Download - lecture (new COPD meds)

NEWLY AVAILABLE COPD

MEDICATIONSRyan Lally, Yury Viknevich

2

Overview• Background on Chronic Obstructive Pulmonary Disorder

(COPD)• Long Acting Muscarinic Antagonists (LAMA)

• Drug Monographs• Clinical Evidence• Cost• Recommendation

• Long Acting Muscarinic Antagonists / Long Acting Beta 2 Agonists (LAMA/LABA) combinations• Drug Monographs• Clinical Review/evidence• Cost• Recommendation

• Summary• References• Questions/Comments

3

Chronic Obstructive Pulmonary Disorder (COPD)

• Symptoms / Presentation:• Dyspnea, chronic cough, and chronic sputum production• Onset in mid-life• Progressive • History of tobacco smoking or exposure to other types of

smoke

• Diagnosis• Spirometry reading of FEV1/FVC < 0.7 confirms presence

of airflow limitation and thus COPD

• COPD costs healthcare systems 50 billion dollars per year in the United States

4

Classification of COPD1

Class Severity FEV1GOLD 1 Mild Fev1 ≥ 80 %

predicted

GOLD 2 Moderate 50 % ≤ FEV1 < 80 % predicted

GOLD 3 Severe 30 % ≤ FEV1 < 50 % predicted

GOLD 4 Very severe FEV1 < 30 % predicted

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Classification of COPD (Continued)1

Patient

Characteristic

Spirometric Classification

Exacerbations per year

mMRC

CAT

A Low Risk, Less Symptoms

GOLD 1-2 ≤ 1 0-1 <10

B Low Risk, More Symptoms

GOLD 1-2 ≤ 1 ≥ 2 ≥ 10

C High Risk, Less Symptoms

GOLD 3-4 ≥ 2 0-1 < 10

D High Risk, More Symptoms

GOLD 3-4 ≥ 2 ≥ 2 ≥ 10

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Treatment options1

Patient

First Choice Second Choice

A SAMA prn or SABA prn

LAMA or LABA or SABA + SAMA

B LAMA or LABA (+ rescue)

LAMA and LABA

C ICS + LABA or LAMA (+ rescue)

LAMA and LABA

D ICS + LABA or LAMA (+ rescue)

ICS and LAMA or ICS + LABA and LAMA or ICS+LABA and PDE-4 (inh) or LAMA and LABA or LAMA and PDE-4 (inh)**Non-pharm: smoking cessation, physical activity, flu and

pneumococal vaccination**

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Long Acting Muscarinic Antagonists• Old• Spiriva HandiHaler, Spiriva Respimat

(Tiotropium)

• New• Seebri Neohaler (Glycopyrrolate)

• Tudorza Pressair (Aclidinium Bromide)

• Incruse Ellipta (Umeclidium)

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Mechanism of Action

• LAMA

• Inhibits M3 receptors (responsible for bronchial contraction and mucous secretion) on smooth muscle of airways, causing bronchodilation

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Spiriva HandiHaler / Spiriva Respimat(Tiotropium)

• Dose• Handihaler – 18 mcg (1 capsule) inhaled daily• Respimat – 5 mcg (2 inhalations) daily

• Side Effects• Dry Mouth• Headache• Pharyngitis• Upper Respiratory Infection• Paradoxical Bronchospasm

• Precautions• CrCl <60 mL/min• Acute bronchospasm• Narrow angle glaucoma

• Contraindicatons• Severe hypersensitivity to milk proteins

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Spiriva Handihaler, Spiriva Respimat (Tiotropium)

• Pregnancy/Lactation• Category C• Risk Cannot be ruled out

• Pharmacokinetics• Tmax: 5-7 minutes• Oxidation followed by glutathione conjugation (25% CYP2D6

and CYP3A4)• Half Life: 5-6 days (powder); 25 hours (Spray)

• Drug-Drug Interactions• Oxymorphone (Paralytic Ileus)• Bupropion / Donepezil (Seizure threshold)• Anticholinergics (Side effects)

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http://www.mims.com/resources/drugs/Thailand/pic/Spiriva%20Handihaler%20inhalation%20powd%20cap%2018%20mcg87bcdb54-86c0-4416-a4da-9fab001e7c2f.GIFhttp://www.mims.com/resources/drugs/malaysia/pic/Spiriva%20Respimat%20inhalation%20soln%202.5%20mcg_puff61e48988-0aa4-4fa7-a4ab-9faa0009e53f.GIF

