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Focus on Idiopathic Pulmonary Fibrosis: Advancing Approaches toDiagnosis, Prognosis, and Treatment
Discussion Points
Diagnosis
Prognosis
Therapy
Imminent future
2
Discussion Points (con't)
Diagnosis– Overview of current approach to IPF
– Approach to CTD
– Approach to HP
– Evolving imaging criteria
– Role of bronchoscopy
– Role of lung biopsy
– Role of MDT
– Future of biomarker‐driven diagnostics
3
IPF Diagnosis: Current Approach
4
IPF
Suspected ILD
Identifiable cause?
Chest HRCT
NO
YES
UIP
Surgical lung biopsy
Possible UIPInconsistent with UIP
Not UIP
UIPProbable UIPPossible UIP
Not IPFIPF/Not IPF
MDD
IPF
Suspected ILD
Identifiable cause?
Chest HRCT
NO
YES
UIP
Surgical lung biopsy
Inconsistent with UIP
Probable UIP
Reprinted from The Lancet Respiratory Medicine, vol. 5, Martinez FJ, Chisholm A, Collard HR, et al, The diagnosis of idiopathic pulmonary fibrosis: current and future approaches, 61-71, Copyright 2017, with permission from Elsevier.
OR per 5‐year Age
Increment
Age (Yrs)
Salisbury ML et al. Respir Med. 2016;118:88-95; Reproduced from Thorax, Brownell R, Moua T, Henry TS, et al, 72(5), 424-429, 2017, with permission from BMJ Publishing Group Ltd.
IPF Becomes Increasingly Likely As the Age of the Patient Increases
5
OR per 5‐year Age
Increment
Age (Yrs)
IPF Becomes Increasingly Likely As the Age of the Patient Increases
6Salisbury ML et al. Respir Med. 2016;118:88-95; Reproduced from Thorax, Brownell R, Moua T, Henry TS, et al, 72(5), 424-429, 2017, with permission from BMJ Publishing Group Ltd.
IPF vs CT ILD Survival in 2 Cohorts
7
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Park JH, Kim DS, Park IN, et al. 2007, Prognosis of fibrotic interstitial pneumonia: idiopathic versus collagen vascular disease-related subtypes. Am J Respir Crit Care Med. 175/7:705-711. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society; Moua T, Zamora Martinez AC, Baqir M, Vassallo R, Limper AH, Ryu JH. Predictors of diagnosis and survival in idiopathic pulmonary fibrosis and connective tissue disease-related usual interstitial pneumonia. Respiratory Research. 2014;15:154. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264556/pdf/12931_2014_Article_154.pdf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) and is available under Public License, https://creativecommons.org/licenses/by/4.0/legalcode.
A Possible Approach to CTD Evaluation
8
History• Joint pain, stiffness, or swelling• Skin thickening or tightening• Rash in sun‐exposed areas• Dryness of the eyes or mouth• Raynaud’s• Heartburn/Regurgitation• Family history of CTD
Physical Examination• Joints• Skin• Hands
Jee AS, Adelstein S, Bleasel J, et al. Role of autoantibodies in the diagnosis of connective-tissue disease ILD (CTD-ILD) and interstitial pneumonia with autoimmune features (IPAF). Journal of Clinical Medicine. 2017;6(5):E51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447942/. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) and is available under Public License, https://creativecommons.org/licenses/by/4.0/legalcode.
