The first triple combination pMDI for COPD: now available in Australia


In the midst of the COVID-19 pandemic, an important addition was made to the treatment armamentarium for physicians who manage chronic obstructive pulmonary disease (COPD), with the approval and listing of Trimbow (beclometasone/ formoterol/ glycopyrronium) on the Pharmaceutical Benefits Scheme (PBS).1,2

Trimbow is the first triple combination in a pMDI of an inhaled corticosteroid (ICS, beclometasone), long-acting β2-agonist (LABA, formoterol), and long-acting muscarinic antagonist (LAMA, glycopyrronium) approved for COPD, and available in a single pMDI device.1,2 Several clinical trials and real-world studies have been published supporting the use of Trimbow;3–7 however, given the backdrop of the pandemic and focus on COVID-19, respiratory specialists and general practitioners (GPs) may be less aware of the data.

Professor Greg King, Research Leader at the Woolcock Institute of Medical Research and Staff Specialist at Sydney’s Royal North Shore Hospital, has a special interest in small airway disease, and manages many of his COPD patients with Trimbow. “Trimbow is a unique triple therapy with its extrafine* formulation. It’s a great option to have because, in terms of aerosol theory, more of the aerosol will be delivered to the lungs and to a greater depth, than dry powder. The science behind the design is very sound.” he said.

The efficacy and safety of Trimbow has been investigated across four regulatory studies –TRILOGY3 and TRINITY,4 and the more recently published studies, TRIBUTE,5 TRIVERSYTI.6 A real-world effectiveness trial, TRICOP,7 has also been published. Prof. King gave his impressions of the three most recently published studies.

TRIBUTE: Trimbow significantly reduced the rate of moderate-to-severe exacerbations compared with LAMA/LABA5

The global TRIBUTE study was conducted in 17 countries involving 187 sites, including primary, secondary and tertiary care centres and special investigation units (n = 1 532).5 The investigators compared the effect of Trimbow twice daily to LAMA/LABA (indacaterol plus glycopyrronium) on the rate of COPD exacerbations over 52 weeks.5 Patients with severe to very severe airflow limitation (GOLD grade 3–4) and at least one moderate to severe exacerbation in the previous 12 months were eligible for the study.5

Trimbow was found to lower the rate of moderate-to-severe exacerbations (primary end point) by 15% compared with the LAMA/LABA comparator (adjusted rate ratio 0.848; 95% CI 0.723–0.995; p=0.043).5

Trimbow was also found to be superior to dual therapy in key secondary endpoints, including change from baseline in forced expiratory volume in 1 second (FEV1), quality of life scores, and patient-reported outcomes at 12 weeks.‡5

The proportion of patients who experienced adverse events was similar between groups, including cases of pneumonia which occurred in 4% of patients for both study arms.5

Prof. King explained how the TRIBUTE study relates to clinical practice: “The way that we prescribe is informed by studies like TRIBUTE. You take this highly selected population, with very severe impairment of FEV1, all experiencing exacerbations, all taking a lot of treatment already. Then if you give them an ICS compared to LABA/LAMA, they do a bit better. This is good to know, but in addition to this, data from real-world studies is very useful,” he said.

 

TRIVERSYTI: Trimbow improved bronchodilation, and was more effective at preventing moderate/severe COPD exacerbations than ICS/LABA6

TRIVERSYTI,6 a multinational study conducted in 63 centres across China, the Republic of Korea and Taiwan, evaluated Trimbow versus budesonide/formoterol fumarate (BUD/FF) in 708 patients with COPD, <50% predicted FEV1, and a history of exacerbations despite being on maintenance therapy.

Trimbow improved pre- and post-dose (2h) FEV1 in COPD patients vs ICS/LABA by 62 mL (95% CI: 38 to 85; p<0.001) and 113 mL (95% CI: 87 to 140; p<0.001), and resulted in 25.9% of patients achieving a ≥100 mL change in FEV1 from baseline, vs 12.1% in the ICS/LABA group (95% CI 1.72 to 3.85; p<0.001).6

Trimbow also lowered the annualised rate of moderate/severe exacerbations by 43% compared with ICS/LABA (p<0.001), and resulted in fewer AEs than ICS/LABA (61.1% vs 67.0%, respectively), including pneumonia (2.3% vs 3.7%, respectively).6

Prof. King shared his perspectives on the TRIVERSYTI study: “It’s interesting that the effect of triple therapy appears to be a lot greater in this population. There could be a racial difference in response, but I think it’s more likely there are cultural/socioeconomic factors involved.”

