Single-Level Radiculopathy. Artificial Disc: It Works BETTER than ACDF

Single-Level Radiculopathy Artificial Disc: It Works BETTER than ACDF Pierce D. Nunley MD Director, Spine Institute of Louisiana Assistant Professor, Louisiana State University

Disclosures Stock ownership: Amedica, Paradigm Spine, and Spineology Clinical/Research Support: Cervical Spine Research Society, K2M, Biomet Spine, Axiomed, Medtronic, Nutech, NuVasive, Spinal Motion, and Vertiflex Patent Holder: K2M and LDR Spine, Safewire. Consultant: Nutech, LDR Spine Speaker s Bureau: LDR and K2M

History Smith and Robinson introduced anterior cervical discectomy and arthrodesis in 1958 as a surgical option for the management of cervical disc disorders 1. Smith GW, Robinson RA. The treatment of certain cervical spine disorders by anterior removal of the intervertebral disc and interbody fusion. J Bone Joint Surg Am. 1958; 40: 607-24 ACDF has gained acceptance as standard of care for patients with persistent radicular and/or myelopathic symptoms that have failed to improve with conservative treatments 2. Rao RD, Currier BL, Albert TJ et al. Degenerative cervical spondylosis: clinical syndromes, pathogenesis and management. J Bone Joint Surg Am 2007; 89: 1360-78

History As longer term results became available, the outcome studies increasingly focused on the potential adverse effects of this procedure 3. 20-32% of patients undergoing ACDF developed CASP within 10 years

History The concern that spinal fusion may be a contributing factor to accelerated ASP led to increased interest in motion preservation 4 Similar stress profiles were recorded from intact specimens and those with the artificial joint inserted. The artificial joint resulted in reduced stresses in the annulus compared with spines with a simulated fusion.

Rationale This led the scientists and surgeons to focus their attention towards developing alternative procedures to ACDF The concept of motion preservation technology was thus born and subsequently led to the development of cervical total disc replacement (c-tdr). Since then several total disc arthroplasty implants have been used for treating cervical degenerative disc disease and the clinical outcomes have been published in the literature.

FDA Clearance of Cervical Discs in U.S. Prestige ST 2007 ProDisc-C 2007 Bryan 2009 PCM 2012 Secure-C 2012 Mobi-C 2013 Prestige LP 2014

Clinical Outcomes

ACDF Outcomes Problems 1. Most published results of the ACDF procedure are retrospective and/or anecdotal from experience of a single surgeon or institution, (class III studies at best.) 2. The outcome instruments used and success criteria used for the ACDF studies have varied according to the different authors judgment and tools available at the time of data acquisition.

c-tdr outcomes c-tdr is a class III medical device, so the FDA requires a Investigational Device Exemption (IDE) Trial. Abundance of level 1 evidence from these IDE, prospective, randomized, controlled trials Interest has led to prospective and retrospective post-market studies Subset analysis applies more scrutiny to c-tdr than was ever applied to ACDF

c-tdr IDE outcomes Studies range from currently enrolling in the clinical trial to approved with 7 year follow-up.

c-tdr IDE outcomes Studies range from currently enrolling in the clinical trial to approved with 7 year follow-up.

c-tdr IDE outcomes Studies range from currently enrolling in the clinical trial to approved with 7 year follow-up.

c-tdr IDE outcomes ProDisc-C reported 7-year follow-up 5 Follow-up rate: 92% Clinical outcomes were similar between groups Secondary surgery rate was significantly different; 7% ProDisc-C vs 18% ACDF (p=0.0099)

c-tdr IDE outcomes Prestige ST reported 7-year follow-up 6 Follow-up rate: 73% Significantly different clinical outcomes Mean NDI Improvement: 37.6 Prestige ST vs 32.6 ACDF (p=0.002) Maintenance or Improvement in neurological status: 88.2% Prestige ST vs 79.7% ACDF (p=0.011) Secondary surgery rate was significantly different; 4.8% Prestige vs 13.7% ACDF (p<0.001)

c-tdr IDE outcomes Prestige LP reported 7-year follow-up 7 Follow-up rate: 75.9% Prestige LP and 70.0% ACDF Secondary surgery rate: 9.6% Prestige LP vs 8.3% ACDF (NS)

c-tdr IDE outcomes PCM reported 5-year follow-up 8 Follow-up rate: 74.8% PCM and 70.3% ACDF Significantly different clinical outcomes Mean NDI: 20.4 PCM vs 28.5 ACDF (p=0.001) Mean VAS Neck: 35 PCM vs 25 ACDF (p=0.002) Secondary surgery rate; 8.1% PCM vs 12.0% ACDF (NS)

c-tdr IDE outcomes Mobi-C reported 5-year follow-up 9 Follow-up rate: 85.5% Mobi-C and 78.9% ACDF Clinical outcomes were similar between groups Secondary surgery rate was significantly different; 3.0% Mobi-C vs 11.1% ACDF (p<0.02)

c-tdr IDE outcomes In addition to long-term clinical outcomes favoring c-tdr, the short term results are also improved: Return to work Faster return to work keeps patients off disability 10,11 NDI Patients experience faster relief in NDI, significance as early as 6 weeks 10-13

c-tdr Cost Effectiveness Using several analytical approaches that consider multiple sources of uncertainty, CTDR was found to be more effective and less costly than ACDF over 7 years. our results suggest that CTDR may provide a sustained economic advantage over ACDF. 14

