TIOSPIR™ (Tiotropium Safety and Performance in Respimat), with over 17,000 COPD patients included, was one of the largest international COPD trials ever conducted, confirmed the comparable mortality and exacerbation efficacy profile of Spiriva® Respimat® 5mcg and Spiriva® HandiHaler® 18mug.(1)
The results showed no difference between Spiriva® Respimat® 5mcg and Spiriva® HandiHaler® 18mcg in:
- risk of death(1)
- risk of first exacerbation1
- on-treatment all-cause mortality(1)
- incidents of cardiovascular adverse events(1)
In particular, in patients with a history of cardiac arrhythmia, there was no difference in mortality between Spiriva® Respimat® 5mcg and Spiriva® HandiHaler® 18mcg.(1)
The results from the three year trial were published in the New England Journal of Medicine on 8 September 2013. TIOSPIR™ was designed to provide evidence of the relative safety and efficacy profile of Spiriva® Respimat® 5 mcg compared with Spiriva® HandiHaler® 18mcg.(1) TIOSPIR™ was specifically designed to be of an adequate size and duration, to enable analysis of all-cause mortality and risk of first COPD exacerbation in a large COPD patient population, with broad inclusion criteria, that closely reflects the real-world COPD patient population.(1)
Commenting on the results, Dr Richard Russell, Consultant Chest Physician, Wexham Park Hospital said “The results of this trial have been hugely anticipated and hopefully will draw a line under the debate on the safety and efficacy profile of Respimat®.
“The results provide clear evidence that Spiriva® Respimat® has an equally good mortality profile in COPD patients to Spiriva® HandiHaler®, including those with a history of cardiac disease.”
The TIOSPIR™ trial demonstrated comparable results for risk of first COPD exacerbation between Spiriva® Respimat® 5mcg and Spiriva® HandiHaler® 18 mcg.(1b) In particular, the median time to the first COPD exacerbation was more than two years for both Spiriva® Respimat® 5mcg (756 days) and Spiriva® HandiHaler® 18mcg (719 days).(1)
COPD exacerbations have a significant impact on patients’ lives and reducing their frequency and severity are principal goals of COPD treatment.(2) TIOSPIR™ builds upon the established efficacy profile of Spiriva® as demonstrated in several trials, including the large-scale, POET-COPD®(1) study that was specifically powered to investigate COPD exacerbations.(3)
- Spiriva® HandiHaler® 18 mcg demonstrated a 28% reduction in the relative risk of a COPD exacerbation leading to hospitalisation (2.1% ARR; HR=0.72; 95% CI, 0.61 to 0.85; p<0.001) compared with the long-acting beta2-agonist salmeterol, as observed in the POET-COPD® trial(4)
- In a separate trial Spiriva® Respimat® 5mcg demonstrated a 27% reduction in the relative risk of hospital admission due to exacerbation (1.8% ARR; HR=0.73 ; 95% CI, 0.59 –0.90; p<0.005) compared with control.(5)
Safety as measured by survival rates
The three year TIOSPIR™ trial also showed an comparable impact on survival – as measured by all-cause mortality for tiotropium (Spiriva® Respimat® 5 mcg vs. HandiHaler® 18 mcg).(1) This adds to evidence from UPLIFT®(2), a four-year trial6 in which Spiriva® HandiHaler® (18mcg) demonstrated there was a 16% reduction in the relative risk of on-treatment mortality (the incidence rate of death was 4.79 per 100 patient years in the control group compared with 4.10 per 100 patient years in the tiotropium group HR (tiotropium/control) =0.84, 95% CI =0.73, 0.97)).(7)
Dr Brian Wong, Head of UK Medical and Scientific Affairs at Boehringer Ingelheim said “We are delighted with the results of this landmark TIOSPIR™ trial, which has met its primary endpoint. The study was designed to answer a specific question and we now have robust clinical evidence that Spiriva® Respimat® has similar safety and exacerbation efficacy compared with Spiriva® HandiHaler®. We hope that these results reassure healthcare professionals that they can provide a choice of device to their COPD patients.”
- Wise RA, Cotton D, Dahl R et al. Tiotropium Respimat Inhaler and the Risk of Death in COPD: The TIOSPIR Trial. NEJM 2013; 369(10).
- National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre. Available from: http://guidance.nice.org.uk/CG101/Guidance/pdf/English. 2010.
- Vogelmeier C, Hederer B, Glaab T et al. Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD. N Engl J Med 2011; 364(12):1093-1103.
- Vogelmeier C, Hederer B, Glaab T et al. Tiotropium versus Salmeterol for the Prevention of Exacerbations of COPD. New Engl J Med: Supplemental Appendix 2011; 364(12).
- Bateman ED, Tashkin D, Siafakas N et al. A one-year trial of tiotropium Respimat plus usual therapy in COPD patients. Respir Med 2010; 104 (10):1460-1472. Respir Med 2010; 104(10):1460-1472.
- Tashkin DP, Celli B, Senn S et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008; 359(15):1543-1554.
- Boehringer Ingelheim. Spiriva 18 microgram inhalation powder, hard capsule. Summary of Product Characteristics. (The Electronic Medicines Compendium) www.medicines.org.uk/emc/medicine/10039/SPC/. Last accessed: September 2013.
- Hochrainer D, Hölz H, Kreher C et al. Comparison of the aerosol velocity and spray duration of Respimat® Soft Mist™ inhaler and pressurized metered dose inhalers. J Aerosol Med 2005; 18(3):273-282.
- Boehringer Ingelheim. Spiriva Respimat 2.5 micrograms solution for inhalation. Summary of Product Characteristics. (The Electronic Medicines Compendium) http://www.medicines.org.uk/emc/medicine/20134/SPC/. Last accessed: September 2013.
- Boehringer Ingelheim. Data on File: SPI13-02(b). 2013.