Introduction
Materials and methods
Patients
Treatment
Clinical assessments
Radiographic assessments
Sandwich enzyme-linked immunosorbent assay for determination of serum MMP-3
Statistical analysis
Results
Demographic characteristics of RA patients at baseline
Characteristics | All patients (n = 56) | Non-progressive group (n = 40) | Progressive group (n = 16) |
P* |
---|---|---|---|---|
Demographic | ||||
Age, yrs, median (IQR) | 48 (37 ~ 57) | 48 (37 ~ 58) | 51 (38 ~ 56) | 0.863 |
Female, n (%) | 43 (77) | 33 (83) | 10 (63) | 0.211 |
Disease duration, mo, median (IQR) | 24 (12 ~ 55) | 17 (12 ~ 36) | 24 (13 ~ 117) | 0.154 |
Short duration, n (%) | 5 (9) | 3 (1) | 2 (13) | 0.941 |
Intermediate duration, n (%) | 32 (57) | 25 (63) | 7 (44) | 0.200 |
Long duration, n (%) | 19 (34) | 12 (30) | 7 (44) | 0.326 |
Core disease activity indicators | ||||
ESR (mm/h), median (IQR) | 56 (37 ~ 72) | 56 (39 ~ 72) | 57 (36 ~ 81) | 0.856 |
CRP (mg/dl), median (IQR) | 1.4 (0.7 ~ 3.3) | 1.3 (0.6 ~ 3.0) | 1.7 (0.9 ~ 5.5) | 0.214 |
RF (mg/ml), median (IQR) | 206 (61 ~ 475) | 211 (42 ~ 465) | 178 (69 ~ 510) | 0.885 |
Anti-CCP (U/ml), median (IQR) | 132 (32 ~ 300) | 78 (26 ~ 300) | 178 (53 ~ 425) | 0.178 |
SDAI, median (IQR) | 27.7 (16.0 ~ 39.5) | 29.3 (14.2 ~ 42.6) | 22.1 (16.3 ~ 36.1) | 0.479 |
CDAI, median (IQR) | 25.0 (14.3 ~ 36.8) | 27.0 (13.0 ~ 39.0) | 19.0 (15.3 ~ 32.8) | 0.345 |
DAS28, median (IQR) | 5.1 (3.8 ~ 5.9) | 5.1 (3.9 ~ 6.1) | 4.6 (3.9 ~ 5.7) | 0.514 |
Poor prognosis features | ||||
Function limitation, n (%) | 30 (54) | 20 (50) | 10 (63) | 0.397 |
RF positive, n (%) | 47 (84) | 32 (80) | 15 (94) | 0.388 |
Anti-CCP positive, n (%) | 46 (82) | 31 (78) | 15 (94) | 0.295 |
Extraarticular disease, n (%) | 1 (2)a
| 0 | 1 (2) | NA |
Bony erosions, n (%) | 52 (93) | 36 (90) | 16 (100) | 0.460 |
Total Sharp score, median (IQR) | 11 (3 ~ 25) | 8 (3 ~ 16) | 22 (13 ~ 43) |
0.003
|
Joint narrow score, median (IQR) | 6 (1 ~ 13) | 3 (1 ~ 8) | 11 (6 ~ 25) |
0.014
|
Erosion score, median (IQR) | 5 (2 ~ 13) | 4 (1 ~ 7) | 13 (8 ~ 20) |
0.001
|
Serum MMP-3 (ng/ml), median (IQR) | 175 (57 ~ 365) | 123 (45 ~ 276) | 316 (195 ~ 563) |
0.010
|
Hepatitis B virus infection, n (%) | 5 (9) | 2 (5) | 3 (19) | 0.135 |