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Seebri Neohaler(Glycopyrrolate)

• Dose• 15.6 mcg (1 capsule) inhalation twice daily

• Side Effects• Nasopharyngitis• Upper Respiratory Infection• Paradoxical Bronchospasm• Angioedema

• Precautions• Prostatic Hyperplasia• Narrow angle glaucoma• Bronchospasm• Concurrent anticholinergic medications

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Seebri Neohaler(Glycopyrrolate)

• Pregnancy/Lactation• Category C• Infant risk Cannot be ruled out

• Pharmacokinetics• Tmax: 5 minutes• Oxidation and Hydrolysis in Liver• Half Life: 33-53 hours

• Drug – Drug Interactions• Potassium (GI lesions)• Oxymorphone (Paralytic Ileus)• Bupropion / Donepezil (Seizure threshold)• Anticholinergics (Side effects)

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http://pharmhint.com/images.rxlist.com/images/rxlist/seebri-neohaler5.gif

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Efficacy and Safety of Twice-Daily Glycopyrrolate Versus Placebo in Patients with COPD: The GEM2

Study2 Edward Kerwin, Thomas M. Siler, Phillip

Korenblat, et al.COPD Foundation9 December 2015

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Methods• 12-week multicenter, randomized, double-blind, parallel-

group, placebo controlled study of 432 patients • Wash out period of 1-7 days• Run-in period of 2 weeks• 12 week randomization• 30 day safety follow-up

• Primary objective: demonstrate the superiority of glycopyrrolate 15.6 mcg bid compared with placebo for FEV1 AUC0-12 h at 12 weeks

• Exclusion: history of asthma and COPD exacerbation needing ABX, PO/IV corticosteroids, and/or hospitalization within 6 weeks before/during screening

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Results• Seebri Neohaler showed statistically significant

improvement in FEV1 and St. George Respiratory Questionnaire (SGRQ) at 12 weeks vs placebo

• Seebri Neohaler showed statistically significant decrease in rescue haler usage vs placebo• No statistical decrease in Total Dyspnea Index

(TDI) between Seebri Neohaler vs placebo• No difference in serious adverse events between

Seebri Neohaler and placebo• Most common were COPD exacerbation, atrial

fibrilation, QTC elongation

• Increased mild/moderate adverse events with Seebri Neohaler

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Tudorza Pressair(Aclidinium Bromide)

• Dose• 400 mcg (1 puff/inhalation) twice daily

• Side Effects• Nasopharyngitis/ Headache/ Cough• Upper Respiratory Infection• Paradoxical Bronchospasm

• Precautions• Urinary Retention• Narrow angle glaucoma• Bronchospasm


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Tudorza Pressair(Aclidinium Bromide)

• Pregnancy/Lactation• Category C• Infant risk Cannot be ruled out

• Pharmacokinetics• Tmax: 10 minutes• Hydralysis via esterases• Half Life: 5-8 hours

• Drug-Drug Interactions• Bupropion/Donepezil (Seizure threshold)• Anticholinergics (side effects)

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http://www.iodine.com/label-content/0be80491-cb6c-488b-964c-18777d7f5ab9-bdf308c5c3f0d25448c0092120a6baf0.jpg

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Efficacy and Safety of Aclidinium Bromide compared with Placebo and Tiotropium in Patients with Moderate-to-

Severe Chronic Obstructive Pulmonary Disease: Results from a 6 week, Randomized, Controlled Phase IIIb Study3

Jutta Beir, Anne-Marie Kirste, et al.COPD: Journal of Chronic Obstructive Pulmonary

DiseaseJuly/02/2013

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Methods• 6 week randomized, double-blind, double-dummy, placebo and

active comparator-controlled, multicenter phase IIIb study• Inclusion criteria• Aged ≥ 40 years• Clinical diagnosis of stable moderate – severe COPD (GOLD B and

D)• Current or former smoker (≥ 10 pack years)

• Exclusion• Aged < 40 years• History or current diagnosis of asthma, or other clinically relevant

respiratory illness• Any respiratory tract infection or COPD exacerbation within 6

weeks of screening (3 months if resulted in hospitalization)• Contraindicated for use of medication

