Background
Patients and methods
Study design
Eligibility of patients
Exclusion criteria
Related to the OA pathology | |
• Bilateral (except asymptomatic and grade I) OA of the knee • Radiological K&L grade I or IV • Chondromatosis or villonodular synovitis of the knee • Recent trauma (< 1 month) of the knee responsible of the symptomatic knee • Acute inflammatory osteoarthritis (Kofus ≥7) • Articular disease resulting from articular dysplasia, aseptic osteonecrosis, acromegaly, Paget’s disease, hemophilia, hemochromatosis…. • Inflammatory disease i.e. rheumatoid arthritis, gout and infectious arthritis, acute calcium pyrophosphate arthritis • Pathologies interfering with the evaluation of OA (radiculalgia in the lower limbs, arteritis…..) • Presence of another joint (other than the target knee) affected by OA (confirmed in radiographs and symptomatic) | |
Related to treatments | |
• Corticosteroids injection in the target knee in the last month before first injection • Hyaluronan injection in the target knee in the last 6 months before first injection • Arthroscopy and surgery in the target knee in the last 6 months before first injection • Oral corticotherapy ≥5 mg/day (in Prednisone equivalent) in the last 3 months before first injection • OA treatments based on curcuma extract (e.g. FLEXOFYTOL) in the last 3 months before first injection • Change in the dosage of symptomatic slow-acting drugs (SYSAD) i.e. chondroitin, glucosamine, diacerein or avocado-soya unsaponifiables in the last 3 months before first injection • Paracetamol and oral NSAIDs before inclusion and follow-up visits (washout period depending on the half-life of the drug). • Osteoporosis-related treatments based on strontium ranelate, selective estrogen-receptor modulator (SERM) and parathormone (PTH) in the last 12 months before first injection • An anticipated need for any forbidden OA treatments during the trial • Contraindications to HYMOVIS®: hypersensitivity to the product components and infections or skin diseases in the area of the injection site • Non-pharmacologic therapy (including physical therapy) for the lower extremities initiated in the month before first injection • Anticoagulant (coumarinic compound) and heparin | |
Related to associated diseases | |
• Severe diseases (liver or renal failure, lung/heart disease, tumor, HIV….) • Allergy or contra-indication to hyaluronan and constituents • Severe alteration of mobility unabling functional evaluation • High risk of hemorrhage and risk of infection at the site of injection • Anticipated need for any surgical or other invasive procedure during the trial including prosthesis in the target knee | |
Related to patients | |
