TONADO study: lung function benefits
Further lung function and quality of life benefits with tiotropium + olodaterol Respimat® fixed dose combination in COPD were presented recently at the European Respiratory Society (ERS) International Congress in Munich.
The 52-week studies, involving more than 5,000 patients with Chronic Obstructive Pulmonary Disease (COPD), showed that tiotropium + olodaterol Respimat® FDC gave further lung function and quality of life benefits to patients, compared to either compound alone.
Data also showed that tiotropium + olodaterol Respimat® FDC was well tolerated with a favourable safety profile that was similar to tiotropium or olodaterol alone. The TONADO results, together with the VIVACITO data presented earlier this year, formed a major part of the recent regulatory submissions in Europe for tiotropium + olodaterol Respimat® FDC in COPD.
COPD is a chronic disease that affects an estimated three million people in the UK. Currently tiotropium (Spiriva®) is the most prescribed COPD maintenance treatment worldwide, with a well-established efficacy and safety profile supported by data from more than 34 million patient years. Olodaterol was specifically designed by Boehringer Ingelheim as a combination partner to tiotropium to provide added benefit for patients with COPD. Olodaterol monotherapy has received approval for the maintenance treatment of COPD in over 30 countries and is marketed under the brand name Striverdi® Respimat® in the UK.
Also presented at the ERS Congress were data from the 52-week WISDOM (Withdrawal of Inhaled Steroids During Optimised bronchodilator Management) trial. This trial evaluated the effect of stepwise inhaled corticosteroid (ICS) withdrawal in patients with moderate to very severe COPD, who had a history of exacerbations and were being treated with triple therapy (LAMA+LABA/ICS). The aim was to investigate whether withdrawing the ICS and maintaining patients on LAMA+LABA therapy increased the risk of them having a COPD exacerbation compared to a group of identical patients who continued taking triple therapy.
The results show that there was not a significant difference in time to first moderate or severe COPD exacerbation (on-treatment) in patients who had their ICS withdrawn, compared to patients who remained on triple therapy.
This result suggests that in patients with moderate to very severe COPD receiving dual bronchodilation therapy (LAMA+LABA), exacerbation risk is non-inferior following stepwise ICS withdrawal compared to patients on ICS. 

New data for idiopathic pulmonary fibrosis drug
New subgroup analysis shows nintedanib slowed disease progression in idiopathic pulmonary fibrosis (IPF) irrespective of patients’ lung function impairment at baseline, according to data presented at the ERS congress.
Nintedanib also reduced the proportion of patients with IPF who experienced disease progression, as measured by categorical Forced Vital Capacity (FVC) decline.
Nintedanib is the first targeted IPF treatment to consistently meet its primary endpoint in two identically designed international Phase III trials.
Dr Charles De Wet, Medical Director at Boehringer Ingelheim UK and Ireland, commented; “The INPULSIS trials have already illustrated that nintedanib can significantly slow disease progression in patients with IPF. This sub-analysis further underlines its efficacy by demonstrating effect in a range of patients with differing lung function impairments at baseline.”
IPF is a progressive and severely debilitating lung disease with a high mortality rate. It causes progressive scarring of the lungs, resulting in continual and irreversible deterioration in lung function and difficulty breathing. In patients with IPF, lung function loss is measured by a decline in a patient’s forced vital capacity (FVC), the maximum volume of breath that can be exhaled. The average IPF patient has lung volume loss of between 150–200mL per year, compared to a normal adult lung volume decline of approximately 50ml per year.
In a separate, additional post-hoc analysis of the INPULSIS™ data, nintedanib reduced the proportion of patients who experienced disease progression, as measured by categorical (absolute or relative) FVC decline. An absolute decline in FVC % predicted of greater than 5% and greater than 10% over 6–12 months has been shown to be predictive of mortality in patients with IPF.

Palliative care and COPD
Patients with COPD would like healthcare professionals to discuss palliative care needs in more detail, according to a new study.
Palliative care refers to care that is focused on making a person comfortable and relieving symptoms, rather than treating a condition. It is often connected with end-of-life care; although it can refer to any stage of care for any life-threatening condition. The research, presented at the ERS, investigated the preferences of patients living with COPD.
A previous study by the same group identified the barriers that some healthcare professionals face in talking about palliative care. This research identified that one of the main reasons professionals avoid the conversation is because of a fear of destroying patients’ hopes for the future.
This study asked patients about this factor and assessed their perspective on discussions surrounding palliative care. Researchers conducted interviews with 12 patients who lived at home with COPD. The semi-structured interviews were then analysed descriptively.
The findings revealed that patients have many worries about the future of their condition but would like to discuss the disease and the management of their symptoms with healthcare professionals. The analysis of the interviews also showed that most patients felt uncomfortable bringing the topic of palliative care up with healthcare professionals and their families as they did not want to burden other people with their concerns.
The main outcome of the interview analysis was that patients felt that healthcare professionals should not be afraid to initiate conversations about palliative care as the patients themselves understood the condition was serious and required this type of conversation. They did not fear that discussions about this type of care could destroy their hopes for the future.
Camilla Mousing, lead author of the study from Aarhus University and VIA University College, said: “The findings of our research are very relevant for healthcare professionals working with patients with life-threatening illness. We have to overcome our fear of talking about this type of care and explain to patients that this does not mean we are giving up on them. Palliative care needs can be addressed from an early stage of an illness to ensure we are increasing the quality of everyday life for our patients. These needs can change on a daily basis for each patient and can be very different between patients. We must be flexible in our approach and ensure we know who is responsible for assessing and taking action.”

