A Study Based on Medical Records That Looks at the Characteristics of Idiopathic Pulmonary Fibrosis Patients Grouped by the Type of Medication They Are Taking

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03958071
• Collaborator: (none)
• Enrollment: 13,264
• Location: 1
• Actual Duration (Months): 3.9
• Patients Per Site Per Month: 3392.6

Study Details

Study Description

Brief Summary

To understand differences in characteristics of Idiopathic Pulmonary Fibrosis (IPF) patients who are prescribed nintedanib compared to those who are prescribed pirfenidone.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Nintedanib; Drug: Pirfenidone; Other: Untreated Cohort

Study Design

• Study Type: Observational
• Actual Enrollment: 13264 participants
• Observational Model: Cohort
• Time Perspective: Retrospective
• Official Title: Characteristics of IPF Patients Initiating Nintedanib, Pirfenidone or no Antifibrotic Treatment in the US
• Actual Study Start Date: Feb 1, 2019
• Actual Primary Completion Date: May 31, 2019
• Actual Study Completion Date: May 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Subjects with Idiopathic Pulmonary Fibrosis	Drug: Nintedanib; Nintedanib initiators; Drug: Pirfenidone; Pirfenidone initiators; Other: Untreated Cohort; Untreated

Outcome Measures

Primary Outcome Measures

1. Baseline Patient Characteristics: Age [Baseline characteristics were recorded 12 months pre-index event (pre-treatment).]

   IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. The patient characteristic age for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.

2. Baseline Patient Characteristics: Sex [Baseline characteristics were recorded 12 months pre-index event (pre-treatment).]

   IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. The patient characteristic sex for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.

3. Baseline Patient Characteristics: BMI [Baseline characteristics were recorded 12 months pre-index event (pre-treatment).]

   The patient characteristic Body mass index (BMI) for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.

4. Baseline Patient Characteristics: Charlson Comorbidity Index (CCI) [Baseline characteristics were recorded 12 months pre-index event (pre-treatment).]

   IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized HIPPA compliant database populated with patient data from ambulatory care records. Charlson Comorbidity Index (CCI) for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts. The Charlson Comorbidity Index is a method of categorizing comorbidities of patients based on the International Classification of Diseases (ICD) diagnosis. Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. A score of zero indicates that no comorbidities were found. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use. Up to 12 comorbidities with various weightings can result in a maximum score of 24. The minimum score is zero.

5. Baseline Patient Characteristics: Number of Participants Using Inhaled Corticosteroids at Baseline [Baseline characteristics were recorded 12 months pre-index event (pre-treatment).]

   IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. Treatment with inhaled corticosteroids for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.

6. Baseline Patient Characteristics: Number of Participants Using Proton Pump Inhibitors at Baseline [Baseline characteristics were recorded 12 months pre-index event (pre-treatment).]

   IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. Treatment with Proton pump inhibitors for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.

Secondary Outcome Measures

1. Odds Ratio of Receiving Treatment (Nintedanib or Pirfenidone) vs no Treatment [Baseline characteristics were recorded 12 months pre-index event (pre-treatment).]

   Odds ratio of receiving nintedanib or pirfenidone vs. no antifibrotic treatment, adjusting for patient characteristics; to identify baseline characteristics that drive initiation of a treatment while minimizing prescription bias. Logistic regression models were developed to assess the odds. Baseline patient characteristics that were sufficiently populated, had ASD >10% or p-value <0.05, and were agreed upon as important variables to include, were included as covariates for a full model. Linearity of age was confirmed before including it as a continuous variable in one version of the model. Backward selection was applied to develop a reduced model, only retaining covariates with p<0.1 after forcing age at index, gender, geographic region, BMI, CCI, and Chronic obstructive pulmonary disease (COPD) into the model. Odds presented for key patient characteristics. Odd ratio of >1 indicates increased odds of receiving treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• With ≥ 1 diagnosis for IPF (the International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 516.3, 516.31, 515, or ICD-10-CM codes J84.112) in the EMR between October 1, 2013 to April 30, 2018

