THE POTENTIAL ROLE OF INTRADISCAL BIACUPLASTY IN REDUCING SPINE DISABILITY AND PROVIDING VALUE Mehul J. Desai, MD, MPH President, International Spine, Pain & Performance Center George Washington University Legislative Fellow 2016, North American Neuromodulation Society Leadership Fellow 2015-2017, American Academy of Physical Medicine & Rehabilitation 10 x 25 Spine Summit: Technology Update July 15, 2016

DISCLOSURES Advisory Board – Halyard Health Advisory Board – Medtronic Stock Options – dorsaVi, Inc.

Objectives To elucidate the role of intradiscal procedures such as biacuplasty in treatment pain of discogenic origin in the lumbar spine. To understand the potential cost-benefits of this procedure as a part of the continuum of spine care.

Costs Approximately 800,000 spinal surgeries in the U.S. annually. From 2001-2010 approximately 3.6 million fusions in the U.S.. Total cost of > $ 287 billion. Average national cost of $14,000 ($11-25K) for a single-level ACDF and $26,000 ($20-37K) for single- level PLIF (direct costs; professional and technical). Indirect costs much higher. Goz V. 2015

Cost-Effectiveness Laminectomy calculated to cost $77,000 per QALY gained. Lumbar fusion calculated to cost $114,000 per QALY gained. In the United States, $100,000 is the maximum at which procedures are considered cost-effective. Tosteson AN et al. 2008

Unsatisfactory Outcomes Rates of development in the literature range from 4- 50%. Frequency of cases in the general population from 0.02-2% ( U.S. 72,000-7,200,000). Conservative estimates that we are adding 80,000- 300,000 new patients to those already suffering from this issue. Cost associated with Post Spine Surgery Syndrome. Taylor RS 2012

Background Internal disc disruption resulting in lumbar discogenic pain is a common cause of chronic low back. Implicated in approximately 40% of younger patients. Schwarzer AC 1995

Discogenic Pain Self-care Analgesic and anti-inflammatory medications Conventional Medical Management (CMM) is the primary treatment option for discogenic LBP Self-care Analgesic and anti-inflammatory medications Physical and cognitive therapies These CMM choices tend to be moderately effective Surgical Interventions Artificial disc replacement Lumbar discectomy Instrumented lumbar fusion

Biacuplasty

Bipolar Cooled RF Lesion 42 mm Describe the image on the left- 18G electrode, 6mm active tip, 22mm spacing. After lesioning for 25 minutes at 80C there are two independent lesions which are 14 mm apart. Describe the image on the right- …. After lesioning for 25 minutes at 55C set temp, the lesion is confluent and measures 42mm across. Testing performed in chicken (37°C) for 25:00 at a set temperature of 55 °C.

Intradiscal Biacuplasty (IDB) Ease of Use Direct percutaneous application of the electrodes into the targeted spinal disc -enables better targeting -reduces complications Large Lesion Cooled probes Bipolar heating configuration High probability to ablate culprit nociceptive nerves Structures nearby (collagen in the posterior annulus, vertebral end plates, nerve roots) are not damaged 42 mm

N = 67 enrolled, 63 treated Biacuplasty (IDB) (n = 29) Conservative Medical Management (CMM) (n = 34) Single level disease confirmed by positive pain reproduction on discography 1, 3, & 6 month follow up Outcomes include measures of: Pain (VAS) Function (SF-36) Disability (ODI) Quality of Life (EQ-5D, PGIC) CMM subjects could elect to cross-over to IDB + CMM at 6-months, or to continue CMM-alone to 12-months IDB + CMM: One ablation procedure/patient CMM continued as prescribed by physician CMM for both groups defined as: Physical Therapy Pharmacological Management Minimally invasion interventions permitted as needed Lumbar-epidural injections Sacro-iliac joint injections Facet-joint or nerve interventions Behavioral Therapy Weight Loss Acupuncture

Methods: Comparative effectiveness RCT comparing Biacuplasty (n = 29) against Conventional Medical Management (n = 34) 1, 3, & 6 month follow up Outcomes include SF-36, VAS, ODI Results: Statistically significant improvement in pain @ 1, 3, & 6 months Trends indicating functional improvement 50% vs 18% Responder rate (2 point/30% decrease in VAS) 42% reported >50% decrease in pain Conclusion: Superior performance of IDB with respect to all study outcomes suggests that it is a more effective treatment for discogenic pain than CMM-alone.