• Participation to a therapeutic clinical trial in the last 3 months before first injection • Under guardianship or judicial protection • Pregnancy, breastfeeding, planned conception, premenopausal women without contraception, tubal ligation or hysterectomy | |
Related to MRI counter-indication | |
• Patient with a pacemaker, an implantable defibrillator, neurosurgical clips, a neurostimulator, cochlear implant, a stent from less than 3 weeks, an insulin pump • Patient with a ferromagnetic splinter in the body, or having wire sutures • Serious mobility problem (Parkinson, tremors), • Claustrophobia |
Prohibited/authorized treatments
Outcomes measures
Primary outcomes
Secondary outcomes
Statistical analysis
Sample size
Analysis of the primary outcome
Analysis of the secondary outcomes
Results
Study population
Patient characteristics
Age (years; mean (SD) | 61.4 (9.6) |
---|---|
Sex (%) | |
Women | 67.4% |
Men | 32.6% |
BMI (Kg/m2; mean (SD)) | 30.6 (5) |
Disease duration (years; mean (SD)) | 4.54 (5.9) |
Evaluated knee (%) | |
Left | 32.6% |
Right | 67.4% |
Radiological score (Kellgren &Lawrence) | |
Score II | 63% |
Score III | 37% |
Primary efficacy outcomes
D0 | D30 | D90 | D180 | D210 | D360 | |
---|---|---|---|---|---|---|
sColl2–1(nM) | n = 46; 498.66 (297.61;647.44) | n = 46; 578.30 (399.97;724.51) | n = 43; 634.46 (439.25;787.76) | n = 43; 635.01 (484.51;824.38) | n = 39; 622.47 (476.03;858.14) | n = 42;722.09 (469.99;883.08) |
Change from baseline | n = 46; 20.84 (−42.75;132.08) | n = 43; 50.25 (−42.03;242.73) | n = 43; 149.62 (28.17;297.19) | n = 39; 138.98 (−52.42;241.88) | n = 42;135.36 (−6.52;319.60) | |
P-value vs D0 | 0.098 | 0.021 | < 0.001 | 0.010 | < 0.001 | |
sColl2-NO2(pg/ml) | n = 30; 340.21 (266.24;425.99) | n = 36; 268.61 (206.13;370.75) | n = 34; 293.75 (233.64;464.92) | n = 34; 336.82 (265.68;450.43) | n = 29; 396.35 (284.85;598.79) | n = 31; 384.53 (303.84;663.99) |
Change from baseline | n = 30; −28.54 (−71.03;53.08) | n = 27; −17.33 (−64.21;67.82) | n = 26; 18.57 (−49.93;120.00) | n = 22; 29.31 (− 67.38;198.32) | n = 25; 69.75 (− 13.51;294.24) | |
P-value vs D0 | 0.243 | 0.907 | 0.225 | 0.272 | 0.027 | |
uCTX-II (ug/mmol creatinine) | n = 37; 0.012 (0.009;0.015) | n = 37; 0.012 (0.009;0.015) | n = 34; 0.010 (0.008;0.016) | n = 37; 0.012 (0.009;0.015) | n = 34; 0.011 (0.008;0.015) | n = 36; 0.012 (0.008;0.016) |
Change from baseline | n = 33; 0.001 (−0.002;0.003) | n = 31; 0.000 (−0.003;0.002) | n = 33; 0.000 (− 0.002;0.002) | n = 31; 0.000 (− 0.002;0.003) | n = 33; 0.000 (− 0.003;0.003) | |
P-value vs D0 | 0.733 | 0.924 | 0.882 | 0.924 | 0.910 | |