Other c-tdr studies15-21

Other c-tdr studies15-21

Other c-tdr studies15-21

Other c-tdr studies Xing D, Ma XL, Ma JX, Wang J, Ma T, Chen Y. A meta-analysis of cervical arthroplasty compared to anterior cervical discectomy and fusion for single-level cervical disc disease. J Clin Neurosci. 2013 Jul;20(7):970-8 The evidence from randomised controlled clinical studies has shown that after 2 years CTDR is equal to fusion surgery in terms of outcomes and complications. 22 Jiang H, Zhu Z, Qiu Y, Qian B, Qiu X, Ji M. Cervical disc arthroplasty versus fusion for single-level symptomatic cervical disc disease: a meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2012 Feb;132(2):141-51 Compared with ACDF, CDA carry a lower incidence of dysphagia complications and reoperation related to adjacentsegment degeneration, and a higher prevalence of neurological and overall success at 2 years postoperatively Future largescale RCTs with long-term follow-up are needed to provide clear evidence 23

Other c-tdr studies Upadhyaya CD, Wu JC, Trost G, Haid RW, Traynelis VC, Tay B, Coric D, Mummaneni PV. Analysis of the three United States Food and Drug Administration investigational device exemption cervical arthroplasty trials. J Neurosurg Spine. 2012 Mar;16(3):216-28. Arthroplasty is associated with a lower rate of secondary surgery and a higher rate of neurological success at 2 years. Arthroplasty may be associated with a lower rate of adjacentlevel disease at 2 years, but further follow-up and analysis are needed to confirm this finding. 24 This study was completed in 2012, with only 3 FDA trials available for review.

Other c-tdr studies McAfee PC, Reah C, Gilder K, Eisermann L, Cunningham B. A meta-analysis of comparative outcomes following cervical arthroplasty or anterior cervical fusion: results from 4 prospective multicenter randomized clinical trials and up to 1226 patients. Spine (Phila Pa 1976). 2012 May 15;37(11):943-52 These findings suggest that cervical arthroplasty is superior to ACDF in overall success, neurological success, and survivorship outcomes at 24 months postoperatively. 25

ISASS Policy statement Anterior cervical discectomy and fusion has an established record of clinical and radiographic efficacy. The safety and efficacy of cervical arthroplasty has been established with a growing body of Level 1 evidence that is compelling enough to no longer consider ctdr investigational. This evidence is bolstered by experience with multiple devices, at multiple sites, in and out of the investigational setting and with short-, intermediate- and long-term follow-up. ctdr is a viable alternative to ACDF in select patients with symptomatic 1- and 2-level cervical radiculopathy or myelopathy.

Bottom Line Over 2500 patients have been enrolled in FDA IDE trials of currently approved c-tdr devices Comparable success rates for both procedures at the average follow-up of 2-7 years Likelihood of secondary surgery is as much as 300% increased with ACDF vs c-tdr C-TDR is the clear choice for patients with single level DDD

References 1. Smith GW, Robinson RA. The treatment of certain cervical spine disorders by anterior removal of the intervertebral disc and interbody fusion. J Bone Joint Surg Am. 1958; 40: 607-24 2. Rao RD, Currier BL, Albert TJ et al. Degenerative cervical spondylosis: clinical syndromes, pathogenesis and management. J Bone Joint Surg Am 2007; 89: 1360-78 3. Hillibrand AS, Carlson GD, Palumbo MA et al. Radiculopathy and Myelopathy at segments adjacent to the site of a previous anterior cervical arthrodesis. J Bone Joint Surg Am. 1999; 81: 519-28 4. Wigfield CC, Skzyoiec D, Jackowski A, Adams MA. Internal stress distribution in cervical intervertebral discs; The influence of an artificial cervical joint and simulated anterior interbody fusion. J Spinal Disord Tech. 2003; 16 (5): 441-449 5. Jansen ME, Zigler JE, Spivak JM et al. ProDisc-C total disc replacement versus anterior cervical discectomy and fusion for single-level symptomatic cervical disc disease; Sevenyear follow-up of the prospective randomized US food and drug administration investigational device exemption study. J Bone Joint Surg Am. 2015; 97:1738-47 6. Burkus JK, Traynelis VC, Haid RW. Clinical and radiographic analysis of an artificial cervical disc: 7-year follow-up from the Prestige prospective randomized controlled clinical trial. J Neursurg Spine. 2014; 21: 516-528 7. Gornet MF, Burkus JK, Shaffrey ME et al. Cervical disc arthroplasty with Prestige LP disc versus anterior cervical discectomy and fusion: seven-year outcomes. Int Journal of Spine Surg. 2016; 10(24): 1-21

