Tipping the Balance Combination Treatment in COPD How do we pive ow patients the optimal choke ? Reed Lee ee eae Depetnen of tena Vrs weINITIAL pharmacological treatment {© 200 Ga tive ir Cree Obamas Lung sassTRISTAN 2003 2007 SUMMIT 2016 Primary endpoint (P.E,)- ICS has no statistically significant effect on FEV, deciine (; p=0,16; A = +9 ml} *PE. Significant difference of SEC vs. components and placebo regarding trough FEV, *SFC combination significantly reducing moderate to severe exacerbations compare to components, but not overall rate of exacerbations. *TRISTAN gives impression that ICS and ICS/LABA may have role in high risk of moderate and severe exacebations in COPD. *SFC significantly reduce exacerbations (consistent to TRISTAN), but is not more effective regarding all cause mortality (P.E.; p=0.052). *Salmeterol is associated with a significant 17% reduction in mortality {p-0.0043), fluticasone provides no reduction (p~0.9918). “All cause mortality was unaffected by combination therapy vs. PBO (P.E.; p=0.137) vs. FF (0.284) vs. VIL (p=0.655)PTT Study Executive Summary INSPIRE 2008 *Mortality was lower in the SFC arm but no differences between SFC and Tiotropium on exacerbation rates over 2 years *DPi vs DPI ee a) SFC better in trough FEV1 dan dyspnea index Cazzolaet * No differences trough FEV1 al 2007OPTIMO 2014 INSTEAD 2014 “This observational study suggests that withdrawal of ICS can be safe provided for moderate COPD patients with a low risk of exacerbation and are left on maintenance treatment with long-acting bronchodilators. This finding can stimulate a controlled clinical trial on this important issue in respiratory medicine. ‘This controlled clinical trials gives evidence (up to 6 months; non-inferior design) to withdrawal ICS in moderate COPD patients with low risk of exacerbations.Dual bronchodilation with LAMA/LABA is non-inferior to triple (ICS containing) ‘combination regarding exacerbations. This result is independent on different subgroup parameter like: GOLD stages, smoking status, age, prior ICS usage, etc. The parameters where ICS use might be beneficial could: frequent exacerbations and blood eosinophil counts 2 300 cells/iL. +In patients with severe/very severe COPD (GOLD D} and frequent exacerbations: Triple therapy (LAMA/LABA/ICS = Ume/Vilan/Flu) improves lung function, quality of life and rate of moderate/severe exacerbations more than LABA/ICS (Vilan/Flu) dual therapy indicating also the power of a LAMA in COPD. DPI Ellipta vs OPI Ellipta+n patients with severe to very severe COPD and frequent exacerbations: “Triple therapy (Gly/Form/Bclo) improves significantly both pre-dose FEV, and 2-hour post-dose FEV, vs. Form/Bclo. DPI vs DPI *For TRILOGY: As the treatment groups are comparable regarding LABA/ICS ‘combination at entry, this study underlines also the power of an anticholinergic agent in COPO. For TRINITY : Triple therapy is better from Tio in term of FEV1 and exacerbation “Triple therapy (Gly/Form/Bclo) had slight less moderate to severe ‘exacerbations vs. LAMA/LABA (Ind/Giy). DPI vs DPI + Triple therapy (Ume/Vil/FC) had significant less moderate to severe ‘exacerbations vs. Vil/FC vs Ume/Vil. FC containing regiment acquired more Pneumonia vs Ume/Vil. DPI vs DPISPARK 2813) Giycopyronism/indacatera! SHINE 2013 ‘Tiotropium - Decramer 2614 Umedidiniun/vilanterol'? unsurpassed in the ——— Len pobecioes LABAMICS FDC INSPIRE 2008 : moderate to severe es exacerbations!” ‘Other LAMA SPARK IEF Glycopyrronium' GLISTEN 2015 POET 2012 INVIGORATE 2013 2. vcraee Metal ance gs Ma 0142427486 2. ea gt Saree of Poca