hheadmin, Author at Hospital Healthcare Europe

Press Releases

Take a look at a selection of our recent media coverage:

Scotland sees advance in treatment of kidney cancer

12th June 2019

Bristol-Myers Squibb has announced that the Scottish Medicines Consortium (SMC) has decided to fund the combination of Opdivo^® (nivolumab) plus Yervoy^® (ipilimumab) for use within NHS Scotland as a first-line treatment option for an advanced form of the most common type of kidney cancer, renal cell carcinoma (RCC), specifically in previously-untreated patients who are considered of intermediate- and poor-prognostic risk.

This recommendation signifies an important landmark in the treatment landscape, representing the first approval of an Immuno-Oncology (I-O) combination therapy for first-line patients with this type of cancer in Scotland. I-O works by stimulating the body’s immune system to recognise and eliminate cancer cells.

In addition to the SMC decision announced today, the combination of nivolumab plus ipilimumab has recently been made available immediately for NHS patients in England via the Cancer Drugs Fund, and has also been approved for use in Wales and Northern Ireland.

“Having the combination of nivolumab and ipilimumab available is a step change in the treatment of advanced kidney cancer. It is great news to be able to treat our patients first-line with this immunotherapy combination, as it has been shown to help certain patients live longer and improve outcomes compared to a current standard of care”, said Dr Balaji Venugopal, Honorary Clinical Senior Lecturer, University of Glasgow.

The SMC recommendation is based on data from the Phase III CheckMate 214 study of 1096 patients, which was stopped early after a planned interim analysis showed that the combination of nivolumab and ipilimumab demonstrated superior overall survival compared to sunitinib, a current standard of care. The co-primary outcome measures were overall survival, objective response rate and progression free survival in IMDC intermediate- and poor- prognostic risk patients:

The combination of nivolumab (3mg/kg) plus low-dose ipilimumab (1mg/kg) demonstrated a significant improvement in overall survival, with a 37% decreased risk of death in intermediate- and poor-prognostic risk patients (n=425), compared to a current standard of care, sunitinib (n=422) (HR 0.63; 99.8% CI: 0.44 to 0.89; p<0.001). The overall survival benefit was observed regardless of PD-L1 expression level. The median overall survival was not yet reached at the point of analysis (95% CI: 28.2 to not estimable [NE]), compared to 26.0 months for patients treated with sunitinib (HR 0.63; 95% CI: 22.1 to NE; p<0.001)
The objective response rate was 42% (95% CI: 37 to 47) in the nivolumab plus ipilimumab arm, versus 27% (95% CI: 22 to 31) in the sunitinib arm (p<0.001). The complete response rate was 9% (n=40) in the nivolumab plus ipilimumab arm, versus 1% (n=5) in the sunitinib arm
The median progression-free survival was 11.6 months (95% CI: 8.7 to 15.5) and 8.4 months (95% CI: 7.0 to 10.8) respectively (HR 0.82; 99.1% CI: 0.64 to 1.05; p=0.03; not significant per the prespecified 0.009 threshold)
The combination therapy was associated with numerically fewer overall Grade 3 or 4 treatment-related adverse events compared to sunitinib (46% [n=250] versus 63% [n=335] respectively). The most common adverse events (>20%) in the combination arm included fatigue, pruritus, diarrhoea, rash and nausea. The most common immune-related adverse events requiring steroid treatment were pneumonitis (59%), hepatitis (35%) and nephritis and renal dysfunction (27%).

“We are delighted that the SMC has accepted the combination of nivolumab plus ipilimumab as an important treatment option for Scottish advanced RCC patients who have an intermediate- and poor-prognostic risk. We will work closely with the SMC and NHS Scotland to support the swift implementation of this advice,” said Lynelle Hoch, General Manager, Bristol-Myers Squibb UK & Ireland. “By taking a collaborative approach to working with NICE and SMC we have been able to ensure this immunotherapy combination with the potential to extend life is available to all eligible patients, no matter where they are living in the UK.”

Scotland sees advance in treatment of kidney cancer

Pharmacies make a lifestyle impact for patients with prostate cancer

In the first study of its kind, researchers from the University of Surrey, funded by the Movember Foundation in partnership with Prostate Cancer UK, developed and tested the feasibility of community pharmacies delivering programmes to improve levels of physical activity and diet of men with prostate cancer and those who have successfully completed treatment for the disease.

The National Institute for Health and Care Excellence (NICE) recommends that men with prostate cancer follow a 12-week exercise programme to reduce symptoms after treatment and improve overall wellbeing, but this is hard to support in a hospital setting.

Nine community pharmacy teams in the south of England were trained to deliver health assessments and lifestyle prescriptions to men with prostate cancer or those who had undergone treatment. Pharmacy teams checked the weight, BMI, blood cholesterol and blood pressure of 116 men and assessed their upper-limb strength (grip strength), lower-limb strength (chair sit to stand) and overall fitness. To help improve strength and fitness levels, a computer algorithm developed by the research team used this assessment data to generate a personalised lifestyle prescription, including exercise and dietary advice, for the participants. In support of the lifestyle changes, pharmacy teams made regular phone calls to assist participants and offer guidance.