References (cont.) 8. Phillips FM, Geisler FH, Gilder KM et al. Long-term outcomes of the US FDA IDE prospective, randomized controlled clinical trial comparing PCM cervical disc arthroplasty with anterior cervical discectomy and fusion. Spine 2015; 40(10): 674-683 9. Hisey MS, Zigler JE, Jackson R et al. Prospective, randomized comparison of one-level Mobi-C cervical total disc replacement vs anterior cervical discectomy and fusion: Results at 5-year follow-up. Int Journal of Spine Surg. 2016;10(10): 1-10 10. Hisey MS, Bae HW, Davis RJ et al. Multi-center, Prospective, Randomized, Controlled Investigational Device Exemption Clinical Trial Comparing Mobi-C Cervical Artificial Disc to Anterior Discectomy and Fusion in the Treatment of Symptomatic Degenerative Disc Disease in the Cervical Spine. Int Journal of Spine Surg. 2014;8(7) 11. Gornet MF, Burkus JK, Shaffrey ME et al. Cervical disc arthroplasty with PRESTIGE LP disc versus anterior cervical discectomy and fusion: a prospective, multicenter investigational device exemption study. J Neursurg Spine. 2015; 23: 558-573 12. Murrey D, Janssen M, Delemarter R, et al. Results of the prospective, randomized, controlled multicenter Food and Drug Administration investigational device exemption study of the ProDisc-C total disc replacement versus anterior discectomy and fusion for the treatment of 1-level symptomatic cervical disc disease. The Spine J. 2009;9:275-286 13. Phillips FM, Lee JY, Geisler FH, et al. A Prospective, Randomized, Controlled Clinical Investigation Comparing PCM Cervical Disc Arthroplasty With Anterior Cervical Discectomy and Fusion. Spine. 2013; 38(15): E907-E918

References (cont.) 14. Radcliff K, Lerner J, Yang C, et al. Seven-year cost-effectiveness of ProDisc-C total disc replacement: results from investigational device exemption and post-approval studies. J Neurosurg Spine. 2016. 24:760-768 15. Zhao Y, Zhang Y, Sun Y et al. Application of cervical disc arthroplasty with Bryan cervical disc: 10 year follow-up results in China. Spine. 2016. 41(2):111-115 16. Garrido BJ, Taha TA and Sasso R. Clinical outcomes of Bryan cervical disc arthroplasty: a prospective, randomized, controlled, single site trial with 48-month follow-up. J Spinal Disord Tech. 2010 Aug;23(6):367-71 17. Quan GM, Vital J, Hansen S. Eight year clinical and radiological follow-up of the Bryan cervical disc arthroplasty. Spine 2011; 36(8): 639-646 18. Sasso RC, Anderson PA, Riew KD and Heller JG. Results of cervical arthroplasty compared with anterior discectomy and fusion: Four-year clinical outcomes in prospective randomized controlled trial. J Bone Joint Surg Am 2011; 93: 1684-92 19. Coric D, Nunley PD, Guyer RD, Mustane D et al. Prospective randomized multicenter study of cervical arthroplasty: 269 patients from the Kineflex/C artificial disc investigational device exemption study with a minimum 2-year follow-up. J Neurosurg: Spine/ June 24, 2011; epub ahead of print 20. Huppert J, Beaurain J, Steib JP and Bernard P et al. Comparison between single and multilevel patients: clinical and radiological outcomes 2 years after cervical disc replacement. Eur Spine J. 2011; Sep 20(9): 1417-26

References (cont.) 21. Zechmeister I, Winkler R, Mad P. Artificial total disc replacement versus fusion for the cervical spine: a systematic review). Eur. Spine J. 2011; 20(2): 177-84 22. Xing D, Ma XL, Ma JX, Wang J, Ma T, Chen Y. A meta-analysis of cervical arthroplasty compared to anterior cervical discectomy and fusion for single-level cervical disc disease. J Clin Neurosci. 2013 Jul;20(7):970-8 23. Jiang H, Zhu Z, Qiu Y, Qian B, Qiu X, Ji M. Cervical disc arthroplasty versus fusion for single-level symptomatic cervical disc disease: a meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg. 2012 Feb;132(2):141-51 24. Upadhyaya CD, Wu JC, Trost G, Haid RW, Traynelis VC, Tay B, Coric D, Mummaneni PV. Analysis of the three United States Food and Drug Administration investigational device exemption cervical arthroplasty trials. J Neurosurg Spine. 2012 Mar;16(3):216-28. 25. McAfee PC, Reah C, Gilder K, Eisermann L, Cunningham B. A meta-analysis of comparative outcomes following cervical arthroplasty or anterior cervical fusion: results from 4 prospective multicenter randomized clinical trials and up to 1226 patients. Spine (Phila Pa 1976). 2012 May 15;37(11):943-52

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