SPIOLTO® Respimat® (tiotropium + olodaterol) for COPD
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SPIOLTO® Respimat®
SPIOLTO® Respimat® (tiotropium + olodaterol) is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).1
Mechanism of Action
SPIOLTO® Respimat® is a fixed dose combination inhalation solution containing the long-acting muscarinic receptor antagonist (LAMA) tiotropium, and the long-acting beta agonist (LABA) olodaterol, which is delivered via the Respimat® soft mist inhaler device.1 The two active ingredients provide additive bronchodilation due to their different modes of action. Since muscarinic receptors appear to be more prominent in the central airways while beta2-adrenoceptors have a higher expression level in the peripheral airways, a combination of tiotropium and olodaterol should provide optimal bronchodilatation in all regions of the lungs.
Tiotropium — tiotropium bromide is a long-acting, specific antagonist at muscarinic receptors.1
Olodaterol — olodaterol has a high affinity and high selectivity to the human beta2-adrenoceptor.1
References
- SPIOLTO® Respimat® Summary of Product Characteristics.
- Efficacy
- Safety Profile
Efficacy
TONADO: Two replicate, randomised, double-blind, active-controlled, phase III trials comparing SPIOLTO® Respimat® with SPIRIVA® Respimat® (tiotropium) and olodaterol Respimat® over 52 weeks in 5,162 adult patients with moderate to very severe COPD. The primary endpoints were lung function measured as FEV1 AUC0–3h and trough FEV1 response in each individual trial, and SGRQ total score (combined analysis of both trials) at 24 weeks.1
OTEMTO: Two replicate, randomised, double-blind, placebo-controlled, phase IIIb trials comparing SPIOLTO® Respimat® with SPIRIVA® Respimat® (tiotropium) and placebo Respimat® over 12 weeks in 1,621 adult patients with moderate to severe COPD. The primary endpoints were SGRQ total score, and lung function measured as FEV1 AUC0–3h and trough FEV1 response in each individual trial.2
If a patient with COPD is not responding to a LAMA monotherapy — such as SPIRIVA® Respimat® (tiotropium) — switching to a dual LAMA + LABA therapy — like SPIOLTO® Respimat® — could offer symptom control in important priority areas.1,2
 |
 | SPIOLTO® Respimat® significantly improved lung function vs SPIRIVA® Respimat®1–4 The TONADO studies showed SPIOLTO® Respimat® significantly improved mean FEV1 AUC0–3h (difference of 110mL; p<0.0001) and trough FEV1 (difference of 60mL; p<0.0001) vs SPIRIVA® Respimat®.1,3 The OTEMTO studies showed SPIOLTO® Respimat® significantly improved mean FEV1 AUC0–3h (difference of 108mL; p<0.0001) and trough FEV1 (difference of 37mL; p<0.01) vs SPIRIVA® Respimat®.2,4 | |||||||
 | SPIOLTO® Respimat® significantly improved breathlessness vs SPIRIVA® Respimat®1,2 TONADO showed a mean TDI focal score of 1.98 units for SPIOLTO® Respimat®, with a significant improvement compared to SPIRIVA® Respimat® (mean difference 0.36, p<0.05).1 The OTEMTO studies showed a mean improvement in TDI focal score of 0.59 units (p<0.01) with SPIOLTO® Respimat® vs SPIRIVA® Respimat®.2 | |||||||
 | SPIOLTO® Respimat®'s health-related QoL vs SPIRIVA® Respimat®1,5 TONADO trial showed the proportion of patients with a clinically meaningful decrease in SGRQ total score was greater for SPIOLTO® Respimat® (57.5%) vs SPIRIVA® Respimat® (48.7%) (p=0.0001).1 OTEMTO showed the proportion of patients with a clinically meaningful decrease in SGRQ total score was greater for SPIOLTO® Respimat® (52%) vs SPIRIVA® Respimat® (41%) (p=0.0022).5 | |||||||
 | Maintaining inhaler continuity GOLD 2023 guidelines recommend that if a patient is taking an inhaled therapy and able to use their device correctly, any new therapy is best prescribed in the same device if possible. For patients currently prescribed SPIRIVA® Respimat® who are advised to switch to a LAMA + LABA, moving to SPIOLTO® Respimat® enables them to keep the inhaler they are familiar with.6 | |||||||
SPIOLTO® Respimat® (tiotropium + olodaterol) delivers statistically significant improvements in lung function (measured by FEV1 AUC0-3h and trough FEV1 response) vs SPIRIVA® Respimat® (tiotropium)1,2
Mean change in FEV1 AUC0–3h (measured at 24 weeks)2
SPIOLTO® Respimat® significantly improved mean trough FEV1 (difference of 60mL; p<0.0001) vs SPIRIVA® Respimat®.1
AUC0–3h, area under the curve 0–3 hours; FEV1, forced expiratory volume in one second.
