Adherence,Persistence,and Effectiveness in Real Life. Multicenter Long-Term Study on the Use of Pirfenidone and Nintedanib in the Treatment of Idiopathic Pulmonary Fibrosis
Restricted accessResearch articleFirst published online December, 2022
Adherence,Persistence,and Effectiveness in Real Life. Multicenter Long-Term Study on the Use of Pirfenidone and Nintedanib in the Treatment of Idiopathic Pulmonary Fibrosis
In the treatment of idiopathic pulmonary fibrosis (IPF), nintedanib and pirfenidone, with their different mechanisms of action, lead to a reduction in the rate of progression of the fibrosis process measured by the reduction of functional decline, and, in particular, the decrease in forced vital capacity (FVC) and of the diffusion capacity of the lungs for carbon monoxide (DLCO). The objective of this study was to analyze real-life adherence, persistence and efficacy in the use of pirfenidone and nintedanib in the treatment of IPF.
Methods:
A non-interventional multicenter retrospective observational pharmacological study in real-life treat-ment at 1 and 2 years was conducted. Furthermore, we analyzed the levels of FVC and DLCO at 6 and 12 months, respectively, from the start of treatment.
Results:
We identified 144 patients in the period between January 2013 and April 2019. From the point of view of adherence, there is no difference between the two drugs, even though patients who used pirfenidone had increasingly higher values: 0.90 vs 0.89, in the first year, and 0.91 vs 0.84, in the second year. In the first year of treatment, the percentage of persistent patients was 67% and 76%, while in the second year, it dropped to 47% and 53% for pirfenidone and nintedanib, respectively.
Conclusion:
The stratification of the adherence values as a function of the response to treatment in terms of FVC at 12 months for both study drugs showed that patients with optimal response scored adherence of more than 90%.
SgallaGIoveneBCalvelloM, et al.Idiopathic pulmonary fibrosis: pathogenesis and management. Respir Res. 2018;19(1):32.
3.
MeyerKC. Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis. Expert Rev Respir Med. 2017;11(5):343–359.
4.
GaySEKazerooniEAToewsGB, et al.Idiopathic pulmonary fibrosis: predicting response to therapy and survival. Am J Respir Crit Care Med. 1998;157(4 Pt 1):1063–1072.
5.
NagaiSKitaichiMHamadaK, et al.Hospital-based historical cohort study of 234 histologically proven Japanese patients with IPF. Sarcoidosis, Vasc Diffuse Lung Dis. 1999;16(2):209–214.
6.
DouglasWWRyuJHSchroederDR. Idiopathic pulmonary fibrosis: Impact of oxygen and colchicine, prednisone, or no therapy on survival. Am J Res Cri Care Med. 2000;61(4 Pt 1):1172–1178.
7.
FlahertyKRToewsGBLynchJP3 rd, et al.Steroids in idiopathic pulmonary fibrosis: a prospective assessment of adverse reactions, response to therapy, and survival. Am J Med. 2001;110(4):278–282.
8.
EntzianPSchlaakMSeitzerU, et al.Antiinflammatory and antifibrotic properties of colchicine: implications for idiopathic pulmonary fibrosis. Lung. 1999;175(1):41–51.
9.
DouglasWWRyuJHSwensenSJ, et al.Colchicine versus prednisone in the treatment of idiopathic pulmonary fibrosis. A randomized prospective study. Members of the Lung Study Group. Am J Res Crit Care Med. 1998;158(1):220–225.
10.
SelmanMCarrilloGSalasJ, et al.Colchicine, D-penicillamine, and prednisone in the treatment of idiopathic pulmonary fibrosis: a controlled clinical trial. Chest. 1998;114(2):507–512.
11.
FiorucciELucantoniGPaoneG, et al.Colchicine, cyclophosphamide and prednisone in the treatment of mild-moderate idiopathic pulmonary fibrosis: comparison of three currently available therapeutic regimens. Eur Rev Med Pharmacol Sci. 2008;12(2):105–111.
12.