Taking a Detailed History Can Help Identify Hypersensitivity Pneumonitis
“Dampness” and mold exposure in the home or workplace– Water damage: flooding; leaking pipes– Standing water: hot tubs, humidifiers– Visible mold– Home ventilation systems, particularly with heat or humidification
Animal exposures– Birds– Down/Feather bedding
Ask about a “second/summer home” and hobbies
9
HRCT Criteria for Usual Interstitial Pneumonia (UIP) Pattern
UIP Pattern (All 4 Features)
Possible UIP (All 3 Features)
Inconsistent with UIP (any)
Subpleural, basal predominance
Reticular abnormality Honeycombing
with/without traction bronchiectasis
Absence of features listed as inconsistent with UIP (column 3)
Subpleural, basal predominance
Reticular abnormality Absence of features listed as
inconsistent with UIP (column 3)
Upper or mid‐lung predominance Peribronchovascular
predominance Extensive ground glass
abnormality (extent > reticular abnormality)
Profuse micronodules (bilateral, predominantly upper lobe)
Discrete cysts (multiple, bilateral, away from areas of honeycombing)
Diffuse mosaic attenuation/air‐trapping (bilateral, in 3 or more lobes)
Consolidation in bronchopulmonary segment(s)/lobe(s)
10
Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Collard HR, Egan JJ, et al; ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis. 2011, An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Respir Crit Care Med. 183(6):788-824. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
Subgroup Analysis by HRCT Diagnostic Subgroups
-108.7 -122.0
-225.7 -221.0
-300
-250
-200
-150
-100
-50
0n=425 n=298 n=213 n=125
Honeycombing on HRCT and/or confirmation of UIP pattern by
surgical lung biopsy
Features of possible UIP pattern* on HRCT and no
surgical lung biopsy
Nintedanib Placebo
Adju
sted
ann
ual r
ate
(SE)
of d
eclin
e in
FV
C (m
L/ye
ar)
Treatment-by-time-by-subgroup interaction
p=0.8139
∆117.0 mL (95% CI: 76.3,
157.8)
∆98.9 mL(95% CI: 36.4,
161.5)
*And traction bronchiectasis.
11Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Raghu G, Wells AU, Nicholson AG, et al. 2017, Effect of nintedanib in subgroups of idiopathic pulmonary fibrosis by diagnostic criteria. Am J Respir Crit Care Med. 195(1):78-85.The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
Fleischner HRCT Criteria for UIP Pattern
Typical UIP Probable UIP Indeterminate UIP Non‐IPF pattern
Distribution Basal(occasionally diffuse) Subpleural Often heterogeneous
Subpleural Basal predominance Often heterogeneous
Variable or diffuse
Upper or mid‐lung Peribronchovascular Subpleural sparing
Features Honeycomb Reticular with peripheral traction bronchiectasis or bronchiolectasis Absence of alternate features
Reticular with peripheral traction bronchiectasis or bronchiolectasis No honeycombing Absence of alternate features
Fibrosis with some inconspicuousnon‐UIP features
Any of the following: Predominant consolidation Extensive GGO Extensive mosaicism Diffuse nodules or cysts
12
Reprinted from The Lancet Respiratory Medicine, Lynch DA, Sverzellati N, Travis WD, et al, Diagnostic criteria for idiopathic pulmonary fibrosis: a Fleischner Society White Paper, doi: 10.1016/S2213-2600(17)30433-2 [Epub ahead of print], Copyright 2017, with permission from Elsevier. http://dx.doi.org/10.1016/S2213-2600(17)30433-2. Accessed December 30, 2017.
ILA Associated With Risk for Mortality
13
Reproduced with permission from JAMA. 2016. Putman RK, Hatabu H, Araki T, et al; Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Investigators; COPDGene Investigators. Association between interstitial lung abnormalities and all-cause mortality. 315(7):672-681. Copyright © 2016. American Medical Association. All rights reserved.
Rough Summary of Cryobiopsy
Study Bleeding PTX
Kropski JA et al. 0/25 (0%) 0/25 (0%)
Pajares V et al. 22/39 (56%) 3/39 (8%)
Casoni GL et al. 1/69 (1%) 19/69 (28%)
Griff S et al. None None
Hernández‐González F et al. 10/33 (30%) 4/33 (12%)
Hagmeyer L et al.17/32 (53%) 6/32 (19%)
Tomassetti S et al. NR NR
Poletti V. None 60/297 (20%)
Lentz RJ et al.4/104 (4%) 3/104 (3%)
OVERALL EXPERIENCE 54/709(8%) 95/709(13%)
14
Diagnostic Yield SafetyStudy Yield
Kropski JA et al.PLoS One. 2013;8(11):e78674
20/25 (80%)
Pajares V et al. Respirology. 2014;19(6):900‐906.