• 85 patients in placebo only group; 171 patients in Aclidinium 400 mcg BID group; 158 patients in tiotropium 18 mcg QD group

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Primary Outcome – FEV1Aclidinium 400 mcg BID vs Placebo, mL (95% CI)

Tiotropium 18 mcg QD vs Placebo, mL (95% CI)

Aclidinium vs. Tiotropium, mL (95% CI)

Day 1 156 (111, 201)

117 (71, 162)

39 (2, 77)

End of Trial (week 6)

150 (94, 205)

140 (83, 196)

10 (-36, 56)

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Results

• Tudorza Pressair vs Placebo

• There was a significant difference in FEV1 increase and COPD symptom improvement

• Tudorza Pressair vs Spiriva Handihaler• No significant difference in FEV1 increase

and COPD symptom improvement• No difference in adverse drug reactions or

COPD exacerbation

• Inhaler preference

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Incruse Ellipta(Umeclidium)

• Dose• 62.5 mcg (1 inhalation) Daily

• Side Effects• Stuffy/Runny Nose/Cough/Sore throat• Headache• Upper Respiratory Infection• Paradoxical Bronchospasm• Angle-closure glaucoma

• Precautions• Urinary retention• Acute bronchospasm• Narrow angle glaucoma


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Incruse Ellipta(Umeclidium)

• Pregnancy/Lactation• Category C• Risk Cannot be ruled out

• Pharmacokinetics• Tmax: 5-15 minutes• Oxidation followed by conjugation (substrate of

CYP2D6)• Half Life: 11 hours

• Drug-Drug Interactions• Oxymorphone (Paralytic Ileus)• Bupropion / Donepezil (Seizure threshold)• Anticholinergics (Side effects)

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http://us.gsk.com/media/423342/incruse_frontopen.jpg

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A randomized, blinded study to evaluate the efficacy and safety of Umeclidinium 62.5 mcg compared with

Tiotropium 18 mcg in patients with COPD4

Gregory Feldman, François Maltais, et al.

International Journal of COPDApril/7/2016

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Methods• 12 week, multicenter, randomized, blinded, double dummy, parallel-

group study

• Inclusion• ≥ 40 years old with diagnosis of COPD• Current or former smoker (10+ pack year history)• Patient B or D

• Exclusion• Pregnancy• Asthma/other significant respiratory disorder/condition effecting

respiratory function• Lung volume reduction surgery• Hospitalization for COPD/pneumonia within 12 weeks prior to visit

1

• 509 patients in experimental group; 508 patients in control group

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Primary Outcome – Trough FEV1 Value

Day 2 28 56 84 85

Drug Umec Tio Umec Tio Umec Tio Umec Tio Umec Tio

n 469 471 453 454 425 432 402 420 392 416

Mean Change from baseline (mL) [SE]

103 [±8]

91 [±8]

144 [±10]

102 [±10]

136 [±11]

89 [±11]

142 [±11]

86 [±11]

154 [±11]

95 [±11]

Difference vs Tio (mL)[95% CI]

13 [-9,35]

N/A 42 [14,69]

N/A 46 [17,76]

N/A 56 [26,85]

N/A 59 [29,88]

N/A

P -Value 0.254 0.003 0.002 <0.001

<0.001

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Safety Outcomes

Safety Measure Umeclidinium 62.5 mcg (n=509)

Tiotropium 18 mcg (n=508)

Any on-treatment adverse events, n (%) 165 (32) 153 (30)Headache*, n (%) 30 (6) 32 (6)Nasopharyngitis*, n (%) 27 (5) 25 (5)Any on-treatment non-fatal serious adverse events, n (%)

17 (3) 14 (3)

COPD exacerbation, n (%) 58 (11) 48 (9)

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Incruse Ellipta vs Spiriva Handihaler

• Statistically significant increase in trough FEV1• No significant difference in quality of life endpoints• No significant difference in rescue inhaler use

• ~60% of patients preferred the Incruse Ellipta inhaler over Spiriva Handihaler (~20% preferred Spiriva Handihaler, ~20% no preference)

• Comparable safety outcomes

>• 95% of patients found the Incruse Ellipta easy or very easy to use (77-79% for Spiriva Handihaler)

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CostProduct Cost PictureSpiriva HandiHaler (tiotropium)

$409

Spiriva Respimat (tiotropium)

