EARLY RESULTS CONFIRM

Clinical and Economic Value of the ATTUNE® Knee System

The ATTUNE® Knee System represents the largest research and development project in the history of DePuy Synthes, backed by a comprehensive evidence generation program that encompasses clinical and patient reported outcomes as well as health economics studies.

Comprehensive Evidence Generation

Positive Early Registry Results

The latest results from the 2017 Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) and National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) confirmed early favorable results for the ATTUNE Knee.

AOANJRR

NJR

97.9%98.9%

98.1%

ATTUNE Cruciate Retaining Knee survivorship at three years.1

ATTUNE Posterior Stabilized Knee survivorship at three years.1

survivorship atfour years.2

The CR ATTUNE Knee performs in line with the overall class of cemented, minimally stabilized total knee arthroplasty (TKA) at three years which has an estimated cumulative percent revision of 2.2%(2.1, 2.3).1 The PS ATTUNE Knee compares favorably with the overall class of posterior stabilized cemented TKA at three years which has an estimated cumulative percent revision of 2.9% (2.8, 3.0).1

The independent analysis of 14,936 ATTUNE Knee implantations, showed that the cumulative revision rate for the ATTUNE Knee is 1.9% at four years (98.1% implant survivorship at four years), which is in line with the overall class of total knee replacement. The 5 year estimated cumulative rate of revision for the ATTUNE Knee is currently based on a sample size of 64 patients, with two late revisions influencing this estimate.

Value-Based Healthcare: From Hospital to Home

39% lower odds of patient discharge to a skilled nursing facility when implanted with an ATTUNE Knee, compared to patients who received a TKA with a Triathlon® Knee, according to the results of a large U.S. hospital administrative database review.3

Going home following TKA vs. being discharged to a skilled nursing facility may potentially impact patient satisfaction and reduce health care costs.

Improvements in Patient Reported Outcomes

One year results from two worldwide studies showed improved patient reported outcomes with the ATTUNE Knee compared to other leading knee systems.4

Confidence in knee performance4

Improved patellofemoral outcomes6-10

Activities of daily living4 Quality of life4

Innovative ATTUNE Knee Features Help Address Unmet Needs

60+ patentsin the U.S. granted for key inventions related to the ATTUNE Knee Implants and Instruments.

ATTUNE GRADIUS® CurveGeometry of the curve is designed to address the unnatural sliding of the femur on the tibia, to provide smooth motion and stability during everyday activities.5

GLIDERIGHT® ArticulationFour independent studies demonstrated improved patello-femoral outcomes, including reduced incidence of symptomatic crepitus when compared to the well performing SIGMA® Knee.7-10 In addition, a fifth study concluded the biomechanics of the PS RP ATTUNE Knee with medialized anatomic patella more closely resembles the biomechanics of the natural knee than the PS RP ATTUNE Knee medialized dome patella.6

www.ATTUNEevidence.com

The third party trademarks used herein are the trademarks of their respective owners.©DePuy Synthes 2017. All rights reserved. DSUS/JRC/0117/1942(2)

www.ATTUNEevidence.com

References1 Australian Orthopaedic Association National Joint Replacement Registry Annual Report. (2017). Tables KT7, KT22, KT 23.

Full summary of all data is available from: https://aoanjrr.sahmri.com/annual-reports-2017

2 National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. Implant Summary Report for DePuy ATTUNE CR and ATTUNE PS. NJR Database extract November 10, 2017, pages 1-17. Licensed for use until May 10, 2018. Available at www.ATTUNEevidence.com (US) and www.provingthepromise.com (EMEA).

3 Etter K, Lerner J, deMoor C, Yoo A, Kalsekar I. Comparative Analysis of Hospital Length of Stay and Discharge Status of Two Contemporary Primary Total Knee Systems. Journal of Knee Surgery. 2017; 193: 1-33.

4 Hamilton WG, Brenkel I, Clatworthy M, Dwyer K, Himden S, Lesko J, Kantor S. Early Patient Reported Outcomes With New Primary vs. Contemporary Total Knee Arthroplasty; A Comparison of Two, Worldwide, Multi-Center Prospective Studies. 2017; American Academy of Orthopaedic Surgeons Annual Meeting, Poster Number 106, San Diego, CA. Study comparators included the SIGMA Knee (89%), Triathlon™ (7%), NexGen® (3%), and Other (1%).

