Real-world use affirms benefit of triple therapy in COPD

Inhaled triple therapy containing beclomethasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium (G) helps improve lung function and symptom control, as well as cut the frequency of exacerbations, in patients with chronic obstructive pulmonary disorder (COPD) treated in a real-world setting, according to data from the TRICOP noninterventional study.

“[TRICOP] largely confirmed the outcomes reported in the controlled clinical trials, fully reproducing the beneficial impact of the fixed-dose triple therapy with BDP/FF/G on [the outcomes examined],” said a trio of investigators from the Hietzing Hospital in Vienna, Austria.

“These improvements were seen both at the level of the entire study population and also in the most affected patients belonging to GOLD groups 3 and 4 or to GOLD B and D. In fact, the average improvement in forced expiratory volume in 1 second (FEV₁) of 138 mL relative to the baseline level seen in GOLD 3 and 4 after 52 weeks exceeded the 70–80 mL seen in comparable patient groups in controlled clinical trials,” the investigators pointed out. [Lancet 2016;388:963-973; Lancet 2017;389:1919-1929]

“Further, with a potentially important impact on patient compliance, [the changes occurred in tandem] with a rapid reduction in symptom scores relating to shortness of breath, sputum, and cough, which were already noticeable 12 weeks after [treatment initiation],” they added.

In total, 265 COPD patients (mean age 67 years, average disease duration 7.8 years) with moderate to very severe airflow limitation (GOLD Grade 2–4: 96.2 percent) and persistent symptoms (GOLD B: 62.3 percent; GOLD D: 34 percent) comprised the TRICOP population. They received BDP 87 µg/FF 5 µg/G 9 µg in a pressurized metered dose inhaler for 52 weeks.

At baseline, one-third of the population engaged in sports activities; 87 percent were either previous or current smokers (average pack-years 43.8). More than half (69 percent) of the patients had pre-existing conditions, the most common of which were hypertension (45 percent), followed by coronary heart disease (25 percent), obesity (13 percent), heart insufficiency (12 percent), and depression (12 percent), among others. Almost half of the patients were already on multi-inhaler triple therapy at baseline.

After 52 weeks of treatment, FEV₁ increased from 1.23 to 1.33 L (p<0.001), FEV₁ %predicted from 43.41 percent to 48.08 percent (p<0.001), forced vital capacity (FVC) from 2.22 to 2.38 L (p<0.001), and FVC %predicted from 62.32 to 67.63 (p<0.001) in the overall population. Results were similar in the subgroup of patients in the GOLD grade 3 and 4 and GOLD group B and D categories. [Respir Med 2021;doi:10.1016/j.rmed.2021.106398]

Symptom scores for dyspnoea, sputum, and cough also improved significantly both in the entire study population and the subgroups.

In the GOLD grade 3 and 4 and GOLD group B and D subgroups, “[there was] a clear-cut reduction in the share of patients experiencing these symptoms daily, while the percentage of those patients experiencing them less frequently or not at all showed a corresponding increase,” the investigators noted.

A clinically relevant improvement in COPD Assessment Test score that occurred at 12 weeks persisted through week 52 in GOLD B and GOLD D patients (p<0.001), paralleled by a significant reduction in moderate and severe exacerbations of 57.4 percent and 27.3 percent, respectively (p<0.001).

Most patients (93.7 percent) continued the treatment after 52 weeks.

Tolerability of the fixed-dose triple therapy was considered very good in 80 percent of the patients, good in 18.5 percent, and acceptable in 1.5 percent. Of the 21 adverse events documented, only five were serious but none were drug-related.

“The fact that many of the observed improvements were fairly pronounced in the overall study population despite the fact that almost half of the patients were already using triple therapy (using two or three application devices) before the onset of this study underscores the effectiveness of the fixed-dose triple therapy,” according to the investigators.

Even more interesting, perhaps, is that the drug is beneficial in patients with moderate airflow obstruction—a population not previously evaluated in trials, they added. This points to the practical use of the triple therapy as maintenance therapy in even a broader segment of patients with COPD not adequately responsive to inhaled corticosteroid/long-acting beta-agonist (LABA) or LABA/long-acting muscarinic antagonist combinations.