$409

Incruse Ellipta (umiclidinium)

$302

Seebri Neohaler (glycopyrrolate)

$357

Tudorza Pressair (aclidinium)

$301

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Recommendation for LAMA Therapy

• Incruse Ellipta (umiclidinium)

• Cheaper then Spiriva

• Preferred inhaler by patients based on ease of use and convenience

• Statistically significant improvement of FEV1 over Spiriva according to primary literature

• Similar safety profile to Spiriva according to primary literature

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New LAMA/LABA Combination Medications

■Umeclidinium Bromide/Vilanterol Trifenatate -- (Anoro Ellipta)

■Glycopyrrolate/Indacaterol -- (Utibron Neohaler)

■Tiotropium Bromide/Olodaterol -- (Stiolto Respimat)

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Mechanism of Action• LAMA• Inhibits M3 receptors (responsible for

bronchial contraction and mucous secretion) on smooth muscle of airways, causing bronchodilation

• LABA • Stimulates Beta 2 receptors in the lungs

causing relaxation of bronchial smooth muscle due to increased activity of Adenyl Cyclase resulting in increased intracellular cAMP

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Anoro (Ellipta Umeclidinium Bromide/Vilanterol Trifenatate)

■Dose– 62.5 mcg / 25 mcg (1 inhalation) daily■Side Effects– Pharyngitis– Chest Pain– Spasm– Lower Respiratory Infection■Precautions– Arrhythmias– Urinary Retention– Bronchospasm■Contraindicatons– Severe hypersensitivity to milk proteins

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Anoro Ellipta

■Pharmacokinetics– Umeclidium■ TMAX = 5-15 minutes■ Extensive metabolism by liver (CYP2D6)■ Half Life: 11 hours– Vilanterol■ Tmax: 5-15 minutes■ Extensive metabolism by liver (CYP3A4)■ Half Life: 11 hours

■Drug – Drug Interactions– QTC elongating drugs– CYP3A4 inhibitors

39http://us.gsk.com/media/154065/anoro_frontdevice_closed_mr20final.jpg

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Utibron Neohaler (Glycopyrrolate/Indacaterol)

•Dose• 15.6 mcg/27.5 mcg (1 capsule) inhaled twice daily

•Side Effects• Nasopharyngitis/Pneumonia• Hypertension• Back Pain• Diarrhea, GERD• Headache

•Precautions• Arrhythmias• Uncontrolled hypertension• Urinary retention/CrCl < 30 mL/min

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Utibron Neohaler■Pregnancy/Lactation– Category C■Pharmacokinetics– Glycopyrrolate:■ Tmax: 5 minutes■ Metabolized via multiple CYP enzymes■ Half Life: 33-53 hours– Indacterol:■ Tmax: 15 minutes■ Metabolized by CYP3A4 and UGT1A1■ Half Life: 40-56 hours

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http://www.referencepreparation.com/uploadfile/article/uploadfile/201602/20160216040102549.jpg

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Stiolto Respimat(Tiotropium Bromide/Olodaterol)

• Dose• 5 mcg / 5 mcg (2 inhalation) daily

• Side Effects• Nasopharyngitis• Back Pain• Angle-closure glaucoma (worsening)• Pneumonia• Urinary Retention

• Precautions• Angle-closure glaucoma• Urinary Retention• Bronchospasm• CrCl <60 mL/min (increased

anticholinergic)

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Stiolto Respimat

■Contraindicatons– Severe hypersensitivity to milk proteins

■Pharmacokinetics– Tiotropium: ■ Tmax: 5-7 minutes■ Metablized CYP2D6, 3A4■ Half life – 25 hours– Olodaterol:■ Tmax: 10-20 minutes■ Metabolized by CYP2C9, 2C8, UGT2B7, 1A1, 1A7, 1A9■ Half life 45 hours

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http://vertassets.blob.core.windows.net/image/f26b9059/f26b9059-17f1-4b89-9cfd-bc3de796b31c/ingelheim.jpg

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Black Box Warning – LABA class• “Use of long-acting beta 2-adrenergic

agonists (LABAs) increases the risk of asthma-related death.”

