1. PUTTING IT ALL TOGETHER: Practical Approach Knee OA Patients Interested in Regenerative Medicine Jay Smith, MD Professor & Vice-Chair of of PM&R Departments of PM&R, Radiology & Anatomy Mayo Clinic, Rochester, MN AAPM&R 2015

2. REGEN MED CONSULT Disclosures Off-label use Off-label use PRP, BMC PRP, BMC Speaking honorarium Speaking honorarium Gulf Coast Ultrasound Institute Gulf Coast Ultrasound Institute Stock/Royalties – TENEX Health Stock/Royalties – TENEX Health Stock/CMO – Sonex Health Stock/CMO – Sonex Health

3. REGEN MED CONSULT Learning Objectives Discuss approach to patient with knee OA interested in regenerative medicine options Discuss approach to patient with knee OA interested in regenerative medicine options Practical Practical Patient encounter Patient encounter Best available science Best available science Level V evidence Level V evidence Focus on PRP & BMC Focus on PRP & BMC Prolotherapy Prolotherapy Structural fat grafts Structural fat grafts Other Other AMSCs – Mayo

4. REGEN MED CONSULT Clinical Presentation 60 y Male with left knee OA 60 y Male with left knee OA ‘’Can those stem cells cure my arthritis?” ‘’Can those stem cells cure my arthritis?” “Dr. X said you can regrow my cartilage.” “Dr. X said you can regrow my cartilage.”

5. REGEN MED CONSULT Be a Good Doctor  Perform a comprehensive physiatric evaluation Confirm diagnosis Confirm diagnosis Ensure reasonable prior Rx Ensure reasonable prior Rx Standard of care Standard of care Identify co-morbidities Identify co-morbidities Influence regen med options Influence regen med options Modify expected outcomes Modify expected outcomes Determine functional limitations & patient goals Determine functional limitations & patient goals “What do you want to achieve?” “What do you want to achieve?”

6. REGEN MED CONSULT History: Sx Profile & Past Eval Presenting symptoms Presenting symptoms Functional consequences Functional consequences Prior evaluation Prior evaluation Prior imaging Prior imaging Standing X-rays < 1 yr Standing X-rays < 1 yr Alignment Alignment MRI? MRI? Bone marrow lesions Bone marrow lesions Meniscal extrusion Meniscal extrusion

7. REGEN MED CONSULT History: Assess Prior Treatments Activity modification Activity modification Weight loss Weight loss PT/Exercise PT/Exercise Strength Strength Aerobics Aerobics Other Other Bracing/Wedges Bracing/Wedges Modalities Modalities PEMF, TENS, etc. PEMF, TENS, etc. Meds Meds Oral Topical Supplements Supplements Injections Injections Cortisone Hyaluronic acid Regen Surgery Surgery Underline – AAOS Guidelines Underline – AAOS Guidelines

8. REGEN MED CONSULT History: Prior Treatments – Why? Identify and discuss gaps in prior treatments Identify and discuss gaps in prior treatments Reinforce importance of holistic approach Reinforce importance of holistic approach (Re)-implement prior to regen med (Re)-implement prior to regen med Integrate into regen med Rx plan Integrate into regen med Rx plan Assess patient’s dedication Assess patient’s dedication Identify prior adverse reactions Identify prior adverse reactions Needle/procedure-phobic Needle/procedure-phobic Reaction to prior regen Rx Reaction to prior regen Rx

9. REGEN MED CONSULT History: Importance of Medical Hx May benefit from “medical tune-up” first May benefit from “medical tune-up” first Metabolic syndrome = pro-inflammatory Metabolic syndrome = pro-inflammatory Disclose limited knowledge & experience Disclose limited knowledge & experience Safety of PRP & BMC reasonably established Safety of PRP & BMC reasonably established Systemic inflammatory/autoimmune D/O’s? Systemic inflammatory/autoimmune D/O’s? Chronic infections (e.g. HIV, Hepatitis)? Chronic infections (e.g. HIV, Hepatitis)? Hematological (incl. marrow) disorders? Hematological (incl. marrow) disorders? History of cancer? History of cancer?  Honest discussion & documentation  Discuss/obtain permission from caregivers

10. REGEN MED CONSULT History: Medications/Supplements PRP PRP Avoid NSAIDs 1-2 weeks before (?after?) Avoid NSAIDs 1-2 weeks before (?after?) Others? Others? BMC (BMSCs) BMC (BMSCs) Immunosuppressives Immunosuppressives Statins Statins Others? Others?  Recommend common sense approach  Consider risks-benefits of medication changes

