Idiopathic pulmonary fibrosis (IPF)

Disease-modifying treatments

This information explores the most up-to-date research for IPF disease-modifying treatments. 

We reviewed this information in February 2016. New research is always being reported, so there may have been changes since. It doesn’t replace your health care professional’s advice.

Contents:

History

Until recently, the main treatment for IPF tried to minimise the ongoing damage to the lungs by reducing inflammation. Until just 5 years ago, people with IPF were treated with triple therapy - a combination of:

  • steroids (prednisolone)
  • an immunosuppressant (azathioprine) an
  • an anti-oxidant tablet called n-acetylcysteine (NAC)

It was thought this combination therapy would help reduce inflammation to allow the lung repair itself.

In 2012, an important clinical trial called the PANTHER trial showed this combination was not effective for IPF and that it might actually be harmful, possibly due to the side effects of these drugs. This means that steroids and immunosuppressants are no longer prescribed as routine treatment in IPF. Clinicians may treat people with other forms of pulmonary fibrosis with this combination (such as hypersensitivity pneumonitis or fibrosis associated with connective tissue diseases). 

If you have IPF, you might sometimes take a low dose of a steroid tablet on its own, as some people find it helps with their cough. Steroids might also be prescribed to treat a sudden worsening of the condition, known as a flare-up or exacerbation, but triple therapy is not now used routinely to treat IPF.

Health care professionals once thought NAC given on its own might be beneficial in pulmonary fibrosis. The final part of the PANTHER trial, designed to look at this issue, was published in 2014. It found NAC alone did not slow the progression of IPF, so it is not universally prescribed. Anecdotal evidence suggests NAC may help relieve the symptoms of coughing in some people.

At present, NAC’s effectiveness is uncertain. It doesn’t have a significant effect in most people with IPF, but it may be helpful in a minority. There’s no evidence it causes harm. It is still widely used to help people who find it difficult to cough up sputum. It makes their sputum less thick and much easier to cough up.

Anti-scarring treatments

In 2012, the results were published of two big trials (CAPACITY 1 and 2) specifically designed to look at a new anti-scarring medication, pirfenidone. These studies showed pirfenidone, also called Esbriet, slowed down how quickly IPF progressed for some people by slowing down the rate at which the lung becomes scarred.

A further study, the ASCEND trial, confirmed these findings in 2014. The rate of decline was approximately halved in the people taking pirfenidone compared to those who didn’t.

Pirfenidone was made available for people with IPF in the UK by NICE (the National Institute for Health and Care Excellence) in 2013. Due to concerns about cost effectiveness, pirfenidone has only been approved by NICE for use by people whose lung function measures within a specific range ( between 50% and 80% of ‘forced vital capacity’ or ‘FVC’).

The guidance also recommends stopping pirfenidone if lung function measured by FVC continues to decline by 10% or more within a 12 month period, while taking the medication. Not everyone with IPF meets the lung function criteria to have this medication prescribed, so it’s not universally available to all with the condition.

In 2011, a study called TOMORROW investigated a new and different kind of drug called nintedanib and found that it too appeared to slow down the rate of lung function decline in IPF. In 2014, two more studies, INPULSIS 1 and 2 explored this further. They confirmed the findings that nintedanib, (also referred to as Ofev) appeared to slow the rate of scarring at similar rates to pirfenidone.

NICE approved the use of nintedanib as a treatment for some people with IPF in the UK in January 2016, so those who qualify have a right now to this treatment. The recommendations are that it is restricted to people whose lung function falls within the same range as pirfenidone.

Both nintedanib and pirfenidone can have side effects and there are some drugs that cannot be taken with them. Your doctor will discuss this with you and may be able to manage the side effects of the drugs by adjusting the doses. Both drugs require patients to have regular blood tests to monitor their liver function.

  • Pirfenidone can cause a photosensitive rash, so it’s recommended you use a high SPF (sun protection factor) sunscreen if you take it (SPF 50 is recommended by most specialist nurses). It may also cause upper gastrointestinal side effects such as nausea and indigestion, and some people lose their appetite and lose weight.
     