• With ≥ 1 prescription for nintedanib between October 1, 2014 and April 30, 2018 (the selection window)

• The date of the first prescription will be defined as the index date

• With ≥ 1 record in the EMR database during the 12 months prior to the index date (the pre-index period)

• With ≥ 1 diagnosis of IPF during the 12 months prior to the index date

• Age ≥ 40 on the index date

• IQVIA will explore also requiring ≥ 1 chest CT scan before first IPF diagnosis during the pre-index period

Exclusion Criteria:

• With ≥ 1 diagnosis of other known causes of interstitial lung disease (ILD) on the date of or after the first IPF diagnosis during the pre-index period

• Other known causes of ILD include conditions such as systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, polymyositis, Sjögren disease, and hypersensitivity pneumonitis (ICD-9-CM codes 135, 237.7, 272.7, 277.3, 277.8, 446.21, 446.4, 495, 500-505, 506.4, 508.1, 508.8, 516.0, 516.1, 516.32-516.37, 516.2, 516.8, 516.9, 517.0, 517.2, 517.8, 518.3, 555, 710.0, 710.0-710.4, 714.0, 714.81, 720, and 759.5, or ICD-10-CM equivalent codes)

• With ≥ 1 prescription for nintedanib prior to the index date

• With ≥ 1 prescription for pirfenidone prior to or on the index date

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Plymouth Meeting	Plymouth	Pennsylvania	United States	19462

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 18, 2018

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT03958071
• Other Study ID Numbers: 1199-0375
• First Posted: May 21, 2019
• Last Update Posted: Nov 15, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pirfenidone; Nintedanib

Study Results

Participant Flow

Recruitment Details	This retrospective database study was conducted to understand differences in characteristics of Idiopathic pulmonary fibrosis (IPF) patients who were newly prescribed pirfenidone or nintedanib, and those who did not receive a prescription for an antifibrotic treatment.
Pre-assignment Detail	The study includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data.

Arm/Group Title	Nintedanib	Pirfenidone	Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
Period Title: Overall Study
STARTED	347	423	12494
COMPLETED	347	423	12494
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Nintedanib	Pirfenidone	Untreated	Total
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.	Total of all reporting groups
Overall Participants	347	423	12494	13264
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71.6 (6.7)	72.1 (6.8)	70.9 (8.9)	70.96 (8.79)
Sex/Gender, Customized (Count of Participants)
Male	234 67.4%	281 66.4%	6179 49.5%	6694 50.5%
Female	113 32.6%	142 33.6%	6314 50.5%	6569 49.5%
Unknown	0 0%	0 0%	1 0%	1 0%
Race/Ethnicity, Customized (Count of Participants)
White	305 87.9%	370 87.5%	10039 80.4%	10714 80.8%
Non-white	16 4.6%	15 3.5%	1093 8.7%	1124 8.5%
Unknown	26 7.5%	38 9%	1362 10.9%	1426 10.8%

Outcome Measures

1. Primary Outcome

Title	Baseline Patient Characteristics: Age
Description	IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. The patient characteristic age for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.
Time Frame	Baseline characteristics were recorded 12 months pre-index event (pre-treatment).

Outcome Measure Data

Analysis Population Description

Includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting.