Trial data
information
TONADO: Two replicate, randomised, double-blind,
active-controlled, phase III trials comparing SPIOLTO®
Respimat® with SPIRIVA® Respimat® (tiotropium) and
olodaterol Respimat® over 52 weeks in 5,162 adult
patients with moderate to very severe COPD. The primary
endpoints were lung function measured as FEV1
AUC0–3h and trough FEV1 response
in each individual trial, and SGRQ total score (combined
analysis of both trials) at 24 weeks.
- References: 1. Buhl R, et al. Eur Respir J. 2015;45:969‒979 and supplementary materials; 2. BI Data on File TOL 14-05(b).
SPIOLTO® Respimat® (tiotropium + olodaterol) delivers statistically significant improvements in lung function (measured by FEV1 AUC0-3h and trough FEV1 response) vs SPIRIVA® Respimat® (tiotropium)1,2
Mean change in FEV1 AUC0-3h (measured at 12 weeks)
SPIOLTO® Respimat® significantly improved mean trough FEV1 (difference of 37mL; p<0.01) vs SPIRIVA® Respimat®.
AUC0–3h, area under the curve 0–3 hours; FEV1, forced expiratory volume in one second.
Trial data
information
OTEMTO: Two replicate, randomised, double-blind,
placebo-controlled, phase IIIb trials comparing SPIOLTO®
Respimat® with SPIRIVA® Respimat® (tiotropium) and
placebo Respimat® over 12 weeks in 1,621 adult patients
with moderate to severe COPD. The primary endpoints were
SGRQ total score, and lung function measured as
FEV1 AUC0–3h and trough
FEV1 response in each individual trial.
- References: 1. Singh D, et al. European Respiratory Society International Congress, Amsterdam, The Netherlands, 26–30 September 2015; PA2958; 2. Singh D, et al. Respir Med. 2015;109:1312-1319 and supplementary materials.
SPIOLTO® Respimat® (tiotropium + olodaterol) delivers statistically significant improvements in breathlessness vs SPIRIVA® Respimat® (tiotropium)1,2
Change in breathlessness in the OTEMTO and TONADO trials, measured by TDI focal score*1,2
OTEMTO (measured at 12 weeks)1
More patients treated with SPIOLTO® Respimat® had a clinically meaningful improvement in TDI focal score (MCID, defined as a value of at least 1 unit) compared to SPIRIVA® Respimat® (54% vs. 41%, p<0.001).3
TONADO (measured at 24 weeks)2
More patients treated with SPIOLTO® Respimat® had a clinically meaningful improvement in TDI focal score (MCID, defined as a value of at least 1 unit) compared to SPIRIVA® Respimat® (54.9% vs. 50.6%, p=0.0546).3,4
*
Breathlessness, as measured by Transitional Dyspnoea Index (TDI) focal score, was a secondary endpoint in the OTEMTO (measured at 12 weeks) and TONADO (measured at 24 weeks) trials. An increase in TDI score indicates an improvement in breathlessness. A 1-unit change in the TDI focal score is considered clinically important.1,2
MCID, minimum clinically important difference; TDI, transition dyspnoea index.
Trial data
information
TONADO: Two replicate, randomised, double-blind,
active-controlled, phase III trials comparing SPIOLTO®
Respimat® with SPIRIVA® Respimat® (tiotropium) and
olodaterol Respimat® over 52 weeks in 5,162 adult
patients with moderate to very severe COPD. The primary
endpoints were lung function measured as FEV1
AUC0–3h and trough FEV1 response
in each individual trial, and SGRQ total score (combined
analysis of both trials) at 24 weeks.
OTEMTO: Two replicate, randomised, double-blind, placebo-controlled, phase IIIb trials comparing SPIOLTO® Respimat® with SPIRIVA® Respimat® (tiotropium) and placebo Respimat® over 12 weeks in 1,621 adult patients with moderate to severe COPD. The primary endpoints were SGRQ total score, and lung function measured as FEV1 AUC0–3h and trough FEV1 response in each individual trial.
