Presentation on theme: "New Therapeutic Options for COPD"— Presentation transcript:
1 New Therapeutic Options for COPD Indacaterol and RoflumilastPrepared by: Christine Liew (F0158)Preceptor: Lee Chuey Ee
2 What is COPD?Chronic Obstructive Pulmonary Disease (COPD) is characterized by progressive, partially reversible airflow obstruction,associated with an enhance chronic inflammatory response in the airways.It is a preventable and treatable respiratory disorder.
3 Table 1: GOLD Classification of Severity of Airflow Limitation in COPD (Based on Post-Bronchodilator FEV1)
4 Table 2: Model of Symptom/Risk Evaluation of COPD
5 Table 3: Classification of COPD Severity based on Spirometric Impairment and Symptoms
6 Treatment Goal for COPD Preventing disease progressionReduce frequency and severity of exacerbationsReduce patient’s symptomsImprove exercise toleranceImprove lung function and general healthImprove quality of life
11 Table 5: Initial Pharmacologic Management of COPD
12 Current treatments available in UMMC SABA : Fenoterol and SalbutamolSAAC: IpratropiumLAAC: TiotropiumInhaled corticosteroid (ICS): Fluticasone, budesonide, beclomethasoneCombinations of LABA and ICS: Salmeterol/ fluticasone, formeterol/budesonideSystemic corticosteroid: PrednisoloneMethylxanthines: Theophylline
13 Limitations 1. Tiotropium Restricted usage in the hospital. Only 100 patients approved to receive subsidized treatment.2. Patients still having multiple exacerbations despite on treatment. Current therapy is insufficient to adequately control COPD.
15 1. Indacaterol Class: Long-acting β2-agonist (LABA) Mechanism of Action (MOA):Stimulate intracellular adenyl cyclase which is responsible for catalyzing the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (AMP).Increased AMP levels cause relaxation of bronchial smooth muscles.
16 Clinical Review on the Efficacy of Indacaterol in Patients with COPD This review comprises of four placebo- controlled clinical studies of indacaterol treatment in patients with moderate-to- severe COPD.Details on the studies is shown in the next slide.
18 Patient inclusion criteria: Clinical diagnosis of moderate-to-severe COPDAged 40 years and aboveSmoking history of at least 20 packs/yearExclusion criteria:-Had recent chest infection or had beenhospitalised for an exacerbation or respiratoryinfection in the 6 weeks before screening- History of asthma- Patient with clinically significant condition thatmight compromised their safety eg unstableischemic heart disease, uncontrolledhypertension, uncontrolled diabetes
19 Baseline Mean duration of COPD from diagnosis of 7 years Mean smoking history of packs per yearMean age of years oldMore males (52-80%) than femalesPatients are allowed to be on ICS, provided the dose and regimen remain unchanged.Spirometry measurements at baseline showed an FEV1 of 53–56% predicted and FEV1/FVC ratio of 0.51–0.53 (both values assessed within 30 min after inhalation of salbutamol 400 μg).Concomitant cardio- or cerebro-vascular conditions were present in 20% of patients, hypertension in 50%, diabetes mellitus in 10%, and hyperlipidaemia in 35%.
21 Figure 2: Effect of Treatment on Breathlessness (assessed using transition dyspnoea index [TDI] )
22 Figure 3: Effect of Treatment on Use of as- needed Salbutamol
23 Figure 4: Effect of Treatment on COPD Exacerbation Rate
24 SummaryIndacaterol is an once-daily LABA with a rapid onset of action (within 5 minutes), a peak effect at approximately 3 hours, and a duration of bronchodilation lasting at least 24 hours.One of its attraction is its once-daily dosing as compared to the other twice-daily dosing bronchodilators. It might improve adherence.It provides a level of bronchodilation that is similar to tiotropium but greater than the twice-daily agents, formoterol and salmeterol.Indacaterol has a good safety profile.
25 Indacaterol is an effective and beneficial maintenance bronchodilator treatment for patients with moderate-to-severe COPD.Indacaterol would be a reasonable first choice for maintenance bronchodilator therapy.
27 2. Roflumilast Class: PDE-4 inhibitor Mechanism of Action (MOA): Selectively inhibit PDE-4 enzyme, thus preventing the breakdown of cAMP which plays an important role in regulating inflammatory cell activity.Consequently, result in reduced inflammation.
28 Clinical Trials Data on Roflumilast There are 4 clinical trials which will be discussed.Details on the trials are shown in the next slide.
29 Table 5: Summary of Roflumilast Phase II and Phase III Clinical Trials, AURA and HERMES
30 Table 5: Summary of Roflumilast Phase II and Phase III Clinical Trials, EOS and HELIOS
31 SummaryRoflumilast is the first selective PDE4 inhibitor approved in Europe as an add-on anti- inflammatory therapy in patients with symptomatic severe COPD with frequent exacerbations.From the clinical trial data, it is shown that roflumilast improves lung function and reduces exacerbation rates in COPD compared with placebo.When used as an add-on treatment to concomitant bronchodilator therapy, roflumilast shows significant and sustained improvement in lung funtion as compared to placebo.
32 Significant adverse effects of PDE4 inhibitors includes nausea, diarrhoe, weight loss and headache. Data should be collected to determine the long-term safety of roflumilast.In conclusion, more studies are needed to solidifies roflumilast place in COPD therapy.
33 Other important areas for further research includes thorough evaluations of the potential synergies and additive effects of:• roflumilast and ICS therapy• roflumilast versus ICS/theophylline asadd-on therapy to long-actingbronchodilators.
34 Figure 5: COPD Treatment Pathway Indicating Suggested Role of PDE4-inhibitors
36 ReferencesGlobal Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease. UK; 2011.Clinical Practice Guidelines: Management of Chronic Obstructive Pulmonary Disease. Ministry of Health Malaysia. 2nd;2009.MicromedexPaul W Jones, Neil Barnes, Claus Vogelmeier, David Lawrence, Benjamin Kramer. Efficacy of Indacaterol in the Treatment of Patients with COPD. Primary Care Respiratory Journal. UK; 2011.Marcos Ribeiro, Kenneth R Chapman. Comparative Efficacy of Indacaterol in COPD. International Journal of COPD. Canada; 2012.David Price, Alison Chisholm, Dermot Ryan, Alan Crockett, Rupert Jones. The Use of Roflumilast in COPD: a primary care perspective. Primary Care Respiratory Journal. UK; 2010.Sabina Antonela Antoniu. New Therapeutic Options in the Management of COPD – focus on roflumilast. UK; 2011.