Estimated impact for the NHS

Other treatments

The beclometasone/formoterol/glycopyrronium (metered dose) inhaler (Trimbow) was the first triple therapy combination inhaler licensed for COPD in the UK. A second triple therapy (dry powder) inhaler containing fluticasone, vilanterol and umeclidinium (Trelegy) has also been licensed in the UK and is the subject of a separate evidence summary.

Four dual-therapy LAMA/LABA combination inhalers are currently available for treating symptoms of COPD:

Combination ICS/LABA inhalers currently licensed for treating COPD include:

Note that not all strengths of all these products are licensed for treating COPD; some strengths are licensed only for treating asthma. Please see the summaries of product characteristics for more information.

ICS are not licensed for monotherapy in COPD and are only available in combination with LABAs. Four single-component LABAs are currently licensed for treating COPD:

Single-component LAMAs licensed for treating COPD are:

Examples of branded products are given but the lists are not intended to be comprehensive. Some originator brands are now off-patent and further generic versions may be available.

Costs of other treatments

Table 3 lists comparative costs for a range of mono, dual and triple-therapy inhalers for COPD compared with the beclometasone/formoterol/glycopyrronium metered dose inhaler (Trimbow). Table 4 gives examples of a range of costs for triple therapy using either a triple-therapy inhaler or a combination of a dual-therapy inhaler containing an ICS/LABA plus a monotherapy inhaler containing a LAMA. These tables do not include all of the currently licensed products or all of the options for triple therapy, but give an indication of the range of treatments and triple therapy options, and their associated acquisition costs (excluding VAT).

Table 3 Examples of costs of inhalers for treating COPD

Treatment

Usual dosage a,b

30-day cost excluding VAT

Single-component LABAs

Formoterol 12 micrograms (Formoterol Easyhaler)

1 puff twice daily

£11.87c,d

Indacaterol 150 micrograms and 300 micrograms (Onbrez Breezhaler)

1 puff daily

£32.19c

Olodaterol 2.5 micrograms (Striverdi Respimat)

2 puffs once daily

£26.35c

Salmeterol 50 micrograms (Serevent Accuhaler)

1 puff twice daily

£35.11c,d

Single-component LAMAs

Aclidinium 322 micrograms (Eklira Genuair)

1 puff twice daily

£28.60c

Glycopyrronium 44 micrograms (Seebri Breezhaler)

1 puff daily

£27.50c

Tiotropium 10 micrograms, dry powder (Braltus)

1 puff daily

£25.80c

Tiotropium 2.5 micrograms, aerosol (Spiriva Respimat)

2 puffs once daily

£23.00c

Umeclidinium 55 micrograms (Incruse Ellipta)

1 puff daily

£27.50c

Combination LAMA/LABA inhalers

Tiotropium/olodaterol 2.5/2.5 micrograms (Spiolto Respimat)

2 puffs once daily

£32.50c

Aclidinium/formoterol 340/12 micrograms (Duaklir Genuair)

1 puff twice daily

£32.50c

Indacaterol/glycopyrronium 85/43 micrograms (Ultibro Breezhaler)

1 puff daily

£32.49c

Umeclidinium/vilanterol 55/22 micrograms (Anoro Ellipta)

1 puff daily

£32.50c

Combination ICS/LABA inhalers

Beclometasone/formoterol 100/6 micrograms (Fostair or Fostair NEXThaler)

2 puffs twice daily

£29.32c

Budesonide/formoterol 320/9 micrograms (Fobumix Easyhaler)

1 puff twice daily

£26.99e,d

Fluticasone furoate/vilanterol 92/22 micrograms (Relvar Ellipta)

1 puff daily

£22.00c

Fluticasone propionate/salmeterol 500/50 micrograms (Aerivio Spiromax and AirFluSal Forspiro)

1 puff twice daily

£29.97e,d

Triple ICS/LABA/LAMA inhalers

Beclometasone/formoterol/glycopyrronium 87/5/9 micrograms (Trimbow)

2 puffs twice daily

£44.50e

Fluticasone/vilanterol/umeclidinium 92/55/22 micrograms (Trelegy)

1 puff daily

£44.50e

a Doses taken from the relevant summary of product characteristics.

b The doses shown do not represent the full range that can be used and they do not imply therapeutic equivalence.

c Costs taken from the Drug Tariff (March 2018). All costs include the inhaler device.

d Lowest cost dry powder formulations selected; other brands and formulations are available.

e Costs taken from MIMS (March 2018). All costs include the inhaler device.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta-2 agonist; LAMA, long-acting muscarinic antagonist.