sPIINP (ng/ml) | n = 45; 599.50 (502.45; 812.42) | n = 42; 667.45 (519.13; 827.70) | n = 40; 708.90 (548.63; 873.46) | n = 41; 780.20 (572.88; 983.53) | n = 37; 858.79 (738.85;1061.52) | n = 37; 1057.41 (726.91;1268.47) |
Change from baseline | n = 41; 31.2 (−87.64;117.27) | n = 40; 74.82 (−83.03;193.95) | n = 41; 96.97 (5.27;298.16) | n = 37; 190.11 (138.91;319.81) | n = 37; 433.90 (136.71;573.78) | |
P-value vs D0 | 0.954 | 0.038 | < 0.001 | < 0.001 | < 0.001 | |
sColl2–1(nM)/sPIINP (ng/ml) | n = 45; 0.72 (0.53; 0.96) | n = 42; 0.80 (0.56; 1.03) | n = 40; 0.69 (0.56; 1.05) | n = 41; 0.81 (0.62; 1.00) | n = 37; 0.69 (0.54;0.93) | n = 37; 0.56 (0.48;0.81) |
Change from baseline | n = 41; 0.04 (−0.11; 0.26) | n = 40; − 0.02 (− 0.18; 0.30) | n = 41; 0.04 (− 0.14; 0.36) | n = 37; − 0.04 (− 0.26; 0.22) | n = 37; − 0.11 (− 0.28; 0.00) | |
P-value vs D0 | 0.291 | 0.677 | 0.257 | 0.678 | 0.005 | |
uCTX-II (ng/mmol creatinine)/ sPIINP (ng/ml) | n = 36; 0.019 (0.012; 0.027) | n = 33; 0.018 (0.012; 0.026) | n = 33; 0.015 (0.011; 0.022) | n = 36; 0.016 (0.011; 0.024) | n = 33; 0.014 (0.011; 0.020) | n = 31; 0.012 (0.008; 0.019) |
Change from baseline | n = 28; −0.001 (− 0.004; 0.003) | n = 30; − 0.004 (− 0.008; 0.002) | n = 32; − 0.003 (− 0.008; 0.001) | n = 30; − 0.004 (− 0.010; − 0.001) | n = 28; − 0.006 (− 0.013; − 0.001) | |
P-value vs D0 | 0.219 | 0.041 | 0.010 | 0.004 | 0.001 | |
sCS-846 (ng/ml) | n = 38; 153.03 (124.60;186.18) | n = 38; 141.94 (125.27;185.74) | n = 36; 150.27 (114.88;180.88) | n = 37; 163.23 (134.32;185.58) | n = 36; 153.50 (121.16;178.61) | n = 39; 157.41 (130.60;186.27) |
Change from baseline | n = 34; −6.35 (−19.86;12.92) | n = 32; −5.52 (−24.24;19.69) | n = 31; −1.54 (− 18.28;22.55) | n = 30; − 1.97 (− 19.82;20.00) | n = 33; 2.67 (− 17.60;19.17) | |
P-value vs D0 | 0.086 | 0.419 | 0.863 | 0.756 | 0.787 | |
sCOMP (ng/ml) | n = 46; 796.15 (615.97;1044.40) | n = 45; 823.23 (617.95;1032.53) | n = 43; 737.14 (602.20;982.47) | n = 43; 740.58 (626.94;968.86) | n = 39; 763.79 (573.95;991.30) | n = 42; 846.46 (613.54;1060.12) |
Change from baseline | n = 45; −14.69 (−94.76;118.464) | n = 43; −4.86 (− 164.98;89.46) | n = 43; −26.32 (− 116.87;79.57) | n = 39; −24.32 (− 98.96;108.31) | n = 42; 15.30 (− 123.31;109.46) | |
P-value vs D0 | 0.934 | 0.310 | 0.404 | 0.701 | 0.936 | |
sMMP-3 (ng/ml) | n = 46; 14.86 (11.99;20.90) | n = 46; 15.75 (12.48;23.64) | n = 43; 16.36 (13.71;22.17) | n = 42; 15.87 (12.05;21.91) | n = 38; 15.95 (12.54;22.27) | n = 42; 14.87 (11.03;19.16) |
Change from baseline | n = 46; 1.19 (−1.11;3.17) | n = 43; 1.61 (− 1.37;3.53) | n = 42; 0.62 (−2.64;3.33) | n = 38; 0.85 (− 1.81;2.68) | n = 42; −0.03 (−3.21;2.57) | |
P-value vs D0 | 0.138 | 0.041 | 0.726 | 0.420 | 0.792 | |