20/39 (52%)
Casoni GL et al.PLoS One. 2014;9(2):e86716.
36/69 (52%)
Griff S et al. BMC Pulm Med. 2014;14:171.
41/52 (79%)
Hernández‐González F et al.Arch Bronconeumol. 2015; 51(6):261‐267.
26/33 (79%)
Hagmeyer L et al. Clin Respir J. 2016;10(5):589‐595.
23/32 (72%)
Tomassetti S et al.Am J Resir Crit Care Med. 2016;193(7):745‐752.
40/58 (69%)
Poletti V.Respiration. 2016;91(4):350.
246/297 (83%)
Lentz RJ et al. J BronchologyInterv Pulmonol. 2017 Aug 7. [Epub ahead of print]
71/104 (68%)
OVERALL EXPERIENCE 523/605 (74%)
Diagnostic Yield in 15 studies of 781 patients
– 81%[Meta‐analysis]
Safety/Complications in 15 studies of 994 patients –Pneumothorax 10%;
Moderate bleeding 12%[Meta‐analysis]
MDT Diagnosis Results in Greater Prognostic Accuracy
MDT=multidisciplinary team; MDTM=multidisciplinary team meeting.
15
Reprinted from The Lancet Respiratory Medicine, vol. 4, Walsh SL, Wells AU, Desai SR, et al, Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study, 557-565, Copyright 2016, with permission from Elsevier.
Unclassifiable ILD Remains Despite All of This Advance
16Reprinted from Chest, 145/4, Ryerson CJ, Vittinghoff E, Ley B, et al, Predicting survival across chronic interstitial lung disease: the ILD-GAP model, 723-728, Copyright 2014, with permission from Elsevier; Hyldgaard C et al. Respirology. 2017;22(3):494-500.
Unclassifiable ILD Remains Despite All of This Advance
17
Unclassifiable ILD in 105/403 (24%)
Unclassifiable ILD in 173/1012 (17%)
Reprinted from Chest, 145/4, Ryerson CJ, Vittinghoff E, Ley B, et al, Predicting survival across chronic interstitial lung disease: the ILD-GAP model, 723-728, Copyright 2014, with permission from Elsevier; Hyldgaard C et al. Respirology. 2017;22(3):494-500.
18Martinez FJ et al. Nat Rev Dis Primers. 2017;3:17074.
Wide Variety of Prognostic Biomarkers Are In Play
With Optimal Results Seen With Five TBBxYielding Excellent Sensitivity/Specificity
Number of random samples to mix
AUC
Mixing 5 is the best
Classification Result
Non-UIP UIP
Central Pathology Label
Non-UIP 22 3
UIP 8 16
Specificity 0.88 (0.68 - 0.97)
Sensitivity 0.67 (0.45-0.84)
Pankratz DG et al. Ann Am Thorac Soc. 2017;14(11):1646-1654.19
Future Diagnostic Approach
20Reprinted from The Lancet Respiratory Medicine, vol. 5, Martinez FJ, Chisholm A, Collard HR, et al, The diagnosis of idiopathic pulmonary fibrosis: current and future approaches, 61-71, Copyright 2017, with permission from Elsevier.
Discussion Points (con't)
Diagnosis
Prognosis
Therapy
21
Traditional Prognostic Factors
Age
FVC
DLCO
Exertional desaturation
Decline in FVC or DLCO
Oxygen requirement
22
HRCT Imaging Features Are Prognostic
23
Reprinted from Respiratory Medicine, vol. 131, Salisbury ML, Tolle LB, Xia M, et al, Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients, 229-235, Copyright 2017, with permission from Elsevier.
24Martinez FJ et al. Nat Rev Dis Primers. 2017;3:17074.