Table 4 Examples of costs of triple therapy for treating COPD

30-day cost excluding VAT a

Combination ICS/LABA inhaler plus a separate LAMA inhaler

Beclometasone/formoterol 100/6 micrograms (Fostairb or Fostair NEXThaler)

Aclidinium 322 micrograms (Eklira Genuair)

£57.92

Glycopyrronium 44 micrograms (Seebri Breezhaler)

£56.82

Tiotropium 10 micrograms, dry powder (Braltus)

£55.12

Tiotropium 2.5 micrograms, aerosol (Spiriva Respimat)

£52.32

Umeclidinium 55 micrograms (Incruse Ellipta)

£56.82

Budesonide/formoterol 320/9 micrograms (Fobumix Easyhaler)

Aclidinium 322 micrograms (Eklira Genuair)

£55.59

Glycopyrronium 44 micrograms (Seebri Breezhaler)

£54.49

Tiotropium 10 micrograms, dry powder (Braltus)

£52.79

Tiotropium 2.5 micrograms, aerosol (Spiriva Respimat)

£49.99

Umeclidinium 55 micrograms (Incruse Ellipta)

£54.49

Fluticasone furoate/vilanterol 92/22 micrograms (Relvar Ellipta)

Aclidinium 322 micrograms (Eklira Genuair)

£50.60

Glycopyrronium 44 micrograms (Seebri Breezhaler)

£49.50

Tiotropium 10 micrograms, dry powder (Braltus)

£47.80

Tiotropium 2.5 micrograms, aerosol (Spiriva Respimat)

£45.00

Umeclidinium 55 micrograms (Incruse Ellipta)

£49.50

Fluticasone propionate/salmeterol 500/50 micrograms (Aerivio Spiromax and AirFluSal Forspiro)

Aclidinium 322 micrograms (Eklira Genuair)

£58.57

Glycopyrronium 44 micrograms (Seebri Breezhaler)

£57.47

Tiotropium 10 micrograms, dry powder (Braltus)

£55.77

Tiotropium 2.5 micrograms, aerosol (Spiriva Respimat)

£52.97

Umeclidinium 55 micrograms (Incruse Ellipta)

£57.47

Triple ICS/LABA/LAMA inhalers

Beclometasone/formoterol/glycopyrronium 87/5/9 micrograms (Trimbow)b

£44.50

Fluticasone/vilanterol/umeclidinium 92/55/22 micrograms (Trelegy)

£44.50

a Costs taken from the Drug Tariff (March 2018) or MIMS (March 2018). Lowest cost dry powder formulations selected unless footnoted otherwise; other brands and formulations are available. All costs include the inhaler device. See table 3 for more details.

b Pressurised metered dose inhaler.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting beta-2 agonist; LAMA, long-acting muscarinic antagonist.

A 30-day supply of combination therapy with beclometasone, formoterol and glycopyrronium costs £44.50 (excluding VAT) when the triple-therapy inhaler (Trimbow) is prescribed. This compares with £56.82 (excluding VAT) when beclometasone and formoterol are prescribed in a dual-therapy inhaler (Fostair or Fostair NEXThaler) together with glycopyrronium in a single therapy inhaler (Seebri Breezhaler). It is the same price as the fluticasone, vilanterol and umeclidinium triple-therapy inhaler (Trelegy).

The acquisition cost of a 30-day supply of combination ICS/LABA inhaler plus a separate LAMA inhaler using the products listed in the table above ranges from about £45.00 to £58.00 (excluding VAT), compared with £44.50 (excluding VAT) for triple-therapy inhaler. This suggests that using triple therapy could lead to annual savings of between £6 and £160 per year when these products are used (based on using 12 inhalers per year; note that inhaler strengths and dosages vary and they may not be equivalent). The tables include the lowest cost dry powder formulations so the saving with triple therapy would be higher where more expensive brands and formulations are currently used.

Current or estimated usage

It is not possible to provide estimated usage of the beclometasone/formoterol/glycopyrronium triple-therapy inhaler based on the available data. This is because it is not currently possible to determine whether prescribing of inhalers is for asthma or COPD, or whether inhalers are used alone or in combination as part of triple therapy.

