Real-world evidence in COPD:
STIOLTO RESPIMAT vs LABA/ICS1
STIOLTO RESPIMAT showed a 54% lower risk of negative outcomes vs LABA/ICS in a retrospective analysis1
26% lower risk of pneumonia1
24% lower risk of exacerbation1
78% lower risk of escalation to triple therapy1
Quint JK et al, Advanced Therapeutics; 2021.
Successfully balanced propensity score matching was used to minimize bias between STIOLTO RESPIMAT and LABA/ICS groups at baseline.1
Results from real-world studies are not intended for comparisons with clinical trials. Real-world studies were observational trials. Differences in study designs, patient populations, outcomes, definitions, and methods of collecting data make it difficult to make comparisons with clinical trials or with each other. Real-world data should be viewed as complementary information.
LABA, long-acting beta2-agonist; ICS, inhaled corticosteroid; AHR, adjusted hazard ratio; CI, confidence interval.
Study Design & Limitations
Expand allA non-interventional analysis was completed comparing patients initiating STIOLTO RESPIMAT with patients on any LABA/ICS fixed-dose combination (FDC) in a US-based real-world setting.1
This study used administrative claims data from January 2013 through March 2019 in the HealthCore Integrated Research Database to examine the risk of COPD exacerbation.
After meeting all study criteria, there were 2684 patients on STIOLTO RESPIMAT and 59,301 patients on LABA/ICS remaining in the study cohort.
Key inclusion criteria were ≥1 prescription for STIOLTO RESPIMAT or LABA/ICS FDC between January 2013 through March 2019 (1st fill date=index date); ≥1 diagnosis code indicating COPD in any position at any time prior to the index date; ≥1 year of continuous health plan eligibility prior to the index date; and aged ≥40 years at the index date.
Patients were excluded if they were aged <40 years at the index date; diagnosis of asthma in the year prior to the index date, lung cancer, interstitial lung disease, or lung transplant; or pre-index date use of STIOLTO RESPIMAT, LABA/ICS, or LABA/LAMA/ICS in free or fixed form.
After reweighting for stratified propensity scores, the total pseudo-population consisted of 2600 patients on STIOLTO RESPIMAT and 40,353 patients on LABA/ICS.
After reweighting, cohorts were well balanced on baseline characteristics. There was still some imbalance in prior exacerbation history, leading to severe exacerbations being adjusted for this model. Patients were followed until the earliest of the following: first occurrence of a COPD exacerbation, community-acquired pneumonia, escalation to triple therapy, switch in treatment, discontinuation of COPD treatment, the end of the study period, the end of continuous health plan eligibility, or (for the main analyses) 1 year after cohort entry.
The outcomes assessed included the risk of first COPD exacerbation as the primary outcome, with secondary outcomes including risk of hospitalization for community-acquired pneumonia, risk of escalation to triple therapy, and combined risk of these 3 outcomes.
LABA, long-acting beta2-agonist; ICS, inhaled corticosteroid; LAMA, long-acting antimuscarinic agent.
Fine stratification and reweighting by exposure propensity score was used to control for any confounding by treatment group; however, this was only possible for measured covariates, and therefore an impact of residual confounding by unmeasured confounders—such as lifestyle factors that are less critical to insurance billing—cannot be ruled out. Furthermore, the nature of the ICD diagnostic codes made it impossible to verify pneumonia as the primary driver of hospitalization. As with any observational study, prescriptions dispensed by a pharmacy but not taken by patients could lead to misclassification of exposure.
ICD, International Classification of Diseases.
STIOLTO® RESPIMAT® (tiotropium bromide and olodaterol) Inhalation Spray is a combination of tiotropium, an anticholinergic, and olodaterol, a long-acting beta2-adrenergic agonist (LABA), indicated for the long-term, once-daily maintenance treatment of patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
Important Limitations of Use
STIOLTO is NOT indicated to treat acute deterioration of COPD and is not indicated to treat asthma.