sIL-6 (pg/ml) | n = 46; 1.62 (1.23;2.16) | n = 45; 1.70 (1.35;2.63) | n = 41; 1.67 (1.29;2.61) | n = 42; 1.54 (1.20;2.33) | n = 37; 1.71 (1.21;2.73) | n = 42; 1.95 (1.35;2.86) |
Change from baseline | n = 45; 0.19 (−0.23;0.51) | n = 41; 0.04 (− 0.30;-0.61) | n = 42; 0.014 (− 0.23;0.49) | n = 37; 0.175 (− 0.28;0.44) | n = 42; 0.26 (− 0.31;1.04) | |
P-value vs D0 | 0.119 | 0.448 | 0.534 | 0.410 | 0.081 | |
sMPO (ng/ml) | n = 44; 176.08 (128.28;251.10) | n = 44; 189.13 (104.79;260.37) | n = 41; 182.85 (132.41;288.12) | n = 41; 184.19 (105.37;264.12) | n = 35; 158.36 (87.61;250.25) | n = 38; 168.92 (11.21;239.39) |
Change from baseline | n = 43; −3.77 (−52.92;69.34) | n = 40; 1.32 (−45.19;75.32) | n = 39; 0.07 (−71.70;78.37) | n = 34; −24.03 (−64.88;39.60) | n = 36; − 11.28 (− 39.45;12.45) | |
P-value vs D0 | 0.767 | 0.412 | 0.816 | 0.183 | 0.202 |
D0 | D30 | D90 | D180 | D210 | D360 | |
---|---|---|---|---|---|---|
sColl2–1(nM) | n = 28; 462.04 (297.03;604.49) | n = 28; 556.76 (399.84;692.02) | n = 28; 653.36 (429.74;757.79) | n = 28; 599.67 (456.70;725.51) | n = 24; 557.73 (460.48;818.09) | n = 27; 598.44 (408.51;858.57) |
Change from baseline | n = 28; 37.03 (−45.30;140.52) | n = 28; 61.29 (−31.90;250.43) | n = 28; 106.88 (31.31;265.17) | n = 24; 145.72 (−40.33;201.72) | n = 27; 123.74 (−6.52;273.51) | |
P-value vs D0 | 0.162 | 0.018 | 0.001 | 0.066 | 0.005 | |
sColl2-NO2 (pg/ml) | n = 20; 335.13 (268.79;467.17) | n = 23; 271.58 (222.80;393.76) | n = 23; 283.65 (212.03;599.42) | n = 22; 317.89 (264.34;450.43) | n = 18; 491.21 (271.25;624.31) | n = 20; 485.38 (307.04;740.40) |
Change from baseline | n = 20; −34.88 (−65.31;62.77) | n = 18; −36.62 (−73.09;87.12) | n = 18; −9.71 (− 65.55;104.32) | n = 14; 44.37 (− 67.38;202.55) | n = 16; 76.89 (−55.92;334.31) | |
P-value vs D0 | 0.498 | 0.832 | 0.899 | 0.426 | 0.175 | |
uCTX-II (ug/mmol creatinine) | n = 24; 0.012 (0.008;0.014) | n = 25; 0.012 (0.009;0.015) | n = 23; 0.010 (0.008;0.016) | n = 26; 0.012 (0.009;0.014) | n = 23; 0.011 (0.007;0.015) | n = 23; 0.010 (0.008;0.014) |
Change from baseline | n = 23; 0.001 (−0.002;0.003) | n = 21; 0.001 (−0.003;0.001) | n = 23; 0.000 (− 0.003;0.003) | n = 21; 0.000 (− 0.002;0.003) | n = 22; − 0.001 (− 0.003;0.002) | |
P-value vs D0 | 0.357 | 0.626 | 0.791 | 0.987 | 0.420 | |
sPIINP (ng/ml) | n = 27; 590.14 (500.89; 740.87) | n = 24; 651.57 (529.91; 875.12) | n = 26; 697.9 (544.21; 858.85) | n = 27; 780.2 (572.88; 999.99) | n = 22; 865.69 (752.23;1075.72) | n = 24; 1002.69 (664.39;1263.72) |
Change from baseline | n = 23; 5.83 (−87.64;87.38) | n = 26; 57.68 (− 96.03;172.51) | n = 27; 90.35 (−23.12;298.16) | n = 22; 198.77 (144.54;368.52) | n = 24; 417.05 (115.26;529.05) | |
P-value vs D0 | 0.791 | 0.434 | 0.004 | < 0.001 | < 0.001 | |