Results from a retrospective cohort study based on the UK Clinical Practice Research Database (n=3,199) found that, over 2 years, 39% of people with COPD who were initially prescribed an ICS in combination with a long-acting bronchodilator (usually a LABA) stepped up to an open triple therapy regimen. The majority of people who were initially using open triple therapy stepped down to a LABA/ICS (25%) or LAMA (31%) during the 2-year follow-up (Wusrt KE et al. 2014). However, the study included a relatively small number of people only, and it started in January 2008 and may not be applicable to current practice.

Likely place in therapy

The NICE guideline on COPD (currently being updated) recommends that triple therapy should be considered in people who remain breathless or have exacerbations despite using an ICS/LABA (add a LAMA) or a LAMA (add an ICS/LABA), irrespective of FEV1. (The NICE guideline was published before any of the LABA/LAMA or ICS/LABA/LAMA combination inhalers were available in the UK). The choice of medication should take into account the person's symptomatic response and preference, and the medicine's potential to reduce exacerbations, its side effects and its cost.

The TRILOGY and TRINITY studies found modest statistically significant improvements in lung function, rates of moderate-to-severe exacerbations of COPD and health-related quality-of-life scores with beclometasone/formoterol/glycopyrronium compared with beclometasone/formoterol dual therapy or tiotropium alone. Improvements in lung function and exacerbation rates generally reached the level considered to be clinically important. Beclometasone/formoterol/glycopyrronium did not improve symptoms of dyspnoea significantly more than beclometasone/formoterol. However, responder analyses showed that more participants had a clinically important improvement in symptoms and health-related quality of life with triple therapy compared with dual therapy. Fixed triple therapy with a single beclometasone/formoterol/glycopyrronium inhaler was found to be similar to open triple therapy with beclometasone/formoterol plus tiotropium in 2 inhalers for all outcomes.

The TRIBUTE study found that beclometasone/formoterol/glycopyrronium reduced the rate of moderate-to-severe exacerbations compared with indacaterol/glycopyrronium. However, although the difference between the groups was statistically significant, it may not have been clinically important. For other outcome measures, beclometasone/formoterol/glycopyrronium and indacaterol/glycopyrronium were generally found to be similar. For example, there were no statistically significant differences between the groups for rates of moderate exacerbations, severe exacerbations, or time to first moderate-to-severe or severe exacerbation. Also, responder analyses showed no difference in terms of the proportion of people who had a clinically important improvement in lung function or health-related quality of life.

The adverse effect profile of beclometasone/formoterol/glycopyrronium is well understood because the active ingredients have been used for many years, alone and in combination. The most frequent adverse effects include oral candidiasis, muscle spasms and dry mouth.

The acquisition cost of the beclometasone/formoterol/glycopyrronium triple-therapy inhaler (Trimbow) is less than that of other combinations of ICS/LABA plus LAMA in 2 inhalers. It costs the same as triple therapy with fluticasone/umeclidinium/vilanterol (Trelegy) (£44.50 for a 30 day's treatment [excluding VAT]; MIMS, March 2018).

Some people may prefer a particular inhaler device or be able to use one device better than another. Some people with COPD are unable to use a spacer, others like to use one. Beclometasone/formoterol/glycopyrronium is supplied in a pressurised metered dose inhaler and can be used with a spacer. Fluticasone/umeclidinium/vilanterol is supplied in a dry powder inhaler and cannot be used with a spacer. Beclometasone/formoterol/glycopyrronium is administered twice daily and fluticasone/umeclidinium/vilanterol is administered once daily.

Until recently, administering triple therapy needed more than 1 inhaler, sometimes using 2 different types of device. Triple therapy in a single inhaler may be preferable for people who have difficulty using more than 1 device or who find their medication regimen difficult or confusing, and have trouble complying with treatment. However, triple therapy lacks flexibility and makes it difficult to amend the individual medicines if treatment needs changing for any reason.

Beclometasone/formoterol/glycopyrronium may be suitable for some people with moderate-to-severe COPD who have found triple therapy beneficial using more than 1 inhaler and can use a pressurised metered dose inhaler (with or without a spacer), but who have difficulty using multiple inhalers.

Local decision makers will need to take safety, efficacy, cost and patient factors into account when considering the likely place in therapy of beclometasone/formoterol/glycopyrronium.