• None of these medications have been approved for use in asthma

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Efficacy and safety of LABA/LAMA fixed-dose combinations approved in the US for

the management of COPD5

Donald Banerji, Donald A. Mahler, and Nicola A. Hanania

Taylor & Francis Group30 May 2016

48

Methods• FLIGHT1/2 were replicate, 12 week, multicenter, randomized, double-blind,

parallel-group, placebo-controlled, and active-controlled studies of 2038 patients with moderate to severe COPD• Compared indacterol (IND)/glycopyrrolate (GLY)27.5/15.6 mcg bid with it

mono-components and placebo • DB2113373 was a 12- or 24- week, randomized, double-blind, placebo-

controlled, and/or active controlled trials of 1532 patients with moderate to very severe COPD• Compared umeclidinium (UMEC)/vilanterol (VI) 62.5/25 mcg qd with it

mono-components and placebo• TOnado 1/2 52-week, multicenter, randomized, active-controlled studies of

5162 patients with moderate to very severe COPD • Compared tiotropium (Tio)/olodaterol (Olo) 5/5 mcg qd and Tio/Olo 2.5/5

mcg qd vs mono-components in patients

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DemographicsFLIGHT 1/2 STUDY

DB2113373 STUDY

TOnado 1/2 STUDY

Age (mean) 63 yo 62-65 yo ≥ 40 yoSmokers 52% 43-62% 37%Moderate COPD 61% 41-52% About 50%Severe COPD 39% 38-51% 38%Very severe COPD 0-13% 12%FEV1 51% predicted 46-51% predictedExacerbation (at least one)

31% About 50%

Using ICS, at baseline

62-65 yo

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Safety – Flight 1/2Medication Total AE, n (%) Serious

AE, n (%)DC due to AE, n (%)

Deaths, n (%)

Major adverse CV events , n (%)

indacterol /glycopyrrolate 27.5/15.6 mcg bid

221 (44) 16 (3.2) 15 (3) 0 221 (44)

indacterol 27.5 mcg bid

195 (38) 18 (3.5) 10 (2) 3 (<1) 195 (38)

glycopyrrolate 15.6 mcg bid

214 (42) 20 (3.9) 8 (1.6) 3 (<1) 214 (42)

Placebo 219 (43) 21 (4.1) 21 (4.1) 1 (<1) 219 (43)

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Results Flight 1/2• indacterol /glycopyrrolate 27.5/15.6 mcg bid

significantly improved FEV1 AUC0-12 h at week 12 vs mono-components [103 mL (indacterol 24.8 mcg bid) and 88 mL (glycopyrrolate 15.6 mcg bid), respectively; all p<0.001]

• indacterol /glycopyrrolate 27.5/15.6 mcg bid significantly improved breathlessness at week 12• Improvement exceeded the minimal clinically important difference (MCID) of 1.64 according

to transition dyspnea index (TDI) unit vs placebo [p<0.001]• indacterol /glycopyrrolate mcg bid provided a statistically significant and clinically meaningful

improvement in health-related quality of life vs indacterol 24.8 mcg bid and glycopyrrolate 15.6 mcg bid (1.7 [p=0.019] and 1.5 [p=0.033]unit improvement according to St. George's respiratory questionnaire (SGRQ), respectively)

• indacterol /glycopyrrolate mcg bid significantly reduced rescue medication use over 12 weeks vs indacterol 24.8 mcg bid and glycopyrrolate 15.6 mcg bid by 0.33 and 0.5 puffs/day [p<0.05], respectively

52

Results

• indacterol /glycopyrrolate 27.5/15.6 mcg bid significantly improved FEV1 AUC0-12 h at week 12 vs mono-components [103 mL (indacterol 24.8 mcg bid) and 88 mL (glycopyrrolate 15.6 mcg bid), respectively; all p<0.001]

• indacterol /glycopyrrolate 27.5/15.6 mcg bid significantly improved breathlessness at week 12• Improvement exceeded the minimal clinically important

difference (MCID) of 1.64 according to transition dyspnea index (TDI) unit vs placebo [p<0.001]

• indacterol /glycopyrrolate mcg bid provided a statistically significant and clinically meaningful improvement in health-related quality of life vs indacterol 24.8 mcg bid and glycopyrrolate 15.6 mcg bid (1.7 [p=0.019] and 1.5 [p=0.033]unit improvement according to St. George's respiratory questionnaire (SGRQ), respectively)


