Introduction
Condoliase is an enzyme that degrades glycosaminoglycans, which are abundant in the nucleus pulposus of intervertebral discs (IVDs). In 2018, it was approved as a chemonucleolytic agent for treating lumbar disc herniation (LDH) by Japanese regulatory authorities. Given that over 10 years have passed since the Japanese phase III trial was conducted, this study aims to assess the long-term effects (≥10 years) of condoliase on IVDs in patients who received condoliase.
Methods
All LDH patients who received a 1.25 U dose of condoliase during the national phase III trial were invited to participate in this study. The primary endpoints were X-ray evaluations (including disc height, posterior intervertebral angle, and vertebral body translation) and MRI assessments (Modic classification and Pfirrmann grade). Secondary endpoints included neurological outcomes and the Oswestry Disability Index (ODI). Data were collected and analyzed at three time points: before treatment (baseline), and 1 and 10 years after condoliase treatment.
Results
Of the 82 patients treated with condoliase in the phase III trial, 37 (45.1%) were available for follow-up, with a mean age of 50.9 years (21 males, 16 females). Among these 37 cases, disc height decreased by ≥30% in 8 cases (21.6%), while only one case showed a posterior intervertebral angle ≥5°, and another exhibited vertebral body translation ≥3 mm. However, none of the patients required surgery due to IVD degeneration or spinal instability. MRI results showed that of the 8 cases classified as Modic Type 1 at one year post-treatment, 7 cases (87.5%) had progressed to Type 2 by the present evaluation. Pfirrmann grades at one year post-treatment were “Grade III” (4 cases), “Grade IV” (32 cases), and “Grade V” (1 case), which shifted to 3, 24, and 10 cases, respectively, at the 10-year mark. At 10 years post-treatment, the mean ODI score was 8.6, incidences of positive straight leg raise (SLR) test, hypoesthesia, muscle weakness, and deep tendon hyporeflexia were 2.7%, 5.4%, 0%, and 21.6%, respectively.
Discussion
This is the first long-term follow-up study, 10 years post-enzyme injection therapy with condoliase. Condoliase achieved satisfactory clinical outcomes and enhanced activities of daily living. Although some progression in Pfirrmann grades and minor instability were observed, no patient required additional surgery, suggesting that chemonucleolysis with condoliase remains a safe and effective treatment option for LDH over the long term.