- References: 1. Singh D, et al. Respir Med. 2015;109:1312‒1319; 2. Buhl R, et al. Eur Resp J. 2015;45:969‒979 and supplementary materials; 3. Ferguson GT, et al. NPJ Prim Care Respir Med. 2017;27:7; 4. SPIOLTO® Respimat® Summary of Product Characteristics.
SPIOLTO® Respimat® (tiotropium + olodaterol) delivers statistically significant improvements in health-related quality of life (as indicated by a reduction in SGRQ total score) vs placebo and SPIRIVA® Respimat® (tiotropium)1–3
OTEMTO: Patients with a ≥4.0 unit improvement in SGRQ score vs baseline (measured at 12 weeks)1
SPIOLTO® Respimat® improved SGRQ total score by 4.7 units vs placebo (p<0.0001), and by 2.1 units vs SPIRIVA® Respimat® (p<0.01).2
TONADO: Patients with a ≥4.0 unit improvement in SGRQ score vs baseline (measured at 24 weeks)1,3
SPIOLTO® Respimat® improved SGRQ total score by 1.23 units vs SPIRIVA® Respimat® (p=0.025).1,3
SGRQ, St George’s Respiratory Questionnaire.
Trial data
information
TONADO: Two replicate, randomised, double-blind,
active-controlled, phase III trials comparing SPIOLTO®
Respimat® with SPIRIVA® Respimat® (tiotropium) and
olodaterol Respimat® over 52 weeks in 5,162 adult
patients with moderate to very severe COPD. The primary
endpoints were lung function measured as FEV1
AUC0–3h and trough FEV1 response
in each individual trial, and SGRQ total score (combined
analysis of both trials) at 24 weeks.
OTEMTO: Two replicate, randomised, double-blind, placebo-controlled, phase IIIb trials comparing SPIOLTO® Respimat® with SPIRIVA® Respimat® (tiotropium) and placebo Respimat® over 12 weeks in 1,621 adult patients with moderate to severe COPD. The primary endpoints were SGRQ total score, and lung function measured as FEV1 AUC0–3h and trough FEV1 response in each individual trial.
- References: 1. SPIOLTO® Respimat® Summary of Product Characteristics; 2. Singh D, et al. Respir Med. 2015;109:1312‒1319; 3. Buhl R, et al. Eur Respir J. 2015;45:969‒979.
SPIRIVA® Respimat® (tiotropium) is indicated as a maintenance bronchodilator treatment to relieve symptoms of adult patients with chronic obstructive pulmonary disease (COPD).
SPIOLTO® Respimat® (tiotropium + olodaterol) is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).
Abbreviations
- AUC0–3h, area under the curve 0–3 hours; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in one second; FVC, forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Lung Disease; LABA, long-acting beta-agonist; LAMA, long-acting muscarinic antagonist; MCID, minimal clinically important difference; QoL, Quality of Life; SGRQ, St George’s Respiratory Questionnaire; TDI, Transitional Dyspnoea Index.
References
- Buhl R, et al. Eur Respir J. 2015;45:969‒979 and supplementary material.
- Singh D, et al. Respir Med. 2015;109(10):1312–9 and supplementary material.
- BI Data on File TOL 14-05(b).
- Singh D, et al. European Respiratory Society International Congress, Amsterdam, The Netherlands, 26–30 September 2015; PA2958.
- SPIOLTO® Respimat® Summary of Product Characteristics.
- Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease: 2023 Report. Available at: https://goldcopd.org/wp-content/uploads/2023/03/GOLD-2023-ver-1.3-17Feb2023_WMV.pdf. (Accessed November 2023).
