Impact of timing of nintedanib initiation among patients newly diagnosed with idiopathic pulmonary fibrosis

Figures & data

Figure 1. Patient identification and attrition. Abbreviations. HRCT, high-resolution computed tomography; IPF, idiopathic pulmonary fibrosis; MAPD, Medicare Advantage with Part D.

Table 1. Patient characteristics.

Characteristic	Total (N = 449)	Timing of nintedanib initiation after IPF diagnosis
		Month 1 (n = 168)	Months 2–3 (n = 149)	Months 4–6 (n = 71)	Months 7–12  (n = 61)	Overall p-value
Age, years, mean (SD)	72.3 (7.6)	72.7 (7.2)	72.2 (7.4)	73.2 (8.7)	70.4 (8.1)	.146
Male sex, n (%)	306 (68.2)	109 (64.9)	105 (70.5)	45 (63.4)	47 (77.1)	.248
Insurance type, n (%)
Commercial	101 (22.5)	37 (22.0)	34 (22.8)	12 (16.9)	18 (29.5)	.388
MAPD	348 (77.5)	131 (78.0)	115 (77.2)	59 (83.1)	43 (70.5)	.395
Geographic region, n (%)
Northeast	60 (13.4)	23 (13.7)	22 (14.8)	12 (16.9)	3 (4.9)	.145
Midwest	125 (27.8)	48 (28.6)	46 (30.9)	18 (25.4)	13 (21.3)	.540
South	218 (48.6)	83 (49.4)	70 (47.0)	29 (40.9)	36 (59)	.214
West	46 (10.2)	14 (8.3)	11 (7.4)	12 (16.9)	9 (14.8)	.079
Index year, n (%)
2014	14 (3.1)	2 (1.2)	3 (2.0)	4 (5.6)	5 (8.2)	.021
2015	79 (17.6)	26 (15.5)	29 (19.5)	12 (16.9)	12 (19.7)	.766
2016	89 (19.8)	34 (20.2)	36 (24.2)	10 (14.1)	9 (14.8)	.258
2017	109 (24.3)	43 (25.6)	33 (22.2)	17 (23.9)	16 (26.2)	.881
2018	122 (27.2)	53 (31.6)	33 (22.2)	19 (26.8)	17 (27.9)	.311
2019	36 (8.0)	10 (6.0)	15 (10.1)	9 (12.7)	2 (3.3)	.126
Baseline Charlson comorbidity score, n (%)
0	125 (27.8)	45 (26.8)	43 (28.9)	21 (29.6)	16 (26.2)	.949
1–2	194 (43.2)	76 (45.2)	59 (39.6)	33 (46.5)	26 (42.6)	.713
3–4	106 (23.6)	39 (23.2)	38 (25.5)	13 (18.3)	16 (26.2)	.646
5+	24 (5.4)	8 (4.8)	9 (6.0)	4 (5.6)	3 (4.9)	.958
Baseline AHRQ comorbidity categories, n (%)^a
Hypertension	303 (67.5)	115 (68.5)	100 (67.1)	50 (70.4)	38 (62.3)	.772
Disorders of lipid metabolism	294 (65.5)	108 (64.3)	97 (65.1)	48 (67.6)	41 (67.2)	.955
Diseases of the heart^b	285 (63.5)	111 (66.1)	89 (59.7)	46 (64.8)	39 (63.9)	.692
Upper gastrointestinal disorders^c	153 (34.1)	61 (36.3)	52 (34.9)	19 (26.8)	21 (34.4)	.551
