Take home message
Introduction
Methods
Subjects
Data collection
Statistical analysis
Results
Clinical characteristics
Switch-IPF cohort (n = 37) | Non-Switch-IPF cohort (n = 225) | Non-Switch-IPF Continued cases (n = 177) | Non-Switch-IPF Discontinued cases (n = 48) | Non-Switch IPF versus Switch-IPF p value | |
---|---|---|---|---|---|
Age, years | 70.0 [65.5–74.0] | 73.0 [68.0–77.0] | 72.0 [67.5–76.0] | 74.0 [68.0–79.0] | 0.0616 |
Sex, male/female | 31 (83.8%)/6 (16.2%) | 185 (82.2%)/40 (17.8%) | 147 (83.0%)/30 (17.0%) | 38 (79.2%)/10 (20.8%) | 1.000 |
cIPF/UIP/IPF | 31 (83.8%)/6 (16.2%) | 175 (77.8%)/50 (22.2%) | 134 (75.7%)/43 (24.3%) | 41 (85.4%)/7 (14.6%) | 0.5186 |
Diagnosis to antifibrotic therapy, months | 13.6 [1.7–31.5] | 15.4 [2.8–47.2] | 12.1 [2.6–44.1] | 31.5 [5.6–66.1] | 0.2324 |
Pirfenidone/Nintedanib | 29 (78.4%), 8 (21.6%) | 130 (57.8%), 95 (42.2%) | 102 (57.6%)/75 (42.4%) | 28 (58.3%)/ 20 (41.7%) | 0.0184 |
History of AE | 0 (0%) | 33 (14.7%) | 25 (14.1%) | 8 (16.7%) | 0.0067 |
Never/former & current smoker | 6 (16.2%), 31 (83.8%) | 46 (20.4%), 179 (79.6%) | 37 (20.9%)/140 (79.1%) | 9 (18.8%)/39 (81.3%) | 0.6602 |
Smoking pack-year | 40.0 [18.0–59.0] | 30.0 [3.0–46.0] | 30.8 [3.0–45.0] | 30.0 [7.5–48.0] | 0.1297 |
BMI, kg/m2 | 24.3 [21.3–25.3] | 22.9 [20.7–25.4] | 23.3 [21.4–25.7] | 21.9 [19.5–23.5] | 0.2329 |
Pulmonary function test | |||||
FVC, %-pred | 73.2 [62.4–83.7] | 67.7 [56.5–79.8] | 68.3 [58.5–80.2] | 61.4 [47.7–77.4] | 0.1018 |
FEV1, %-pred | 75.3 [67.6–87.6] | 74.4 [63.3–92.2] | 76.4 [64.5–90.9] | 73.1[55.8–90.9] | 0.7480 |
FEV1/FVC, % | 83.4 [79.9–88.9] | 86.4 [79.9–92.2] | 85.4 [79.8–91.4] | 90.2 [80.4–94.5] | 0.0438 |
DLCO, % | 62.2 [50.2–67.6] (n = 37) | 58.3 [43.4–72.0] (n = 185) Unable to perform (n = 14) | 58.4 [44.0–71.5] (n = 153) Unable to perform (n = 7) | 57.6 [38.1–77.7] (n = 32) Unable to perform (n = 7) | 0.3516 |
GAP stage, I, II, III | 18 (48.6%), 19 (51.4%), 0 (0%) | 76 (38.2%), 90 (45.2%), 33 (16.6%) | 63 (39.4%), 74 (46.3%), 23 (14.4%) | 13 (33.3%), 16 (41.0%), 10 (25.6%) | 0.0267 |
6-min walk test | |||||
Distances, m | 432 [345–515] (n = 28) | 400 [310–484] (n = 134) | 400 [308–484] (n = 116) | 400 [180–482] (n = 18) | 0.1990 |
Minimum SpO2 < 90% | 19/28 (67.9%) | 100/134 (74.6%) | 87/116 (75.0%) | 13/18 (72.2%) | 0.4845 |
UCG | |||||
TRV ≥ 2.9 m/s | 2 (8.7%) (n = 29) | 24 (17.9%) (n = 134) | 16 (15.4%) (n = 104) | 8 (26.7%) (n = 30) | 0.1719 |