Safety Information
Once-daily SPIOLTO® Respimat® is generally well-tolerated1
TONADO: two replicate, randomised, double-blind, parallel-group, active-controlled, phase III trials comparing SPIOLTO® Respimat® with SPIRIVA® Respimat® (tiotropium) and olodaterol Respimat® over 52 weeks in 5,162 adult patients with moderate to very severe COPD. The primary endpoints were lung function measured as FEV1 AUC0–3h and trough FEV1 response in each individual trial, and SGRQ total score (combined analysis of both trials) at 24 weeks.1
Tiotropium + oldaterol (5/5μg) delivered via Respimat® inhaler was generally well-tolerated with an adverse event profile similar to the profiles of the monotherapies.1–4
Most adverse events were mild or moderate with no new safety risks seen beyond the known effects of the ingredients.1–4
The proportion of patients who discontinued tiotropium + oldaterol (5/5μg) delivered via Respimat® inhaler due to an adverse event was comparable to tiotropium (5μg) or olodaterol (5μg) monotherapy delivered via Respimat® inhaler.1
Common and uncommon adverse events reported for SPIRIVA® Respimat® and SPIOLTO® Respimat® in COPD2,3
| Common (≥1/100 to <1/10) | Uncommon (≥1/1000 to <1/100) | |
|---|---|---|
| SPIRIVA® Respimat® | Dry mouth | Dizziness, headache, cough, pharyngitis, dysphonia, constipation, oropharyngeal candidiasis, rash, pruritus, urinary retention, dysuria |
| SPIOLTO® Respimat® | - | Dizziness, headache, tachycardia, cough, dysphonia, dry mouth |
Serious undesirable effects consistent with anticholinergic effects: glaucoma, constipation, intestinal obstruction including ileus paralytic and urinary retention.
See Summary of Product Characteristics for a complete list of adverse events.
SPIRIVA® Respimat® (tiotropium) is indicated as a maintenance bronchodilator treatment to relieve symptoms of adult patients with chronic obstructive pulmonary disease (COPD).
SPIOLTO® Respimat® (tiotropium + olodaterol) is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).
Abbreviations
COPD, chronic obstructive pulmonary disease.
References
- Buhl R, et al. Eur Resp J. 2015;45:969–79.
- SPIOLTO® Respimat® Summary of Product Characteristics.
- SPIRIVA® Respimat® Summary of Product Characteristics.
- STRIVERDI® Respimat® (olodaterol) Summary of Product Characteristics.
Advantages of the Respimat® Soft Mist Inhaler
Not all patients with COPD have the ability to generate enough inspiratory flow to inhale their medication correctly.1
Various inhaler characteristics will influence a patients' inhaler preference, including ease of use, convenience, and environmental impact. The ideal inhaler will also deliver the drug dose to the lungs, regardless of inspiratory flow.2
The Respimat® Soft Mist Inhaler provides a consistent dose to the lungs, independent of inspiratory ability*.3,4
 | Ability to inhale | Respimat®: lower inspiratory effort expected compared to tested DPIs*†3,4Respimat® requires a lower inspiratory effort to achieve optimal flow rate compared with tested DPIs. | |||||||
 | Drug lung deposition | Respimat®: greater drug lung deposition vs tested DPIs†3,4 | |||||||
 | Inhaler technique | Respimat®: "slow and steady" inhalation5Respimat® requires "slow and steady" inhalation, compared with the "quick and deep" inhalation required by DPIs. | |||||||
Footnotes / abbreviations
*
Lower inspiratory effort expected to achieve optimal flow rate from an in vitro study, where air flow resistance was compared between different devices at specified flow rates.4 Recommended inspiratory flow rates are specific to each device.
†
These studies simulated the upper airways (in vitro) and the lower airways (in silico) of patients with moderate and very severe COPD. For very severe COPD breathing patterns, the modelled dose delivered to lungs was 67% of the nominal dose with Respimat® (tiotropium) vs 51% with Breezhaler® (glycopyrronium), 42% with Genuair® (aclidinium), 55% with Ellipta® (vilanterol), and 41% with Ellipta® (fluticasone). Vilanterol and fluticasone were measured separately when delivered from a nominal dose, delivered as combination of vilanterol and fluticasone from the Ellipta® device.4 Vilanterol and fluticasone are not licensed as monotherapy agents through the Ellipta® device.
Breezhaler® is a registered trademark of Novartis, Genuair® is a registered trademark of AstraZeneca, Ellipta® is a registered trademark of GlaxoSmithKline.
COPD, chronic obstructive pulmonary disease; DPI, dry powder inhaler; SMI, soft mist inhaler.
References
- Mahler DA. Ann Am Thorac Soc. 2017;14:1103–7.
- Dekhuijzen PNR, et al. Patient Prefer Adherence. 2016;10:1561–72.
- Ciciliani AM, et al. Ann Am Thorac Soc COPD. 2021;18(1):91−100.
- Ciciliani AM, et al. Int J Chron Obstruct Pulmon Dis. 2017;12:1565–77.
- Murphy A. How to help patients optimise their inhaler technique. Pharm J. 2016;297(7891).
PC-GB-108821
November 2023