Arm/Group Title	Nintedanib	Pirfenidone	Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
Measure Participants	347	423	12494
Mean (Standard Deviation) [years]	71.6 (6.7)	72.1 (6.8)	70.9 (8.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Pirfenidone
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2810
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	-0.1027
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1421
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	-0.0780
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0048
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.0159
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

2. Secondary Outcome

Title	Odds Ratio of Receiving Treatment (Nintedanib or Pirfenidone) vs no Treatment
Description	Odds ratio of receiving nintedanib or pirfenidone vs. no antifibrotic treatment, adjusting for patient characteristics; to identify baseline characteristics that drive initiation of a treatment while minimizing prescription bias. Logistic regression models were developed to assess the odds. Baseline patient characteristics that were sufficiently populated, had ASD >10% or p-value <0.05, and were agreed upon as important variables to include, were included as covariates for a full model. Linearity of age was confirmed before including it as a continuous variable in one version of the model. Backward selection was applied to develop a reduced model, only retaining covariates with p<0.1 after forcing age at index, gender, geographic region, BMI, CCI, and Chronic obstructive pulmonary disease (COPD) into the model. Odds presented for key patient characteristics. Odd ratio of >1 indicates increased odds of receiving treatment.
Time Frame	Baseline characteristics were recorded 12 months pre-index event (pre-treatment).

Outcome Measure Data

Analysis Population Description

Includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting.

Arm/Group Title	Overall Population
Arm/Group Description	Patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment, first prescribed Nintedanib or first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.
Measure Participants	13264
Age	1.022
Gender	0.490
BMI category: Overweight	1.359
BMI category: Obese	1.833
BMI category: Very obese	1.638
Comorbidities: COPD	0.581
Comorbidities: Heart failure	0.449
Comorbidities: Stroke	0.449
Comorbidities: Hypertension	0.663
Comorbidities: Peripheral arterial diseases	0.383
Comorbidities: Severe diseases	0.463
Gastroesophageal reflux disease	1.621

3. Primary Outcome

Title	Baseline Patient Characteristics: Sex
Description	IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. The patient characteristic sex for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.
Time Frame	Baseline characteristics were recorded 12 months pre-index event (pre-treatment).

Outcome Measure Data

Analysis Population Description

Includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. One patient from the untreated cohort was missing gender information and is not shown in the table

Arm/Group Title	Nintedanib	Pirfenidone	Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
Measure Participants	347	423	12493
Male	234 67.4%	281 66.4%	6179 49.5%
Female	113 32.6%	142 33.6%	6314 50.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Pirfenidone
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7681
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.0214
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.3710
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.3490
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

4. Primary Outcome

Title	Baseline Patient Characteristics: BMI
Description	The patient characteristic Body mass index (BMI) for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.
Time Frame	Baseline characteristics were recorded 12 months pre-index event (pre-treatment).

Outcome Measure Data

Analysis Population Description

Includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting.

Arm/Group Title	Nintedanib	Pirfenidone	Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
Measure Participants	347	423	12494
Mean (Standard Deviation) [kilogram/height in meters squared(kg/m²)]	29.5 (6.4)	30.1 (5.8)	28.6 (6.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Pirfenidone
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1659
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	-0.1257
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0112
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.1566
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.3019
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

5. Primary Outcome

Title	Baseline Patient Characteristics: Charlson Comorbidity Index (CCI)
Description	IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized HIPPA compliant database populated with patient data from ambulatory care records. Charlson Comorbidity Index (CCI) for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts. The Charlson Comorbidity Index is a method of categorizing comorbidities of patients based on the International Classification of Diseases (ICD) diagnosis. Each comorbidity category has an associated weight (from 1 to 6), based on the adjusted risk of mortality or resource use, and the sum of all the weights results in a single comorbidity score for a patient. A score of zero indicates that no comorbidities were found. The higher the score, the more likely the predicted outcome will result in mortality or higher resource use. Up to 12 comorbidities with various weightings can result in a maximum score of 24. The minimum score is zero.
Time Frame	Baseline characteristics were recorded 12 months pre-index event (pre-treatment).

Outcome Measure Data

Analysis Population Description

Includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting.

Arm/Group Title	Nintedanib	Pirfenidone	Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
Measure Participants	347	423	12494
Mean (Standard Deviation) [Score on a scale]	0.71 (1.0)	0.79 (1.1)	1.09 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Pirfenidone
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3260
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	-0.0209
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	-0.2694
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	-0.2352
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(X1-X2)/sqrt((s1^2+s2^2)/2). Where X denotes sample means in each cohort, and s denotes sample variances.