Wide Variety of Prognostic Biomarkers Are In Play
PBMC Gene Expression Predicts Poor Outcome in IPF
25
Reprinted from The Lancet Respiratory Medicine, vol. 5, Herazo-Maya JD, Sun J, Molyneaux PL, et al, Validation of a 52-gene risk profile for outcome prediction in patients with idiopathic pulmonary fibrosis: an international, multicentre, cohort study, 857-868, Copyright 2017, with permission from Elsevier.
26Huang Y et al; COMET-IPF Investigators. Am J Respir Crit Care Med. 2017;196(2):208-219.
Gene Expression Signature Linked to Survival‐associated (TLR)
Pathways and Inversely Linked to Microbial “Richness”
Discussion Points (con't)
Diagnosis
Prognosis
Therapy
– Which agent?
– Whom to treat?
– How to assess response?
27
TreatmentStrong For
ConditionalFor
Conditional Against
StrongAgainst
Bosentan/Macitentan X
Ambrisentan X
Imatinib X
NAC/Azathioprine/Prednisone X
NAC X
Anticoagulation X
Pirfenidone X
Nintedanib X
Antacid therapy X
Sildenafil X
Raghu G et al; American Thoracic Society; European Respiratory Society; Japanese Respiratory Society; Latin American Thoracic Association. Am J Respir Crit Care Med. 2015;192(2):e3-e19.):E3-E19.
28
An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline: Treatmentof Idiopathic Pulmonary Fibrosis: An Update of the 2011 Clinical Practice Guideline
Discuss the efficacy and safety of FDA‐approved therapies
Listen to patient’s preferences and concerns
Focus on symptom control and management of comorbidities
Set treatment expectations
Look at the option of lung transplantation
Treatment options
Risks and benefits
Personal preferences
Values and concerns
Physician provides Patient provides
Mutually acceptable decision
Engaging in a Shared Decision‐Making Process
29
Network Meta‐analysis Suggests Little Difference Between Pirfenidone and Nintedanib Percent % FVC Decrease 10
0.01 0.1 1 10 100
Pirfenidone vs placebo
Nintedanib vs placebo
Pirfenidone vs nintedanib
0.52 (0.41‐0.67)
0.61 (0.48‐0.78)
0.86 (0.60‐1.20)
Adapted from Canestaro WJ et al. Chest. 2016;149(3):756-766.30
Pirfenidone and Nintedanib Attenuate Loss of FVC Across Multiple Patient Subgroups
Pirfenidone Nintedanib
31
Reproduced with permission of European Respiratory Society. Noble PW et al. Eur Respir J. 2016;47:243-253; Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Costabel U, Inoue Y, Richeldi L, et al. 2016, Efficacy of nintedanib in idiopathic pulmonary fibrosis across prespecified subgroups in INPULSIS. Am J Repir Crit Care Med. 193(2):178-185. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
Patterns of Pirfenidone Discontinuation in RECAP
32
Reasons for Discontinuation Number of Discontinuations
Reproduced with permission of European Respiratory Society. Costabel U et al. European Respiratory Journal. 2017;50(suppl 61):Abstract OA3399.
Long‐term Safety of Pirfenidone in Real‐World Setting (PASSPORT Registry)
33
European Registry of IPF patients newly prescribed pirfenidone
Followed for 2 years after first prescription
Adapted from Cottin V et al. European Respiratory Journal. 2017;50(suppl 61):Abstract PA2806.
Change in FVC After Initial 10% FVC Decrease in CAPACITY/ASCEND Trials
34
Event Pirfenidone (n=34)
Placebo (n=68)
P value
> 10% in FVC or death
2 (5.9%) 19 (27.9%) .009
No further in FVC
20 (58.8%) 26 (38.2%) .059
Death 1 (2.9%) 14 (20.6%) .018
Nathan SD, Albera C, Bradford WZ, et al. Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax. 2016;71(5):429-435. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4862066/pdf/thoraxjnl-2015-207011.pdf. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) and is available under Public License, https://creativecommons.org/licenses/by/4.0/legalcode.