  • Nintedanib cannot be taken by people on blood thinning or anti-coagulant medication such as warfarin or by people who have recently had significant bleeding or blood clotting problems such as stroke, heart attack or after major surgery. Its main side effect is diarrhoea, but this can often be managed.
  Pirfenidone Nintedanib
Trials CAPACITY 1&2, ASCEND TOMORROW, INPULSIS
Number of people in trial CAPACITY 779 ASCEND: 555 

TOMORROW: 432

INPULSIS: 1066
Effect on lung function Only 6.7% of pirfenidone patients were observed to have more than 10% decline in FVC over 12 months compared to 11% of patients taking placebo

TOMORROW: 131ml less decline in FVC each year in nintedanib patients compared to placebo

INPULSIS : 125ml less decline in FVC each year in nintedanib patients compared to placebo 
Other outcomes

Less reduction in six minute walk test distance with pirfenidone treatment

Fewer deaths in pirfenidone treated group

Less frequent flare-ups: 3.6% nintedanib vs 9.6% taking placebo
Medication format and dose

3 capsules three times (2403 mg total) daily with food

Capsules, 150mg twice daily
Drug side effects

Nausea: 36% with pirfenidone compared to 17% placebo

Indigestion: 19% compared to 7% placebo

Weight loss or anorexia:11% compared to 4% placebo

Photosensitivity: 12% compared to 2% placebo

INPULSIS:

Diarrhoea:76.5% taking nintedanib -3% classified as serious - vs 39.7% placebo
When it’s not advised to take these drugs

Using other drugs at the same time, including omeprazole (lansoprazole and other antacids are OK), fluvoxamine, ciprofloxacin, fluoexetine, paroxetine, amiodarone, and fluconazole

Avoid drinking grapefruit juice

Using anti-coagulant treatments

Major surgery planned or within last 3 months

Recent heart attack or haemorrhagic stroke

Recent history of significant bleeding from the bladder, bowel or lung

New anti-scarring medications are being tested in trials, as well as combination therapies using both pirfenidone and nintedenib, the only two currently available drugs. We hope the results will mean we soon have more treatment options to offer patients.

Currently anti-scarring therapy can only be prescribed through specialist centres in the UK. These centres have expertise in making the diagnosis of IPF and discriminating IPF from other forms of interstitial lung disease (ILD). These centres will arrange monitoring of blood tests and manage side effects of the treatment. At present, anti-scarring therapy cannot be prescribed by GPs or non-specialists.

Further information

Pulmonary rehabilitation

Pulmonary rehabilitation can help you cope with breathlessness and is an important part of treatment. It’s a physical exercise programme combined with education, general awareness, advice and support on keeping healthy and managing your breathlessness. A variety of health care professionals including nurses, respiratory therapists and physical therapists will take part.

IPF can lead to a cycle of breathlessness and inactivity. If you feel short of breath, you may become less active which can lead to greater breathlessness. Pulmonary rehabilitation aims to break this cycle. 

Breathlessness can make you fear activity. The less active you are, the more likely you are to feel breathless.

Pulmonary rehabilitation and exercise are effective treatments for other lung diseases. A review of the available studies also suggested that if you have IPF, you could also benefit.

The studies reviewed suggested physical training programmes helped to improve people’s levels of activity. People said they felt generally better after completing the exercise programmes too.

The studies reviewed suggested physical training programmes help to improve people’s levels of activity. People said they felt generally better after completing the exercise programmes too. The studies also suggested a small improvement in symptoms of breathlessness compared with patients not doing the programme. But the differences observed were small and are not yet confirmed.

There are no studies yet showing how long the improvement in wellbeing lasts for people with IPF..

Further information:

Next: Managing symptoms >

Last medically reviewed: February 2016. Due for review: February 2018

This information uses the best available medical evidence and was produced with the support of people living with lung conditions. Find out how we produce our information. If you’d like to see our references get in touch.