sColl2–1 (nM)/sPIINP (ng/ml) | n = 27; 0.66 (0.49; 0.96) | n = 24; 0.69 (0.45; 0.93) | n = 26; 0.78 (0.60; 1.00) | n = 27; 0.76 (0.60; 0.94) | n = 22; 0.61 (0.54;0.82) | n = 24; 0.52 (0.44;0.62) |
Change from baseline | n = 23; 0.07 (−0.09; 0.24) | n = 26; 0.00 (− 0.08; 0.34) | n = 27; 0.04 (− 0.21; 0.20) | n = 22; − 0.04 (− 0.40; 0.12) | n = 24; − 0.12 (− 0.30; − 0.01) | |
P-value vs D0 | 0.465 | 0.258 | 0.665 | 0.306 | 0.022 | |
uCTX-II (ng/mmol creatinine)/ sPIINP (ng/ml) | n = 23; 0.018 (0.010; 0.028) | n = 21; 0.025 (0.011; 0.029) | n = 22; 0.015 (0.010; 0.018) | n = 25; 0.016 (0.011; 0.024) | n = 22; 0.012 (0.008; 0.016) | n = 20; 0.011 (0.007; 0.019) |
Change from baseline | n = 18; −0.001 (− 0.004; 0.003) | n = 20; − 0.002 (− 0.007; 0.002) | n = 22; − 0.004 (− 0.008; 0.002) | n = 20; − 0.003 (− 0.011; − 0.001) | n = 19; −0.007 (− 0.013; − 0.002) | |
P-value vs D0 | 0.777 | 0.218 | 0.046 | < 0.001 | < 0.001 | |
sCS-846 (ng/ml) | n = 23; 140.14 (117.75;186.18) | n = 23; 127.73 (123.57;188.92) | n = 24; 131.47 (113.90;174.13) | n = 24; 156.04 (127.58;183.30) | n = 23; 161.33 (120.75;174.33) | n = 25; 164.94 (135.04;204.99) |
Change from baseline | n = 21; − 1.82 (− 17.50;5.25) | n = 21; −7.30 (−23.49;7.85) | n = 20; 13.64 (−5.99;20.73) | n = 19; 1.534 (− 15.11;29.84) | n = 21; 11.30 (−4.93;24.80) | |
P-value vs D0 | 0.352 | 0.212 | 0.231 | 0.651 | 0.143 | |
sCOMP (ng/ml) | n = 28; 802.85 (613.44;1050.03) | n = 28; 855.56 (607.44;1097.99) | n = 28; 746.93 (611.46;979.58) | n = 28; 751.8 (617.94;977.22) | n = 24; 770.23 (584.69;1014.59) | n = 27; 800.09 (613.54;1060.12) |
AChange from baseline | n = 28; 26.33 (−43.24;152.94) | n = 28; 5.75 (−107.05;107.18) | n = 28; − 10.06 (− 109.63;121.00) | n = 24; − 33.70 (− 113.39;103.32) | n = 27; 13.56 (− 133.86;109.46) | |
P-value vs D0 | 0.176 | 0.929 | 0.947 | 0.678 | 0.797 | |
sMMP-3 (ng/ml) | n = 28; 14.67 (11.89;21.58) | n = 28; 16.43 (12.14;23.93) | n = 28; 15.98 (13.92;22.67) | n = 28; 16.00 (12.23;22.15) | n = 24; 16.53 (12.9;23.0) | n = 27; 15.63 (11.56;24.06) |
Change from baseline | n = 28; 1.19 (−0.91;2.97) | n = 28; 1.94 (− 0.19;4.29) | n = 28; 0.91 (−2.52;3.48) | n = 24; 1.39 (− 0.92;2.7) | n = 27; 0.46 (−1.99;3.58) | |
P-value vs D0 | 0.282 | 0.006 | 0.348 | 0.071 | 0.511 | |
sIL-6 (pg/ml) | n = 28; 1.47 (1.10;2.00) | n = 27; 1.60 (1.22;2.35) | n = 27; 1.67 (1.28;2.42) | n = 28; 1.49 (1.11;2.47) | n = 23; 1.48 (1.13;2.23) | n = 27; 1.83 (0.97;2.86) |
Change from baseline | n = 27; 0.21 (−0.12;0.48) | n = 27; 0.03 (− 0.30;-0.61) | n = 28; − 0.004 (− 0.11;0.49) | n = 23; 0.21 (− 0.09;0.46) | n = 27; 0.33 (− 0.13;1.13) | |
P-value vs D0 | 0.030 | 0.481 | 0.348 | 0.108 | 0.017 | |