Long‐term Tolerability of Nintedanib(INPULSIS®‐ON)
35Crestani B et al. Presented at: European Respiratory Society (ERS) International Congress; September 9-13, 2017; Milan, Italy. Abstract OA3402.
Long‐term Tolerability of Nintedanib(INPULSIS®‐ON)
36Crestani B et al. Presented at: European Respiratory Society (ERS) International Congress; September 9-13, 2017; Milan, Italy. Abstract OA3402.
Most frequent adverse events leading to treatment discontinuation in INPULSIS® and INPULSIS®‐ON
Progression of IPF
Diarrhoea
Weight decreased
Nausea
Impact of FVC Decline in Nintedanib‐Treated Patients
FVC Decline in INPULSIS® and INPULSIS®‐ON
37Adapted from Richeldi L et al. European Respiratory Journal. 2017;50(suppl 61):Abstract PA4892.
Recruiting Clinical Trials for IPF
38
Intervention Target Phase StatusGSK3008348 αvβ6 integrin 1 Recruiting
Dasatinib + quercetin BCR‐ABL + COX/LOX 1 Recruiting
KD025 ROCK2 2 Recruiting
Pirfenidone + sildenafil Multiple + PDEs 2 Recruiting
Tipelukast LT + PDE3/4, 5‐LO 2 Recruiting
GBT440 Hemoglobin 2 Recruiting
GLPG1690 Autotaxin 2 Recruiting
Rituximab Autoantibodies 2 Recruiting
Nintedanib + sildenafil TKs + PDEs 3 Recruiting
Nebulized fentanyl Dyspnea 3 Recruiting
Cotrimoxazole or doxycycline
Lung microbiome 3 Recruiting
Palliative care Your patient N/A Recruiting
Home‐basedrehabilitation
Your patient – Recruiting
Azithromycin Cough – Recruiting
www.clinicaltrials.gov. Accessed October 19, 2017.
IPF Studies Closed to Enrollment
39
Intervention Mechanism/Target Phase Trial Status
Autologous mesenchymal stem cells
Immunomodulation 1
Ongoing
FG‐3019 Anti‐CTGF (FG‐3019) 2
Lebrikizumab Anti‐IL‐13 2
PRM‐151 Pentraxin‐2 2
Sirolimus mTOR inhibition ‐‐
Laparoscopic antireflux surgery Gastroesophageal reflux 2
Tralokinumab Anti‐IL‐13 2
Completed
Pamrevlumab Anti‐CTGF (FG‐3019) 2
Carbon monoxide Injury/inflammation 2
PBI‐4050 Anti‐fibrotic 2
SAR156597 Anti‐IL‐4, Anti‐IL‐13 2
www.clinicaltrials.gov. Accessed October 19, 2017.
IPF Studies Closed to Enrollment
40
Intervention Mechanism/Target Phase Trial Status
Autologous mesenchymal stem cells
Immunomodulation 1
Ongoing
FG‐3019 Anti‐CTGF (FG‐3019) 2
Lebrikizumab Anti‐IL‐13 2
PRM‐151 Pentraxin‐2 2
Sirolimus mTOR inhibition ‐‐
Laparoscopic antireflux surgery Gastroesophageal reflux 2
Tralokinumab Anti‐IL‐13 2
Completed
Pamrevlumab Anti‐CTGF (FG‐3019) 2
Carbon monoxide Injury/inflammation 2
PBI‐4050 Anti‐fibrotic 2
SAR156597 Anti‐IL‐4, Anti‐IL‐13 2
A Phase II Clinical Trial of Low‐Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis
Rosas IO, Goldberg HJ, Collard HR, El‐Chemaly S, Flaherty K, Hunninghake GM, Lasky JA, Lederer DJ, Machado R, Martinez FJ, Maurer R, Teller D, Noth I, Peters E, Raghu G, Garcia
JGN, and Choi AMK.
