Effectiveness of Intra-Articular SBCG Injections for Knee OA
Effectiveness of Intra-Articular SBCG Injections for Knee OA
A total of 123 patients were initially screened for the study between December 2007 and February 2008, 50 did not meet the inclusion criteria or refused to participate. A total of 74 subjects were randomly assigned to one of the two treatment groups, one refused to receive the allocated intervention, 21 refused to continue at some point during the trial due to personal reasons and 1 due to a rash that according with the physician should not continue with the treatment. Thus, 51 patients finished the intervention and follow up period (Figure 1).
(Enlarge Image)
Figure 1.
Flow of patients through the study.
The baseline demographic characteristics of the patients that initiated the study and the patients that completed the study did not differ among the experimental groups (Table 1). The majority of patients were female (61/73), mean ± SD age was 54.9 ± 9.3 years. The body mass index mean was 31.6 ± 4.7 Kg/m. Baseline radiographic analysis showed no significant difference among treatment groups in joint-space narrowing and marginal osteophytes formation, within each knee compartment. In the majority of the patients (59/73), pain intensity in the target knee was reported from moderate to severe.
After one year in the study 27 and 29 subjects from SBCG1 and SBCG2, respectively, finished the intervention period (Figure 1); all of them received the allocated intervention. Most of the drop outs (85%) were voluntary for personal reasons, which are expected due to the long duration of the study. The statistical power with the subjects that finished the study was above 90%.
Baseline and unadjusted as well as adjusted mean changes of the WOMAC subscales and global scores at different time points until 18 months are shown in Table 2. At the end of the intervention, patients in SBCG1 and SBCG2 groups, showed a significant improvement compared with their baseline values in all WOMAC subscales: 81% and 77% in pain, 92% and 79% in stiffness and 90% and 81% in physical functioning, respectively. The changes in WOMAC total score along the period of treatment are shown in Figure 2. The mean score that decreased at 12 months was maintained 6 months after treatment suspension. There was no difference within treatments during intervention or during post-treatment period.
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Figure 2.
Monthly changes in WOMAC pain index by treatment group. Means (±SEM) are adjusted for baseline values. All post-treatment measurements were significantly different from baseline value. There were no significant differences between treatments.
Baseline values and unadjusted and adjusted mean changes of the Lequesne functional index subscales and global scores at different time points until 18 months are shown in Table 3. After 12 months of treatment, patients in both groups showed a significant improvement in all score subscales, for SBCG1 and SBCG2 groups, there was a 74% and 69% reduction in pain, 74% and 71% improvement in maximum walking distance and 65% and 56% improvement in the daily activities subscale, respectively. Figure 3 shows the changes in Lequesne's functional Index along the study period. During the first 3 months of intervention the Lequesne's functional index score decreased substantially and from month 4 to month 12 the improvement was maintained. After intervention period there was a reduction in the Lequene's total score of about 68% and 69% with SBCG1 and SBCG2 groups, respectively, compared with baseline values. There was no difference within treatments during intervention and post-intervention period.
(Enlarge Image)
Figure 3.
Monthly changes in Lequesne's functional index by treatment group. Means (±SEM) are adjusted for baseline values. All post-treatment measurements were significantly different from baseline value. There were no significant differences between treatments.
Joint space narrowing, within the knee joint during treatment with intra-articular administration of SBCG1 and SBCG2 is shown in Figure 4. After the 12 month-period of treatment there was a significant decrease in joint-space width of −0.37 (95% CI: −0.64, −0.10) mm in SBCG1 group, and there was no significant change in SBCG2 group: 0.15 (−0.33, 0.63) mm. The mean joint space change of SBCG2 was significantly higher than SBCG1 group after 4 and 18 months.
(Enlarge Image)
Figure 4.
Joint space width changes in patients completing the intervention and 6 months follow-up. Errors bars represent SEM. *Different to baseline value in Paired T-test (p < 0.05). Significantly different from SBCG2 in a Generalized Estimating Equation model that considered the correlation between both knees from each subject, and also considered the baseline evaluation values as a covariate.
The percentage of patients who experienced any adverse event, during this study did not differ between both groups (32% and 37% for SBCG1 and SBCG2, respectively). The majority of adverse events (77%) were related to knee OA: knee pain, nuisance or weakness, stiffness, burning and numbness. The rest of the events were not related with the knee or the intervention: respiratory or gastrointestinal infections, headache and lumbar pain among others. None of the reported adverse events was classified as severe. The laboratory tests during all evaluations did not indicate abnormal values in patients.