sMPO (ng/ml) | n = 27; 199.49 (140.46;264.05) | n = 28; 240.45 (134.93;308.59) | n = 28; 187.17 (142.02;336.18) | n = 28; 208.81 (114.126;285.47) | n = 22; 161.96 (82.81;241.45) | n = 24; 174.51 (93.23;216.50) |
Change from baseline | n = 27; 36.24 (−41.33;96.54) | n = 27; 30.40 (−48.99;84.18) | n = 27; 22.83 (−71.70;95.12) | n = 21; −16.46 (−62.60;39.60) | n = 23; − 4.74 (− 43.30;24.41) | |
P-value vs D0 | 0.160 | 0.237 | 0.481 | 0.317 | 0.555 |
Secondary efficacy outcomes
Biological parameters
MRI features
D0 | D180 | D360 | |
---|---|---|---|
WORMS total score | 63.95 (27.78) | 64.39 (27.71) | 64.08 (28.03) |
Change from baseline | 0.38 (1.77) | 0.96 (2.75) | |
p value | 0.183 | 0.037 | |
Cartilage | 23.83 (11.27) | 23.01 (11.13) | 23.03 (11.45) |
Change from baseline | 0.18 (0.70) | 0.45 (1.21) | |
p value | 0.188 | 0.025 | |
Cyst | 2.73 (2.65) | 2.83 (2.65) | 2.90 (2.62) |
Change from baseline | 0.10 (0.30) | 0.23 (0.63) | |
p value | 0.125 | 0.047 | |
Effusion | 0.93 (0.69) | 0.76 (0.54) | 0.77 (0.54) |
Change from baseline | −0.17 (0.38) | −0.15 (0.54) | |
p value | 0.016 | 0.148 |
Mean T2 relaxation time (ms) | SD of relaxation time (ms) | ||||
---|---|---|---|---|---|
Median (IQR) n = 38 | p-value | Median (IQR)n = 38 | p-value | ||
Whole Patella- whole layer | D180 vs D0 D360 vs D0 | 2.822 (− 3.872; 8.996) 1.168 (− 7.721; 9.410) | 0.403 0.593 | 0.627 (−3.895; 7.427) 0.236 (− 9.654; 7.812) | 0.480 0.960 |
Whole Patella- top layer | D180 vs D0 D360 vs D0 | 4.446 (−6.977; 16.697) 4.937 (− 10.051; 21.672) | 0.320 0.327 | 6.644 (− 21.994; 20.796) 1.413 (− 16.726; 28.354) | 0.593 0.603 |
Whole Patella- middle layer | D180 vs D0 D360 vs D0 | 1.236 (−2.881; 6.889) 0.125 (− 6.598; 7.365) | 0.356 0.803 | 0.788 (− 4.667; 6.221) − 0.333 (− 11.132; 13.976) | 0.603 0.870 |
Whole Patella- bottom layer | D180 vs D0 D360 vs D0 | 0.202 (− 3.239; 5.418) − 0.228 (− 2.205; 5.368) | 0.545 0.633 | 1.115 (− 2.416; 5.700) 0.408 (− 4.172; 6.304) | 0.320 0.644 |
Medial trochlea - whole layer | D180 vs D0 D360 vs D0 | −2.354 (− 16.342; 4.102) − 2.429 (− 12.540; 0.968) | 0.061 0.019 | −1.959 (− 8.472; 1.353) − 0.818 (− 6.424; 1.126) | 0.008 0.107 |
Medial trochlea - top layer | D180 vs D0 D360 vs D0 | −1.768 (− 8.476; 1.722) − 1.777 (− 9.093; 2.549) | 0.027 0.075 | −1.774 (− 6.983; 1.804) − 0.449 (− 5.186; 1.711) | 0.023 0.229 |
Medial trochlea - middle layer | D180 vs D0 D360 vs D0 | 1.606 (− 14.664; 2.549) − 1.45 (− 10.896; 0.991) | 0.032 0.024 | −2.074 (− 9.846; 2.389) − 0.796 (− 7.151; 0.737) | 0.011 0.033 |
Medial trochlea- bottom layer | D180 vs D0 D360 vs D0 | −2.303 (− 21.865; 7.574) − 1.852 (− 16.764; 0.791) | 0.16 0.023 | −2.703 (− 13.902; 2.017) − 1.574 (− 8.096; 2.390) | 0.006 0.124 |