Laboratory | |||||
Hb, g/dl | 14.0 [13.2–15.1] | 13.5 [12.3–14.7] | 13.6 [12.4–14.8] | 13.3 [12.1–14.7] | 0.0612 |
TP, g/dl | 7.5 [7.2–7.9] | 7.4 [6.9–7.8] | 7.5 [7.0–7.8] | 7.3 [6.7–7.8] | 0.0855 |
Alb, g/dl | 4.1 [4.0–4.2] | 3.9 [3.6–4.1] | 3.9 [3.6–4.1] | 3.7 [3.5–4.0] | 0.0006 |
LDH, U/L | 241 [210–270] | 230 [203–273] | 228 [203–268] | 244 [206–280] | 0.8415 |
CRP, mg/dl | 0.2 [0.1–0.5] | 0.3 [0.1–0.6] | 0.3 [0.1–0.6] | 0.3 [0.1–0.6] | 0.5156 |
KL-6, U/ml | 1124 [776–1473] | 1062 [798–1524] | 1057 [796–1560] | 1105 [817–1402] | 0.7003 |
SP-D, ng/ml | 232 [136–345] | 249 [165–370] | 247 [158–375] | 251 [188–369] | 0.7278 |
Treatment | |||||
None | 30 (81.1%) | 128 (56.9%) | 126 (71.2%) | 22 (45.8%) | 0.0060 |
LTOT | 6 (16.2%) | 85 (37.8%) | 65 (36.7%) | 20 (41.7%) | 0.0144 |
Flow rate during rest | |||||
< 1, 1–3, > 3, L/min | 4, 2, 0 | 40, 42, 3 | 30, 32, 3 | 10, 10, 0 | |
Immunosuppressants | 3 (8.1%) | 50 (22.2%) | 37 (20.9%) | 13 (27.1%) | 0.0486 |
PSL | 3 | 30 | 23 | 8 | |
PSL + CyA | 0 | 11 | 7 | 4 | |
PSL + CPA | 5 | 3 | 2 | ||
PSL + Tac | 4 | 4 | 0 |
Causes of switching antifibrotics and its timing
First-line treatment (n = 37) [Pirfenidone (n = 29), Nintedanib (n = 8)] | Second-line treatment (n = 37) Nintedanib (n = 29), Pirfenidone (n = 8) | ||
---|---|---|---|
Disease progression | 17 (45.9%), [2, 15] | Gastrointestinal side effects | 4 (5.4%), [1, 3] |
Gastrointestinal disorders | 12 (32.4%), [3, 9] | Rash | 1 (2.7%), [1, 0] |
Photosensitivity | 2 (5.4%), [2, 0] | Rash and dizziness | 1 (2.7%), [0, 1] |
Liver enzyme elevation | 2 (5.4%), [1, 1] | Dizziness | 1 (2.7%), [1, 0] |
Peripheral eosinophilia | 1 (2.7%), [1, 0] | Gastrointestinal perforation | 1 (2.7%), [1, 0] |
Lung cancer development | 1 (2.7%), [1, 0] | ||
Vasospastic angina suspected | 1 (2.7%), [0, 1] | ||
Patients’ will | 1 (2.7%), [1, 0] |
Pulmonary function tests between initiations of first-line antifibrotic therapy and initiations of second-line antifibrotic therapy
Feasibility of second-line antifibrotics
Causes of death and prognosis
Switch-IPF (n = 17) | Non-Switch-IPF All cases (n = 130) | Non-Switch-IPF Continued cases (n = 96) | Non-Switch-IPF Discontinued cases (n = 34) | Non-Switch IPF versus Switch-IPF p value | |
---|---|---|---|---|---|
Chronic respiratory failure | 9 (52.9%) | 74 (56.9%) | 55 (57.3%) | 19 (55.9%) | 0.7988 |
Acute exacerbation | 4 (23.5%) | 32 (24.6%) | 23 (24.0%) | 9 (26.5%) | 1.0000 |