After a three-month period, participants were invited back to the pharmacy to assess progress. Moderate and vigorous physical activity levels amongst the group were found to have increased significantly by 34 minutes over three months. A reduction in weight by 1kg on average was observed amongst participants, with BMI down by 0.3kg/m² and cholesterol decreasing by 0.4mmol/l. Grip strength increased on average by 0.2kg (meaning that men were stronger in their arms) and more chair sit to stands reflected better leg strength. These results indicate that support offered by community pharmacies can make a real difference in improving the physical fitness and wellbeing of men.

Sara Faithfull, Professor of Cancer Nursing Practice at the University of Surrey, said: “Exercise and diet have been shown to reduce symptoms of prostate cancer treatment and lessen chances of cardiovascular disease. It is understandable that men who have successfully beaten cancer are reluctant to embark on an exercise regime by themselves, so they need help to know what to do and how much is required to make a difference.”

“Community pharmacies can make a really positive impact to this issue by providing valuable guidance and support for increasing activity levels and ensuring more informed dietary decisions are made. It is encouraging to see a measurable improvement over only three months, but we need to examine further how this could be effective in the longer term.”

Heather Blake, Director of Support and Influencing from Prostate Cancer UK said: “We know that regular exercise and a healthy diet can help some men manage many of the side effects of prostate cancer treatments, as well as improving their mental health and wellbeing.

“We are therefore pleased that this study shows that community pharmacies can support men with prostate cancer to improve their physical activity and cardiovascular health. We now need to determine how this improvement can be sustained over longer periods of time.”

Owen Sharp, CEO of the Movember Foundation said: “We know that some men who have been through prostate cancer treatment are at a higher risk of developing heart disease.

“This study shows that with the right support from community pharmacists, men can be empowered to take charge of their condition which has a positive impact on both their quality of life and overall health.”

Dr Agnieszka Lemanska, Lecturer in Integrated Care at the University of Surrey, said: “Community pharmacies are well placed in many respects to help facilitate lifestyle changes amongst patients. The potential benefits of lifestyle interventions in living with and beyond prostate cancer include decreased disease reoccurrence as well as improvements in quality of life, energy levels and physical function.”

Pharmacies make a lifestyle impact for patients with prostate cancer

Expert analysis: Adult food allergy vs food intolerance

11th June 2019

Food allergy in adults is usually mediated by IgE antibodies, with one or more immediate typical allergic symptoms (flushing, hives, itching, swelling, vomiting, diarrhoea, difficulty breathing) to trigger foods.¹

The most common non-IgE-mediated food allergy in adults is eosinophilic oesophagitis, characterised by symptoms of reflux, dysphagia and food impaction, with eosinophilic infiltration provoking structural changes in the oesophagus.¹ Food intolerance has no immune trigger. Sufferers may experience reactions due to pharmacological effects, an enzyme deficiency or gastro-intestinal disorder such as irritable bowel syndrome (IBS).² If symptoms include hives and facial swelling, but their onset is not linked to any specific food, then a differential diagnosis of spontaneous urticaria/angio-oedema may need to be considered. A robust diagnosis is important to ensure the correct management is implemented and unnecessary food exclusion is avoided as there may be adverse nutritional consequences, especially if a major food group, such as milk, wheat or fruits/vegetables are excluded.³

IgE-mediated food allergy affects around 4% of adults, lower than in children but with a greater risk of fatal anaphylaxis.^4,5 Milk, egg, wheat and soy allergy often resolves by the age of 18 years; despite this, milk and wheat are the foods most frequently suspected by adults to cause symptoms.^6–8 A small number of adults can have a severe persisting milk allergy from childhood. Adults sensitised to, but tolerant of, milk (typically those with severe eczema), who exclude it for a long period then reintroduce it, risk developing a milk allergy due to subsequent non-recognition by the IgE antibodies.⁹ The most probable cause of symptoms to milk in adults is lactose intolerance although respiratory symptoms associated with milk are also frequently reported by those with asthma or other lung conditions.^10,11

Wheat allergy

Wheat allergy is very rare, although wheat is one of the triggers of food-dependant exercise-induced anaphylaxis (FDEIA).^12,13 This food allergy is characterised by a lack of reaction to the trigger food unless it is consumed in large quantities or in close proximity to a cofactor (exercise, aspirin, non-steroidal anti-inflammatory drugs, alcohol).¹⁴ Apart from wheat, other common trigger foods of FDEIA include shellfish, tomatoes, celery and nuts.¹⁵ Wheat-associated symptoms in adults are most often gastro-intestinal, thus a diagnosis of coeliac disease should first be excluded before considering other causes.¹⁶ Those suffering with IBS may be wheat intolerant due to poor digestion of the fermentable carbohydrates.^17,18 Others may avoid wheat due to non-coeliac gluten sensitivity, although it has been demonstrated that less than 15% of those considered to be gluten intolerant are likely to have this condition.^19,20