Use of a LABA, including STIOLTO RESPIMAT, without an inhaled corticosteroid (ICS) is contraindicated in patients with asthma.
STIOLTO is contraindicated in patients with hypersensitivity to tiotropium, ipratropium (atropine derivatives), olodaterol, or any component of this product.
In clinical trials and postmarketing experience with tiotropium, immediate hypersensitivity reactions, including angioedema (including swelling of the lips, tongue, or throat), itching, or rash have been reported. Hypersensitivity reactions were also reported in clinical trials with STIOLTO.
WARNINGS AND PRECAUTIONS
LABA as monotherapy (without an ICS), for asthma increases the risk of asthma-related death, and in pediatric and adolescent patients, increases the risk of asthma-related hospitalizations.
Do not initiate STIOLTO in patients with acutely deteriorating COPD, which may be a life-threatening condition, or used as rescue therapy for acute symptoms. Acute symptoms should be treated with an inhaled short-acting beta2-agonist.
STIOLTO should not be used more often or at higher doses than recommended, or with other LABAs as an overdose may result.
If immediate hypersensitivity reactions occur, such as urticaria, angioedema, rash, bronchospasm, anaphylaxis, or itching, discontinue STIOLTO at once and consider alternative treatment. Patients with a history of hypersensitivity reactions to atropine or its derivatives should be closely monitored for similar hypersensitivity reactions to STIOLTO.
If paradoxical bronchospasm occurs, discontinue STIOLTO immediately and institute alternative therapy.
STIOLTO can produce a clinically significant cardiovascular effect in some patients, as measured by increases in pulse rate, systolic or diastolic blood pressure, and/or symptoms. If such effects occur, STIOLTO may need to be discontinued.
Use caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, in patients with known or suspected prolongation of the QT interval, and in patients who are unusually responsive to sympathomimetic amines.
Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a physician immediately if signs or symptoms of acute narrow-angle glaucoma develop.
Use with caution in patients with urinary retention especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to consult a physician immediately should any of these signs or symptoms develop.
Patients with moderate to severe renal impairment (creatinine clearance of <60 mL/min) should be monitored closely for anticholinergic side effects.
Be alert to hypokalemia and hyperglycemia.
ADVERSE REACTIONS
The most common adverse reactions with STIOLTO (>3% incidence and higher than an active control) were: nasopharyngitis, 12.4% (11.7%/12.6%), cough, 3.9% (4.4%/3.0%), and back pain, 3.6% (1.8%/3.4%).
DRUG INTERACTIONS
Use caution if administering adrenergic drugs because sympathetic effects of olodaterol may be potentiated.
Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of olodaterol.
Use with caution in patients taking non–potassium-sparing diuretics, as the ECG changes and/or hypokalemia may worsen with concomitant beta-agonists.
The action of adrenergic agents on the cardiovascular system may be potentiated by monoamine oxidase inhibitors or tricyclic antidepressants or other drugs known to prolong the QTc interval. Therefore, STIOLTO should be used with extreme caution in patients being treated with these drugs. Use beta-blockers with caution as they not only block the therapeutic effects of beta-agonists, but may produce severe bronchospasm in patients with COPD.
Avoid co-administration of STIOLTO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.
STIOLTO is for oral inhalation only.
The STIOLTO cartridge is only intended for use with the STIOLTO RESPIMAT inhaler.
Inform patients not to spray STIOLTO into the eyes as this may cause blurring of vision and pupil dilation.
CL-STO-100021 6.5.2019
Please see full Prescribing Information, Patient Information, and Instructions for Use for STIOLTO RESPIMAT.
REFERENCES
-
Quint JK, Montonen J, Esposito DB, et al. Effectiveness and safety of COPD maintenance therapy with tiotropium/olodaterol versus LABA/ICS in a US claims database. Adv Ther. 2021;38(5):2249-2270.
-
STIOLTO RESPIMAT [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; November 2021.