53

Results


• indacterol /glycopyrrolate 27.5/15.6 mcg bid significantly improved breathlessness at week 12• Improvement exceeded the minimal clinically important difference (MCID) of 1.64 according to transition dyspnea index (TDI) unit vs

placebo [p<0.001]



54

Results


• indacterol /glycopyrrolate 27.5/15.6 mcg bid significantly improved breathlessness at week 12• Improvement exceeded the minimal clinically important difference (MCID) of 1.64 according to transition dyspnea

index (TDI) unit vs placebo [p<0.001]



55

Safety - DB2113373Medication Total AE, n

(%)Serious AE, n (%)

DC due to AE, n (%)

Deaths, n (%)


Umeclidinium/vilanterol 62.5/25 mcg qd

212 (51) 21 (5.1) 23 (5.6) 3 (<1) NR

Umeclidinium 62.5 mcg qd

216 (52) 27 (6.5) 34 (8.1) 3 (<1) NR

Vilanterol 25 mcg

204 (48) 24 (5.7) 24 (5.7) 3 (<1) NR

Placebo 130 (46) 9 (3.2) 9 (3.2) 0 NR

56

Results - DB2113373• Umeclidinium/vilanterol 62.5/25 mcg qd significantly

improved trough FEV1 = 52 and 95 mL at week 24 compared with mono-components (p=0.004 and p<0.001), respectively

• Umeclidinium/vilanterol 62.5/25 mcg qd improved TDI total score at 24 weeks compared with mono-components (0.03 and 0.4 units, respectively

• Umeclidinium/vilanterol 62.5/25 mcg qd improved SGRQ total score compared with mono-components at 24 weeks (0.82 and 0.32 units, respectively)

• Umeclidinium/vilanterol 62.5/25 mcg qd reduced rescue medication use over 24 weeks compared with Umeclidinium 62.5 mcg qd (0.6 puffs/day [p≤0.001]); however, increased use with vilanterol 25 mcg qd (0.1 puffs/day [p<0.05]

57

Result

• Umeclidinium/vilanterol 62.5/25 mcg qd significantly improved trough FEV1 = 52 and 95 mL at week 24 compared with mono-components (p=0.004 and p<0.001), respectively




58

Result





59

Result




• Umeclidinium/vilanterol 62.5/25 mcg qd reduced rescue medication use over 24 weeks compared with Umeclidinium 62.5 mcg qd (0.6 puffs/day [p≤0.001]); however, increased with vilanterol 25 mcg qd (0.1 puffs/day [p<0.05]

60

Safety - TOnado 1/2Medication Total AE, n

(%)Serious AE, n (%)

DC due to AE, n (%)

Deaths, n (%)


tiotropium/olodaterol 5/5 mcg qd

761 (74) 169 (16) 76 (7.4) 18 (1.7) NR

olodaterol 5 mcg qd

795 (77) 181 (17) 103 (9.9) 14 (1.3) NR

tiotropium 5 mcg qd

757 (73) 172 (17) 93 (9) 17 (1.6) NR

61

Results - TOnado 1/2

• tiotropium/olodaterol 5/5 mcg qd significantly improved both primary end points at 24 weeks compared with mono-components (FEV1= 85 and 60 mL for olodaterol 5 mcg qd and tiotropium 5 mcg qd, respectively [all p<0.001]

• tiotropium/olodaterol 5/5 mcg qd significantly improved TDI score at week 24 compared with mono-components (0.42 units [p<0.005] and 0.36 units [p<0.05] vs olodaterol 5 mcg qd and tiotropium 5 mcg qd, respectively

• tiotropium/olodaterol 5/5 mcg qd significantly improved SGRQ total score compared with olodaterol 5 mcg qd and tiotropium 5 mcg qd (1.7 units [p<0.01] and 1.2 [p<0.05], respectively)

• tiotropium/olodaterol 5/5 mcg qd reduced the weekly mean daily (24 h) rescue medication use vs the mono-components throughout the 52 week treatment, but no values or statistical analysis has been reported

62

Results

• tiotropium/olodaterol 5/5 mcg qd significantly improved both primary end points and 24 weeks compared with mono-components (FEV1= 85 and 60 mL for olodaterol 5 mcg qd and tiotropium 5 mcg qd, respectively [all p<0.001]




63

Results



• tiotropium/olodaterol 5/5 mcg qd significantly improved SGRQ total score compared with olodaterol 5 mcg qd and tiotropium 5 mcg qd (1.7 units [p<0.01] and 1.2 units [p<0.05], respectively)


64

Results





65

CostDrug Cost

Anaro Ellipta (Umeclidinium/vilanterol)*60 units

$378.82

Ultibron Neohaler (Indacaterol/glycopyrrolate)*60 units

$357.37

Stiolto Respimat (Tiotropium/olodaterol) * 4 gm

$378.82

66

Recommendations• By using different receptor types at

submaximal doses, combination agents may incr therapeutic benefits while minimizing dose-dependent AE.

