Tiotropium fixed dose combination shows lung function benefits
New phase III data show lung function benefits of tiotropium + olodaterol fixed-dose combination go beyond tiotropium (Spiriva) alone in COPD patients.
The results were presented at the American Thoracic Society (ATS) 2014 International Congress in San Diego and demonstrate that the fixed-dose combination (FDC) of tiotropium + olodaterol in patients with COPD significantly improved lung function over 24-hours compared with tiotropium (Spiriva) or olodaterol (Striverdi) monotherapies, or placebo.
VIVACITO is the first study presented from the TOviTO Phase III clinical trial programme investigating tiotropium + olodaterol FDC in more than 8,000 patients.
Once-daily tiotropium + olodaterol FDC is an investigational treatment that contains the well-established, once-daily LAMA, tiotropium, combined with olodaterol, a new once-daily LABA, delivered via the Respimat Soft Mist Inhaler.
Commenting on the results, Dr Richard Russell, Consultant Chest Physician, Wexham Park Hospital, said: “Many patients with COPD continue to experience symptoms despite current treatment options, which can impair their ability to perform daily activities.
“New treatment options are needed to help control COPD symptoms better and improve quality of life. The significant improvement in lung function demonstrated by the fixed-dose combination of tiotropium + olodaterol in the VIVACITO study compared to both tiotropium monotherapy and placebo is encouraging and will come as welcome news to both physicians and patients looking for new and better ways to manage COPD.”
Additionally, tiotropium + olodaterol FDC was shown to have a similar safety and tolerability profile to
tiotropium alone.
Further data from the Phase III TOviTO clinical trial programme are due to report later this year.
This includes results from the 52-week Phase III TONADO 1&2 trials, investigating the effect of tiotropium + olodaterol FDC on lung function and quality of life in patients with COPD.


New drug for idiopathic pulmonary fibrosis
Phase III trial results published in the New England Journal of Medicine (NEJM) and released at the ATS show nintedanib slows disease progression in idiopathic pulmonary fibrosis (IPF) by approximately 50% compared with placebo.
Nintedanib is the first targeted IPF treatment to consistently meet its primary endpoint in two identically designed international phase III trials.
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 the two, 52-week INPULSIS trials, involving 1,066 patients, nintedanib significantly reduced the annual decline in FVC by approximately 50% compared to patients taking placebo.
Study investigator Professor Luca Richeldi, Professor of Respiratory Medicine, Chair of Interstitial Lung Disease at the University of Southampton, said: “These results should be welcomed because, for the first time, we have a targeted drug that has consistently met its primary endpoint, the reduction of the annual decline in FVC, in two large Phase III trials. Patients with IPF currently have very limited treatment options and there is a high unmet need for effective treatments that can specifically alter the course of this deadly disease by slowing disease progression.”
Both key secondary endpoints were met in the INPULSIS-2 trial. There was significantly less deterioration in quality of life (as measured by the St. George’s Respiratory Questionnaire) and a reduced risk of a first acute exacerbation in patients taking nintedanib, compared to placebo.
In both trials, the most common adverse events were gastrointestinal in nature, of mild to moderate intensity, generally manageable and rarely leading to treatment discontinuation. 


New data on COPD drug combination
Data was also presented at the ATS from a late-stage clinical study looking at the safety and efficacy of the addition of a long-acting muscarinic antagonist umeclidinium (UMEC) and to the inhaled corticosteroid and long-acting beta2 agonist combination medicine, fluticasone proprionate and salmeterol (FSC).
The study showed that, for the primary endpoint of trough FEV1 at day 85, the addition of UMEC (at either dose) to FSC 250/50mcg resulted in a statistically significant improvement in lung function when compared with placebo added on to FSC 250/50mcg, in patients with COPD.
The addition of UMEC (at either dose) to FSC 250/50mcg also demonstrated statistically significant improvements in secondary efficacy endpoints of 0-6 hour weighted mean FEV1 at day 84 and mean number of puffs of rescue medicine per day (weeks 1-12) compared with the addition of placebo to FSC 250/50mcg.
Darrell Baker, SVP and Head, Global Respiratory Franchise, GSK said: “We are pleased to be able to share these results with physicians from across the world at this international congress. The ATS provides a forum for scientific discussion and we look forward to understanding the scientific and healthcare communities’ perspectives of these new data.”
There were no notable differences between UMEC (at either dose) added to FSC 250/50mcg and placebo added to FSC 250/50mcg in incidence rates of on-treatment adverse events or in changes from baseline in vital signs.
This was a 12-week, randomised, double-blind, parallel-group study. Approximately 600 eligible patients were randomised 1:1:1 to once-daily UMEC 62.5mcg, UMEC 125mcg, or placebo, added to FSC (250/50mcg twice daily). UMEC and placebo were administered via Ellipta dry powder inhaler and FSC via Diskus inhaler. The primary endpoint was trough forced expiratory volume in one second (FEV1) on day 85. Secondary endpoints were 0–6-hour post-dose weighted mean (WM) FEV1 on day 84 and rescue albuterol use (percentage of rescue-free days and puffs/day). Safety endpoints included the incidence of on-treatment adverse events (AEs), vital signs and COPD exacerbations. 


