Trelegy Ellipta: Is There Any Downside To Taking All Three Medications Together?

Is There Any Downside to Taking Trelegy Ellipta?

Dear Dr. Mahler:

I read your recent post and have heard of Ellipta, though now Trelegy may be one step newer…
Is there any downside to taking all these helpers at once?
I was thinking, although it is more to do in a day, that keeping them separate might be a good thing.  More effect from each on their own?
Maybe not!
Thanks.

Katherine from Greensboro, NC

Dear Katherine:

Thanks for commenting on my recent post about a new 3-in-1 approved inhaler by the Food and Drug Administration (FDA) for those with COPD on September 18.

Please note that this single inhaler contains three different medications for treatment of those with COPD. These medications are already combined together and are available. These are Anoro Ellipta (different bronchodilators – vilanterol and umeclidinium) and Breo Ellipta (a bronchodilator – vilanterol – and an inhaled corticosteroid – fluticasone). So, the pharmaceutical company, GlaxoSmithKline, combined all three medications together in a dry powder inhaler called Trelegy Ellipta. They performed various studies (called randomized clinical trials) as required by the Food and Drug Administration. The company then submitted the results to the FDA for review and consideration of approval.

Although it may seem confusing, the different Ellipta inhalers along with numerous other inhalers developed by other pharmaceutical companies provide many options for health care providers to hopefully make it easier for you to breathe with activities and to reduce the chances of having a flare-up (called exacerbation). These treatment strategies are provided by the a group of experts in COPD called the GOLD committee.

You asked about a downside to taking all three medications together. Please note that current recommendations for the use of inhaled corticosteroids in treating those with COPD is for those individuals who have had 2 flare-ups (exacerbations) in the past one year OR one flare-up that was “bad enough” to require hospitalization. The reason for this recommendation is that inhaled corticosteroids can have side effects. The most concerning is an increased risk of pneumonia. Other possible side effects include a yeast infection in the throat, bruising of the skin, and thinning of the bones (called osteoporosis).

As with all medications, your health care provider should consider the likely benefits of the medications along with possible side effects. Some people call this “weighing the balance.”

A scale to weigh the benefits and risks of Trelegy Ellipta

A scale represents weighing the benefits and risks of a medication

 

I hope that this information is helpful. I encourage you to discuss the available inhalers with your health care professional.

Best wishes,

Donald A. Mahler, M.D.

Tiotropium Slows Worsening (Decline in Lung Function) in Early COPD

Tiotropium Slows Worsening (Progression) in Those with Early COPD

Background: Tiotropium (brand name: Spiriva) is a once daily long-acting inhaled bronchodilator that has been approved for treatment of COPD for over 10 years. Studies show that it opens the airways to make it easier to breathe, reduces air trapped in the lungs, and improves both quality of life and ability to exercise.

Spiriva HandiHaler - tiotropium slows worsening of COPD

Spiriva HandiHaler dry powder inhaler

 

However, no bronchodilator has been shown to slow the expected worsening (progression) in breathing tests over time.

Study: Dr. Zhou and other investigators in China compared the changes in breathing tests of Spiriva HandiHaler and a placebo (inactive medication) over 2 years in those with “early-stage” COPD. The authors proposed that regular use of this bronchodilator would slow the expected decline in lung function as measured by expiratory volume in one second (FEV1).

FEV1 is used to grade COPD severity and assess COPD prognosis

Diagram of spirometry to diagnose COPD. FEV1 is the amount of air exhaled in one second.

Only patients with “early-stage” COPD were studied with FEV1 of 50% or higher of the predicted value. The study was conducted in 24 centers in mainland China between October 2011 and September 2015. The findings were reported in the September 7, 2017, issue of the New England Journal of Medicine, volume 377; pages 923-936.

Results: 841 patients completed the trial: 388 received tiotropium and 383 received placebo. Average age was 64 years, and 85% were men. Most patients did not complain of any shortness of breath.

The annual decline in FEV1 was significantly less in those treated with tiotropium compared with placebo when breathing tests were performed after inhaling albuterol in the pulmonary function laboratory at 2 years. The difference between treatments was 22 milliliters per year.

