A Cochrane review [Abstract] 1 included 6 studies comparing tiotropium in addition to inhaled corticosteroid (ICS) and long-acting beta2-agonist (LABA) combination therapy to tiotropium alone, with a total of 1 902 subjects with chronic obstructive pulmonary disease (COPD). The duration, type of combination treatment and definition of outcomes varied. There was no significant statistical difference in mortality, episodes of exacerbation or pneumonia, or adverse events (table T1).Reduction in all-cause hospitalisations with the use of combined therapy (tiotropium + LABA/ICS) was found (number needed to treat 19.7, 95% CI 10.75 to 123.41). The mean health-related quality of life and lung function were significantly different when combination therapy was added to tiotropium, although the size of the average benefits of additional combination therapy were small, St George's Respiratory Questionnaire (MD -3.46; 95% CI -5.05 to 1.87: 4 trials, n=1446) and forced expiratory volume in one second (MD 0.06 l; 95% CI 0.04 to 0.08).
| Outcome | Relative effect (95% CI) | Assumed riskTiotropium | Corresponding risk (95% CI) Tiotropium + LABA/ICS | Number of participants (studies) |
|---|---|---|---|---|
| Mortality (all-cause) | OR 1.80(0.55 to 5.91) | 8 / 1000 | 15 / 1000(5 to 47) | 961(2) |
| Hospital admission (all causes) | OR 0.61(0.40 to 0.92) | 156 / 1000 | 101 / 1000(69 to 145) | 961(2) |
| Exacerbation - at 12-month follow-up | OR 0.89(0.56 to 1.41) | 628 / 1000 | 601 / 1000(486 to 704) | 301(1) |
| Serious adverse events (non-fatal) | OR 0.86(0.57 to 1.30) | 60 / 1000 | 52 / 1000(35 to 76) | 1758(4) |
Another Cochrane review [Abstract] 2 included one trial comparing tiotropium in addition to ICS and LABA combination therapy to tiotropium plus LABA, with a total of 293 subjects. The trial suffered from high and uneven withdrawal rates between the treatment arms. The difference between the number withdrawing due to lack of efficacy was significantly lower in the tiotropium + LABA and ICS group (25/145) than in the tiotropium + LABA group (54/148; OR 0.36; 95% CI 0.21 to 0.63). There was no statistically significant difference between the groups in health-related quality of life (MD -1.02; 95% CI -5.10 to 3.06; St George's Respiratory Questionnaire), in the number of patients who had one or more exacerbations (OR 0.81; 95% CI 0.51 to 1.30), in the number of hospitalisations due to exacerbation (OR 0.63; 95% CI 0.34 to 1.17) nor in the rate of adverse events.
Comment: The quality of evidence is downgraded imprecise results (limited study size for each comparison).
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