Previous medications | ||||
DMARDs and corticosteroids naïve, n (%) | 26 (46) | 21 (53) | 5 (31) | 0.253 |
Corticosteroids, n (%) | 17 (30) | 11 (28) | 6 (38) | NA |
Irregular, n (%) | 9 (16) | 5 (13) | 4 (25) | NA |
Prednisolone 10 mg/d, n (%) | 4 (7) | 4 (10) | 0 (0) | NA |
Prednisolone 5 mg/d, n (%) | 4 (7) | 2 (5) | 2 (13) | NA |
Methotrexate, n (%) | 21 (38) | 12 (30) | 9 (56) | NA |
Leflunomide, n (%) | 10 (18) | 7 (18) | 3 (19) | NA |
Sulfasalazine, n (%) | 3 (5) | 2 (5) | 1 (6) | NA |
Hydroxychloroquine, n (%) | 7 (13) | 3 (8) | 4 (25) | NA |
Cyclosporin A, n (%) | 2 (4) | 2 (5) | 0 | NA |
Infliximab, n (%) | 2 (4) | 0 | 2 (12) | NA |
YSP, n (%) | 2 (4) | 2 (5) | 0 | NA |
Clinical response and radiographic outcome
Disease activity indicators | 1st month | 3rd month | 6th month | 12th month |
---|---|---|---|---|
28TJC, median (IQR) | 4 (1 ~ 9)*** | 2 (0 ~ 4)*** | 0 (0 ~ 4)*** | 1 (0 ~ 5)*** |
28SJC, median (IQR) | 2 (0 ~ 4)*** | 0 (0 ~ 3)*** | 0 (0 ~ 1)*** | 0 (0 ~ 1)*** |
Pain VAS, median (IQR) | 2.0 (1.7 ~ 4.0)*** | 2.0 (0 ~ 3.0)*** | 1.0 (0 ~ 2.8)*** | 1.0 (0 ~ 3.0)*** |
PtGA, median (IQR) | 3.0 (3.0 ~ 5.0)*** | 3.0 (1.0 ~ 4.0)*** | 2.0 (0.3 ~ 3.0)*** | 2.0 (0 ~ 3.8)*** |
PrGA, median (IQR) | 3.0 (2.3 ~ 4.0)*** | 2.0 (1.0 ~ 4.0)*** | 2.0 (0 ~ 3.0)*** | 2.0 (0 ~ 3.0)*** |
HAQ, median (IQR) | 0.28 (0 ~ 0.94)*** | 0.15 (0 ~ 0.50)*** | 0 (0 ~ 0.25)*** | 0 (0 ~ 0.46)*** |
CRP, mg/dl, median (IQR) | 0.44 (0.33 ~ 1.19)*** | 0.33 (0.30 ~ 0.95))*** | 0.34 (0.18 ~ 0.49)*** | 0.33 (0.30 ~ 0.89)*** |
Normal CRPa, % | 54 | 59 | 77 | 70 |
ESR, mm/h, median (IQR) | 34 (18 ~ 48)*** | 29 (16 ~ 38)*** | 21 (15 ~ 36)*** | 26 (13 ~ 42)*** |
Norma ESRb, % | 27 | 38 | 41 | 39 |
DAS28c, median (IQR) | 3.5 (2.6 ~ 4.4)*** | 2.7 (2.0 ~ 3.9)*** | 2.2 (1.5 ~ 3.2)*** | 2.6 (1.5 ~ 3.3)*** |
Remission, % | 27 | 43 | 53 | 48 |
LDA, % | 20 | 20 | 20 | 21 |
MDA, % | 44 | 30 | 20 | 26 |
HDA, % | 9 | 7 | 7 | 5 |
SDAId, median (IQR) | 14.5 (7.6 ~ 24.2)*** | 8.9 (4.1 ~ 17.5)*** | 5.3 (1.0 ~ 12.0)*** | 6.4 (0.3 ~ 12.3)*** |
Remission, % | 7 | 18 | 39 | 34 |
LDA, % | 34 | 41 | 36 | 38 |
MDA, % | 38 | 30 | 16 | 19 |
HDA, % | 21 | 11 | 9 | 9 |
CDAIe, median (IQR) | 13.7 (7.1 ~ 22.8)*** | 8.0 (4.0 ~ 15.9)*** | 4.5 (1.0 ~ 11.5)*** | 5.5 (0 ~ 11.0)*** |