Peanut and tree nut allergy

Peanut and tree nut allergies usually start in childhood; peanut allergy resolves before adolescence in one third or more of sufferers, whereas only 10% of those allergic to tree nuts will experience resolution.^21–25 A concomitant allergy to tree nuts is only likely in less than 40% of peanut allergic individuals, so it is important that sensitisation and allergy to tree nuts is individually assessed, especially since severe reactions to nuts are more frequent in teenagers and adults.^26,27 New onset symptoms to tree nuts or peanuts in adults is usually due to a condition known as pollen-food syndrome (PFS) or oral allergy syndrome.²⁸ Over 60% of birch-sensitised individuals are likely to develop PFS due to specific IgE antibodies against birch pollen recognising and reacting to similar proteins in plant foods, although grass and weed pollens are also involved.^29,30 Consumption of the trigger food, usually raw tree nuts, apples, kiwifruit and stone fruits (peaches, plums, cherries), causes immediate mild to moderate localised oropharyngeal symptoms.³¹ Another plant food allergy which mainly occurs in adult life also involves cross-reactions between allergenic proteins in plant foods called lipid transfer proteins (LTP).³² Food triggers are often similar to those reported in PFS, but due to their high resistance to heating and digestion, LTP allergens cause reactions to both raw and cooked food especially in the presence of co-factors.^33–35

Fish allergy

Fish allergy usually starts in childhood, whereas shellfish allergy is a common new-onset food allergy manifesting in adult life.^36,37 Reported reactions to shellfish are most often to crustaceans (shrimp, crab, lobster) rather than molluscs (mussels, scallops, clams, oyster, squid).³⁸ The primary shellfish allergen, tropomyosin, is water soluble and heat stable, so allergic symptoms can be triggered by inhalation of cooking vapours or by the residue of prawns in cooking oils.^39,40 The lack of similarity between tropomyosin and β-parvalbumin, the main allergen in fish, usually means cross-reactivity between fish and shellfish is unlikely, although this can occur possibly due to co-sensitisation to other allergenic proteins found in both.^39,41–43 Scombroid poisoning, caused by an excessive level of histamine due to the bacterial decarboxylation of histidine, is a common differential diagnosis for seafood allergy.³⁹ However, there are some adults who are sensitive to much smaller amounts of natural histamine in foods. Histamine intolerance is difficult to diagnose as there are no validated tests, so dietary exclusion and reintroduction is the only option. Foods likely to contain high levels of histamine include red/brown fish (mackerel, salmon, herring, sardines, tuna), shellfish, pork products, aged meat, mature or aged cheeses, and fermented foods such as wine.⁴⁴

Allergy to food additives

Additives can cause food intolerance, but the best studied of these is sodium metabisulphite, an additive used to preserve foods and prevent browning. Sodium metabisulphite use was greatly reduced in the 1990s after many reported instances of severe adverse reactions, especially in those with asthma.⁴⁴ Foods most often implicated include white and rose wine, sparkling wine, lager, cider, light coloured dried fruits, raw peeled potato products, light coloured fruit cordials and preserved lemon and lime juice. Should tests to the obvious foods not reveal the cause of a severe allergic reaction in adults, and food intolerance has been ruled out, it might be that a hidden allergen is the cause of the problem. This could be an LTP allergen or an allergy linked to co-factors, but other less obvious ‘hidden’ food allergens might need to be considered. These include buckwheat, legumes (soy, lupin, chick peas flour, pea protein, lentils, fenugreek, guar gum), pectin, mycoprotein, psyllium, mustard, celery and natural food colourings such as carmine (cochineal).⁴⁵

