What Predicts A Positive Response to Adding Tiotropium to ICS-LABA for Asthma?

Patients with asthma responding to tiotropium were younger and had a higher positive bronchodilator response rate than those who did not respond.

Tiotropium as add-on therapy to inhaled corticosteroids-long-acting beta 2 agonists (ICS-LABA) for patients with uncontrolled asthma may be more effective in those with positive bronchodilator response (BDR) or asthma-chronic obstructive pulmonary disease overlap (ACO), according to study findings published in the World Allergy Organization Journal.

Study investigators assessed the clinical characteristics, lung function, symptom scores, and exacerbation rates of patients using and responding to tiotropium as well as patients who did not use and/or respond to tiotropium using the Cohort for Reality and Evolution of Adult Asthma in Korea. The researchers also predictors of adult asthma.

Participants, who came from 39 tertiary referral centers, were individuals with asthma who were at least 18 years old, took ICS-LABA, and had at least 2 consecutive lung function tests at 3-month intervals.

A response to tiotropium was defined as (1) having an increase in forced expiratory volume in 1 second (FEV1) of at least 10% or 100 mL; (2) an increase in asthma control test (ACT) score of at least 3; or (3) no exacerbation 3 months after initiating tiotropium.

Of the 2169 patients enrolled in the study, 413 used tiotropium and 1756 did not. Those who used tiotropium were significantly older (59.2 ± 13.5 vs 49.6 ± 16.0 years, P <.001) and more frequently were male (62.7% vs 43.2%, P < .001) vs those who did not use tiotropium. Those who used tiotropium also had significantly lower mean (SD) FEV1 (63.2 [19.6]% vs 81.9 [18.7]%; P <.001) and FEV1/forced vital capacity (59.6 [13.3]% vs 73.0 [11.3]%; P <.001), as well as a higher annual exacerbation rate (1.0 [2.5] vs 0.7 [2.0]; P =.023).

The mean (SD) change in FEV1 at 3 months from before the start of tiotropium or during registration for those using tiotropium was 46.3 (381.7) mL vs 89.8 (420.4) mL in those not using tiotropium, with no significant difference.

In a comparison of patients in whom FEV1 increased by at least 10% or 100 mL after 3 months of tiotropium use (n=133) vs those with no FEV1 increase (n=82), change in FEV1 was 360.7 (311.1) mL in those who responded to tiotropium use and -147.5 (278.6) mL in those who did not respond to tiotropium use (P <.001).

Tiotropium add-on therapy might be considered for symptomatic uncontrolled asthma despite ICS-LABA use, especially for cases with positive BDR or ACO.

Those who responded to tiotropium were younger (56.7 [13.8] years vs 60.7 [12.5] years; P =.029) and had a higher rate of positive BDR compared with those who did not respond (38.1% vs 6.5%; P <.001).

Regarding predictors of treatment response to tiotropium, a positive BDR had a significant association with an increase in FEV1 of at least 10% or 100 mL (odds ratio [OR], 6.8; 95% CI, 1.6-47.4; P =.021). Physician-diagnosed ACO and having an initial ACT score of less than 20 were significant after adjustment (OR, 12.6; 95% CI, 1.8-161.5; P =.024; OR, 24.1; 95% CI, 5.45-158.8; P <.001).

Among those using tiotropium, those who had an increased FEV1 had a longer exacerbation-free duration compared with those with no FEV1 increase (P =.014), with a hazard ratio of 0.5 for time to first asthma exacerbation (95% CI, 0.3-0.9; P =.016).

Study limitations include the lack of analysis of the effects of other asthma medications; non-inclusion of those who currently smoked; lack of control of the dosage of tiotropium that was used; and lack of assessment of adherence to tiotropium or other medications.

“Tiotropium add-on therapy might be considered for symptomatic uncontrolled asthma despite ICS-LABA use, especially for cases with positive BDR or ACO,” concluded the researchers. “Patients with poor ACT scores are more likely to improve their ACT after administration of tiotropium. Furthermore, an increase in FEV1 in tiotropium users could lead to a delay in asthma exacerbation.


Shim J-S, Jin J, Kim S-H, et al. Clinical predictors of treatment response to tiotropium add-on therapy in adult asthmatic patients: from multicenter real-world cohort data in Korea. World Allergy Organ J. Published online November 20, 2022. doi:10.1016/j.waojou.2022.100720