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COPD: Delay Before Start of Triple Therapy May Increase Risk for Exacerbations


Delay in initiating triple therapy (TT) after a second moderate disease exacerbation in patients with chronic obstructive pulmonary disease (COPD) is associated with a significant risk for an increase in future events, including severe exacerbations, according to findings presented at the American College of Chest Physicians (CHEST) 2022 Annual Meeting, held from October 16 to 19, 2022, in Nashville, Tennessee.

The study authors report that study participants who received TT within 30 days of a moderate COPD event were significantly less likely to have a severe exacerbation within a year of beginning treatment compared with those for whom TT delayed for ≥6 months.

Persons with COPD who experience moderate exacerbations are at high risk for subsequent events, according to authors of the PRIMUS (Prompt Initiation of Maintenance Therapy in the US) study. However, they note, treatment intensification for these patients is often delayed.

The investigators drew on the data captured in the PRIMUS study to assess whether prompt initiation of TT after a patient’s second moderate COPD exacerbation within 12 was associated with reduced risk for future exacerbations.

PRIMUS researchers tapped IBM MarketScan health care claims databases from January 1, 2010, to December 31, 2019, for patients aged ≥40 years with a diagnosis of COPD. Eligibility required open or closed TT, with the earliest prescription fill on the index treatment date; ≥2 moderate exacerbations within 12 months prior to the index treatment; and 12 months of continuous enrollment before or after the index exacerbation (the second moderate event). Exclusions were made for cases of select respiratory diseases and cancer.

Investigators stratified the final patient cohort (n=17 988) into 3 groups based on timing of a TT prescription after the index exacerbation:

  • Prompt within 30 days (25.6%)
  • Delayed 31-180 days (42.7%)
  • Very delayed 181+ days (31.7%)

Study participants had an average (SD) age of 61.3 (10.9) years, 61.5% were women, and 98% had received baseline monotherapy or dual therapy.


Proportion of patients who had ≥1 exacerbations by length of TT initiation delay:

  • Prompt 66.6%
  • Delayed 81.3%
  • Very delayed 88.5% (p<.01)

The mean number of moderate or severe exacerbations for each TT group was 1.5 (±1.7), 2.1 (±1.8), and 2.9 (±2.2) for the prompt, delayed, and very delayed, respectively (P<.01).

The PRIMUS investigators also report an increase in the proportion of patients who experienced an exacerbation during the study period across the TT groups: an 8.4% increase in the prompt group; a 12.6% increase among patients in the delayed TT group; and a 17.2% increase in the very delayed group.

“Delays in starting TT may introduce avoidable risks of future exacerbations including hospitalizations,” concluded the investigators. “These results support a more proactive approach to the management of COPD following moderate exacerbation events, particularly initiation of TT.”

Reference: Evans KA, Pollack M, Tkacz J, et al. Promptly initiating triple therapy following second moderate exacerbation among patients with COPD in the United States: analysis of the PRIMUS study. Chest. 2022;162:SupplA1901-1902.

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