Vitamin D deficiency associated with widespread pain
A new study, presented at Rheumatology 2014, has found that vitamin D deficiency is associated with the development of chronic widespread pain.
The research has unveiled the link using data from over 2,300 men in the European Male Ageing Study. It suggests that this may be a result of other adverse health and lifestyle factors such as depression, obesity and physical inactivity.
The research, which was conducted at the University of Manchester, found that those with vitamin D deficiency at the start of the study were more than twice as likely to develop chronic widespread pain as those with the highest levels.
After an average follow up of 4.3 years, one in 15 men who had no symptoms at the start of the study had developed chronic widespread pain. Those who developed the condition were more likely to be depressed, obese, physically inactive and have additional health conditions.
After taking adverse health and lifestyle factors into account the apparent link with vitamin D deficiency disappeared, suggesting that these factors have a significant effect on the development of chronic widespread pain and that there may be a complex interplay between the factors that cause the condition.
Vitamin D deficiency is common in the UK population, with more than half of all adults expected to have an insufficient level of the vitamin. It can cause weakness as well as musculoskeletal pain. Chronic widespread pain, which affects around one in five people, can be caused by rheumatic and neurological disorders.
Lead researcher Paul McCabe said: “Musculoskeletal pain is a recognised symptom of severe vitamin D deficiency states such as osteomalacia. What is less clear is whether vitamin D deficiency has a role in explaining more common chronic pain symptoms including chronic widespread pain. Our research highlights the complex relationship between vitamin D and factors such as obesity and depression in the development of chronic widespread pain. Further research is required to determine whether treatment of vitamin D deficiency may prevent the development of chronic pain.”
The research “Low vitamin D and the risk of developing chronic widespread pain: results from the European Male Ageing Study” from Paul McCabe et al was presented as a poster abstract (number 33) at Rheumatology 2014. 

 
New effective way to diagnose latent tuberculosis
A study co-authored by the University of Birmingham has identified the most effective way to test people with latent tuberculosis (TB), a potentially fatal infection that has increased in the UK in recent years.
Diagnosing latent TB is important because the bacterium can persist in the body like a “Trojan Horse”, only to emerge and reactivate months or even years later. Treating individuals with latent TB can prevent disease developing and so prevent them infecting others.
The research study centred on Nepalese soldiers recruited to the Brigade of Gurkhas of the British Army, who were tested for latent TB using all the tests currently available. One of these, called T-Spot, was found to be better than others at detecting latent TB when used on its own.
As a result, this test has been adopted by the Ministry of Defence (MoD) as a more efficient way to identify latent TB infections. The study’s authors say it offers a strategy for diagnosing this “silent infection”, which is notoriously difficult to detect, and could be used in civilian populations.
TB is caused by the bacterium Mycobacterium tuberculosis, and is spread through the inhalation of tiny droplets from coughs or sneezes of an infected person. Most people acquire infections abroad and will not develop the disease. However, about two billion people around the world carry the bacteria in their body and 5–10% go on to develop active TB.
While treatment can be effective, it lasts for six months and failure to complete it can result in resistance to drugs and the reactivation of infection, making cure more difficult. This makes diagnosis of latent infections a key strategy to control disease in countries like the UK.
The study, published this month in the scientific journal PLOS ONE, was funded by the MoD and is co-authored by Adam Cunningham, Professor of Functional Immunity at the School of Immunity and Infection at the University of Birmingham and by Dr Matt O’Shea from Oxford and Birmingham Universities who is a Surgeon Lieutenant Commander in the Royal Navy, together with Dr Tom Fletcher from Liverpool University, who is a Major in the Royal Army Medical Corps, and Duncan Wilson, Colonel and Professor of Military Medicine at Birmingham.
The study, carried out over several months in 2012, involved 166 Gurkha recruits—nearly the whole of that year’s cohort—and found that nearly 20% had latent TB using the T-Spot test. There are more than 3,000 Gurkhas in the British Army at any one time.
At the moment, there are three tests used to detect TB: two called Interferon-Gamma Release Assays (IGRAs) are blood tests based around a molecule called IFNg.