References

Muraro A et al. EAACI food allergy and anaphylaxis guidelines: diagnosis and management of food allergy. Allergy 2014;69:1008–25.
Boyce JA et al. Guidelines for the diagnosis and management of food allergy in the United States: report of the NIAID-sponsored expert panel. J Allergy Clin Immunol 2010;126(6 Suppl):S1–58.
Skypala IJ, McKenzie R. Nutritional issues in food allergy. Clin Rev Allergy Immunol 2018;May 15:doi: 10.1007/s12016-018-8688-x.
Burney P et al. Prevalence and distribution of sensitization to foods in the European Community Respiratory Health Survey: a EuroPrevall analysis. Allergy 2010;65:1182–8.
Turner PJ et al. Increase in anaphylaxis-related hospitalizations but no increase in fatalities: an analysis of United Kingdom national anaphylaxis data, 1992–2012. J Allergy Clin Immunol 2015;135:956-9–63.
Savage J, Sicherer S, Wood R. The natural history of food allergy. J Allergy Clin Immunol Pract 2016;4:196–203.
Golley S et al. Motivations for avoiding wheat consumption in Australia: results from a population survey. Public Health Nutr 2015;18:490–9.
van Gils T et al. Prevalence and characterization of self-reported gluten sensitivity in The Netherlands. Nutrients 2016;8(11).
Nachshon L et al. Food allergy to previously tolerated foods: Course and patient characteristics. Ann Allergy Asthma Immunol 2018;121(1):77–81
Deng Y et al. Lactose intolerance in adults: Biological mechanism and dietary management. Nutrients 2015;7:8020–35.
Wuthrich B et al. Milk consumption does not lead to mucus production or occurrence of asthma. J Am Coll Nutr 2005;24:547S–555S
Nwaru BI et al. Prevalence of common food allergies in Europe: a systematic review and meta-analysis. Allergy 2014;69:992–1007.
Christensen MJ et al. Exercise lowers threshold and increases severity, but wheat-dependent, exercise-induced anaphylaxis can be elicited at rest. J Allergy Clin Immunol Pract 2018;6(2):514–20.
Cardona V et al. Co-factor-enhanced food allergy. Allergy 2012 Oct;67(10):1316–8.
Hompes S et al. Elicitors and co-factors in food-induced anaphylaxis in adults. Clin Transl Allergy 2013;3(1):38.
Lebwohl B, Sanders DS, Green PHR. Coeliac disease. Lancet 2018 Jan 6;391(10115):70–81.
Monsbakken KW, Vandvik PO, Farup PG. Perceived food intolerance in subjects with irritable bowel syndrome – aetiology, prevalence and consequences. Eur J Clin Nutr 2006;60:667–72.
Gibson PR, Shepherd SJ. Evidence-based dietary management of functional gastrointestinal symptoms: The FODMAP approach. J Gastroenterol Hepatol 2010;25:252–8.
Catassi C et al. Diagnosis of non-celiac gluten sensitivity (NCGS): The Salerno Experts’ Criteria. Nutrients 2015;7:4966–77.12.
Elli L et al. Evidence for the presence of non-celiac gluten sensitivity in patients with functional gastrointestinal symptoms: Results from a multicenter randomized double-blind placebo-controlled gluten challenge. Nutrients 2016;8:84.7.
Peters RL et al. Natural history of peanut allergy and predictors of resolution in the first 4 years of life: A population-based assessment. J Allergy Clin Immunol 2015;135:1257–66.
Bégin P et al. Natural resolution of peanut allergy: a 12-year longitudinal follow-up study. J Allergy Clin Immunol Pract 2013;1:528–30.
Neuman-Sunshine DL et al. The natural history of persistent peanut allergy. Ann Allergy Asthma Immunol 2012;108:326–31.
Wainstein BK, Saad RA. Repeat oral food challenges in peanut and tree nut allergic children with a history of mild/moderate reactions. Asia Pac Allergy 2015;5:170–6.
Fleischer D et al. The natural history of tree nut allergy. J Allergy Clin Immunol 2005;116:1087–93.
Lomas JM, Järvinen KM. Managing nut-induced anaphylaxis: challenges and solutions. J Asthma Allergy 2015;8:115–23.
Deschildre A et al. Peanut-allergic patients in the MIRABEL survey: characteristics, allergists’ dietary advice and lessons from real life. Clin Exp Allergy 2016;46:610–20.
Skypala IJ et al. The prevalence of PFS and prevalence and characteristics of reported food allergy; a survey of UK adults aged 18-75 incorporating a validated PFS diagnostic questionnaire. Clin Exp Allergy 2013;43:928–40.
Werfel T et al. Position paper of the EAACI: food allergy due to immunological cross-reactions with common inhalant allergens. Allergy 2015;70:1079–90.
Skypala IJ et al. Development and validation of a structured questionnaire for the diagnosis of oral allergy syndrome in subjects with seasonal allergic rhinitis during the UK birch pollen season. Clin Exp Allergy 2011;41(7):1001–11.
Gunawardana NC, Rey-Garcia H, Skypala IJ. Nutritional management of patients with pollen food syndrome: Is there a need? Curr Treat Options Allergy 2018;5(4):500–14.
Asero R et al. Lipid transfer protein: a pan-allergen in plant-derived foods that is highly resistant to pepsin digestion. Int Arch Allergy Immunol 2001;124:67–69.31.
Pascal M et al. Lipid transfer protein syndrome: clinical pattern, cofactor effect and profile of molecular sensitization to plant-foods and pollens. Clin Exp Allergy 2012;42:1529–39.
Asero R et al. The clinical relevance of lipid transfer protein. Clin Exp Allergy 2018;48:6–12.
Van Winkle RC, Chang C. The biochemical basis and clinical evidence of food allergy due to lipid transfer proteins: a comprehensive review. Clin Rev Allergy Immunol 2014;46:211–24.
Worm M et al. Triggers and treatment of anaphylaxis: an analysis of 4,000 cases from Germany, Austria and Switzerland. Dtsch Arztebl Int 2014 May 23;111(21):367–75.
Kamdar TA et al. Prevalence and characteristics of adult-onset food allergy. J Allergy Clin Immunol Pract 2015;3:114–15.
Khan F et al. Adult seafood allergy in the Texas Medical Center: A 13-year experience. Allergy Rhinol (Providence) 2011;2:e71–7.
Ruethers T et al. Seafood allergy: A comprehensive review of fish and shellfish allergens. Mol Immunol 2018 Aug;100:28–57.
Lehrer SB et al. Transfer of shrimp allergens to other foods through cooking oil. J Allergy Clin Immunol 2007;119(S1):S112.
Kuehn A et al. Identification of enolases and aldolases as important fish allergens in cod, salmon and tuna: component resolved diagnosis using parvalbumin and the new allergens. Clin Exp Allergy 2013;43(7):811–22.
Sørensen M et al. Cross-reactivity in fish allergy: A double-blind, placebo-controlled food-challenge trial. J Allergy Clin Immunol 2017;140(4):1170–2.
González-Fernández J et al. Possible allergenic role of tropomyosin in patients with adverse reactions after fish intake. Immunol Invest. 2018 May;47(4):416–29.
Skypala IJ et al. Sensitivity to food additives, vaso-active amines and salicylates: a review of the evidence. Clin Transl Allergy 2015;5:34.
Skypala IJ. Food-induced anaphylaxis: Role of hidden allergens and cofactors. Front Immunol 2019 Apr 3;10:673.