Lateral trochlea - whole layer | D180 vs D0 D360 vs D0 | − 2.167 (− 10.398; 0.720) − 2.107 (− 11.110; 0.938) | 0.001 0.006 | − 0.804 (− 6.646; 2.799) − 0.508 (− 3.996; 0.839) | 0.110 0.117 |
Lateral trochlea - top layer | D180 vs D0 D360 vs D0 | − 0.410 (− 8.520; 4.261) 0.169 (− 5.191; 7.014) | 0.623 0.848 | 1.069 (− 7.704; 10.070) 0.670 (− 3.756; 8.526) | 0.972 0.387 |
Lateral trochlea - middle layer | D180 vs D0 D360 vs D0 | −3.663 (− 11.111; 0.482) − 2.380 (− 10.532; 0.399) | 0.001 0.001 | − 1.473 (− 9.228; 0.898) − 1.547 (− 7.190; − 0.374) | 0.009 0.003 |
Lateral trochlea - bottom layer | D180 vs D0 D360 vs D0 | −2.538 (− 26.748; 0.497) − 2.677 (− 20.622; 0.621) | 0.001 0.002 | −1.188 (− 8.698; 0.999) − 2.245 (− 9.955; 1.961) | 0.005 0.012 |
Mean T2 relaxation time (ms) | SD of relaxation time (ms) | ||||
---|---|---|---|---|---|
Median (IQR) n = 38 | p-value | Median (IQR) n = 38 | p-value | ||
Whole Femur- whole layer | D180 vs D0 D360 vs D0 | −0.537 (−10.658; 2.368) − 1.595 (−9.338; 1.532) | 0.050 0.014 | −1.315 (−4.361; 2.227) − 0.588 (− 4.128; 1.634) | 0.160 0.279 |
Whole Femur- top layer | D180 vs D0 D360 vs D0 | − 1.589 (−6.682; 2.216) − 1.678 (− 6.797; 3.763) | 0.080 0.131 | − 0.697 (− 7.715; 5.048) 1.159 (− 5.690; 6.124) | 0.574 0.545 |
Whole Femur- middle layer | D180 vs D0 D360 vs D0 | −0.596 (10.378; 1.938) − 1.249 (− 10.187; 0.967) | 0.030 0.008 | −1.524 (− 5.920; 1.637) − 0.305 (− 5.309; 1.955) | 0.86 0.174 |
Whole Femur- bottom layer | D180 vs D0 D360 vs D0 | −0.259 (− 10.454; 3.226) − 2.051 (− 10.495; 1.684) | 0.094 0.009 | −0.944 (− 8.002; 1.725) − 0.402 (− 8.032; 1.057) | 0.027 0.055 |
Medial weight bearing femur- whole layer | D180 vs D0 D360 vs D0 | 0.318 (− 14.381; 3.036) − 1.680 (− 13.240; 2.583) | 0.198 0.147 | −1.320 (− 6.054; 2.027) − 0.585 (− 5.550; 1.085) | 0.059 0.124 |
Medial weight bearing femur- top layer | D180 vs D0 D360 vs D0 | −1.119 (− 8.54; 3.575) − 1.923 (− 7.076; 4.147) | 0.219 0.480 | 0.493 (−4.423; 3.233) − 1.741 (− 3.532; 10.667) | 0.782 0.717 |
Medial weight bearing femur- middle layer | D180 vs D0 D360 vs D0 | 0.115 (− 12.221; 2.005) − 1.725 (− 8.003; 0.934) | 0.086 0.057 | −1.335 (− 8.136; 1.699) − 1.718 (− 6.450; 0.685) | 0.037 0.050 |
Medial weight bearing femur- bottom layer | D180 vs D0 D360 vs D0 | −0.261 (− 13.971; 5.085) − 2.727 (− 10.766; 3.163) | 0.254 0.053 | −1.506 (− 11.723; 1.387) − 2.298 (− 8.391; 0.853) | 0.010 0.012 |
Lateral weight bearing femur- whole layer | D180 vs D0 D360 vs D0 | −3.129 (− 8.423; 1.453) − 1.748 (− 8.187; 2.160) | 0.011 0.032 | 0.179 (− 3.713; 2.078) − 0.123 (− 3.475; 2.057) | 0.613 0.613 |
