1. New Models of Care in Idiopathic Pulmonary Fibrosis
Implementing New
Pharmacologic Therapies

2. History of Pharmacotherapy for IPF
2012
PANTHER trial results released
Prednisone, azathioprine and N-acetylcysteine combination therapy associated with an increased risk for death and hospitalization when used for IPF
October 2014
2 agents receive FDA approval for the treatment of mild-to-moderate IPF
Pirfenidone
Nintedanib
Raghu G, et al, 2012; King TE, et al, 2014; Richeldi L, et al, 2014

3. Pirfenidone: Benefits
Efficacy
ASCEND trial showed a reduced decrease in FVC compared to placebo at 52 weeks
Early disease
No apparent difference in efficacy in early vs advanced disease, arguing for early treatment
Progressive disease
ASCEND post-hoc analysis trial showed a significant reduction in further decline of FVC in patients who continued on pirfenidone after an initial decline of ≥10% in FVC
Mortality
Trend toward a mortality benefit at 52 weeks in the combined CAPACITY trials and the ASCEND trial
King TE, et al, 2014.

4. Pirfenidone: AE Profile*
Adverse Event
% Patients
Nausea
37.6
Dyspnea
30.9
Progression of IPF
29.3
Diarrhea
28.1
Rash
25.0
Dizziness
21.2
Dyspepsia
18.4
Vomiting
15.9
Weight loss
15.6
* Taken from pooled data from 5 clinical trials (ie, Compassionate-use trial, CAPACITY I and II,
ASCEND + extension) of pirfenidone in IPF in a total of 1299 patients.
Cotton & Mayer, 2015; Collard HR, et al, 2015.

5. Nintedanib: Benefits Efficacy Early disease Progressive disease
Demonstrated in INPULSIS I and II phase 3 trials
150 mg bid dose produced a significant slowing in reduction in FVC
Early disease
Similar efficacy in treatment subgroups, independent of disease severity and type of IPF on diagnosis
Progressive disease
Results from the TOMORROW extension trial suggest that benefits in slowing disease progression may be maintained to week 76
Mortality
Trend toward a mortality benefit at 52 weeks in pooled INPULSIS trials
Richeldi L, et al, 2014; Richeldi L, et al, 2015.

6. Nintedanib: AE Profile*
*Results From the TOMORROW Trial and Extension
Adverse Event
% Patients
Diarrhea
64.7
Nausea
23.5
Vomiting
16.5
Decreased appetite
15.3
Cough
12.9
Nasopharyngitis
Bronchitis
Earache
Headache
Upper Abdominal Pain
IPF Progression
10.6
Upper Respiratory Tract Infection
Fatigue
Dyspnea
9.4
Back Pain
8.2
Richeldi L, et al, 2011.

7. Current Standards of Management of IPF
Consider therapy with an antifibrotic agent.
Manage cough.
Promote exercise and pulmonary rehabilitation.
Recommend appropriate vaccinations.
Infections are poorly tolerated in these patients.
Manage comorbidities.
Clinical trial considerations
Lung transplant consideration

8. Common Comorbidities in IPF
Pulmonary
Extra-Pulmonary
Emphysema
Coronary artery disease
Pulmonary hypertension
Heart failure
Lung cancer
Gastroesophageal reflux disease
Venous thromboembolism
Obstructive sleep apnea
Depression

9. Treatment Strategies for Comorbidities in IPF
Accurate diagnosis
Disease-targeted therapy
Pulmonary rehabilitation and oxygen therapy
Evaluation for lung transplant

10. 2015 IPF Guideline Updates: Treatment
2011 guidelines did not recommend any therapy for IPF
Published before the approval pharmacologic therapies specific to IPF.
“2015 Update to Guidelines for the Treatment of Idiopathic Pulmonary Fibrosis” includes 2 new FDA-approved therapies
Pirfenidone - conditional recommendation based on a moderate confidence in estimate of effects
Nintedanib - conditional recommendation based on a moderate confidence in estimate of effects
Unknown in both agents:
Therapeutic benefits of patients excluded from trials
Optimal duration of therapy
Long-term effects
Updated guidelines to be published in the American Journal of Respiratory and Critical Care Medicine in August 2015.
Raghu G. ATS 2015; May 2015; Denver, CO.