Multiple myeloma results published in NEJM
Data from the FIRST (Frontline Investigation of lenalidomide and dexamethasone vs. standard thalidomide) trial have been published in The New England Journal of Medicine (NEJM).
FIRST, a phase III, multi-centre study of 1,623 patients newly diagnosed with multiple myeloma (NDMM) and ineligible for stem cell transplant, included 72 patients from the UK. After a median follow-up of 37 months, the trial met its primary endpoint (progression-free survival), demonstrating a 28% reduction in the risk of progression or death for patients treated with continuous lenalidomide plus low-dose dexamethasone (LEN + LoDex) compared with those receiving melphalan, prednisone and thalidomide (MPT) for 72 weeks, the standard of care. Median PFS was 25.5 months for patients receiving continuous LEN + LoDex versus 21.2 months for those receiving MPT.
In addition, the pre-planned interim analysis of overall survival demonstrated a 22% reduction in the risk of death in favour of patients receiving continuous LEN + LoDex versus patients receiving MPT although the difference did not cross the pre-specified superiority boundary (P<0.0096). All other secondary endpoints, including response rates, time to disease progression and time to treatment failure, consistently showed improvement for patients receiving continuous LEN + LoDex compared with those receiving MPT.
Commenting on the publication in the NEJM, Dr Adrian Kilcoyne, Medical Director, Celgene UK & Ireland said: “While multiple myeloma is a debilitating and incurable disease, results from the FIRST study indicate that continuous treatment with lenalidomide may be able to keep newly diagnosed patients in remission for longer than with the current standard of care. This is encouraging as lengthy remission is an important goal for patients and is associated with a good prognosis.”
Lenalidomide is not currently licensed for NDMM in the UK or any other countries. However, data from the FIRST study have been used to support a filing to the European Medicines Agency (EMA) for the use of lenalidomide as a potential treatment for NDMM.

C. difficile drug cost-effective in cancer patients
New data presented at the 54th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2014) show that overall treatment costs for cancer patients with clostridium difficile infection (CDI), based on a decision tree analysis, are lower with fidaxomicin compared to current standard of care, vancomycin, resulting in a potential cost saving of €5,600 per patient.
Patients who have received chemotherapy and those with solid tumours can be particularly susceptible to CDI due to their long hospital stays and exposure to many antibiotics and chemotherapeutic agents. These patients are also prone to recurrent episodes of CDI.
This pharmacoeconomic model combined data from a study exploring the resolution of CDI in cancer patients treated with either fidaxomicin or vancomcyin and a recent cost-of-illness analysis on CDI conducted at the University Hospital of Cologne.
The analysis explored direct cost parameters including drug costs, treatment on the general ward and intensive care unit as well as microbiological diagnostics for clostridium difficile. Mean overall treatment costs per patient treated with fidaxomicin and vancomycin were €22,200 versus €27,800. The lower costs associated with fidaxomicin are primarily due to the significantly lower rate of recurrence in patients treated with fidaxomicin compared to vancomycin.
“Patients with cancer represent a vulnerable population who are at high risk of CDI, often resulting from their compromised immune system. CDI can be a devastating addition for patients who are already battling pre-existing conditions. We have already seen the superior reductions in CDI recurrence with fidaxomicin so we are pleased to see it also clearly demonstrating cost effectiveness,” said Sebastian Heimann, health economist at the University Hospital of Cologne, Germany and lead investigator of the study. 

Antidote for rapid reversal of Pradaxa study launched
Boehringer Ingelheim announced that the multinational RE-VERSE AD clinical trial—the study investigating the emergency reversal of the anticoagulant effect of dabigatran etexilate (Pradaxa®)—has been initiated in the UK.
The trial involves a number of sites in the UK and is part of the next step in the clinical development of idarucizumab, the investigational antidote for rapid reversal of dabigatran-induced anticoagulation.
Idarucizumab has demonstrated immediate, complete and sustained reversal of the anticoagulant effect of dabigatran in a 145 participant healthy volunteer study. Now, the antidote will be investigated in the clinical setting in patients taking dabigatran etexilate. This is the first time that an antidote under development for a novel oral anticoagulant
is investigated in a study in patients.
The study will provide further knowledge on the potential of the specific antidote to support the management of patients taking dabigatran etexilate who may benefit from rapid reversal of dabigatran-induced anticoagulation.