Conclusions: The authors concluded that tiotropium slows worsening in those with early-stage COPD as measured by post-bronchodilator FEV1.

My Comments: The current recommendations for prescribing one or two long-acting bronchodilators is to reduce symptoms and to reduce the risk of a flare-up (exacerbation) in those with COPD. However,this study challenges that approach by showing that early treatment slows progression of COPD as measured by breathing tests.

An editorial in the September 7 issue of the New England Journal of Medicine by Drs. Ko and Wong from the Chinese University of Hong Kong suggested it is likely that other long-acting bronchodilators would provide a similar benefit.

In caring for those with COPD in my practice, I have observed that many individuals have stable breathing tests when tested over several years. I believe that this stability is likely due to two factors: 1. regular use of long-acting bronchodilators; and 2. avoiding a COPD flare-up (exacerbation).

Loss of Lung Function Noted with Flare-ups (Exacerbations) of COPD

Loss of Lung Function Greater in Mild COPD

Background: With a sudden flare-up of COPD, individuals have more shortness of breath, coughing, and/or wheezing. These are called an exacerbation. Studies show that flare-ups are associated with worse health status and are associated with increased risk of dying. However, it is unknown whether flare-ups cause more loss of lung function than expected with just getting older.

Study: The COPDGene study enrolled over 10,000 individuals who were current or former smokers with and without COPD. This report describes the first 2,000 patients with COPD who returned for a follow-up visit 5 years later. During the study, flare-ups were recorded by patients every 6 months.  The study was published in the February 1, 2017, issue of the American Journal of Respiratory and Critical Care Medicine (volume 195; pages 324-330).

Results: More than 1/3 of subjects (37%) had a flare-up during the 5 years. These flare-ups were associated with greater excess decline (worsening) in the amount of air exhaled in one second (FEV1) in all stages (1, 2, and 3) of COPD.  This excess decline was greatest in those with mild COPD where each flare-up was associated with an additional 23 milliliters per year decline in FEV1. If the flare-up was severe and required the person to be hospitalized, there was an even greater decline in FEV1 of 87 milliliters per year.

Dr. Dransfield is first author of the article that describes loss of lung function with acute exacerbations of COPD.

Dr. Mark T. Dransfield, Professor of Medicine at the University of Alabama at Birmingham.

Conclusions: Dr. Dransfield and colleagues concluded that sudden flare-ups are associated with greater declines (worsening) of lung function in those with COPD, especially with mild disease. In contrast, there was no worsening of lung function when current and former smokers without COPD had similar respiratory infections.

My Comments: It is well known that flare-ups due to chest infections result in inflammation (redness and swelling) in the breathing tubes (airways).  This can cause narrowing of the breathing tubes and plays a role in the decline in how the lungs work.

Also, these findings raise the possibility that preventing flare-ups (exacerbations) could prevent worsening of lung function, and thereby slow or prevent progression of the disease. Treatment with medications may need to be considered in those with mild-moderate COPD and not wait until the condition is more severe. 

You may wish to discuss how you can reduce the risk of a flare-up with your health care professional.

Less than 20% Receive Education About Monitoring a COPD Flare-up

Results of Study Show Need for a COPD Flare-up Action Plan

Less than 1 of 5 patients with COPD received information from their doctors on how to self-monitor for signs of an impending COPD flare-up according to Anja Frei, Ph.D., of the University of Zurich. Dr. Frei presented these findings at the International Conference of the European Respiratory Society in London. A flare-up means an increase in cough, mucus production, and/or more short of breath. About 2/3 of flare-ups are due to a chest infection (bacterial or viral), while about 1/3 are due exposure to air pollution. The medical word for a COPD flare-up is an exacerbation. 

Photo on right shows acute bronchitis with yellow mucus inside the airway

Photo on right shows acute bronchitis with yellow mucus inside the airway. This can cause a COPD flare-up.

 

Of 317 individuals with COPD living in Switerzerland who were surveyed,  just 53 remembered ever being told to monitor their own symptoms. About 36% recalled being given instructions to change medications in case of deteriorating breathing. 29% of those COPD took action when a flare-up occurred; some called their primary care provider, some used short-acting albuterol inhaler for relief, and others avoided aggravating situations.

