BACKGROUND: Chemonucleolysis with condoliase significantly improved clinical symptoms in patients with lumbar disc herniation. We evaluated the surgical intervention rate and outcomes for >1 year after condoliase treatment.
METHODS: This was a follow-up study of patients who received condoliase or placebo in two previous randomized, placebo-controlled clinical trials with 1-year follow-ups. A post-treatment surgery survey and on-site examination were administered and patients\' data from the clinical trial records and additional interview data were analyzed to evaluate the surgical intervention rate. Patients\' lumbar disease symptoms, Oswestry Disability Index, and imaging features were evaluated.
RESULTS: Among the patients (condoliase, n = 228; placebo, n = 128) enrolled in the clinical trials, additional post-treatment surgery data were available for 231 patients after the clinical trials ended, and 179 patients underwent post-trial examinations, at least 5 years and 17 months after the end of the clinical trials. The surgical intervention rate in the placebo and condoliase groups was 20.7% (95% confidence interval: 14.2-29.7) and 13.4% (95% confidence interval: 8.8-20.2), respectively. The mean change in Oswestry Disability Index score from pre-injection in placebo and condoliase groups was -24.7 ± 15.0 and -32.7 ± 18.6 (between-group difference: -8.0 ± 17.3; 95% confidence interval: -13.2 to -2.7). Modic Type 2 changes were observed, particularly in the condoliase group. No relationship between lumbar disease symptoms and change in imaging features was found.
CONCLUSIONS: This follow-up study more than 1 year revealed no new safety concerns of condoliase. However, because the study had several limitations, such as large loss of follow-up, further research is needed.

Low back pain with or without radicular leg pain is an extremely common health condition significantly impacting patient\'s activities and quality of life. When conservative management fails, epidural injections providing only temporary relief, are frequently utilized. Intradiscal oxygen-ozone may offer an alternative to epidural injections and further reduce the need for microdiscectomy.
To compare the non-inferiority treatment status and clinical outcomes of intradiscal oxygen-ozone with microdiscectomy in patients with refractory radicular leg pain due to single-level contained lumbar disc herniations.
Multicenter pilot prospective non-inferiority blocked randomized control trial conducted in three European hospital spine centers.
Forty-nine patients (mean 40 years of age, 17 females/32 males) with a single-level contained lumbar disc herniation, radicular leg pain for more than six weeks, and resistant to medical management were randomized, 25 to intradiscal oxygen-ozone and 24 to microdiscectomy. 88% (43 of 49) received their assigned treatment and constituted the AS-Treated (AT) population.
Primary outcome was overall 6-month improvement over baseline in leg pain. Other validated clinical outcomes, including back numerical rating pain scores (NRS), Roland Morris Disability Index (RMDI) and EQ-5D, were collected at baseline, 1 week, 1-, 3-, and 6-months. Procedural technical outcomes were recorded and adverse events were evaluated at all follow-up intervals.
Oxygen-ozone treatment performed as outpatient day surgeries, included a one-time intradiscal injection delivered at a concentration of 35±3 μg/cc of oxygen-ozone by a calibrated delivery system. Discectomies performed as open microdiscectomy inpatient surgeries, were without spinal instrumentation, and not as subtotal microdiscectomies. Primary analyses with a non-inferiority margin of -1.94-point difference in 6-month cumulative weighted mean leg pain NRS scores were conducted using As-Treated (AT) and Intent-to-Treat (ITT) populations. In post hoc analyses, differences between treatment groups in improvement over baseline were compared at each follow-up visit, using baseline leg pain as a covariate.
In the primary analysis, the overall 6-month difference between treatment groups in leg pain improvement using the AT population was -0.31 (SE, 0.84) points in favor of microdiscectomy and using the ITT population, the difference was 0.32 (SE, 0.88) points in favor of oxygen-ozone. The difference between oxygen-ozone and microdiscectomy did not exceed the non-inferiority 95% confidence lower limit of treatment difference in either the AT (95% lower limit, -1.72) or ITT (95% lower limit, -1.13) populations. Both treatments resulted in rapid and statistically significant improvements over baseline in leg pain, back pain, RMDI, and EQ-5D that persisted in follow-up. Between group differences were not significant for any outcomes. During 6-month follow-up, 71% (17 of 24) of patients receiving oxygen-ozone, avoided microdiscectomy. The mean procedure time for oxygen-ozone was significantly faster than microdiscectomy by 58 minutes (p<.0010) and the mean discharge time from procedure was significantly shorter for the oxygen-ozone procedure (4.3±2.9 hours vs. 44.2±29.9 hours, p<.001). No major adverse events occurred in either treatment group.
Intradiscal oxygen-ozone chemonucleolysis for single-level lumbar disc herniations unresponsive to medical management, met the non-inferiority criteria to microdiscectomy on 6-month mean leg pain improvement. Both treatment groups achieved similar rapid significant clinical improvements that persisted and overall, 71% undergoing intradiscal oxygen-ozone were able to avoid surgery.

