Key points from the evidence

The content of this evidence summary was up-to-date in February 2015. See summaries of product characteristics (SPCs), British national formulary (BNF) or the MHRA or NICE websites for up-to-date information.

Summary

Olodaterol (Striverdi Respimat) is a new a long‑acting beta‑2 agonist (LABA) for chronic obstructive pulmonary disease (COPD).

In two 48‑week studies, olodaterol statistically significantly improved lung function in people with moderate to very severe COPD compared with placebo over 24 weeks, and was not statistically significantly different from formoterol. Statistically significant improvements in health‑related quality of life were seen with olodaterol compared with placebo, but the results were less conclusive for dyspnoea (breathlessness) and the studies were not designed to assess exacerbations.

Although olodaterol appears to improve lung function as well as formoterol, little evidence is available comparing it directly with other LABAs and long‑acting muscarinic antagonists (LAMAs) for COPD, particularly in terms of patient‑oriented outcomes such as exacerbations, breathlessness and quality of life.

Effectiveness

  • In 2 RCTs (n=904 and n=934), olodaterol was statistically significantly better than placebo in improving mean FEV1 AUC0–3 response (both p<0.0001) and mean trough FEV1 response (both p<0.01) in people with COPD (92% moderate to severe) at 24 weeks.

  • When data for the 2 studies were combined, there were no statistically significant differences in lung function between olodaterol 5 micrograms daily and formoterol 12 micrograms twice daily.

  • Based on combined data, olodaterol statistically significantly improved health‑related quality of life scores compared with placebo (p=0.0034) at 24 weeks.

  • Results were less conclusive for dyspnoea scores and the studies were not designed to assess exacerbations.

  • Head‑to‑head data comparing olodaterol and formoterol were not reported for symptomatic end points.

  • Olodaterol was often co‑administered with tiotropium and inhaled corticosteroids (ICS) and only limited data support its use alone.

Safety

  • In the 2 RCTs, most adverse events were reported to be mild to moderate in severity. The majority of treatment‑emergent adverse events were respiratory events, such as exacerbations of COPD, cough and dyspnoea.

  • The public assessment report for olodaterol notes that, in studies, the adverse effects of olodaterol were as expected for a LABA. However, only about 500 people have been treated for over 48 weeks and data are limited in people with significant cardiac comorbidity.

  • According to the summary of product characteristics, the most common adverse effects of olodaterol are nasopharyngitis, dizziness and rash (incidence between 1 in 100 and 1 in 1000).

Patient factors

  • Olodaterol, indacaterol, glycopyrronium and tiotropium are administered once daily. Formoterol, salmeterol and aclidinium are administered twice daily.

  • Olodaterol is administered using a Respimat inhaler containing a cartridge of inhalation solution. Other LABAs and LAMAs are available as solutions or dry powder formulations in various different inhaler devices. Some patients may prefer a particular product.

  • In common with many other devices, the Respimat device cannot be used with a spacer.

Resource implications

  • The 30‑day cost of olodaterol is £26.35

  • The 30‑day costs of other LABAs and LAMAs range from £27.50 to £34.87, apart from formoterol, the cost of which ranges from £11.87 to £24.80.

    (Costs excluding VAT; MIMS, December 2014.)

Introduction and current guidance

According to the NICE guideline on chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care (partial update), in people with stable COPD who remain breathless or have exacerbations despite using short‑acting bronchodilators as needed, the following should be offered as maintenance therapy:

  • if forced expired volume in 1 second (FEV1) is 50% predicted or more: either a LABA or LAMA

  • if FEV1 is less than 50% predicted: either a LABA with an inhaled corticosteroid (ICS) in a combination inhaler, or a LAMA. Consider a LAMA in addition to a LABA where an ICS is declined or not tolerated.

See the NICE guideline or the NICE pathway on COPD for full details.

This evidence summary considers the best available evidence to support the use of olodaterol (a LABA) for COPD.

Full text of introduction and current guidance.

Product overview

Olodaterol 2.5 microgram solution for inhalation (Striverdi Respimat; Boehringer Ingelheim) received a marketing authorisation for maintenance bronchodilator treatment in people with COPD in October 2013 and was launched in the UK in June 2014.

The recommended dose of olodaterol is 5 micrograms (2 puffs) once daily, which is administered using a Respimat inhaler containing a cartridge of inhalation solution.

Full text of product overview.

Evidence review

  • This evidence summary is primarily based on 2 identical randomised controlled trials of olodaterol that were designed to fulfil EU regulatory requirements (Koch et al. 2014).

  • The studies (n=904 and n=934) investigated the efficacy and safety of olodaterol 5 micrograms and 10 micrograms daily, and formoterol 12 micrograms twice daily compared with placebo over 48 weeks in people with COPD (92% moderate to severe and 8% severe across both studies). Apart from LABAs, usual COPD maintenance treatment was continued (for example, overall, 26% of participants took LAMAs [tiotropium] and 48% took ICS). The 3 co‑primary endpoints (measured at 24 weeks) were FEV1 area under the curve from 0–3 hours (AUC0−3) response (change from pre‑treatment baseline), trough FEV1 response, and Transitional Dyspnoea Index (TDI) focal scores. St. George's Respiratory Questionnaire (SGRQ; a measure of health‑related quality of life) total scores were used as a key secondary endpoint. Efficacy results for the 10 microgram dose are not discussed in this evidence summary because this dose is not licensed in the UK.

