Background
Methods
Study population
Definition of exposure to oral OA therapies
Covariates
Clinical and demographics data
Imaging characteristics
Statistical analyses
Results
Characteristics at index date
Knee replacement | ||
---|---|---|
Case (n = 218) | Control (n = 540) | |
Time to KR after cohort entry, % (n) | ||
Between year 1 and year 2 | 10.6% (23) | – |
Between year 2 and year 3 | 15.1% (33) | – |
Between year 3 and year 4 | 18.8% (41) | – |
Between year 4 and year 5 | 17.9% (39) | – |
Between year 5 and year 6 | 12.8% (28) | – |
Between year 6 and year 7 | 7.8% (17) | – |
Between year 7 and year 8 | 8.3% (18) | – |
Between year 8 and year 9 | 8.7% (19) | – |
Median (IQR) (years) | 4.3 (1.0–8.9) | |
OAI subcohort, % (n) | ||
Progression | 61.9% (135) | 58.5% (316) |
Incidence | 38.1% (83) | 41.5% (224) |
Age (years), median (IQR) | 68.9 (61.8–74.3) | 68.6 (61.6–73.8) |
Female, % (n) | 60.6% (132) | 61.1% (330) |
Race, % (n) |
(n = 217)
| |
White or Caucasian | 83.9% (182) | 78.0% (421) |
Black or African American | 12.5% (27) | 19.4% (105) |
Asian | 1.8% (4) | 0.4% (2) |
Other non-white | 1.8% (4) | 2.2% (12) |
Income level USD, % (n) | ||
Less than $25,000 | 10.6% (23) | 12.4% (67) |
$25,000 to < $50,000 | 28.0% (61) | 30.6% (165) |
$50,000 to < $100,000 | 38.0% (83) | 38.9% (210) |
$100,000 or greater | 23.4% (51) | 18.1% (98) |
Education level, % (n) | ||
Less than high school graduate | 0.9% (2) | 4.1% (22) |
High school graduate | 19.3% (42) | 10.9% (59) |
Some college | 26.6% (58) | 30.7% (166) |
College graduate | 18.3% (40) | 18.2% (98) |
Some graduate school | 6.9% (15) | 7.2% (39) |
Graduate degree | 28.0% (61) | 28.9% (156) |
Knee replacement | ||
---|---|---|
Case (n = 218) | Control (n = 540) | |
(n = 204)
|
(n = 537)
| |
BMI ≥ 27 kg/m2, % (n) | 75.0% (153) | 70.6% (379) |
WOMAC, median (IQR) | ||
Pain (0–20) | 6.0 (4.0–9.0) | 5.0 (3.0–8.0) |
Function (0–68) | 22.2 (14.9–31.0) | 18.0 (8.5–25.5) |
Stiffness (0–10) | 3.0 (2.0–4.0) | 3.0 (2.0–4.0) |
Total (0–98) | 31.2 (21.8–43.0) | 25.0 (13.0–37.0) |
KOOS, median (IQR) | ||
Pain (0–100) | 61.1 (47.2–72.2) | 66.7 (55.6–79.3) |
Symptoms (0–100) | 64.3 (50.0–78.6) | 75.0 (58.9–85.7) |
QoL (0–100) | 43.8 (31.3–56.3) | 56.3 (43.8–68.8) |
Kellgren-Lawrence grade, % (n) | ||
0 | 1.4% (3) | 1.7% (9) |
1 | 3.7% (8) | 3.7% (20) |
2 | 19.3% (42) | 23.9% (129) |
3 | 31.6% (69) | 29.8% (161) |
4 | 44.0% (96) | 40.9% (221) |
(n = 211)
|
(n = 524)
| |
JSW (mm), median (IQR) | 2.0 (0.8–4.6) | 2.8 (1.1–4.6) |
Cartilage volume (mm3), median (IQR) |
(n = 201)
|
(n = 510)
|
Global knee | 11,037 (9127 - 13,634) | 11,058 (9351 - 13,508) |
Medial compartment | 5127 (3971 - 6482) | 5219 (4176 - 6502) |
Lateral compartment | 6028 (4864 - 7480) | 6043 (4970 - 7265) |
BML |
(n = 201)
|
(n = 511)
|
Global | ||
Median (IQR) | 2.0 (0.6–4.4) | 1.7 (0.4–3.8) |
BML ≥ 1%, % (n) | 65.7% (132) | 61.5% (314) |
Medial compartment | ||
Median (IQR) | 0.014 (0.0–0.058) | 0.021 (0.0–0.057) |
BML ≥ 1%, % (n) | 34.9% (76) | 42.2% (228) |
Lateral compartment | ||
Median (IQR) | 0.005 (0.0–0.025) | 0.0 (0.0–0.018) |
BML ≥ 1%, % (n) | 23.9% (52) | 20.7% (112) |
(n = 215)
|
(n = 532)
| |
Meniscal extrusion, % (n) | 39.5% (85) | 38.5% (205) |
Knee replacement | ||
---|---|---|
Oral OA therapies, % (n) | Case (n = 161)a | Control (n = 360)a |
Acetaminophen | ||
No exposure | 70.2% (113) | 75.0% (270) |
Exposure 1–79% | 26.7% (43) | 22.5% (81) |
Exposure ≥ 80% | 3.1% (5) | 2.5% (9) |