6. Primary Outcome

Title	Baseline Patient Characteristics: Number of Participants Using Inhaled Corticosteroids at Baseline
Description	IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. Treatment with inhaled corticosteroids for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.
Time Frame	Baseline characteristics were recorded 12 months pre-index event (pre-treatment).

Outcome Measure Data

Analysis Population Description

Includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting.

Arm/Group Title	Nintedanib	Pirfenidone	Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
Measure Participants	347	423	12494
Count of Participants [Participants]	125 36%	134 31.7%	3311 26.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Pirfenidone
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2042
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.09
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.21
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.11
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

7. Primary Outcome

Title	Baseline Patient Characteristics: Number of Participants Using Proton Pump Inhibitors at Baseline
Description	IQVIA's GE Centricity Electronic medical records database was used for this study. This is an anonymized Health Insurance Portability and Accountability Act of 1996 (HIPPA) compliant database populated with patient data from ambulatory care records. Treatment with Proton pump inhibitors for Idiopathic Pulmonary Fibrosis (IPF) patients at 12-month pre-treatment (baseline) was compared between each of the cohorts (nintedanib vs. pirfenidone, nintedanib vs. untreated, pirfenidone vs. untreated), differences are presented in absolute standardized differences (ASD), differences were tested using t-test for means of continuous variables, Wilcoxon signed tank test for medians of continuous variables, and Chi-square test for categorical variables.
Time Frame	Baseline characteristics were recorded 12 months pre-index event (pre-treatment).

Outcome Measure Data

Analysis Population Description

Includes all patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis from Oct 1, 2013 to Oct 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting.

Arm/Group Title	Nintedanib	Pirfenidone	Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
Measure Participants	347	423	12494
Count of Participants [Participants]	113 32.6%	133 31.4%	3141 25.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Pirfenidone
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7395
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.0241
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Nintedanib, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.1644
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Pirfenidone, Untreated
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments
	Method	Chi-squared
	Comments
Method of Estimation	Estimation Parameter	Absolute standardized differences (ASD)
	Estimated Value	0.1403
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	ASD=(p1-p2)/(sqrt(p1^(1-p1)+p2(1-p2))/2). Where p denotes proportion of a binary variable in each cohort.

Adverse Events

Adverse Event Reporting Description	Not applicable; the IQVIA GE Centricity EMR database is a secondary database which consists of fully de-identified data. Therefore, it is not possible to identify/report individual case safety reports. All-Cause Mortality, Serious, and Other (Not Including Serious) Adverse Events were not monitored/assessed.
Arm/Group Title	Nintedanib		Pirfenidone		Untreated
Arm/Group Description	Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Nintedanib from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Nintedanib prescription.		Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were first prescribed Pirfenidone from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date was the date of the first Pirfenidone prescription.		Cohort of patients with an Idiopathic pulmonary fibrosis (IPF) diagnosis who were not prescribed antifibrotic treatment (i.e., no prescription for nintedanib nor pirfenidone during the data window) from October 1, 2014 to October 31, 2018. Data derived from IQVIA's GE Centricity EMR (Electronic medical records) data. The EMR consisted of patient data from ambulatory care records in the US, representing the US population receiving healthcare in the ambulatory setting. The index date for the untreated cohort was randomly assigned to mimic the distribution of time from the earliest IPF diagnosis to index in the two treatment cohorts.
All Cause Mortality
	Nintedanib		Pirfenidone		Untreated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Serious Adverse Events
	Nintedanib		Pirfenidone		Untreated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Nintedanib		Pirfenidone		Untreated
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

Limitations common to retrospective database studies: high proportion of missing data and it is possible that patients who received out-of-system care and treatments were not fully captured in the data.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.