  • After 24 weeks, in both studies compared with placebo, olodaterol 5 micrograms and formoterol 12 micrograms statistically significantly improved the mean FEV1 AUC0–3 response (all p<0.0001) and mean trough FEV1 response (all p<0.05). The authors report that, when data for the 2 studies were combined, there were no statistically significant differences in lung function outcomes between olodaterol 5 micrograms and formoterol 12 micrograms. However, no data are reported and it is unclear whether this analysis was pre‑specified.

  • Based on the combined data set, in the pre‑specified analysis, there was no statistically significant difference in TDI focal scores between olodaterol 5 micrograms or formoterol 12 micrograms and placebo after 24 weeks. However, a high rate of discontinuations was identified in the placebo group in 1 study (25.3% compared with 15.9−18.9% in active treatment groups); therefore, a post hoc analysis that accounted for discontinuations was undertaken. It found that the difference between placebo and olodaterol 5 micrograms (p=0.0270), but not formoterol 12 micrograms, was statistically significant.

  • When data were combined for the 2 studies, olodaterol 5 micrograms, but not formoterol 12 micrograms, statistically significantly improved SGRQ total scores compared with placebo (p=0.0034) at 24 weeks. The hierarchical testing model used in the studies means that the SGRQ results should be considered as descriptive only (because tests ranked above those for SGRQ scores in the model did not demonstrate statistical significance). Nevertheless, around half of people taking olodaterol 5 micrograms saw an improvement of 4 points or more compared with one‑third of those taking placebo (p<0.0001).

  • In the 2 studies, trough FEV1 response, TDI focal scores and SGRQ total scores were all below the values considered to be the minimum clinically important differences. However, the improvements in lung function and SGRQ scores seen with olodaterol were comparable to those seen with the established therapy, formoterol, and the public assessment report for olodaterol states that this demonstrates the clinical relevance of the findings. The public assessment report also notes that a minimum clinically important difference might not be static, and might be dependent on the patient population studied or the severity of the disease, as well as use of concomitant medication. Patients in the studies were permitted to take background treatment for COPD (except for LABAs) in all of the olodaterol studies, which was not the case in earlier COPD drug development programmes, when minimum clinically important differences were determined.

  • Little evidence is available comparing olodaterol directly with other active treatments for COPD, particularly in terms of patient‑oriented outcomes. Koch et al. (2014) found there were no statistically significant differences in lung function outcomes between olodaterol 5 micrograms and formoterol 12 micrograms. However, these are disease‑orientated outcomes and no comparisons between the active treatments are presented for other, patient‑oriented outcomes. In addition, no head‑to‑head studies have compared olodaterol and the other LABA that is licensed for once‑daily (rather than twice‑daily) treatment of COPD, indacaterol. An indirect meta‑analysis outlined in this evidence summary (Roskell et al. 2014) found that olodaterol and indacaterol were of similar efficacy but the results should be interpreted with caution because the studies included in the analysis are inherently dissimilar. Comparative efficacy data for tiotropium are limited to 6‑week cross over studies (Lange et al. 2014 and NCT01040728). There are no direct comparisons with other LABAs and LAMAs.

  • The public assessment report for olodaterol advises that 4312 people have been treated with olodaterol monotherapy. Of these, only 265 were treated with olodaterol 5 micrograms, and 258 were treated with olodaterol 10 micrograms, for more than 48 weeks. Data in people with cardiac co‑morbidity are limited.

  • According to the summary of product characteristics, the most common adverse effects of olodaterol are nasopharyngitis, dizziness and rash (incidence between 1 in 100 and 1 in 1000). Hypertension and arthralgia have been reported rarely (incidence between 1 in 1000 and 1 in 10,000). Adverse effects are usually mild or moderate in intensity. The summary of product characteristics also notes that, as olodaterol is a LABA, the occurrence of adverse effects related to the beta‑adrenergic agonist class should be taken into consideration.

Full text of evidence review.

Context

The 30‑day cost of olodaterol is £26.35. This is lower than the 30‑day costs of the other LABAs (indacaterol and salmeterol) and LAMAs (aclidinium, glycopyrronium and tiotropium) which range from £27.50 to £34.87, apart from formoterol, the costs of which range from £11.87 to £24.80. (Costs excluding VAT; MIMS, December 2014).

Full text of context.

Estimated impact for the NHS

The NICE guideline on COPD recommends that the choice of treatment should take into account the person's symptomatic response and preference, and the medicine's potential to reduce exacerbations, side effects and costs.

Specialists involved in the production of this evidence summary consider that olodaterol is likely to be used alone in people with moderate COPD, who remain breathless or have exacerbations despite using short‑acting bronchodilators as needed, particularly those who prefer the Respimat device over other inhaler devices, in line with the NICE guideline on COPD. However, only limited data supports its use alone, rather than in combination with a LAMA or ICS; more evidence is needed comparing olodaterol with other LABAs and LAMAs, such as indacaterol, salmeterol and tiotropium, in terms of patient‑oriented outcomes such as breathlessness, exacerbations and quality of life.

Olodaterol is less likely to be used in people with more severe COPD because it is not currently available in combination with an ICS. No inhalers containing an ICS alone are licensed for treating COPD in the UK because of safety concerns over using ICS without a LABA. A combination inhaler containing olodaterol and tiotropium is currently in development.

Local decision makers will need to take these factors into account when considering the likely place in therapy of olodaterol.

Full text of estimated impact for the NHS.

About this evidence summary

'Evidence summaries: new medicines' provide summaries of key evidence for selected new medicines, or for existing medicines with new indications or formulations, that are considered to be of significance to the NHS. The strengths and weaknesses of the relevant evidence are critically reviewed within this summary to provide useful information for those working on the managed entry of new medicines for the NHS, but this summary is not NICE guidance.