Henrotin et al. BMC Musculoskeletal Disorders
(2022) 23:650
Page 7 of 11
Table 2 Primary and secondary outcomes – Absolute change from baseline in ITT population 6 Weeks 12 Weeks Placebo RIE 200 mg RIE 400 mg Placebo
RIE 200 mg RIE400 mg
WOMAC Pain (primary outcome)
Mean (SE) 95% CI
1.29 (0.31) -1.89; -0.68 < 0.0001 -5.60 (1.52) -8.58; -2.62 0.0002 -0.48 (0.17) -0.81; -0.14 0.0052 --3.60 (1.08) --5.72; -1.49 0.0009 -5.12 (1.89) -8.83; -1.42 0.0068
-1.91 (0.31) -2.52; -1.29 < 0.0001 0.2718 -7.28 (1.54) -10.31; -4.25 < 0.0001 0.6573 -0.79 (0.17) -1.13; -0.45 < 0.0001 0.3299 -4.30 (1.09) -6.45; -2.16 < 0.0001 0.8609 -9.22 (1.92) -12.99; -5.46 < 0.0001 0.2223 4.55 (19.07) -50.00, 75.00 0.9761 -0.41 (1.75) -4.0, 7.6 0.9391 0.26 (1.23) -2.0, 6.0 0.9996
-1.79 (0.32) -2.41; -1.16 < 0.0001 0.4199 -7.66 (1.57) -10.73; -4.59 < 0.0001 0.5416 -0.95 (0.17) -1.29; -0.60 < 0.0001 0.0970 -4.61 (1.11) -6.79; -2.44 < 0.0001 0.7301 -5.32 (1.95) -9.15; -1.50 -1.17 (16.32) -50.00, 50.00 0.0544 -0.36 (1.75) -6.7, 3.5 0.9838 0.0064 0.9960
-1.98 (0.31) -2.59; -1.36 < 0.0001 -10.22 (1.54) -13.25; -7.20 < 0.0001 -1.14 (0.17 -1.47; -0.80 < 0.0001 -6.69 (1.09) -8.84; -4.55 < 0.0001 -3.84 (1.89) -7.55; -0.14 0.0421
-2.01 (0.31) -2.63; -1.40 < 0.0001 0.9955 -9.41 (1.54) -12.44; -6.38 < 0.0001 0.9036 -1.08 (0.17) -1.41; -0.74 < 0.0001 0.9587 -5.95 (1.09) -8.10; -3.81 < 0.0001 0.8480 -8.51 (1.92) -12.27; -4.75 < 0.0001 0.1485 2.27 (21.36) -50.00, 50.00 0.9785 -0.39 (1.69) -4.5, 3.0 0.9349 0.39 (1.37) -4.0, 6.0 1.0000 37.48 (216.29) -94.3, 1339.4 0.9601
-2.46 (0.32) -3.09; -1.84 < 0.0001 0.4517 -11.29 (1.57) -14.36; -8.21 < 0.0001 0.8441 -1.01 (0.17) -1.35; -0.67 < 0.0001 0.8310 -7.36 (1.11) -9.54; -5.19 < 0.0001 0.8742 -10.93 (1.95) -14.76; -7.11 < 0.0001 0.0176 3.13 (20.65) -50.00, 50.00 0.9212 -0.30 (1.94) -6.9, 3.8 0.9724 0.22 (0.81) -3.0, 2.0 0.6386 36.62 (184.88) -96.5, 1052.0 0.9950
P value vs baseline P value vs placebo
WOMAC global
Mean (SE) 95% CI
P value vs baseline P value vs placebo
WOMAC stiffness
Mean (SE) 95% CI
P value vs baseline P value vs placebo
WOMAC function
Mean (SE) 95% CI
P value vs baseline P value vs placebo
VAS pain
Mean (SE) 95% CI
P value vs baseline P value vs placebo Mean (SD) Min., Max P value vs placebo Mean (SD) Min., Max P value vs placebo Mean (SD) Min., Max P value vs placebo Mean (SD) Min., Max P value vs placebo
SF-36
5.97 (16.91) -25.00, 50.00
2.61 (19.04) -50.00, 50.00
20 m walking test
-0.31 (1.30) -4.1, 3.2
-0.18 (1.53) -4.2, 4.2
SPPB
0.21 (0.86) -2.0, 2.0
0.05 (0.72) -2.0, 2.0 0.5601
0.34 (0.94) -2.0, 2.0
IPAQ
107.48 (298.81) -90.2, 1693.8
173.08 (560.57) -100.0, 3400.0 0.9493
102.46 (279.33) -89.6, 1300.0 0.9306
38.38 (275.67) -95.0, 2000.0
RIE had no significant effect on the other second- ary end-points (IPAQ, SF-36, walking distance in tread- mill test, SPPB, and evaluation of associated treatments needed to manage OA) except for the IPAQ score at 400 mg in the normal BMI group at 12 weeks ( p = 0.017). After 12 weeks of treatment, over 60% of patients ful- filled the OMERACT-OARSI criteria in RIE 400 mg group, but only 45% in the placebo ( p = 0.04) (Fig. 4). There were two not-related-to-product Serious Adverse Events (SAE) reported in this study. One partici- pant had a severe SAE as they were diagnosed with pros- tate cancer. This participant was withdrawn from the trial due to SAE after visit 1. The other participant had a mod- erate SAE due to renal calculus. This participant recov- ered within three days and remained in the trial. There were 123 AEs reported by 87 (42.9%) partici- pants in total for the Safety Population ( N = 203). In addi- tion, 95.1% of AEs were mild to moderate intensity. There were 29 participants (42.6%) in the placebo group who reported ≥ 1 AE(s), 32 participants (46.4%) in the RIE 200 mg group who reported ≥ 1 AEs, and 26 participants
(2.26) mm (placebo = -0.37 (2,16) mm). The reduc- tion was statistically different versus placebo for both doses (200 mg -10.88 (3.04); 95% CI, -17.64 to -4.12 p = 0.0008 and 400 mg -12.99 (3.13); 95% CI, -19.95 to -6.04 p < 0,0001) (Fig. 3). No significant effect of RIE was observed in the normal BMI group. The WOMAC global score, stiffness, and physical func- tion subscores decreased significantly with time in all groups. The decrease tended to be more important in the RIE treated groups than in the placebo groups but no significant difference between groups was observed (Table 2). RIE at 400 mg was significantly more efficient than placebo to decrease the WOMAC stiffness score in the normal BMI group after 6, but not 12 weeks of treat- ment (p = 0.042). In the normal BMI group, a higher decrease in the WOMAC pain, physical function, and global scores were observed in the RIE 200 mg group than in the placebo group after 6 weeks of treatment (WOMAC global pain: p = 0.007742; WOMAC physical function: p = 0.0027; WOMAC global: p = 0.0026) (Addi- tional file 3).
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