Overall, indacaterol/glycopyrronium showed a small but statistically significant improvement in lung function (forced expired volume in 1 second [FEV1]) compared with active comparators (indacaterol, glycopyrronium, tiotropium and fluticasone/salmeterol) in people with moderate to very severe chronic obstructive pulmonary disease (COPD) for up to 52 weeks. Indacaterol/glycopyrronium also showed small statistically significant improvements in dyspnoea, health status and use of rescue medication compared with active comparators. These improvements are of uncertain clinical benefit. Nevertheless, the European Medicines Agency states that, although the differences between treatments were often not large enough to be clinically relevant in the total population, responder analyses have shown that differences can be important to individual patients.
The NICE clinical guideline on COPD recommends that the choice of drug treatment should take into account the person's symptomatic response and preference, and the drug's potential to reduce exacerbations, its side effects and costs. The use of dual therapy with a component long-acting muscarinic antagonist (LAMA) and long-acting beta2 agonist (LABA) may be considered if an inhaled corticosteroid (ICS; as part of combination therapy with a LABA) is declined or not tolerated. It is noted that NICE developed these recommendations in 2010, which predates the publication of the key clinical evidence for indacaterol, glycopyrronium and aclidinium.
The indacaterol/glycopyrronium combination inhaler is expected to be less expensive than the combined cost of the single-component inhalers and may be more convenient for people. However, compared with established drugs such as formoterol, salmeterol and tiotropium, the comparative efficacy and long-term safety of indacaterol and glycopyrronium (alone or in combination) is unclear, particularly in terms of reducing exacerbations. In addition, although the combination inhaler delivers the same clinically effective dose of indacaterol as the single-component inhaler, the stated doses are different which may confuse prescribers and patients.
In SPARK, indacaterol/glycopyrronium statistically significantly reduced the risk of moderate to severe exacerbations in people with severe or very severe COPD by 12%. However, the European Medicines Agency concluded that the 12% reduction was considered to be 'very small' and not supportive of the manufacturer's requested indication of 'exacerbation reduction'. Similarly, the full NICE guideline on COPD considers a relative reduction in the risk of exacerbations of 20% or more to be clinically important.
Specialists involved in producing this evidence summary consider that indacaterol/glycopyrronium may be used to relieve symptoms in people with COPD who remain symptomatic on a LABA or LAMA. However, current evidence does not support the use of indacaterol/glycopyrronium to reduce exacerbations in people with COPD, either as an intermediate step between LAMA monotherapy and LAMA plus LABA/ICS triple therapy, or as an alternative to LABA/ICS.