Conclusions: Inhaled CO is well tolerated and can be safely administered to IPF patients in the ambulatory setting; however,
inhaled CO did not result in significant changes in prespecified study endpoints. The feasibility of administering outpatient inhaled therapies for the treatment of IPF is encouraging and should be
pursued in future studies.
Chest 2017; Published on‐line as 10.1016/j.chest.2017.09.052
www.clinicaltrials.gov. Accessed October 19, 2017.
IPF Studies Closed to Enrollment
41www.clinicaltrials.gov. Accessed October 19, 2017.
Intervention Mechanism/Target Phase Trial Status
Autologous mesenchymal stem cells
Immunomodulation 1
Ongoing
FG‐3019 Anti‐CTGF (FG‐3019) 2
Lebrikizumab Anti‐IL‐13 2
PRM‐151 Pentraxin‐2 2
Sirolimus mTOR inhibition ‐‐
Laparoscopic antireflux surgery Gastroesophageal reflux 2
Tralokinumab Anti‐IL‐13 2
Completed
Pamrevlumab Anti‐CTGF (FG‐3019) 2
Carbon monoxide Injury/inflammation 2
PBI‐4050 Anti‐fibrotic 2
SAR156597 Anti‐IL‐4, Anti‐IL‐13 2
FibroGen Presents Latest Data From Phase 2b Study of Pamrevlumab in Idiopathic Pulmonary Fibrosis at European
Respiratory Society (ERS) International Congress 2017
Pamrevlumab met the primary endpoint of FVC % predicted with statistical significance, as well as absolute FVC volume: in this study, the primary endpoint was met as the average decline in FVC % predicted of 2.85 in the pamrevlumab arm was statistically smaller than
the average decline of 7.17 in the placebo arm, a difference of 4.33. These results are consistent with the decline in FVC % predicted by 2.29 observed in a subgroup of similar pamrevlumab‐treated patients in an earlier phase 2 open‐label IPF study.
Is IPF Combination Therapy the Answer?
Combination Therapy and the Start of a New Epoch for Idiopathic Pulmonary Fibrosis?
Maher TM
Maher TM. Am J Respir Crit Care Med. 2018;197(3):283-284.42
NHLBI‐funded “large simple” trial
IPF—“all comers”
Intervention: Cotrimoxazole (or doxycycline)
Control: Standard of care
Primary outcome: Time to respiratory hospitalization or death
Currently open to enrollment
Ongoing Studies With Cotrimoxazole
43ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02759120. Updated November 8, 2017. Accessed December 29, 2017; BioMed Central Ltd. http://www.isrctn.com/ISRCTN17464641. Accessed December 29, 2017.
CleanUP IPF
National Institute for Health Research (UK) trial
IPF
Intervention: Cotrimoxazole
Control: Placebo
Primary outcome: Time to death (all causes), lung transplant, or first nonelective hospital admission
Currently open to enrollment
EME‐TIPAC
INJOURNEY™ Study Results: NintedanibWith Add‐On Pirfenidone
Nintedanib150 mg bidWith Add‐On Pirfenidone(n = 53), n (%)
Nintedanib150 mg bid(n = 51), n (%)
Any AE(s) 47 (88.7) 45 (88.2)
Most frequent AEs
Diarrhea 20 (37.7) 16 (31.4)
Nausea 22 (41.5) 6 (11.8)
Vomiting 15 (28.3) 6 (11.8)
Fatigue 10 (18.9) 6 (11.8)
Upper abdominal pain
7 (13.2) 4 (7.8)
Decrease appetite 6 (11.3) 5 (9.8)
Dyspnea 2 (3.8) 8 (15.7)
Headache 7 (13.2) 1 (2.0)
Any SAE(s) 2 (3.8) 5 (9.8)
Any fatal AE(s) 0 0
44Reprinted with permission of the American Thoracic Society. Copyright © 2018 American Thoracic Society. Vancheri C, Kreuter M, Richeldi L, et al; INJOURNEY Trial Investigators. 2018, Nintedanib with add-on pirfenidone in idiopathic pulmonary fibrosis. Results of the INJOURNEY Trial. Am J RepirCrit Care Med. 197(3):356-363. The American Journal of Respiratory and Critical Care Medicine is an official journal of the American Thoracic Society.