Other common baseline comorbidities, n (%)^d
COPD	171 (38.1)	68 (40.5)	63 (42.3)	21 (29.6)	19 (31.2)	.182
Obstructive sleep apnea	81 (18.0)	41 (24.4)	21 (14.1)	9 (12.7)	10 (16.4)	.065
Heart failure	81 (18.0)	32 (19.1)	28 (18.8)	12 (16.9)	9 (14.8)	.901
Pulmonary hypertension	45 (10.0)	17 (10.1)	12 (8.1)	9 (12.7)	7 (11.5)	.672
Baseline IPF-related assessments and treatments
Count of days with a claim for oxygen therapy, mean (SD)	1.6 (3.1)	1.7 (3.3)	1.6 (3.3)	1.4 (2.8)	1.2 (2.7)	.655
Pulmonary rehabilitation, n (%)	6 (1.3)	2 (1.2)	3 (2.0)	1 (1.4)	0 (0.0)	.885
Spirometry testing, n (%)	274 (61.0)	120 (71.4)	86 (57.7)	34 (47.9)	34 (55.7)	.003
Count of days with a claim for spirometry testing, mean (SD)	0.7 (0.6)	0.8 (0.6)	0.7 (0.6)	0.5 (0.6)	0.6 (0.6)	.010
HRCT, n (%)	272 (60.6)	120 (71.4)	89 (59.7)	29 (40.9)	34 (55.7)	<.001
Count of days with a claim for HRCT, mean (SD)	0.7 (0.7)	0.8 (0.6)	0.7 (0.7)	0.4 (0.5)	0.6 (0.6)	<.001
Baseline all-cause HCRU
Ambulatory visit, n (%)	448 (99.8)	167 (99.4)	149 (100)	71 (100)	61 (100)	1.000
Count of ambulatory visits PPPM, mean (SD)	3.0 (2.5)	3.1 (2.5)	3.1 (2.4)	2.8 (3.1)	3 (2.3)	.809
Emergency department visit, n (%)	148 (33.0)	47 (28.0)	51 (34.2)	28 (39.4)	22 (36.1)	.295
Inpatient stay, n (%)	117 (26.1)	45 (26.8)	41 (27.5)	18 (25.4)	13 (21.3)	.835
Pharmacy fill, n (%)	441 (98.2)	165 (98.2)	147 (98.7)	70 (98.6)	59 (96.7)	.780
Count of pharmacy fills PPPM, mean (SD)	3.3 (2.5)	3.5 (2.4)	3.3 (2.4)	3.4 (2.9)	3.1 (2.4)	.700
Baseline all-cause PPPM healthcare costs, 2019 US$, mean (SD)
Total	2,325 (5,898)	2,152 (2,718)	2,159 (3,521)	2,005 (3,156)	3,576 (13,967)	.361
Medical	1,927 (5,662)	1,694 (2,107)	1,716 (2,769)	1,705 (3,084)	3,340 (13,951)	.222
Ambulatory	677 (1,017)	768 (1,263)	620 (683)	580 (1,074)	678 (861)	.482
Emergency department	78 (224)	63 (182)	96 (300)	73 (129)	84 (201)	.624
Inpatient	1,033 (4,748)	743 (1,510)	892 (2,328)	978 (2,772)	2,241 (11,742)	.194
Other	138 (721)	119 (236)	109 (383)	75 (123)	336 (1,816)	.137
Pharmacy	398 (1,254)	458 (1,336)	443 (1,584)	300 (615)	236 (284)	.569