NSAIDs | ||
No exposure | 37.3% (60) | 51.4% (185) |
Exposure 1–79% | 38.5% (62) | 33.3% (120) |
Exposure ≥ 80% | 24.2% (39) | 15.3% (55) |
COX-2 inhibitors | ||
No exposure | 86.3% (139) | 91.1% (328) |
Exposure 1–79% | 7.5% (12) | 4.7% (17) |
Exposure ≥ 80% | 6.2% (10) | 4.2% (15) |
Narcotics | ||
No exposure | 88.8% (143) | 89.7% (323) |
Exposure 1–79% | 10.0% (16) | 7.5% (27) |
Exposure ≥ 80% | 1.2% (2) | 2.8% (10) |
Glucosamine/chondroitin sulfate | ||
No exposure | 45.3% (73) | 45.8% (165) |
Exposure 1–79% | 23.0% (37) | 23.1% (83) |
Exposure ≥ 80% | 31.7% (51) | 31.1% (112) |
Occurrence of KR
Crude OR | 95% CI |
p
b
| |
---|---|---|---|
Race: white or Caucasian (reference other race) | 1.84 | (1.13–2.99) |
0.015
|
Education level: college graduate or above (reference less than college graduate) | 0.95 | (0.65–1.38) | 0.778 |
BMI ≥ 27 kg/m2 (reference < 27 kg/m2) | 1.65 | (1.06–2.58) |
0.027
|
WOMAC | |||
Function | 1.04 | (1.02–1.06) | < 0.001 |
Stiffness | 1.25 | (1.12–1.40) |
0.001
|
Total | 1.03 | (1.02–1.04) |
< 0.001
|
KOOS | |||
Pain | 0.98 | (0.97–0.99) | < 0.001 |
Symptoms | 0.98 | (0.97–0.99) | < 0.001 |
QoL | 0.97 | (0.96–0.98) | < 0.001 |
X-ray (JSW) | 0.93 | (0.85–1.01) | 0.092 |
MRI | |||
BML | |||
By increase of 1% | 1.04 | (0.99–1.09) | 0.144 |
BML ≥ 1% (reference < 1%) | 1.41 | (0.95–2.11) | 0.091 |
Meniscal extrusion (reference no extrusion) | 1.18 | (0.80–1.73) | 0.404 |
Acetaminophen | NSAIDs | COX-2 inhibitors | Narcotics | Glucosamine/chondroitin sulfate | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
n
| ORb | 95% CI |
p
c
|
n
| ORb | 95% CI |
p
c
|
n
| ORb | 95% CI |
p
c
|
n
| ORb | 95% CI |
p
c
|
n
| ORb | 95% CI |
p
c
| |
Primary analysis | ||||||||||||||||||||
In the 3 years prior to index date (n = 521: 161 KR/360 controls) | ||||||||||||||||||||
Exposure 1–79%a | 124 | 1.09 | (0.66–1.78) | 0.745 | 313 | 1.05 | (0.64–1.72) | 0.839 | 68 | 1.13 | (0.48–2.67) | 0.784 | 67 | 1.00 | (0.48–2.09) | 0.995 | 120 | 0.85 | (0.50–1.48) | 0.573 |
Exposure ≥ 80%a | 14 | 1.11 | (0.30–4.09) | 0.872 | 44 | 1.66 | (0.93–2.95) | 0.086 | 21 | 1.15 | (0.47–2.83) | 0.761 | ND | 163 | 0.73 | (0.43–1.23) | 0.236 | |||
Secondary Analyses | ||||||||||||||||||||
In the 2 years prior to index date (n = 642: 193 KR/449 controls) | ||||||||||||||||||||
Exposure 1–79%a | 210 | 1.10 | (0.66–1.84) | 0.722 | 369 | 0.96 | (0.60–1.54) | 0.853 | 88 | 1.40 | (0.57–3.48) | 0.465 | 77 | 1.19 | (0.54–2.58) | 0.670 | 255 | 0.70 | (0.39–1.26) | 0.235 |
Exposure ≥ 80%a | 20 | 1.46 | (0.69–3.11) | 0.322 | 58 | 1.41 | (0.88–2.26) | 0.159 | 27 | 1.18 | (0.55–2.52) | 0.671 | ND | 166 | 1.00 | (0.65–1.55) | 0.989 | |||
In the 4 years prior to index date (n = 363: 121 KR/242 controls) | ||||||||||||||||||||
Exposure 1–79%a | 113 | 1.34 | (0.74–2.41) | 0.333 | 234 | 1.40 | (0.78–2.52) | 0.256 | 50 | 1.63 | (0.64–4.13) | 0.303 | 50 | 1.43 | (0.62–3.33) | 0.405 | 156 | 0.65 | (0.33–1.25) | 0.191 |
Exposure ≥ 80%a | ND | 26 | 1.65 | (0.75–3.66) | 0.215 | ND | ND | 83 | 0.63 | (0.32–1.21) | 0.165 | |||||||||
In the 5 years prior to index date (n = 228: 82 KR/146 controls) | ||||||||||||||||||||
Exposure 1–79%a | 60 | 1.38 | (0.66–2.88) | 0.397 | 110 | 1.88 | (0.85–4.20) | 0.121 | 18 | 1.35 | (0.41–4.49) | 0.623 | 33 | 1.19 | (0.48–2.93) | 0.706 | 54 | 0.90 | (0.37–2.14) | 0.803 |
Exposure ≥ 80%a | 15 | 1.66 | (0.44–6.35) | 0.457 | 45 | 2.27 | (0.90–5.71) | 0.081 | ND | ND | 70 | 0.73 | (0.33–1.64) | 0.445 |