accents Gauatudiem 3. Wika, Uke Lan Pong Mg 202-198 208 4 Wadehe, A et An Rese Ct Cre Med 1008:177418.28.S Wogehmne” © eal M Erg J Wed 20:3,2661088-2108,& Cecrmer, ML cal Lrcet Ree Med 20382528 ‘327. lon,OMG. era Reso Med. 2016, 0.3016 rs 2.20 7 ee ua ey Ieee a nto t Ty‘GOLD: LAMA+LABA is considered if highly symptomatic | Group C Group D Bes hing Lal LAMA or tala LAMA LAMASLABA* or ICS+LABA** os sat Q [Group A Group B aw A Bronchodilator LAMA or LABA Der! ct iniag || ieeeistcia| i ai, eco (cpl | ee CAT <10 io eee yiatiam Ce) Internist, Respirologist and intonsivistWHICH LAMA/LABA FDC ? + ene aha a) Pa Teenie int‘SPARK: Tiotropium is COMPARABLE to Dual bronchodilators (QVA149 = Indicaterol+Glycopirinium) combinationin reducing moderate to severe exacerbations Woe Ia ranyrenemOrraN Detention eater stag TSN Coen abel ‘0th the diflrence between the combination [QVAI43} ans tetvopum in maserate ot severe and hoes eae recto 98% Bae} ‘echo Lanett Mee 2013.1 198 208,exacerbation Time to first COPD exacerbation Umecidiniam/vlanters 625/25 ua vs, Totroplen Mandi Maler 18 se a 1s pom 10-26% i 22 (95% 05-26% pon, be s terest ofvmectainkam @ J aetaral FOC cs ee Drcromer Sty S=209) newer vty 2215) havard rato (Umecieium/ulantero| vs Tetum) 6 Decramer Me Lance Aes Mes. 2016:2472-86Tiotropium+Olodaterol (T+O) FDC phase III clinical trial programme: TOviTO® Ceva Wicaksono Pitoyo, MD ee See ern toe TyFigure 4. Trough FEV, response over 52 weeks: combined analysis a Se nossimioin —o— smi © RORBSmIaN —— T2s(m0Lw —— o8tmi02 ee 4Ore peoa eta.tay 20037 245) Onps.o87 omms% emes.037) eee oesRisk of escalation to triple therapy’, COPD exacerbation” and pneumonia requiring hospitalization with T/O versus LABA/ICS are re wasancs och oaremoz esemasess) 24028297 orepanoan sanciar.say 2490237. 249) onps.csy ozemem omexes) Jennifer K. Quint et at Poster in ATS 2020 be eae) einer ncaaThree main types of handheld inhalers Ga *,? Gi Ceva Wicaksono Pitoyo, MD Te ee en ene ryThe inspiratory effort required to produce sufficient flow rate varies between different inhalers!* ‘An SMil can be used at lower flow rates than DPIs, as its aerosol generations is independent of the airfiow rate’ ‘ @ turbonaier @ tite Genaair Disks oreesnaler © Respimat 5 4 Inspatory fort (a) a0 Flow rate achieved (L/min) ivan a DP ty pow as Sh faa eeu Internist, Respirologis Ree eeSoft Mist Inhaler provides higher lung deposition than pMDIs and a OPI‘? With Respimat ®, the medication can reach the large and small airways of the patients’ lungs! ShoaPrehad Se A Dever 2 na a ee eames . ystam ea Ta) ist, Respirologist and Intensivi ARI JICCIM 2020Comparisons of pMDIs, DPls and SN oo Ea. Compact © ° ° Multi-dos ° Some ° ° ° ° NA Lae) ° dination required ° ° effort inspiratory flow ° Some ° Jed by humidity ° ° Low oropharyngeal deposition ° High lung deposition ° Requires priming before fst ° ° ARI JICCIM 2020‘Treatment can impact disease progression -> Improvement of lung function, 1 physical activities and quality of life help keep COPO patients engaged in daily activities GOLD 2020 recommends LAMA as fundamental intial treatment for COPD: 2 choline tone has important olen COPD treatment conser sever factors when initiating IS treatment 3 Tiotropium consistent in reducing exacerbation, everanon- inferior if ‘compared with dual bronchodilators FDC Fixed LABA/LAMA with tiotropium inside (Tiotropium/Olodaterot FDC 4 ‘5'Sug), significant improves lung. function, reduces breathlessness, improves physical activity that impacts patient's quality of life Ce ea CAD Internist, Respirologist and Intensivist SPEAKER Nee)