11. REGEN MED CONSULT History: Final Considerations Document date of last physical examination Document date of last physical examination < 1 year < 1 year Screening tests Screening tests Lab tests Lab tests Communicate with caregiver Communicate with caregiver “Permission” “Permission” Medication modifications Medication modifications Further evaluations Further evaluations

12. REGEN MED CONSULT Physical Examination Knee Knee Gait Gait Alignment Alignment Motion loss Motion loss Instability Instability Mechanical Sxs Mechanical Sxs Hip/Spine/Neuro Hip/Spine/Neuro Be sure it is a regen med treatable knee problem Be sure it is a regen med treatable knee problem Tendinosis, CPPD/gout, saphenous neuritis Tendinosis, CPPD/gout, saphenous neuritis

13. REGEN MED CONSULT Imaging Standing radiographs Standing radiographs K-L staging K-L staging Alignment Alignment MRI MRI Bone marrow lesions Bone marrow lesions May be painful May be painful Recognized & treated? Recognized & treated? Osteonecrosis Osteonecrosis Meniscal extrusion? Meniscal extrusion? Choi Eur J Orthop Surg Traum 2014

14. REGEN MED CONSULT Discussion & Treatment Options  Discuss diagnosis & Rx options Review “standard of care” Rx options Review “standard of care” Rx options Context of prior Rx Context of prior Rx Do nothing  surgery Do nothing  surgery Review regen med Rx options Review regen med Rx options Off-label, non-reimbursed Off-label, non-reimbursed Discuss patient specific options: Discuss patient specific options: Evaluation Evaluation Patient preferences Patient preferences Patient goals Patient goals

15. REGEN MED CONSULT Rx Options: Standard of Care Consider “standard of care” options Consider “standard of care” options Lateral wedge/brace Lateral wedge/brace Trial of crutches (e.g. BML) Trial of crutches (e.g. BML) “Need quick fix” – cortisone “Need quick fix” – cortisone Preparation for later regen Rx Preparation for later regen Rx Surgery may be best option Surgery may be best option

16. REGEN MED CONSULT Rx Options: PRP Discuss rationale, preparation & delivery Discuss rationale, preparation & delivery Multiple studies, including RCTs Multiple studies, including RCTs Reasonably safe Reasonably safe Physiologic > Regenerative Physiologic > Regenerative Slower onset vs. cortisone Slower onset vs. cortisone 40-60% improvement X 6-12 mos. 40-60% improvement X 6-12 mos. May be better in K-L 1-2 May be better in K-L 1-2 Can be repeated (long term safety?) Can be repeated (long term safety?)

17. REGEN MED CONSULT Rx Options: BMC Discuss rationale, preparation & delivery Discuss rationale, preparation & delivery CE vs. BMC/BM-MNCs CE vs. BMC/BM-MNCs Details regarding BMA Details regarding BMA Few studies, no RCTs Few studies, no RCTs Reasonably safe Reasonably safe Mechanism of action? Mechanism of action? Potential disease modification Potential disease modification Expanded vs. BMC/BM-MNCs Expanded vs. BMC/BM-MNCs

18. REGEN MED CONSULT Rx Options: BMC 50% chance of > 50% improvement 50% chance of > 50% improvement 50-60% improvement (wide variability) 50-60% improvement (wide variability) Not all respond Not all respond May be slow onset (> 3 months) May be slow onset (> 3 months) Max improvement 3-6 months Max improvement 3-6 months Durability?, but hope > 12 months Durability?, but hope > 12 months Can be repeated, long term safety? Can be repeated, long term safety? More effective in K-L 3-4 vs. PRP? More effective in K-L 3-4 vs. PRP?

19. REGEN MED CONSULT Decision-Making & Documentation Discuss off-label use of PRP and BMC Discuss off-label use of PRP and BMC Discuss FDA positions (e.g. SVF) Discuss FDA positions (e.g. SVF) Discuss non-coverage by third party payors Discuss non-coverage by third party payors ABNs/Waivers ABNs/Waivers Set realistic expectations Set realistic expectations Be honest Be honest Under-promise & over-deliver Under-promise & over-deliver “At worst it’s a waste of time and money” “At worst it’s a waste of time and money” Document Document

20. REGEN MED CONSULT THANK YOU Questions & Discussion