Primary care providers discussing Action Plan for COPD flare-up

Primary care providers discussing Action Plan for COPD flare-up

According to Claudia Steurer-Stey, M.D., “We have a lot of work to do in education of these patients. The general practioner who sees the majority of their patients is a very important target of our work so they can improve the quality of primary care.”

My Comments: All those with COPD should have a written action plan for what to do if/when they an experience a COPD flare-up.

Here is a Simple COPD Action Plan if You Have a Flare-up

♦ If you are more short of breath, use albuterol sulfate and/or ipratropium bromide inhalers every 2 – 4 hours as needed

Albuterol sulfate – brand names are ProAir, Proventil, and Ventolin

Ipratropium bromide – brand name is Atrovent

Combination of albuterol sulfate and ipratropium bromide –

brand names are Combivent Respimat and DuoNeb solution (in nebulizer)

♦ If you cough up yellow or green mucus, call or see your health care provider to ask if an antibiotic is appropriate.

♦ If use of albuterol sulfate and/or ipratropium bromide does not help improve your breathing difficulty, call or see your health care provider to ask if prednisone is appropriate.

♦ If you cannot speak in full sentences or cannot fall asleep at night because of breathing difficulty, call or see your health care provider, go to an Urgent Care center, or go to the nearest Emergency Department.

 

 

 

 

Preventing Hospital Readmission for COPD Exacerbation

An exacerbation of COPD means a worsening of symptoms including more shortness of breath, increased coughing, and possible coughing up more mucus, especially if the color is yellow or green. If the exacerbation is severe, it may require hospitalization for treatment.  Starting in October 2014, hospitals in the United States have been judged on their ability to reduce 30-day, all-cause unplanned readmissions for COPD after an initial hospitalization for a COPD exacerbation. The U.S. Centers for Medicare and Medicaid Services (CMS) will penalize hospitals for what they consider excessive admissions. In a 2015 editorial in the Journal of COPD Foundation (volume 2; pages 4 – 7), Dr Sidney Braman of the Icahn School of Medicine at Mount Sinai in New York City commented on strategies for preventing hospital readmissions for those with COPD.

Dr. Sidney Braman, Professor of Medicine

Dr. Sidney Braman, Professor of Medicine

 

This information directly applies to someone who has COPD because everyone wants to stay out of the hospital unless it is necessary.

Dr. Braman outlined four elements of medical care:

  1. COPD guideline-directed treatment protocols for Emergency Department visits and hospitalized patients
  2. patient/caregiver education on smoking cessation, inhaler use and an Action Plan for an exacerbation
  3. patient assessment of oxygen needs, medical conditions other than COPD, goals of care, and breathing tests
  4. a follow-up plan that includes a phone call at 48-72 hours after discharge, a visit within 7-10 days with a health care provider, participation in pulmonary rehabilitation when available, and appropriate use of community home care services.

An Action Plan is important so that you know what to do if you experience more  breathing difficulty. Here are four steps of an Action Plan that you can consider and discuss with your doctor.

Step 1. If your have more shortness of breath:
>use pulse-lips breathing
>try to relax
>use your rescue inhaler. For most, this will be albuterol aerosol from an inhaler. Alternatively, albuterol can be inhaled as a solution from a nebulizer. Other rescue medications are ipratropium (Atrovent) and albuterol and ipratropium combination (Combivent) inhaled as a mist or a solution from a nebulizer.

Step 2. If you cough up yellow or green mucus, then most likely you have a bacterial chest infection. You should contact your doctor to ask about an antibiotic. White-gray mucus suggests either inflammation or a viral infection. Remember, we do not have effective antibiotics for most viruses that cause a chest infection (bronchitis or pneumonia).

Step 3. If your breathing is much worse and the rescue medication is not helping enough, you should contact your doctor to ask about prednisone. This medication fights inflammation which develops in your breathing tubes when a chest infection occurs.

Step 4. If your breathing difficulty becomes quite severe, you need to go to the nearest Emergency Department. Either have someone drive you there or call 911 for an ambulance.