• Improved pulmonary function, dyspnea, and health-related quality of life, and reduced exacerbations (in some cases)

• Ultibron Neohaler has a better efficacy, safety, and cost analysis compared to the other combination products

67

Summary• Incruse Ellipta has shown similar

efficacy and safety to Spiriva Handihaler for less cost and increased favorability/convenience

• Ultibron Neohaler has a better efficacy, safety, and cost analysis compared to the other combination products

68

References1) Global Initiative for Chronic Obstructive Lung Disease (GOLD). Pocket Guide to COPD Diagnosis, Management, and Prevention. Updated 2007 available at www.goldcopd.com

2) Edward Kerwin, Thomas M. Siler, Phillip Korenblat, et al. Efficacy and Safety of Twice-Daily Glycopyrrolate Versus Placebo in Patients with COPD: The GEM2 Study. COPD foundation. 9 December 2015; (3) 2; 549-559

3) Beier J, Kirsten A, et al. Efficacy and Safety of Aclidinium Bromide Compared to Placebo and Tiotropium in Patients with Moderate-Severe Chronic Obstructive Pulmonary Disease: Results from a 6-Week, Randomized, Controlled Phase liib Study. COPD: Journal of Chronic Obstructive Pulmonary Dusease. 02 Jul 2013. Available from pubmed.

4) Feldman G, Maltais F, et al. A randomized, blinded study to evaluate the efficacy and safety of umeclidinium 62.5 mcg compared with tiotropium 18 mcg in patients with COPD. International Journal of COPD. 2016. Available from pubmed

5) Donald Banerji, Donald A. Mahler, Nicola A. Hanania. Efficacy and safety of LABA/LAMA fixed-dose combinations approved in the US for the management of COPD. Taylor and Francis Group. 2016 May 30

6) All drug information from Micromedex

69

Case 1 - DM

■ DM is a 49 year old male with a 33 year ppd smoking history. The patient was diagnosed with COPD 4 years ago, and his current medications include Tudorza Pressair and ProAir HFA.

■ He presents to the clinic today for a refill on his ProAir, and he explains that he is using his Tudorza Pressair every morning and that he “never forgets”.

■ What more do you want to know?■ What do you think is the best course of action?

70

Case 2 - CB

■ CB is a 61 year old male patient who presents to the the clinic for a follow up with his PCP. CB explains that he went to the emergency room last week because he was unable to breath and had a productive cough. He was diagnosed with a COPD exacerbation and discharged the next day on prednisone therapy.

■ CB’s current COPD regimen includes Spiriva Handihaler, and ProAir HFA. He used to use a Combivent Respimat inhaler but “could never figure the darn thing out”

■ CB explains that he travels frequently for work as a sports analyst, and explains that he often forgets to pack his Spiriva capsules. He would like to know if there is a different inhaler you could prescribe him that he would still only need to use once per day, and has the medication built in.

71

What is the Best Option for CB

1) Incruse Ellipta2) SeeBri Neohaler3) Tudorza Pressair4) Spiriva Respimat

72

Case 3 - CD

■ CD is a 47 yo Caucasian established patient at the clinic. Patient is a 10 pack smoker whom had their last Influenza vaccination last year. Patient is classified as a D category according to the GOLD guidelines. Current medications: ASA 81 mg Qdaily, amlodipine besylate 10 mg PO Qdaily, HCTZ 25 mg PO Qdaily, lisinopril 40 mg PO Qdaily, albuterol 90 mcg 2 puffs q4-6hr prn, and spiriva 2 PO inhalations Qdaily. Patient is compliant with their medication; however, they are using the albuterol frequently,

– Is there any other information that you would like to have?– What non-pharmacological options would you recommend? – According to the new information presented, what medication(s)

would you recommend?

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Questions?

Download - lecture (new COPD meds)

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