the best care to patients fast.’
Sue Schilling, the chief executive of Alopecia UK, said the decision was a monumental day for those with the condition.
‘For far too long, patients with alopecia areata have gone without a licensed treatment option available via NHS pathways.
‘If new treatments are only available privately, it becomes a case of the “haves and the have nots”. This latest NICE recommendation will go some way to address this.’
But she said people with alopecia still face substantial barriers including difficulties in getting a dermatology referral from their GP, unacceptable dermatology waiting times, and even some NHS trusts making the decision not to allow dermatology appointments for alopecia patients.
She added: ‘There is no longer the excuse of there being no licensed treatment available. I urge key decision-makers within the NHS to keep referral pathways open for patients with alopecia areata.’
A version of this article was originally published by our sister publication Pulse.
2nd February 2024
Updated guidance from the National Institute for Health and Care Excellence (NICE) on identifying and managing sepsis in over-16s recommends better targeting of antibiotics for suspected sepsis.
The updates specify that secondary care teams should target antibiotic use as more is learned about a patient’s condition to ensure the right people receive treatment as soon as possible but the medicines are not overused, which can lead to antibiotic resistance.
Clinicians should use the NEWS2 risk score to assess those with suspected sepsis in those aged over 16 who are not or have not been recently pregnant and are in an acute setting or ambulance, the guidelines state.
NICE said use of NEWS2 should lead to more people with suspected sepsis graded at a lower risk level where treatment should begin within one to three hours and the diagnosis clarified before antibiotics are given, targeted at a specific infection if possible.
People graded by NEWS2 as being the most severely ill should be prioritised and continue to receive broad-spectrum antibiotics within an hour, the guideline adds.
The new NICE recommendations also aim to ensure better communication and inclusivity for patients with suspected sepsis if they have learning disabilities, autism or where English is not their first language.
This includes assessing these individuals at every stage of the healthcare journey with extra care if they cannot give a good history and tailoring the timing, content and delivery of information to the person’s needs and preferences.
Detail on identifying the source of infection and involving surgical teams have also been broadened to cover risk of sepsis in all parts of the body and a wider range of interventions.
This partial update to the 2016 guidelines also urges immediate hospital transfer for patients who meet any high-risk criteria for sepsis.
GPs or ambulance services must pre-alert secondary care when a patient with suspected sepsis is on their way, the new recommendations state.
And in remote and rural locations where transfer time to emergency department is likely to be more than an hour, GPs and ambulance services should have mechanisms in place to start antibiotics straightaway while ensuring due consideration is given to both patient safety and antimicrobial stewardship, NICE said.
Altered mental state, raised respiratory rate, new need for oxygen, low blood pressure, raised heart rate or not passing urine, a mottled or ashen appearance, cyanosis or a non-blanching rash are all listed as high-risk factors that primary healthcare professionals should look for.
Figures suggest there are at least 245,000 sepsis cases diagnosed in the UK every year.
Professor Jonathan Benger, NICE chief medical officer said the guidance would help ensure antibiotics are targeted to those at the greatest risk of severe sepsis, so they get rapid and effective treatment.
He said: ‘We know that sepsis can be difficult to diagnose so it is vital there is clear guidance on the updated NEWS2 so it can be used to identify illness, ensure people receive the right treatment in the right clinical setting and save lives.
‘This update is the latest part of the process to ensure NICE guidance is as current as possible. We recognise this is a vital and rapidly evolving area, so this is the latest in a series of planned updates to our guidance.’
UK Sepsis Trust founder Dr Ron Daniels welcomed the update and said: ‘We particularly support that the update continues to recommend the identification of high-risk factors, whilst reinforcing the importance of clinical judgement to prevent injudicious use of antibiotics.
‘The recommendation for GPs and ambulance services to consider how they give antibiotics to people that are at high risk of sepsis is increasingly relevant as transit times increase, and could be potentially transformational in terms of patient outcomes.
He added: ‘We’re now presented with an opportunity to deliver a coordinated and cohesive approach to the recognition and management of sepsis across the NHS.’
23rd January 2024
The poly ADP-ribose polymerase (PARP) inhibitor talazoparib (brand name Talzenna) has been recommended by the National Institute for Health and Care Excellence (NICE) to treat a type of locally advanced or metastatic breast cancer.
The final draft guidance from NICE recommends talazoparib for the treatment of adults with BRCA 1 or 2 mutated HER2-negative locally advanced or metastatic breast cancer after prior chemotherapy.
Evidence from a clinical trial showed that talazoparib increases how long people live without their cancer getting worse compared with chemotherapy. The trial did not show any difference in how long people live.