Expert analysis: Adult food allergy vs food intolerance

Phase IIIa clinical trial data presented for oral semaglutide

10th June 2019

Findings presented from two Phase IIIa clinical trials evaluated oral semaglutide 14mg vs Jardiance^® (empagliflozin 25mg) in PIONEER 2 and oral semaglutide 14mg versus Victoza^® (liraglutide 1.8mg) in PIONEER 4 over 52 weeks in adults with type 2 diabetes.

Data from both trials were presented at the American Diabetes Association (ADA) 79th Scientific Sessions.

In PIONEER 2, oral semaglutide 14 mg demonstrated a superior HbA1c reduction of 1.3% compared to a 0.9% reduction with empagliflozin 25 mg for the primary endpoint at 26 weeks (p<0.0001) and a statistically significant reduction in HbA1c for the secondary endpoint at 52 weeks. Furthermore, for the secondary endpoint, the reduction in body weight with oral semaglutide was similar to empagliflozin with no statistical differences at both 26 and 52 weeks (3.8kg for oral semaglutide at both 26 and 52 weeks, 3.7kg and 3.6kg for empagliflozin, respectively).

In PIONEER 4, for the primary endpoint at 26 weeks, oral semaglutide 14 mg demonstrated a non-inferior reduction in HbA1c vs liraglutide 1.8mg (1.2% vs 1.1%, respectively) and a superior reduction vs placebo (1.2% vs 0.2%, respectively) in adults with type 2 diabetes inadequately controlled on metformin, with or without a sodium-glucose co-transporter-2 (SGLT-2) inhibitor. For the secondary endpoint at 52 weeks, oral semaglutide demonstrated statistically significant reductions in HbA1c vs both liraglutide 1.8mg (1.2% vs 0.9%, respectively) and placebo (1.2% vs 0.2%, respectively). For the secondary endpoint of change in body weight, oral semaglutide demonstrated superior reductions compared to both liraglutide 1.8mg and placebo at 26 weeks (4.4 kg for oral semaglutide, 3.1kg for liraglutide 1.8mg and 0.5kg for placebo) and statistically significant reductions compared to both at 52 weeks (4.3 kg for oral semaglutide, 3.0kg for liraglutide 1.8mg and 1.0kg for placebo).

In PIONEER 2, the most common adverse event for oral semaglutide was nausea, which diminished over time, affecting 20% of people treated with oral semaglutide. The nausea rate for empagliflozin was 2%. The proportion of people who discontinued treatment due to adverse events was 11% for those treated with oral semaglutide compared to 4% for those treated with empagliflozin.

In PIONEER 4, the most common adverse event for oral semaglutide was nausea, which diminished over time, affecting 20% of people treated with oral semaglutide. For people treated with liraglutide 1.8mg and placebo, 18% and 4%, respectively, experienced nausea. The proportion of people who discontinued treatment due to adverse events was 11% for those treated with oral semaglutide compared to 9% with liraglutide 1.8mg and 4% with placebo.

These results are based on the primary statistical approach known as the treatment policy (TPol) estimand, which was used to assess the effects of oral semaglutide regardless of discontinuation of trial product and/or use of rescue medication.

“Despite their proven efficacy and safety profile, GLP-1 receptor agonists are underutilised in clinical care” said Ildiko Lingvay, PIONEER 2 and 4 investigator and professor at the Departments of Internal Medicine and Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas. “As a treating physician, I’m encouraged by these findings and the potential of investigational oral semaglutide to be the first oral GLP-1 receptor agonist available as a treatment option for people living with type 2 diabetes.”

Phase IIIa clinical trial data presented for oral semaglutide

Protons to play a vital role in the battle against prostate cancer

Proton beam therapy, an innovative form of radiotherapy that delivers cancer treatment in a more targeted manner, has recently arrived in the UK through the Rutherford Cancer Centres and an NHS facility.

As the number of patients treated with this precision therapy grows, there is a debate about the benefits that this innovative treatment can bring.

Recent estimates show that up to 20% of UK prostate cancer patients each year could be better treated with high energy proton beam therapy. Each year in the UK 47,000 men are diagnosed with prostate cancer.

A study released last month by the University of Pennsylvania revealed that the risk of side effects from toxicity to the body was two-thirds lower for proton beam therapy patients compared to conventional radiation therapies. Researchers leading the study also highlighted that overall survival rates were similar in both groups, indicating the reduced toxicity with proton beam therapy did not come at the cost of effectiveness.

The range of estimates for the use of protons in radical radiotherapy ranges from 1% (UK, NHS) to 20% in the US. Recent policy studies from several European countries indicate a 10-15% utilisation of protons in patients treated with radical radiotherapy. This would require between 10-20 high energy proton beam therapy machines for the UK. Unless there is an urgent policy change, the overall quality of British radiotherapy will fall below European levels by 2020.

Speaking at the Particle Therapy Co-Operative Group conference (PTCOG), Professor Karol Sikora, Chief Medical Officer of Proton Partners International, will outline a bleak future for UK prostate cancer patients unless radical action is taken to increase the number of advanced British radiotherapy clinics.

Professor Sikora said: “Whilst proton beam therapy is not a magic bullet for all types of cancer, we have seen first-hand its effectiveness in significantly reducing the risk of side effects from toxicity and enabling patients to have a much better quality of life during and after treatment.”