Lateral weight bearing femur- top layer | D180 vs D0 D360 vs D0 | 0.580 (−7.286; 4.058) − 0.628 (− 6.597; 3.953) | 0.664 0.364 | −0.375 (− 11.374; 5.426) 0.897 (− 5.299; 6.409) | 0.412 0.792 |
Lateral weight bearing femur- middle layer | D180 vs D0 D360 vs D0 | −1.075 (− 7.777; 1.477) − 1.264 (− 9.870; 1.896) | 0.005 0.045 | 0.183 (− 3.536; 1.522) − 0.589 (− 3.179; 1.625) | 0.395 0.349 |
Lateral weight bearing femur- bottom layer | D180 vs D0 D360 vs D0 | −1.599 (− 12.514; 2.41) − 2.164 (− 10.944; 3.286) | 0.015 0.100 | −1.053 (− 5.959; 0.667) − 0.699 (− 6.740; 1.931) | 0.005 0.110 |
Pain and function
VAS (mm) | D30 vs D0 | D90 vs D0 | D180 vs D0 | D210 vs D0 | D360 vsD0 |
---|---|---|---|---|---|
Knee pain at rest | n = 46 −21.7 (23.7) | n = 43 − 20.1 (24.5) | n = 43 − 26.9 (25.1) | n = 39 − 29.9 (24.4) | n = 41 − 29.8 (23.8) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Knee pain while walking | n = 45 − 25.5 (24.0) | n = 42 − 26.9 (24.7) | n = 42 − 30.2 (29.4) | n = 39 − 31.3 (31.1) | n = 40 − 31.5 (31.5) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Patient’s global assessment of disease activity | n = 45 − 22.7 (27.8) | n = 42 − 21.0 (26.4) | n = 42 − 23.9 (28.5) | n = 39 − 30.5 (30.6) | n = 40 − 25.3 (31.5) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Investigator global assessment of disease activity | n = 42 − 21.0 (22.3) | n = 40 − 21.4 (25.0) | n = 41 − 23.0 (24.9) | n = 37 − 24.4 (23.9) | n = 37 − 25.8 (25.5) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
KOOS scores | D30 vs D0 | D90 vs D0 | D180 vs D0 | D210 vs D0 | D360 vsD0 |
---|---|---|---|---|---|
Pains | n = 45 16.173 (18.13) | n = 42 16.968 (18.36) | n = 42 20.106 (21.62) | n = 39 20.664 (20.22) | n = 41 21.341 (18.68) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Symptoms | n = 45 11.164 (16.04) | n = 42 10.431 (17.05) | n = 42 13.747 (14.59) | n = 39 12.790 (16.27) | n = 41 14.184 (17.27) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Activity of daily living | n = 45 16.97 (16.08) | n = 42 15.384 (18.49) | n = 42 19.60 (20.80) | n = 39 19.92 (17.72) | n = 41 20.51 (16.82) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Sports/ Recreation function | n = 45 15.963 (19.21) | n = 41 17.31 (27.40) | n = 40 18.65 (28.17) | n = 38 21.930 (26.79) | n = 40 17.563 (24.17) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
Quality of life | n = 45 16.898 (26.82) | n = 42 15.774 (25.43) | n = 42 19.643 (26.54) | n = 39 23.077 (26.45) | n = 41 18.902 (29.23) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |
KOOS total | n = 45 77.171 (76.99) | n = 42 73.368 (85.49) | n = 42 90.854 (88.37) | n = 39 97.820 (85.82) | n = 41 91.95 (83.47) |
P-value | < 0.001 | < 0.001 | < 0.001 | < 0.001 | < 0.001 |