NICE originally rejected talazoparib for breast cancer in July 2023, but reversed the decision after the manufacturer Pfizer offered an increased – and confidential – discount to the drug’s price.
The draft guidance states: ‘When considering the condition’s severity and its effect on quality and length of life, the most likely cost-effectiveness estimates for talazoparib are within the range that NICE considers an acceptable use of NHS resources. So talazoparib is recommended.’
The final guidance is expected to be published on 21 February 2024, and this will make talazoparib the first targeted treatment for this type of advanced breast cancer available in the NHS. This treatment would be instead of chemotherapy.
Current treatments include chemotherapy (mainly taxanes) and best supportive care, and alternative treatment options have been limited.
Helen Knight, director of medicines evaluation at NICE, said: ‘[This] announcement addresses a significant need by giving people with these types of cancer access to an additional treatment. And because talazoparib is taken as a once-daily tablet it means it’s much more convenient for people who would otherwise need to go into hospital for intravenous chemotherapy.
‘Although some uncertainty in the clinical evidence remains, when considering the impact of advanced breast cancer and its effect on quality and length of life, the improved discount from the company means we can now recommend talazoparib for use in the NHS.’
Earlier in January, talazoparib was approved by the European Commission in combination with the androgen receptor blocker enzalutamide in eligible patients with prostate cancer.
17th January 2024
The National Institute for Health and Care Excellence (NICE) has recommended that empagliflozin can be used as an option for treating chronic kidney disease (CKD) in adults under some circumstances.
It has to be prescribed as an add-on to standard care including the highest tolerated dose of angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker unless contraindicated, a Technology Appraisal has stated.
Under the recommendations, patients with CKD must also have an estimated glomerular filtration rate of:
Clinicians in both primary and secondary care should make prescribing decisions based on cost of suitable treatments including dapagliflozin after discussing the pros and cons with the patient, NICE said.
The committee noted that some patients already take dapagliflozin as an add-on to standard care and empagliflozin would be used in a similar way but with a potentially broader population.
Evidence from the EMPA-KIDNEY trial suggests that empagliflozin plus standard care is more effective than standard care alone for CKD but there were limits on who was included in the studies, NICE said.
There are also no trials directly comparing empagliflozin plus dapagliflozin but it is likely that effectiveness and safety is similar, the committee said.
It was acknowledged that CKD can progress more quickly in some ethnic minority groups in people under 55 with type 2 diabetes but this could not be considered in the decision making, the committee noted.
The SGLT2 inhibitor is already recommended by NICE for the treatment of adult patients with type 2 diabetes and adult patients with heart failure with reduced ejection fraction.
NICE’s decision to include empagliflozin as an option in some patients with CKD means it must be made available within three months.
In papers published by the NICE committee, it notes that the use of SGLT2 inhibitors is not yet well established in clinical practice and there is ‘scope to expand the use of this drug class in this indication to slow CKD disease progression’.
Empagliflozin was approved by the European Medicines Agency for the treatment of adult patients with CKD in July 2023.
A version of this article was originally published by our sister publication Pulse.
12th January 2024
Around 1.4 million more people in the UK will be eligible for antiviral treatment nirmatrelvir plus ritonavir (brand name Paxlovid) if they test positive for Covid-19 after final draft guidance from the National Institute for Health and Care Excellence widens access.
It follows a partial review of the evidence that identified additional groups of people who are at increased risk of severe Covid-19.
Under the recommendations, nirmatrelvir plus ritonavir will be available after a positive Covid-19 test to people aged 85 and over, as well as people who are resident in a care home or are already hospitalised and are aged 70 years and over, have a body mass index greater than 35 kg/m2 or have diabetes or heart failure.
People with end-stage heart failure who have a long-term ventricular assistance device and those on the organ transplant waiting list will also be eligible.
The eligibility is in addition to the 3.9 million people who were already identified as being as increased risk of progression to severe illness if they were infected with Covid-19, NICE said.
Those who are eligible can get free lateral flow tests from participating pharmacies and should take a test as soon as they have symptoms, even if mild, NICE reiterated before calling their GP, NHS 111 or hospital specialist if they test positive.
Helen Knight, director of medicines evaluation said: ‘Our review of the evidence on the use of Paxlovid has found it offers value for money for a wider group of patients.
‘This is good news for people who may contract Covid-19 in the coming months and will help alleviate pressure on the health service.‘
She added: ‘Although we are no longer in a pandemic, Covid-19 is still circulating and we are pleased that more people at risk of severe disease can benefit from Paxlovid.’
Nirmatrelvir plus ritonaviris is an antiviral medicine, given as two separate tablets to people within five days of Covid-19 symptom onset.
Nirmatrelvir stops the virus from growing and spreading, and ritonavir helps nirmatrelvir from being broken down in the body while it is working.