It is important to note that there is now an emerging consensus in Europe and North America that proton beam therapy may be a better treatment option for 10 – 15% of patients who receive radical radiotherapy. The UK remains the only country at odds with this consensus, where NHS cancer indications suggest only 1% of radical radiotherapy patients can be better treated with PBT.

The UK currently has four operational proton beam therapy centres with two more due to come online in the next 18 months. There is a lack of capacity to meet this growing need for specialised cancer care and the public and private sectors must work in tandem to ensure that the UK bridges the gap with other developed nations in the battle against prostate cancer.

Timon Colegrove successfully underwent proton beam therapy treatment for prostate cancer last year and echoed the calls for enhanced availability of proton beam therapy where appropriate. Mr Colegrove said: “I was very fortunate to receive proton beam therapy and I am a firm advocate of greater availability of this pioneering form of cancer care.”

Protons to play a vital role in the battle against prostate cancer

Research finds that high fibre during pregnancy reduces risk of coeliac disease in children

7th June 2019

High fibre intake during pregnancy is linked with a decreased risk of coeliac disease in children, research presented at the 52nd Annual Meeting of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) has shown.¹

Experts from Norway found that the risk of paediatric coeliac disease was 8% lower per 10g increase in fibre intake during pregnancy. For those with the highest fibre intake (>45 grams per day), the risk was 34% lower in comparison to the lowest fibre intake (<19 grams per day). High fibre intake from fruits and vegetables, rather than from cereals, were associated with the lowest risk.

The population-based study assessed over 88,000 children born between 1999 and 2009. Researchers measured mothers’ intake of fibre and gluten during pregnancy before analysing whether each child had received a clinical diagnosis of coeliac disease in a mean follow-up time of 11 years.

“Currently, there is very limited data on the association between maternal fibre or gluten intake during pregnancy and the risk of coeliac disease in children“, commented Dr Ketil Størdal, lead researcher of the study. “As this is the first study on maternal fibre intake, we cannot yet recommend any specific dietary measures during pregnancy to prevent coeliac disease and this needs to be further studied but we are currently assessing whether maternal fibre intake could impact on children’s gut flora. This is one of the potential ways in which these findings can be explained.”

Notably, the research also found that maternal gluten intake during pregnancy was not associated with a higher risk of the disease. “Our findings do not support gluten restriction for pregnant women“, concluded Dr Størdal.

The importance of early diagnosis

Diagnosed cases of coeliac disease only represent a small fraction of the total number of people affected and most children remain undiagnosed. Diagnosing coeliac disease as early as possible is essential for ensuring optimal growth, development and symptom management. There are many serious associated health complications if coeliac disease is left undiagnosed, including impaired weight gain and growth problems, delayed puberty, iron-deficiency anaemia, chronic fatigue and osteoporosis.

“By providing early detection programmes for children, we can achieve earlier diagnosis and treatment, reduce the risk of future associated health complications and give children the opportunity to thrive“, explained Tunde Koltai, Chair of the Association of European Coeliac Societies. “Greater public awareness and the establishment of national detection programmes for early identification of paediatric coeliac diseases are two steps to achieve earlier diagnoses.“

Reference

Størdal K et al. Maternal gluten and fibre intake during pregnancy and risk of childhood celiac disease: the Norwegian mother and child cohort study. Presented at the 52nd Annual Meeting of ESPGHAN; 2019

Research finds that high fibre during pregnancy reduces risk of coeliac disease in children

Opioid analgesics increase the risk of pneumonia among persons with Alzheimer’s disease

6th June 2019

Opioid analgesics were associated with a 30% increase in the risk of pneumonia in persons with Alzheimer’s disease, a recent study from the University of Eastern Finland shows.

The risk was most pronounced in the first two months of use. This is the first study to investigate the association between opioids and pneumonia in this population. The results were published in the Journal of Alzheimer’s Disease.¹

The risk of pneumonia was highest among those using strong opioids, such as oxycodone or fentanyl, but the risk was also increased among those using buprenorphine, tramadol or codeine. Persons with active cancer were excluded from the study, and other diseases and drug use were accounted for in the analyses. Opioids impair the cough reflex and respiratory functions and cause sedation, possibly underlying the increased risk for pneumonia.

Pneumonia is a severe but relatively common complication among persons with Alzheimer’s disease, and often leads to hospitalisation and even death. Opioids are important in the treatment of severe acute pain, but treatment should be initiated at a low dose and regularly assessed for both benefit and harm. The diagnosis and assessment of pain is challenging among persons with Alzheimer’s disease due to problems in communication.

The study is part of the MEDALZ cohort, which included 5623 persons with Alzheimer’s disease diagnosed in Finland during 2010-2011. Each person initiating opioid use was matched with a comparison person with Alzheimer’s disease who did not initiate opioid use but had the same age, gender and year of Alzheimer’s diagnosis. Data for the study were derived from Finnish nationwide registers.

Reference

Hamina A et al. Hospital-treated pneumonia associated with opioid use among community dwellers with Alzheimer’s disease. J Alzheimer’s Dis;Published online 20 May 2019. DOI: 10.3233/JAD-181295

Opioid analgesics increase the risk of pneumonia among persons with Alzheimer’s disease

Higher oestrogen levels linked to more severe disease in scleroderma

Oestrogen is the quintessentially female hormone.