Results
A total of 123 patients were initially screened for the study between December 2007 and February 2008, 50 did not meet the inclusion criteria or refused to participate. A total of 74 subjects were randomly assigned to one of the two treatment groups, one refused to receive the allocated intervention, 21 refused to continue at some point during the trial due to personal reasons and 1 due to a rash that according with the physician should not continue with the treatment. Thus, 51 patients finished the intervention and follow up period (Figure 1).
(Enlarge Image)
Figure 1.
Flow of patients through the study.
The baseline demographic characteristics of the patients that initiated the study and the patients that completed the study did not differ among the experimental groups (Table 1). The majority of patients were female (61/73), mean ± SD age was 54.9 ± 9.3 years. The body mass index mean was 31.6 ± 4.7 Kg/m. Baseline radiographic analysis showed no significant difference among treatment groups in joint-space narrowing and marginal osteophytes formation, within each knee compartment. In the majority of the patients (59/73), pain intensity in the target knee was reported from moderate to severe.
After one year in the study 27 and 29 subjects from SBCG1 and SBCG2, respectively, finished the intervention period (Figure 1); all of them received the allocated intervention. Most of the drop outs (85%) were voluntary for personal reasons, which are expected due to the long duration of the study. The statistical power with the subjects that finished the study was above 90%.
Baseline and unadjusted as well as adjusted mean changes of the WOMAC subscales and global scores at different time points until 18 months are shown in Table 2. At the end of the intervention, patients in SBCG1 and SBCG2 groups, showed a significant improvement compared with their baseline values in all WOMAC subscales: 81% and 77% in pain, 92% and 79% in stiffness and 90% and 81% in physical functioning, respectively. The changes in WOMAC total score along the period of treatment are shown in Figure 2. The mean score that decreased at 12 months was maintained 6 months after treatment suspension. There was no difference within treatments during intervention or during post-treatment period.
(Enlarge Image)
Figure 2.
Monthly changes in WOMAC pain index by treatment group. Means (±SEM) are adjusted for baseline values. All post-treatment measurements were significantly different from baseline value. There were no significant differences between treatments.
Baseline values and unadjusted and adjusted mean changes of the Lequesne functional index subscales and global scores at different time points until 18 months are shown in Table 3. After 12 months of treatment, patients in both groups showed a significant improvement in all score subscales, for SBCG1 and SBCG2 groups, there was a 74% and 69% reduction in pain, 74% and 71% improvement in maximum walking distance and 65% and 56% improvement in the daily activities subscale, respectively. Figure 3 shows the changes in Lequesne's functional Index along the study period. During the first 3 months of intervention the Lequesne's functional index score decreased substantially and from month 4 to month 12 the improvement was maintained. After intervention period there was a reduction in the Lequene's total score of about 68% and 69% with SBCG1 and SBCG2 groups, respectively, compared with baseline values. There was no difference within treatments during intervention and post-intervention period.
(Enlarge Image)
Figure 3.
Monthly changes in Lequesne's functional index by treatment group. Means (±SEM) are adjusted for baseline values. All post-treatment measurements were significantly different from baseline value. There were no significant differences between treatments.
Joint space narrowing, within the knee joint during treatment with intra-articular administration of SBCG1 and SBCG2 is shown in Figure 4. After the 12 month-period of treatment there was a significant decrease in joint-space width of −0.37 (95% CI: −0.64, −0.10) mm in SBCG1 group, and there was no significant change in SBCG2 group: 0.15 (−0.33, 0.63) mm. The mean joint space change of SBCG2 was significantly higher than SBCG1 group after 4 and 18 months.
(Enlarge Image)
Figure 4.
Joint space width changes in patients completing the intervention and 6 months follow-up. Errors bars represent SEM. *Different to baseline value in Paired T-test (p < 0.05). Significantly different from SBCG2 in a Generalized Estimating Equation model that considered the correlation between both knees from each subject, and also considered the baseline evaluation values as a covariate.
The percentage of patients who experienced any adverse event, during this study did not differ between both groups (32% and 37% for SBCG1 and SBCG2, respectively). The majority of adverse events (77%) were related to knee OA: knee pain, nuisance or weakness, stiffness, burning and numbness. The rest of the events were not related with the knee or the intervention: respiratory or gastrointestinal infections, headache and lumbar pain among others. None of the reported adverse events was classified as severe. The laboratory tests during all evaluations did not indicate abnormal values in patients.
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