UK public health officials have reported rising levels of winter bugs in the past week with rates of flu, Covid-19 and norovirus continuing to rise.
The latest figures also show a rise in Covid-19 hospitalisations in the last week of 2023 as well as patients admitted to ICU with complications of the virus.
13th December 2023
The recent UK approval of ruxolitinib for the blood cancer polycythaemia vera marks a significant milestone in tackling unmet need for an under-represented patient population. Here, consultant haematologist Professor Claire Harrison speaks to Rod Tucker about ongoing challenges for the condition’s management, how this latest approval will benefit patients and clinicians, and other key research in the pipeline.
Ruxolitinib is a Janus kinase 2 (JAK2) inhibitor with diverse indications covering conditions such as eczema, psoriasis, vitiligo and myelofibrosis.
Most recently, in the UK at least, it has been added to the treatment arsenal for the rare blood cancer polycythaemia vera (PV) after its recommendation in October 2023 by the National Institute for Health and Care Excellence (NICE).
Professor Claire Harrison, consultant haematologist, professor of myeloproliferative neoplasms at Guy’s and St. Thomas’ NHS Foundation Trust in London, UK, has dedicated much of the last decade to researching ruxolitinib for use in PV and was instrumental in securing NICE’s endorsement.
‘It’s [a good] example of following a scientific story from discovery of the mutation, development of the drug, testing it in a more severe but related condition (myelofibrosis) then putting it into second line for PV,’ she says.
Despite the approval, there’s still work to be done to achieve the next ambition of ruxolitinib being approved for first-line use in PV. And Professor Harrison is on hand to get the ball rolling.
Today, diagnosing PV is much easier than when Professor Harrison first started as a consultant in 2001.
Previously, the diagnosis was arrived at following a series of tests to exclude all other possible causes of a patient’s symptoms and abnormal blood count. But after the description of a JAK2 mutation which is present in 97–98% of patients with PV, the diagnosis can be arrived at much more quickly.
‘This particular mutation for which it’s very easy to test for. It’s a cheap test and, for the most part, if it’s present, the patient has either got PV or one of the family of conditions, or it has very low levels of mutations but is likely to change into that,’ Professor Harrison says.
In general, the lay perception of a cancer diagnosis is that it represents a death sentence, and it becomes difficult to assuage patients of this fear.
While PV is incurable and lowers life-expectancy, it is not usually life-threatening, although Professor Harrison says some patients do present with life-threatening blood clots.
‘It’s a cancer but some low-risk patients we just treat with aspirin and phlebotomy, so removing blood,’ she says. ‘So that’s quite tricky saying “you’ve got cancer, but all we’re going to give you is an aspirin and take a pint of blood off you”, and other patients we do give treatments to, but we have limited options.’
Moreover, while these treatments do provide a clinical benefit in some patients, they frequently fail to alleviate symptoms.
This has become abundantly clear from the findings of the ongoing prospective REVEAL study. This showed that patients with PV experience symptoms that affect their quality of life and lead to work productivity impairments with an overall negative impact on their lives.
‘So, 80% of patients will complain of fatigue,’ Professor Harrison says. ‘It’s PV, it’s not a nothing condition: 20% of patients have to give up work or reduce their working time, others do die of the condition and the average life-expectancy is probably 15 to 20 years.’
Professor Harrison also highlights poor awareness of PV. ‘What patients would say, probably, is that people don’t understand the condition, GPs don’t understand the condition and their employers don’t understand the condition. It takes up a lot of their time and it has a big burden on their quality of life.’
She hopes that greater awareness of the condition will make it easier for people to support and make adaptations for this patient group.
There haven’t been any new treatments for PV in around 20 years, with hydroxyurea and interferon alpha having long been the two options.
But that all changed with the description of the mutation. Professor Harrison says that after first helping with diagnosis, these learnings aided the development of drugs that could target the downstream effects of that mutation, principally JAK inhibitors.
‘These were first tested and used in more aggressive conditions in the family such as myelofibrosis. But with the advent of these drugs and their use in PV, we have been able to show that we can address some of the other unmet needs for patients,’ she says.
‘I could comment on how disappointing it is that the UK is five years behind the rest of Europe in the approval of ruxolitinib for PV, but I would prefer to celebrate that it’s a really important milestone for patients that they have an alternative therapy.’
This is particularly important as resistance or intolerance to treatments can develop in some patients, and there are other side effects and contraindications that mean traditional treatments may not be suitable.
‘An important side effect of hydroxyurea, which is also a side effect of ruxolitinib, is skin cancer,’ says Professor Harrison. ‘That’s something that we need to manage very carefully. If a patient has a skin cancer on hydroxyurea, we will sometimes change the therapy.