It is surprising, then, that a Medical University of South Carolina (MUSC) study found that a type of oestrogen, oestradiol, was more abundant in older men with scleroderma than in postmenopausal women with the disease. The MUSC team reports the findings of their National Institutes of Health (NIH)-funded study in Arthritis Research & Therapy.

The team also found that men with scleroderma and higher levels of estradiol had more severe disease and heart involvement. Those with the Scl-70 autoantibody and higher levels of estradiol had a greater risk of death.

In scleroderma, the body makes too much connective tissue. This causes thickening of the skin and internal organs and, ultimately, organ damage. Women are three times more likely, and women in their child-bearing years nine times more likely, to have the disease than men. Men, however, have more severe disease.

Scleroderma develops in women during their child-bearing years, when oestrogen levels are at their highest. This has led researchers to speculate that oestrogen may play a role in the disease, as well as other autoimmune diseases.

Further fuelling that speculation were findings from hormone replacement therapy trials that women’s skin thickened during therapy and then returned to normal after completion of treatment.

Carol Feghali-Bostwick, PhD, the SmartState and Kitty Trask Holt Endowed Chair for Scleroderma Research at MUSC and senior author of the article, has previously reported that similar thickening occurred in skin cultures exposed to oestradiol.

The MUSC team’s recent findings provide some of the first evidence to confirm a link between high oestrogen levels and the development of scleroderma. They also begin to explain why men, in whom the disease is less frequent, often have more severe symptoms.

“It seems reasonable to say that oestradiol is probably one of the reasons why men have more severe disease,” said Feghali-Bostwick.

“We always understood that women were more predisposed to getting autoimmune diseases,” said DeAnna Baker Frost, MD, PhD, first author of the article.

“We always thought that oestrogen played a role, but we needed additional research to identify associations between elevated oestrogen levels and clinical aspects of scleroderma. And so it was exciting to see that estrogen likely is playing a role in disease outcomes or maybe the development of autoimmune diseases.”

The team tested oestradiol and scleroderma autoantibody levels in banked samples from 83 men aged 50 years and older with diffuse cutaneous systemic sclerosis, a type of scleroderma. They also tested samples from 37 healthy men of a similar age. They then used a variety of statistical approaches and the careful clinical annotations accompanying each sample to determine whether estradiol levels were linked to any of the clinical traits of scleroderma.

Male patients with diffuse cutaneous scleroderma had significantly higher levels of estradiol (average, 30.6pg/ml) than both healthy men (average, 12.9pg/ml) and postmenopausal women with the disease (24.2pg/ml). Those with higher estradiol levels (average, 43.7pg/ml) had significantly more heart involvement than those with lower levels (29.4pg/ml). Finally, for patients with the Scl-70 autoantibody, increasing levels of estradiol in the serum was associated with a significantly greater risk of death.

But how is it possible for men to have such high levels of a hormone associated with the female reproductive system?

“Men can convert their testosterone to oestrogen via an enzyme called aromatase,” explained Feghali-Bostwick.

“They’re converting testosterone in their tissues. You don’t to have to have ovaries to make oestrogen. Other tissues can also form oestrogen.”

Aromatase can convert other tissues such as fat into oestrogen in women as well. Preventing that conversion could be a novel therapeutic approach to scleroderma.

Aromatase inhibitors are already being used to treat women, particularly postmenopausal women, with hormone-receptor positive breast cancer. The MUSC team would like to conduct a small trial to assess the efficacy of aromatase inhibitors in patients with scleroderma.

Even if the costs of a trial in patients with scleroderma prove to be too high, Feghali-Bostwick believes there is much to learn from existing data from large breast cancer trials of aromatase inhibitors. For example, she would be very curious how the aromatase inhibitors affected patients who had both breast cancer and scleroderma.

“What happened to their scleroderma when they were treated with aromatase inhibitors?” asked Feghali-Bostwick.

“Knowing that would help inform us about the utility of aromatase inhibitors. It’s hard to access the large breast cancer study data. However, doing so would provide us key information in assessing whether aromatase inhibitors have a role in scleroderma.”

Meanwhile, Baker Frost is conducting experiments to establish a causal link between higher estradiol levels and scleroderma.

“I think we also have to show concretely that having high oestrogen levels is the causative factor for the clinical characteristics of scleroderma,” said Baker Frost.

“So we’re doing a lot of studies with human tissues, and soon tissues from scleroderma patients, to show that if we treat these cells and tissues with estrogen, then the downstream effects will be the high levels of tissue scarring that you see with scleroderma.”

The MUSC’s team findings also point to oestrogen as a potential environmental trigger for scleroderma. Most people who develop the disease are likely genetically susceptible. However, research suggests that the environment also plays a role. “Oestrogen is around us. It’s not just what your body produces,” explained Feghali-Bostwick.

“There are a lot of things you get exposed to that affect oestrogen levels – things like endocrine disrupters and oestrogen mimics. So I think it’s just part of understanding what environmental factors may be involved in the development not just of scleroderma but also of related autoimmune diseases.”