Safety of Combined Pirfenidone and Nintedanibin Patients With Idiopathic Pulmonary Fibrosis
45Flaherty KR et al. Presented at: European Respiratory Society (ERS) International Congress; September 9-13, 2017; Milan, Italy. Abstract PA2805.
Weighing Risks and Benefits of Laparoscopic Anti‐Reflux Surgery in Patients With IPF (WRAP‐IPF)
46ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01982968. Updated October 26, 2016. Accessed December 29, 2017.
Phase 2
Primary outcome: decline in FVC between enrollment and 48 weeks
Enrollment 58
Estimated completion November 2017
Inclusion criteria:– Confirmed diagnosis of idiopathic pulmonary fibrosis
– Abnormal GER on 24‐hour pH monitoring (DeMeester score > 14.7)
– Able to provide informed consent
– Willing to undergo laparoscopic anti‐reflux surgery
Discussion Points (con't)
Diagnosis
Prognosis
Therapy
Imminent future
47
Nintedanib Clinical Trials in ILDs
48ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03062943. Updated February 24, 2017. Accessed December 29, 2017; ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02999178. Updated December 25, 2017. Accessed December 29, 2017; ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02597933. Updated December 4, 2017. Accessed December 29, 2017.
A Study of Nintedanib for LymphAngioleioMyomatosis (LAM)
• Recruiting participants for open‐label, phase 2 trial
Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF‐ILD)
• Recruiting participants for double‐blind, randomized, placebo‐controlled phase 3 trial
SENSCIS (Safety and Efficacy of Nintedanib in Systemic SClerosIS) Study
• Recruiting patients with scleroderma‐related lung fibrosis for double‐blind, randomized, placebo‐controlled phase 3 trial
Pirfenidone Clinical Trials in ILDs
49Khanna D et al. J Rheumatol. 2016;43(9):1672-1679; ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02808871. Updated June 14, 2017. Accessed December 29, 2017; ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02958917. Updated May 3, 2017. Accessed December 29, 2017; ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03099187. Updated December 22, 2107. Accessed December 39, 2017.
Safety and Tolerability of Pirfenidone in Par cipants With Systemic Sclerosis−Related Inters al Lung Disease (SSc‐ILD) (LOTUSS)
• Open‐label, phase 2 trial is completed
Phase 2 Study of Pirfenidone in Patients With RA‐ILD
• Recruiting participants for randomized, placebo‐controlled phase 2 study
Study of Efficacy and Safety of Pirfenidone in Patients With Fibrotic HP Study
• Recruiting participants for randomized, placebo‐controlled trial
A Study of Pirfenidone in Patients With Unclassifiable Progressive Fibrosing ILD
• Recruiting participants for double‐blind, randomized, placebo‐controlled phase 2 trial
Nintedanib Clinical Trials in ILDs
50ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03062943. Updated February 24, 2017. Accessed December 29, 2017; ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02999178. Updated December 25, 2017. Accessed December 29, 2017; ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02597933. Updated December 4, 2017. Accessed December 29, 2017.
A Study of Nintedanib for LymphAngioleioMyomatosis (LAM)
• Recruiting participants for open‐label, phase 2 trial
Efficacy and Safety of Nintedanib in Patients With Progressive Fibrosing Interstitial Lung Disease (PF‐ILD)
• Recruiting participants for double‐blind, randomized, placebo‐controlled phase 3 trial
SENSCIS (Safety and Efficacy of Nintedanib in Systemic SClerosIS) Study
• Recruiting patients with scleroderma‐related lung fibrosis for double‐blind, randomized, placebo‐controlled phase 3 trial