HauberHPBlaukovitschM. Current and future treatment options in idiopathic pulmonary fibrosis. Inflamm Allergy Drug Targets. 2010;9(3):158–172.
13.
BehrJMaierKDegenkolbB, et al.Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Adjunctive therapy to maintenance immunosuppression. Am J Res Cri Care Med. 1997;156(6):1897–1901.
14.
DemedtsMBehrJBuhlR, et al.High-dose acetylcysteine in idiopathic pulmonary fibrosis. New Eng J Med. 2005;353(21):2229–2242.
15.
TomiokaHKuwataYImanakaK, et al.A pilot study of aerosolized N-acetylcysteine for idiopathic pulmonary fibrosis. Respirology. 2005;10(4):449–455.
16.
JohnsonMAKwanSSnellNJ, et al.Randomised controlled trial comparing prednisolone alone with cyclophosphamide and low dose prednisolone in combination in cryptogenic fibrosing alveolitis. Thorax. 1989;44(4):280–288.
17.
CollardHRRyuJHDouglasWW, et al.Combined corticosteroid and cyclophosphamide therapy does not alter survival in idiopathic pulmonary fibrosis. Chest. 2004;125(6):2169–2174.
18.
RaghuGBrownKKBradfordWZ, et al.A placebo-controlled trial of interferon gamma-1b in patients with idiopathic pulmonary fibrosis. New Eng J Med. 2004;350(2):125–133.
19.
AntoniouKMNicholsonAGDimadiM, et al.Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis. Eur Res J. 2006;28(3):496–504.
20.
KingTEJrAlberaCBradfordWZ, et al.Effect of interferon gamma-1b on survival in patients with idiopathic pulmonary fibrosis (INSPIRE): a multicentre, randomised, placebo-controlled trial. Lancet. 2009;374(9685):222–228.
21.
RaghuGKingTEJrBehrJ, et al.Quality of life and dyspnoea in patients treated with bosentan for idiopathic pulmonary fibrosis (BUILD-1). Eur Res J. 2010;35(1):118–123.
22.
KingTEJrBrownKKRaghuG, et al.BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis. Am J Res Cri Care Med. 2011;184(1):92–99.
23.
RaghuGBrownKKCostabelU, et al.Treatment of idiopathic pulmonary fibrosis with etanercept: an exploratory, placebo-controlled trial. Am J Res Critic Care Med. 2008;178(9):948–955.
24.
KuboHNakayamaKYanaiM, et al.Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest. 2005;128(3):1475–1482.
25.
MoolmanJABardinPGRossouwDJ, et al.Cyclosporin as a treatment for interstitial lung disease of unknown aetiology. Thorax. 1991;46(8):592–595.
26.
HommaSSakamotoSKawabataM, et al.Cyclosporin treatment in steroid-resistant and acutely exacerbated interstitial pneumonia. Int Med. 2005;44(11):1144–1150.
27.
GrgicALausbergHHeinrichM, et al.Progression of fibrosis in usual interstitial pneumonia: serial evaluation of the native lung after single lung transplantation. Res Int Rev Thoracic Dis. 2008;76(2):139–145.
28.
GhofraniHAWiedemannRRoseF, et al.Sildenafil for treatment of lung fibrosis and pulmonary hypertension: a randomised controlled trial. Lancet. 2002;360(9337):895–900.
29.
MaddenBPAllenbyMLokeTK, et al.A potential role for sildenafil in the management of pulmonary hypertension in patients with parenchymal lung disease. Vasc Pharm. 2006;44(5):372–376.
30.
CollardHRAnstromKJSchwarzMI, et al.Sildenafil improves walk distance in idiopathic pulmonary fibrosis. Chest. 2007;131(3):897–899.
31.
NathanSDNoblePWTuderRM. Idiopathic pulmonary fibrosis and pulmonary hypertension: connecting the dots. Am J Res Critic Care Med. 2007;175(9):875–880.
32.
JacksonRMGlassbergMKRamosCF, et al.Sildenafil therapy and exercise tolerance in idiopathic pulmonary fibrosis. Lung. 2010;188(2):115–123.
