Condoliase therapy for lumbar disc herniation -2 year clinical outcome-

Lumbar disk herniation (LDH) is a common disease caused by a protruding nucleus pulposus through a damaged annulus fibrosus. The symptoms are characterized by buttocks and lower-limb pain caused by compressed nerve roots. While conservative treatment is usually effective, surgical treatment is required in cases refractory to prolonged conservative treatment [1]. A prospective study indicated that surgical treatment had better clinical outcomes than those associated with conservative treatment in LDH patients over 10 years [2]. Although surgical treatment has several advantages for patients, it has the potential risk of surgical complications, recurrence of herniation, and reoperation [3]. Chemonucleolysis, considered an intermediate treatment between conservative and surgical treatment, is a less invasive treatment for LDH that induces chemical dissolution of the nucleus pulposus of the intervertebral disc [4]. Chemonucleolysis with chymopapain, first reported by Smith [5] has been widely used as an alternative treatment for LDH in the 1980s and the 1990s throughout Europe and the United States, with excellent clinical outcomes [6,7]. However, chymopapain is currently unavailable owing to severe adverse events, such as anaphylaxis, infection, hemorrhage, and neurological complications [7].

Chondroitin sulfate ABC endolyase (condoliase), a pure mucopolysaccharidase derived from the gram-negative rod Proteus vulgaris, has high substrate specificity for chondroitin sulfate and hyaluronic acid, which are glycosaminoglycans of proteoglycans and abundant in the nucleus pulposus [8,9]. In contrast to chymopapain, condoliase lacks protease activity, thus inducing chemonucleolysis with less damage to surrounding tissues, such as nerves and vessels [[10], [11], [12]]. Following a phase III clinical trial with significantly better improvements in leg pain than those observed with placebo, chemonucleolysis with condoliase was approved in Japan for clinical use for LDH in 2018 [13,14].

After clinical usage, the reported effectiveness of this treatment is 62–85% without any major adverse event [[15], [16], [17], [18], [19], [20]]. However, the follow-up periods of these reports were no longer than one year; thus, long-term clinical data for condoliase therapy are still insufficient. Therefore, this study aimed to investigate the 2-year clinical outcomes using radiographic evaluation after chemonucleolysis with condoliase in patients with LDH.

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