Prof. King also pointed out the pneumonia data, noting that this is a common focus for modern COPD trials: “The pneumonia story goes way back now. The signal is there in the data; there’s no question about that, and it’s probably a dose effect so the more steroids you give, the more risk you have, but you don’t hear about it in conference meetings anymore. I think people accept the fact that there is a risk with high doses of inhaled corticosteroid, but compared to the risks associated with acute exacerbations of COPD i.e. of heart attacks, stroke and death, and the fact that pneumonia doesn’t worsen overall outcomes, I don’t think it really adds to concerns about inhaled corticosteroid treatment in COPD patients.”

 

TRICOP: use of Trimbow has been supported in the real-world setting, with improvements in lung function, symptom control and reduced exacerbations7

The TRICOP real-world effectiveness, non-interventional study conducted across 24 sites in Austria followed 265 COPD patients with moderate to very severe airflow limitation (GOLD Grade 2–4: 96.2%) and persistent symptoms (GOLD B: 62.3%, GOLD D: 34%) for 52 weeks. The patients were treated with Trimbow twice daily, which was evaluated for effectiveness in terms of change in symptoms, exacerbations, lung function (FEV1 and force vital capacity, FVC) and other COPD endpoints vs baseline.7

Trimbow significantly improved FEV1 and FVC at 52 weeks vs baseline, with predicted FEV1 rising from 43.41 ± 17.07% to 48.08 ± 19.37% (p<0.001), and predicted FVC rising from 62.32 ± 18.40% to 67.63 ± 19.89% (p<0.001).7

Trimbow also significantly reduced the number of exacerbations reported, from 257 events in 63% of patients at baseline to 118 events in 37% of patients at final follow-up visit.5 Tolerability of Trimbow was reported as ‘very good’ and ‘good’ in 80% and 18.5% of patients, respectively, with 93.7% of patients choosing to remain on Trimbow beyond the study.7

Prof. King explained that he looks to real-world studies with increasing interest. “Real-world studies are a really useful complement to clinical studies. Yes, we’ve learned some great things from clinical trials in the last five years, like the importance of eosinophils as a biomarker of steroid response, but registration studies start to read the same after a while. When you add real-world data in less-restrictive populations, like TRICOP, it can give you a better idea of how a drug will potentially benefit your patients,” he said.

Trimbow provides another therapy option for clinicians treating COPD

Prof. King acknowledged the challenges faced by clinicians, especially GPs, when choosing appropriate therapies: “I have lots of patients on Trimbow, those with moderate to severe airway disease, but I also use other triple therapies too. Having choice in triples is great, but it puts significant responsibility on the treating physician, and on GPs; having too many devices and formulations can be confusing… …I think the pulmonary deposition of Trimbow is a differentiator, but whether that’s clinically important is another question. So, one approach is to trial different triples in your patients to find the option that is best for them – depending on their disease pattern, your clinical judgment, and, of course, the patient’s preferred device.”

Disclosure

This article was sponsored by Chiesi. Any views expressed in the article are those of the expert alone and do not necessarily reflect the views of the sponsor. Before prescribing, please review the Trimbow product information via the TGA website. Treatment decisions based on these data are the responsibility of the prescribing physician.

*Mass median aerodynamic diameter (MMAD) particle size <2 μm.1

Health-related quality of life measured via St George’s Respiratory Questionnaire (SGRQ).

Patient reported outcomes recorded using the EXAcerbations of Chronic pulmonary disease Tool Patient-Reported Outcome (EXACT-PRO) questionnaire.

 

References:

  1. Trimbow Approved Product Information.
  2. gov.au
  3. Singh D et al. Lancet 2016; 388 (10048): 963–973.
  4. Vestbo J et al. Lancet 2017; 389 (10082): 1919–1929.
  5. Papi A et al. Lancet. 2018;391:1076–84.
  6. Zheng J et al. Resp Research. 2021;22:90.
  7. Marth K et al. Respir Med. 2021;182:106398.

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