Remission, % | 7 | 18 | 39 | 38 |
LDA, % | 34 | 45 | 36 | 36 |
MDA, % | 34 | 26 | 16 | 16 |
HDA, % | 25 | 11 | 9 | 11 |
Serum MMP-3, ng/ml, median (IQR) | 112 (49 ~ 347) | 130 (32 ~ 183) | 74 (32 ~ 183)* | 52 (32 ~ 116)*** |
Normal serum MMP-3f, % | 32 | 38 | 46 | 62 |
RF, mg/ml, median (IQR) | 119 (39 ~ 252)*** | 72 (20 ~ 169)*** | 49 (14 ~ 137)*** | 78(16 ~ 142)*** |
Anti-CCP, U/ml, median (IQR) | 85 (11 ~ 300)** | 53 (13 ~ 296)*** | 65 (16 ~ 297)** | 112(14 ~ 300)* |
Dynamic change of disease activity indicators and serum MMP-3
Predictors of one-year radiographic progression
Disease activity indicators | Accuracy |
P
| 95 % CI
| Cutoff point | PPV (%) | NPV (%) |
OR (95 % CI) |
P
|
---|---|---|---|---|---|---|---|---|
Baseline | ||||||||
Serum MMP-3 | 0.721 | 0.010 | 0.572 ~ 0.870 | 159 ng/ml | 46.7 | 92.3 | 10.500 (2.097 ~ 52.581) | 0.004 |
Total Sharp score | 0.753 | 0.003 | 0.613 ~ 0.893 | 15 | 54.5 | 88.2 | 9.000 (2.359 ~ 34.334) | 0.001 |
1st month | ||||||||
CRP | 0.680 | 0.037 | 0.525 ~ 0.835 | 1.76 mg/dl | 66.7 | 78.7 | 7.400 (1.567 ~ 34.935) | 0.011 |
Serum MMP-3 | 0.758 | 0.003 | 0.605 ~ 0.911 | 264 ng/ml | 64.7 | 87.2 | 12.467 (3.175 ~ 48.950) | < 0.001 |
3rd month | ||||||||
Serum MMP-3 | 0.766 | 0.002 | 0.606 ~ 0.926 | 178 ng/ml | 64.7 | 87.2 | 15.857 (3.412 ~ 73.687) | < 0.001 |
6th month | ||||||||
28SJC | 0.667 | 0.052 | 0.503 ~ 0.832 | NA | NA | NA | NA | NA |
CRP | 0.681 | 0.035 | 0.525 ~ 0.838 | 0.64 mg/dl | 58.3 | 79.5 | 5.444 (1.395 ~ 21.244) | 0.015 |
Serum MMP-3 | 0.830 | < 0.001 | 0.696 ~ 0.963 | 161 ng/ml | 75.0 | 90.0 | 27.000 (5.834 ~ 24.962) | < 0.001 |
Dynamic serum MMP-3 and T2T strategy
Serum MMP-3 | Accuracy |
P
| 95 % CI
| Cutoff point | PPV (%) | NPV (%) |
OR (95 % CI) |
P
|
---|---|---|---|---|---|---|---|---|
Baseline | 0.745 | 0.044 | 0.564 ~ 0.925 | 242 ng/ml | 37.5 | 95.8 | 13.800 (1.464 ~ 130.070) | 0.022 |
1st month | 0.801 | 0.013 | 0.606 ~ 0.996 | 297 ng/ml | 55.6 | 93.5 | 18.125 (2.592 ~ 126.721) | 0.003 |
3rd month | 0.784 | 0.020 | 0.564 ~ 1.003 | 193 ng/ml | 55.6 | 93.5 | 18.125 (2.592 ~ 126.721) | 0.003 |
6th month | 0.840 | 0.005 | 0.658 ~ 1.022 | 161 ng/ml | 62.5 | 93.8 | 25.000 (3.302 ~ 189.259) | 0.002 |