‘Interferon does cause quite serious mood disturbance – sometimes suicidal ideation – so it can’t really be used in patients who’ve got a significant history of anxiety or depression.
‘Similarly, [hydroxyurea] can’t be used for the 20% of patients below the age of 40 who might want to conceive a child. But we have the option to alternate between the first-line therapies.’
One of the key studies that led to the approval of ruxolitinib for PV in the UK was MAJIC-PV. This phase II trial, for which Professor Harrison was the lead author, randomised patients to either ruxolitinib or best available care in those intolerant or resistant to hydroxyurea, which is the current standard care therapy.
What was clear from MAJIC-PV was the superiority of ruxolitinib, with 43% of patients achieving a complete response based on several haematological criteria compared with only 26% of those receiving current best practice care.
While ruxolitinib does not cure PV, the MAJIC-PV trial provided reassurance that over five years no new longer-term safety issues emerged, Professor Harrison notes.
The trial also uncovered several additional biological actions of the drug. During the study, researchers measured the amount of abnormal JAK2 present in patients. This enabled clinicians to determine whether treatments had any effect on the aberrant mutations that were present.
Surprisingly, in those assigned ruxolitinib, there was a reduction in the level of this mutation.
As such, the MAJIC-PV study hinted at a mutation-specific effect of the drug which hadn’t previously been observed. Furthermore, this reduction in the level of abnormal JAK was associated with an increased life expectancy and a reduction in PV-related complications for patients.
‘Interestingly, when we were using the drug to treat patients with myelofibrosis, colleagues in Italy were reporting that their patients who had myelofibrosis but had the autoimmune condition alopecia, the hair was coming back,’ Professor Harrison adds. This hints at the wider benefits of ruxolitinib as an anti-inflammatory drug which is being harnessed in for example the treatment of eczema.
Delving deeper, Professor Harrison also describes how in research by colleague Adam Mead ruxolitinib appeared to modify PV at the stem cell level using research tools enaling the analysis of mutations at a single cell level.
Despite MAJIC-PV showing that ruxolitinib reduced levels of the abnormal JAK mutations, the current NICE approval recommends that the drug is used second-line for patients who either become resistant to or intolerant of hydroxyurea.
Notwithstanding this restriction, Professor Harrison still feels that it is important for patients to have access to ruxolitinib as another treatment option, either because of contra-indications or adverse effects from the currently available drugs.
Another consideration is the issue of drug resistance. ‘All of the available drugs are generally effective for the majority of patients, but over time, around 20–25% of patients will become resistant to that drug,’ she explains.
As a result, relying on a single drug isn’t the most effective way of controlling a patient’s blood count over time.
Encouraged by the findings from MAJIC-PV, a further phase III open-label trial, MITHRIDATE, for which Professor Harrison is the chief investigator, is starting to enrol patients.
It is designed to compare ruxolitinib with either hydroxyurea or interferon alpha as first-line therapy for high-risk PV patients.
Ruxolitinib also has a powerful effect on disease related symptoms for example patients with PV experience pruritus (itching) which can be extremely disabling, and the drug has a big impact on this troublesome symptom.
Although it is too early to draw any conclusions, Professor Harrison is hopeful that the MITHRIDATE trial will demonstrate the advantages of using ruxolitinib as a first-line treatment option and perhaps offer further insight into the drug’s disease-modifying properties.
While the introduction of JAK inhibitors such as ruxolitinib are a welcome addition to a clinician’s arsenal in the treatment of PV, Professor Harrison believes that future treatments need to focus on the off-target effects of these drugs such as immune suppression.
Although the development of JAK mutation-specific therapies in PV would be an advantage, Professor Harrison is of the opinion that it is just as important to improve understanding of how and when to use ruxolitinib in patients with PV.
Alongside the potential development of mutation-specific drugs, there is increasing interest in immune-mediated therapy.
‘I think we’ve had this massive step forward with description of molecular markers and therapies targeting JAK. We’ll probably go to treating PV earlier, and treating with a disease-modifying therapy,’ she concludes.
But focusing on the latest developments, Professor Harrison believes the introduction of innovations such as ruxolitinib would not have been possible without the support of various charities such as MPN Voice and Blood Cancer UK, as well as various academic centres and companies such as Novartis.
Working collaboratively, it has been possible to clearly demonstrate that ruxolitinib can go a long way towards helping to relieve the symptom burden of patients living with polycythaemia vera and improve quality of life for this under-represented patient population.
Download Hospital Healthcare Europe free app
© Cogora 2024
Cogora Limited. 1 Giltspur Street, London EC1A 9DD
Registered in the United Kingdom. Reg. No. 2147432
