Table 1.
Long-term studies of ICSs as monotherapy for patients with COPD
| Study | Inclusion criteria/patients, n | Treatment | Primary efficacy outcome | Secondary efficacy outcomes | Safety |
|---|---|---|---|---|---|
| Wise et al7 | Participants from LHS (smoking-cessation trial) who were current smokers or had quit within 2 years; 40–69 years of age; FEV1:FVC <0.7; FEV1 30%–90% predicted; N=1,116 (ICS n=559, Pbo n=557); baseline postbronchodilator FEV1% predicted, ICS 69%, Pbo 67% | Triamcinolone acetonide MDI 100 µg/inhalation; Pbo identical vehicle MDI; six inhalations BID; total daily ICS dose 1,200 µg | Rate of decline in FEV1 postbronchodilator NS; mean decline, ICS 44.2 mL/year, Pbo 47.0 mL/year (95% CI for difference −11.0 to 5.4) | Respiratory symptoms (ATS questionnaire) at 36 months, NS for cough, phlegm, wheezing; dyspnea, P=0.02 (no dyspnea, ICS 68.2%, Pbo 61.5%); new or worsening respiratory symptoms per 100 PY, ICS 21.1, Pbo 28.2 (P=0.005); respiratory hospitalizations per 100 PY, ICS 0.99, Pbo 2.1 (P=0.07); respiratory ED visits per 100 PY, ICS 1.3, Pbo 1.0 (P=0.36); respiratory outpatient visits, ICS 1.2, Pbo 2.1 (P=0.03); airway reactivity, P=0.02 at 9 and 33 months in favor of ICS; HRQoL (SF36), mental health subscale score (change from baseline to 36 months), ICS −2.3; Pbo −0.1 (P=0.03) | All-cause mortality, ICS n=15; Pbo n=19 (P=0.49); thrush, ICS n=5; Pbo n=2; moderate-severe throat irritation, ICS 2.3%, Pbo 1.1% (P=0.02); moderate-severe bruising, ICS 0.8%, Pbo 0.4%; cataracts, ICS n=122, Pbo n=114; BMD (% change from baseline to 36 months), lumbar spine – ICS -0.35, Pbo 0.98 (P=0.007); femoral neck – ICS −2, Pbo −0.22 (P<0.001) |
| Pauwels et al8 | Current smokers ≥5 cigarettes/day or smoking history ≥10 years or ≥5 pack-years; FEV1:slow vital capacity <0.7; FEV1 50%–100% predicted, N=1,277 (ICS n=634, Pbo n=643); baseline prebronchodilator FEV1, ICS 77%, Pbo 77% | Budesonide DPI 400 µg; Pbo DPI; BID for 3 years | Change over time in FEV1: over the first 6 months, ICS improved FEV1 at rate of 17 mL/year vs Pbo decline of 81 mL/year (P<0.001) From 9 months to end of treatment, NS difference: ICS −57 mL/year, Pbo −69 mL/year >3 years in study completers: ICS −140 mL, Pbo −180 mL (P=0.05) | ICS had more beneficial effect in patients who smoked less; age, sex, baseline FEV1, presence or absence of serum IgE antibodies, and reversibility of airflow limitation had no effect on outcome | Skin bruising, ICS n=63 (10%), Pbo n=27 (4%) (P<0.001); oral candidiasis, ICS n=31, Pbo n=10 (P<0.001); BMD (measured in 194 patients), femoral trochanter decline – ICS 0.04%, Pbo 0.38% (P=0.02); cataracts, bone fractures, diabetes similarly distributed between groups |
| Vestbo et al9 | 30–70 years of age; FEV1:FVC <0.7; no self-reported asthma; N=290 (ICS n=145, Pbo n=145); baseline postbronchodilator FEV1, ICS 86%, Pbo 87% | Budesonide DPI; Pbo DPI; 800 µg in morning and 400 µg in evening for 6 months followed by 400 µg BID for 30 months | Rate of FEV1 decline: ICS 46.0 mL/year, Pbo 49.6 mL/year (P=0.70), with no effect of sex, smoking status, or baseline FEV1 | Symptoms decreased in both treatment groups with no differences; exacerbations, ICS 155, Pbo 161; reversibility to β2-agonist from visit one to end of study, ICS 8.1% to 6.7%, Pbo 7.2% to 8.2% | Pneumonia: ICS n=16, Pbo n=24 |
| Burge et al10 | Current or former smokers; 40–75 years of age; nonasthmatic COPD; FEV1 postbronchodilator ≥0.8 L, but <85% predicted normal; FEV1:FVC <0.7; N=751 (ICS n=376, Pbo n=375); baseline postbronchodilator FEV1% predicted, ICS 50%, Pbo 50% | Fluticasone propionate MDI with spacer 500 µg; Pbo MDI with spacer; BID for 3 years | Decline in FEV1 postbronchodilator: ICS 50 mL/year, Pbo 59 mL/year (P=0.16), with no effect of smoking status, age, sex, or FEV1 response to oral corticosteroids At 3 and 36 months, predicted mean FEV1 76 and 100 mL higher with ICS vs Pbo, respectively (P<0.001) |
Exacerbation rate (median), ICS 0.99/year, Pbo 1.32/year (P=0.026); SGRQ similar at baseline and 6 months, thereafter increased over time and worsened at a faster rate with Pbo (3.2 units/year) vs ICS (2.0 units/year) (P=0.004) | Hoarseness/dysphonia, ICS n=35, Pbo n=16; throat irritation, ICS n=43, Pbo n=27; oral candidiasis, ICS n=41, Pbo n=24; bruising, ICS n=27, Pbo n=15; fractures, ICS n=9, Pbo n=17; cataracts, ICS n=5, Pbo n=7 |
Abbreviations: ATS, American Thoracic Society; BID, bis in die (twice daily); BMD, bone-mineral density; DPI, dry-powder inhaler; ED, emergency department; ERS, European Respiratory Society; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; HRQoL, health-related quality of life; ICS, inhaled corticosteroid; LHS, lung health study; MDI, metered-dose inhaler; NS, not significant; Pbo, placebo; PY, person-years; SGRQ, St George’s Respiratory Questionnaire.