Lung cancer | 1 (5.9%) | 6 (4.6%) | 5 (5.2%) | 1 (2.9%) | 0.5850 |
Pneumothorax | 0 (0%) | 6 (4.6%) | 6 (6.3%) | 0 (0%) | 1.0000 |
Infection | 2 (11.8%) | 3 (2.3%) | 3 (3.1%) | 0 (0%) | 0.1024 |
Others | 1 (5.9%) | 9 (6.9%) | 4 (4.2%) | 5 (14.7%) | 1.0000 |
Differences in prognosis calculated from diagnosis of IPF
Prognostic implications of “switching antifibrotics” and prognosis of “patients with IPF who switched antifibrotics”
Predictor | HR | 95% CI | p value | HR | 95% CI | p value | |
---|---|---|---|---|---|---|---|
Univariate analysis | Multivariate analysis 1 | ||||||
Age, year | 1.024 | 1.000–1.050 | 0.0481 | Age, year | 1.003 | 0.978–1.029 | 0.8402 |
Gender, male | 1.054 | 0.652–1.624 | 0.8218 | Gender, male | 1.455 | 0.905–2.438 | 0.1365 |
History of AE, yes | 2.413 | 1.518–3.677 | < 0.0001 | History of AE, yes | 1.062 | 0.602–1.777 | 0.8268 |
Pirfenidone | 1.002 | 0.694–1.425 | 0.9892 | BMI, per 1 kg/m2 increase | 0.956 | 0.904–1.009 | 0.1051 |
Period: Diagnosis-administration | 1.001 | 0.996–1.005 | 0.7124 | FVC, per 1% increase | 0.978 | 0.967–0.989 | 0.0001 |
BMI, per 1 kg/m2 increase | 0.905 | 0.860–0.953 | 0.0001 | LTOT, yes | 1.774 | 1.205–2.590 | 0.0032 |
FVC,per 1% increase | 0.970 | 0.959–0.980 | < 0.0001 | Patients with IPF who switched antifibrotics | 0.392 | 0.221–0.656 | 0.0007 |
FEV1, per 1% increase | 0.989 | 0.979–0.999 | 0.0261 | Multivariate analysis 2 | |||
FEV1/FVC, per 1% increase | 1.061 | 1.038–1.089 | < 0.0001 | Age, year | 1.005 | 0.979–1.032 | 0.7131 |
DLCO, per 1% increase | 0.974 | 0.962–0.986 | < 0.0001 | Gender, male | 1.536 | 0.940–2.618 | 0.0992 |
TP, per 1 g/dl increase | 0.978 | 0.763–1.271 | 0.8647 | History of AE, yes | 1.214 | 0.684–2.267 | 0.5247 |
Alb, per 1 g/dl increase | 0.601 | 0.411–0.896 | 0.0105 | BMI, per 1 kg/m2 increase | 0.940 | 0.883–0.997 | 0.0440 |
KL-6, per 1 U/ml increase | 1.000 | 1.000–1.000 | 0.0003 | FVC, per 1% increase | 0.980 | 0.968–0.991 | 0.0007 |
SP-D, per 1 ng/ml increase | 1.001 | 1.000–1.002 | 0.0510 | KL-6, per 1 U/ml increase | 1.000 | 1.000–1.000 | 0.0217 |
LTOT, yes | 2.575 | 1.847–3.574 | < 0.0001 | LTOT, yes | 1.660 | 1.103–2.468 | 0.0135 |
Patients with IPF who switched antifibrotics | 0.318 | 0.182–0.506 | < 0.0001 | Patients with IPF who switched antifibrotics s | 0.374 | 0.206–0.638 | 0.0006 |
Switching antifibrotics (time dependent covariate) | 0.895 | 0.517–1.550 | 0.692 |