OBJECTIVE Chemonucleolysis with condoliase has the potential to be a new, less invasive therapeutic option for patients with lumbar disc herniation (LDH). The aim of the present study was to determine the most suitable therapeutic dose of condoliase. METHODS Patients between 20 and 70 years of age with unilateral leg pain, positive findings on the straight leg raise test, and LDH were recruited. All eligible patients were randomly assigned to receive condoliase (1.25, 2.5, or 5 U) or placebo. The primary end point was a change in the worst leg pain from preadministration (baseline) to week 13. The secondary end points were changes from baseline in the following items: worst back pain, Oswestry Disability Index (ODI), SF-36, and neurological examination. For pharmacokinetic and pharmacodynamic analyses, plasma condoliase concentrations and serum keratan sulfate concentrations were measured. The safety end points were adverse events (AEs) and radiographic and MRI parameters. Data on leg pain, back pain, abnormal neurological findings, and imaging parameters were collected until week 52. RESULTS A total of 194 patients received an injection of condoliase or placebo. The mean change in worst leg pain from baseline to week 13 was -31.7 mm (placebo), -46.7 mm (1.25 U), -41.1 mm (2.5 U), and -47.6 mm (5 U). The differences were significant at week 13 in the 1.25-U group (-14.9 mm; 95% CI -28.4 to -1.4 mm; p = 0.03) and 5-U group (-15.9 mm; 95% CI -29.0 to -2.7 mm; p = 0.01) compared with the placebo group. The dose-response improvement in the worst leg pain at week 13 was not significant (p = 0.14). The decrease in the worst leg pain in all 3 condoliase groups was observed from week 1 through week 52. Regarding the other end points, the worst back pain and results of the straight leg raise test, ODI, and SF-36 showed a tendency for sustained improvement in each of the condoliase groups until week 52. In all patients at all time points, plasma condoliase concentrations were below the detectable limit (< 100 μU/ml). Serum keratan sulfate concentrations significantly increased from baseline to 6 hours and 6 weeks after administration in all 3 condoliase groups. No patient died or developed anaphylaxis or neurological sequelae. Five serious AEs occurred in 5 patients (3 patients in the condoliase groups and 2 patients in the placebo group), resolved, and were considered unrelated to the investigational drug. Severe AEs occurred in 10 patients in the condoliase groups and resolved or improved. In the condoliase groups, back pain was the most frequent AE. Modic type 1 change and decrease in disc height were frequent imaging findings. Dose-response relationships were observed for the incidence of adverse drug reactions and decrease in disc height. CONCLUSIONS Condoliase significantly improved clinical symptoms in patients with LDH and was well tolerated. While all 3 doses had similar efficacy, the incidence of adverse drug reactions and decrease in disc height were dose dependent, thereby suggesting that 1.25 U would be the recommended clinical dose of condoliase. Clinical trial registration no.: NCT00634946 (clinicaltrials.gov).

OBJECTIVE: The study was designed to evaluate the effectiveness of the combination of chemonucleolysis and psoas compartment block (PCB) for the treatment of lumbar disc herniations (LDHs) and to explore the role of PCB in managing postoperative pain of collagenase injection.
METHODS: Two groups of patients (N = 192) were treated in different ways, respectively. Group A (N = 95) was treated with chemonucleolysis only (the injection of oxygen-ozone combined with collagenase into the lumbar disc and the epidural space); group B (N = 97) was treated with chemonucleolysis and PCB. After the treatment, the patients were followed-up, and the therapeutic effect was assessed at 1 week, 1 month, 3 months, and 6 months by the relative pain reduction, visual analog scale (VAS) pain scores, and the Oswestry Disability Index (ODI) scores.
RESULTS: In group A, treatment success rate was 64.2% (61 of 95), 82.1% (78 of 95), 84.2% (80 of 95), and 86.3% (82 of 95) at 1 week, 1 month, 3 months, and 6 months, respectively. In group B, treatment success rate was 86.5% (84 of 97), 89.6% (87 of 97), 93.8% (91 of 97), and 91.7% (89 of 97) at 1 week, 1 month, 3 months, and 6 months, respectively. There was statistically significant difference in outcome between two groups at 1 week, but there were no statistically significant difference in outcome between two groups at 1 month, 3 months, and 6 months. VAS scores and ODI were significantly decreased in both group A and group B, when compared with the baseline values in the same group at all points of follow-up. Group B produced a significant reduction in the VAS scores and ODI when compared with group A at: 1-week, 1-month, 3-month, 6-month follow-up.
CONCLUSIONS: Computer tomography (CT)-guided chemonucleolysis combined with PCB leads to rapid pain relief, fewer postoperative pain of collagenase injection happen, and should be regarded as a useful treatment for the management of LDH.