SF 36 PF mean improvement 18 points ODI mean improvement 11 points VAS mean improvement 2.4 SF 36 PF mean improvement 18 points ODI mean improvement 11 points

Main Inclusion Criteria Completion of the 6-month follow up of the original effectiveness study Consent to continue follow up for additional 6-month following either IDB after crossing over or remaining in CMM group Main Exclusion Criteria Major deviations from protocol criteria 22 active treatment patients reported 12-month data. 25/28 available chose to crossover 22/25 Crossovers reported 6-month data Manuscript Accepted, Pain Medicine

41% of IDB group maintained >50% decrease in pain at 12 months IDB: 55% Responder Rate (>2 points VAS or 30% decrease) vs. CMM: 18% at 12 months 41% of IDB group maintained >50% decrease in pain at 12 months Crossover group responded the same to treatment as originally treated group

Crossover subjects responded similarly to originally treated subjects

Clinically relevant improvements in Pain, Function and Quality of Life maintained through 12 month time point All metrics reflect similar, consistent message. The outcomes of this study suggest: IDB + CMM more effectively reduces discogenic LBP than CMM, and can rescue individuals who continue suffering from discogenic pain despite of CMM IDB + CMM enables better physical functioning, less disability, and a greater positive impact on patients’ health when compared to CMM-alone The positive effects of IDB + CMM are durable, lasting up to 12-months after a single IDB treatment The superior performance of the IDB + CMM treatment with respect to all study outcomes suggests that IDB + CMM is a more effective treatment for discogenic LBP than CMM-alone for carefully selected patients

N = 64 enrolled, 59 treated in 1:1 randomization scheme Pain Med. 2013 Mar;14(3):362-73 N = 64 enrolled, 59 treated in 1:1 randomization scheme Biacuplasty (n = 29) Sham Procedure (n = 30) One and two level disease included All patients had positive pain reproduction on discography 1, 3, & 6 month follow up Outcomes include SF-36, NRS, ODI 6 month follow up for all patients Study unblinded at 6 months & sham patients allowed to cross over to treatment Dr. Kapural and team were previously at Cleveland Clinic and now practices at Wake Forest University. Study was conducted at both centers. First ever double-blind randomized study of TransDiscal vs. placebo. 16 patients were single level, 11 were two level 25/30 sham patients chose to have TransDiscal biacuplasty at 6 month follow up.

Pain Med. 2013 Mar;14(3):362-73 Results: No procedure-related complications Statistically significant improvements in pain and function @ 6 mths 16 mg reduction in daily opioid use Authors conclude that TransDiscal biacuplasty should be recommended to select patients with discogenic low back pain All p < 0.05

all observed time points. Pain Med. 2015 Mar;16(3):425-31 Long term follow up 22 active tx (12 mth) 20 “cross-over” (6 mth) Sustained improvements in pain and function Slight reduction in opioid use No adverse events Halyard Multicenter trial is in final data collection stages and should be published later this year. It is a multicenter trial (9 centers across US) including 67 patients that compares TransDiscal to conservative medical management (what is being done today that doesn’t involve surgery). At the 6 month time point, we are seeing very similar results as shown here (consistency of procedure). So between the two RCTS/studies, one indicates this procedure is better than nothing. The other will show that it is better than what you are doing now for these patients. Conclusions: Clinically significant improvements after IDB initially reported at 6 months were maintained at 9 and 12 months. The cross-over subjects had similar improvement in all outcome measures at all observed time points.

Conclusions Where is the appropriate place to position this procedure? Demonstrated effectiveness and reduction in disability? Questions about durability? Cost-effectiveness? $3000-5000 per procedure. Should this be a treatment for patient under the age of 50 with discogenic low back pain prior to and earlier in the continuum of care than surgery?