33.
DanielsCELaskyJALimperAH, et al.Imatinib treatment for idiopathic pulmonary fibrosis: Randomized placebo-controlled trial results. Am J Res Critic Care Med. 2010;181(6):604–610.
34.
RosasIOGoldbergHJCollardHR, et al.A Phase II clinical trial of low-dose inhaled carbon monoxide in idiopathic pulmonary fibrosis. Chest. 2018;153(1):94–104.
35.
OldhamJMMaSFMartinezFJ, et al.TOLLIP, MUC5B, and the response to n-acetylcysteine among individuals with idiopathic pulmonary fibrosis. Am J Res Critic Care Med. 2015;192(12):1475–1482.
36.
LeyBCollardHR. Epidemiology of idiopathic pulmonary fibrosis. Cli Epidemiol. 2013;5:483–492.
37.
KingTEJrBradfordWZCastro-BernardiniS, et al.A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Eng J Med. 2014;370(22):2083–2092.
38.
VaroneFSgallaGIoveneB, et al.Nintedanib for the treatment of idiopathic pulmonary fibrosis. Exp Opin Pharmacother. 2018;19(2):167–175.
39.
MorrowTJ. Idiopathic pulmonary fibrosis: the role of the pharmacy benefit manager in providing access to effective, high-value care. Am J Man Care. 2015;21(14 Suppl):s294–s301.
40.
QuittnerALZhangJMarynchenkoM, et al.Pulmonary medication adherence and health-care use in cystic fibrosis. Chest. 2014;146(1):142–151.
41.
SantoleriFSoricePLasalaR, et al.Patient adherence and persistence with Imatinib, Nilotinib, Dasatinib in clinical practice. PloS one. 2013;8(2):e56813.
42.
CramerJARoyABurrellA, et al.Medication compliance and persistence: terminology and definitions. Value Health. 2008;11(1):44–47.
43.
HarariSCaminatiAAlberaC, et al.Efficacy of pirfenidone for idiopathic pulmonary fibrosis: an Italian real life study. Res Med. 2015;109(7):904–913.
44.
HughesGToellnerHMorrisH, et al.Real world experiences: Pirfenidone and Nintedanib are effective and well tolerated treatments for idiopathic pulmonary fibrosis. J Clin Med. 2016;5(9):78.
45.
HarariSCaminatiAPolettiV, et al.A Real-life multicenter national study on nintedanib in severe idiopathic pulmonary fibrosis. Res Int Rev Thoracic Dis. 2018;95(6):433–440.
46.
BennettDRefiniRMValentiniML, et al.Pirfenidone therapy for familial pulmonary fibrosis: a real-life study. Lung. 2019;197(2):147–153.
47.
JouneauSGamezASTracletJ, et al.A 2-year observational study in patients suffering from idiopathic pulmonary fibrosis and treated with pirfenidone: a French ancillary study of PASSPORT. Res Int Rev Thoracic Dis. 2019;98(2):1–10.
48.
KardasPLewekPMatyjaszczykM. Determinants of patient adherence: a review of systematic reviews. Front Pharmacol. 2013;4:91.
49.
ColemanCILimoneBSobierajDM, et al.Dosing frequency and medication adherence in chronic disease. J Manag Care Pharm: JMCP. 2012;18(7):527–539.
50.
ColemanCIRobertsMSSobierajDM, et al.Effect of dosing frequency on chronic cardiovascular disease medication adherence. Curr Med Res Opinion. 2012;28(5):669–680.
51.
IpatovaAYKoernerPHMillerRT, et al.Retrospective analysis of medication utilization and Clinical outcomes in patients with idiopathic pulmonary fibrosis treated with nintedanib or pirfenidone. Clin Med Insights Circ Respir Pulm Med. 2019;13:1179548419834922.
52.
MargaritopoulosGATrachalakiAWellsAU, et al.Pirfenidone improves survival in IPF: results from a real-life study. BMC Pulm Med. 2018;18(1):177.