Higher oestrogen levels linked to more severe disease in scleroderma

Long-term data from pivotal Phase III studies of ibrutinib presented at ASCO and EHA

Janssen has announced long-term follow-up results from two pivotal Phase III studies of Imbruvica^® (ibrutinib) in patients with chronic lymphocytic leukaemia (CLL), a type of non-Hodgkin lymphoma and the most common form of leukaemia in adults.¹

One set of data – results from the RESONATE^TM study (PCYC-1112) at a median follow-up of 65.3 months (range, 0.3–71.6) – showed treatment with ibrutinib monotherapy sustained progression-free survival (PFS) benefit compared to ofatumumab in patients with previously treated CLL, with a median PFS of 44.1 months versus 8.1 months, respectively.²

A consistent PFS benefit with ibrutinib was observed across all baseline disease and patient characteristics, including patients with genomically defined high-risk disease.1 The median overall survival (OS) was 67.7 months in the ibrutinib arm and 65.1 months in the ofatumumab arm, without censoring or adjustment for crossover from ofatumumab to ibrutinib.² Additionally, no new safety events were identified in this long-term follow-up.1 The RESONATE^TM results were presented at the 55th American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, and selected for the Best of ASCO 2019 Meetings, which highlight cutting-edge science and reflect leading research in oncology (abstract #7510).

The second data set – results from the RESONATE^TM-2 study (PCYC-1115/1116) at a median follow-up of five years (range, 0.1–66 months) – demonstrated durable PFS with ibrutinib monotherapy (estimate of 70%) versus chlorambucil (estimate of 12%) in patients with previously untreated CLL, including those with genomically defined high-risk disease.²

The OS benefit was also sustained in patients treated with ibrutinib (estimate of 83%) versus chlorambucil (estimate of 68%). In addition, no new safety concerns were observed.3The RESONATE^TM-2 data will be presented in full during an oral presentation at the 24th European Hematology Association (EHA) Congress in Amsterdam on Friday, June 14 (abstract #S107).³

“Since its first European approval in 2014, ibrutinib has redefined treatment paradigms for CLL, and these study results offer further evidence to both clinicians and patients of the longer-term benefits and tolerability ibrutinib offers as a single agent,” said Peter Hillmen, MB ChB, PhD, Professor of Experimental Haematology and Honorary Consultant Haematologist at Leeds Teaching Hospitals NHS Trust, United Kingdom and investigator in both studies. “Not only is superior progression-free survival and overall survival maintained with ibrutinib follow-up, but frequently the quality of response rates improves from partial to complete over time.”

“Ibrutinib has already impacted more than 140,000 patients, and the RESONATE and RESONATE-2 long-term follow-up studies provide important data in support of its continued use in the effective management of CLL,” said Dr Patrick Laroche, Europe, Middle East and Africa (EMEA) Haematology Therapeutic Area Lead, Janssen-Cilag France. “We are excited to explore how best this BTK inhibitor can continue to enhance the lives of people living with CLL, both as a monotherapy and in newer combination regimens, and as an alternative option to intensive chemotherapy.”

References

American Cancer Society. What Is Chronic Lymphocytic Leukemia? Available at: https://www.cancer.org/cancer/chronic-lymphocytic-leukemia/about/what-is…. Last accessed May 2019.
Barr P et al. Final analysis from RESONATETM: Six-year follow-up in patients (pts) with previously treated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) on ibrutinib. Poster presentation at 55th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, USA, 31 May–4 June 2019.
Tedeschi A et al. Five-year follow-up of patients receiving ibrutinib for first-line treatment of Chronic Lymphocytic Leukemia. Abstract S107. Available at: https://learningcenter.ehaweb.org/eha/2019/24th/267308/alessandra.tedesc…. Last accessed May 2019.

Long-term data from pivotal Phase III studies of ibrutinib presented at ASCO and EHA

Common skin bacterium puts children with severe eczema at higher risk of food allergy

In a study published in the Journal of Allergy and Clinical Immunology, scientists from King’s College London have found that young children with severe eczema infected with Staphylococcus aureus (SA) bacterium, are at a higher risk of developing a food allergy.¹

Staphylococcus aureus (SA) is found in the nose and the skin of healthy individuals; however, SA is more common in sufferers of eczema, especially severe eczema.

The team of scientists found that young children with severe eczema who are infected with SA produce more IgE against peanut, egg and milk indicating they have a food allergy to each of these.

These children were also more likely to have their egg allergy persist at the age of 5 or 6 years in comparison to children that did not have SA present.

Lead author Dr Olympia Tsilochristou from King’s College London said: “This is significant as most children with egg allergy usually outgrow this at an earlier age.

“We do not know yet the exact mechanisms that lead from eczema to food allergy however our results suggest that the bacteria Staphylococcus aureus could be an important factor contributing to this outcome.”

These results build on the earlier ones from the Learning Early About Peanut Allergy (LEAP) study which demonstrated that infants who were at a high-risk of developing peanut allergy but consumed a peanut-containing snack throughout the study were prevented from later developing a peanut allergy.

In this current study, scientists found that children with SA on their skin and/or nose were more likely to develop peanut allergy despite them being fed with peanut from early ages as part of the LEAP study protocol.

Co-author Professor du Toit said: “These findings indicate that SA may have reduced the chance of young infants gaining tolerance to peanut, even if peanut was eaten in early childhood.”

Professor Lack, who conceived and led the LEAP study, said that “SA could be considered as an additional risk factor for the development of food allergy.”