Abbreviations. AHRQ, Agency for Healthcare Research and Quality; COPD, chronic obstructive pulmonary disease; HCRU, healthcare resource utilization; IPF, idiopathic pulmonary fibrosis; MAPD, Medicare Advantage with Part D; PPPM, per patient per month; SD, standard deviation.

^aComorbidities identified using Clinical Classifications Software from the Agency for Healthcare Research and Quality²⁸.

^bIncludes heart valve disorders, cardiomyopathy, myocardial infarction, atherosclerosis, angina, pulmonary heart disease, conduction disorders, dysrhythmias, ventricular fibrillation, and heart failure.

^cIncludes esophageal disorders, ulcer, gastritis, and duodenitis.

^dComorbidities identified on the basis of codes on medical claims during the baseline period.

Figure 2. Weighted marginal structural models of first all-cause hospitalization.

Table 2. Unadjusted weighted marginal structural model of 12-month all-cause medical costs^a.

Independent variable	Cost ratio (95% CI)	p-Value	Predicted value, 2019 US$
Nintedanib initiation month		.289
Month 1	Reference group	–	14,668
Months 2–3	1.63 (0.96–2.78)	.071	23,957
Months 4–6	1.69 (0.92–3.10)	.090	24,788
Months 7–12	1.55 (0.90–2.68)	.115	22,748

^aResults are presented for patients with 12 months of follow-up (or less if due to death); n = 200. Patients were weighted to represent all patients who initiated treatment within 12 months of the index date (censoring weight) and to balance groups of patients who initiated treatment in different months (treatment weight).

Table 3. Adjusted weighted marginal structural model of 12-month all-cause medical costs^a,b.

Independent variable	Cost ratio (95% CI)	p-Value	Predicted value, 2019 US$
Nintedanib initiation month		.020
Month 1	Reference group	–	17,428
Months 2–3	1.69 (1.20–2.38)	.003	29,423
Months 4–6	1.21 (0.81–1.81)	.359	21,045
Months 7–12	1.35 (0.91–2.00)	.140	23,459
Baseline variables
Age category		.002
40–59	Reference group	–
60–69	0.61 (0.34–1.12)	.110
70–79	0.40 (0.23–0.69)	.001
80+	0.56 (0.31–1.03)	.062
Sex
Female	Reference group	–
Male	1.03 (0.72–1.46)	.887
Geographic region		.048
Northeast	Reference group	–
Midwest	0.73 (0.43–1.26)	.257
South	0.87 (0.57–1.34)	.523
West	1.40 (0.83–2.36)	.206
Insurance type
Commercial	Reference group	–
MAPD	0.90 (0.61–1.33)	.601
Index year		.088
2014	Reference group	–
2015	0.73 (0.47–1.14)	.172
2016	0.62 (0.38–1.01)	.053
2017	0.67 (0.40–1.11)	.118
2018	1.16 (0.69–1.93)	.577
Charlson comorbidity score category		.035
0	Reference group	–
1–2	0.71 (0.49–1.05)	.088
3+	0.56 (0.36–0.87)	.010
HCRU
All-cause inpatient visit	1.90 (1.17–3.10)	.009
All-cause ED visit count		.115
0	Reference group	–
1	1.19 (0.78–1.82)	.412
2+	1.77 (1.03–3.03)	.038
All-cause office visit count		.418
0–5	Reference group	–
6–8	1.13 (0.72–1.78)	.586
9–12	1.37 (0.93–2.02)	.116
13+	1.29 (0.89–1.87)	.185
Count of days with a claim for spirometry testing^c		.348
0	Reference group	–
1	1.06 (0.80–1.40)	.682
2+	1.65 (0.84–3.23)	.148
Count of days with a claim for HRCT		.023
0	Reference group	–
1	0.70 (0.52–0.94)	.017
2+	1.09 (0.66–1.82)	.731
Count of days with a claim for oxygen therapy		.009
0	Reference group	–
1–3	2.69 (1.34–5.43)	.006
4+	1.43 (1.01–2.01)	.043
Pulmonary rehabilitation	2.24 (1.06–4.75)	.035

Abbreviations. ED, emergency department; HCRU, healthcare resource utilization; HRCT, high-resolution computed tomography; MAPD, Medicare Advantage with Part D.

^aResults are presented for patients with 12 months of follow-up (or less if due to death); n = 200.

^bVariables used for calculating weights in the marginal structural model were as follows. Baseline: month with splines, categorical age, sex, geographic region, index year, categorical baseline Charlson comorbidity score, categorical count of all-cause ED visits, inpatient visit, categorical count of all-cause office visits, categorical count of days with a claim for spirometry testing, categorical count of days with a claim for HRCT, categorical count of days with a claim for oxygen therapy, and pulmonary rehabilitation. Current month: all-cause ED visit, all-cause inpatient visit, all-cause office visit, spirometry test, HRCT, categorical count of days with a claim for oxygen therapy, and pulmonary rehabilitation. Previous month: all-cause ED visit, all-cause inpatient visit, all-cause office visit, spirometry test, HRCT, categorical count of days with a claim for oxygen therapy, and pulmonary rehabilitation.

^cMultiple spirometry tests within 30 days were counted as 1 test.

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