5 Clary, C W., Fitzpatrick, C.K., Maletsky, L.P., & Rullkoetter, P. J. (2012) Improving Dynamic Mid-stance Stability: An Experimental and Finite Element Study. Orthopaedic Research Society, 58th Annual Meeting, Poster Number 1044, San Francisco, CA.

6 Azhar A, Mannen E, Smoger L et al. Evaluation of in-Vivo Mechanics for Medialized Dome and Medialized Anatomic Patellofemoral Geometries During Knee Extension and Lunge. International Society for Technology in Arthroplasty (ISTA): e-Poster, 5-8 October 2016, Boston, MA.

7 Indelli PF, Pipino G, Johnson P, Graceffa A, Marcucci M. Posterior-stabilized total knee arthroplasty: a matched pair analysis of a classic and its evolutional design. Arthroplasty Today 206;2(4):193-198, 2016.

8 Martin JR, Jennings JM, Watters TS, Levy DL, McNabb DC, Dennis DA, Femoral Implant Design Modification Decreases the Incidence of Patellar Crepitus in Total Knee Arthroplasty. The Journal of Arthroplasty. 2017; 32(4): 1310-3.

9 Ranawat CS, White PB, West S, Ranawat AS, Clinical and Radiographic Results of Attune and PFC Sigma Knee Designs at 2-Year Follow-Up: A Prospective Matched-Pair Analysis. J Arthroplasty 2017;32:431-6.

10 Toomey SD, Daccach JA, Shah JC, Himden SE, Lesko JP, Hamilton WG. Comparative Incidence of Patellofemoral Complications Between 2 Total Knee Arthroplasty Systems in a Multicenter, Prospective Clinical Study. J Arthroplasty 2017;32(9S): S187-S192.

Australian Orthopaedic Association National Joint Replacement Registry 2017 Annual Report

Extracted from Table KT7 Cumulative Percent Revision of Cemented Primary Total Knee Replacement by Prosthesis Combination

AOANJRR | 2017 ANNUAL REPORT

192 aoa.org.au Data Per iod 1 September 1999 – 31 December 2016

PROSTHESIS TYPES

There have been 516 femoral and tibial prosthesis combinations used in primary total knee replacement reported to the Registry. In 2016, 119 femoral and tibial combinations were used. This is eight less than in 2015. The cumulative percent revision of the 144 combinations with more than 400 procedures per combination are listed in Tables KT7 to KT9. Although the listed combinations are a small proportion of all possible combinations, they represent 96.4% of all primary total knee replacement. The ‘Other’ group is the combined outcome of the remaining 372 prosthesis combinations with less than 400 procedures reported per combination. There are 63 cemented femoral and tibial prosthesis combinations with more than 400 procedures. Of those with a 16 year cumulative percent revision, the Nexgen CR/Nexgen is the

lowest at 5.1% (Table KT7). There are 39 cementless femoral and tibial prosthesis combinations with more than 400 procedures. Of those with a 16 year cumulative percent revision, the Nexgen CR/Nexgen is the lowest at 4.4% (Table KT8).

There are 42 combinations of primary total knee replacement using hybrid fixation and with more than 400 procedures. The PFC Sigma CR/PFC Sigma has the lowest 16 year cumulative percent revision (4.8%) (Table KT9).

Table KT7 Cumulative Percent Revision of Cemented Primary Total Knee Replacement by Prosthesis Combination

Femoral Component

Tibial Component

N Revised

N Total 1 Yr 3 Yrs 5 Yrs 10 Yrs 15 Yrs 16 Yrs

ACS ACS Mobile 12 533 1.0 (0.4, 2.4) 1.9 (0.9, 3.9) AGC AGC 195 3497 0.5 (0.3, 0.9) 2.5 (2.0, 3.0) 3.6 (3.0, 4.3) 5.6 (4.8, 6.5) 8.8 (7.4, 10.4) 9.6 (7.6, 12.1) Active Knee Active Knee 48 1698 0.9 (0.5, 1.5) 2.4 (1.7, 3.4) 3.7 (2.7, 5.0) 4.8 (3.4, 6.6) Advance Advance II 56 918 1.5 (0.9, 2.6) 4.2 (3.1, 5.7) 4.8 (3.6, 6.4) 7.1 (5.4, 9.4) Apex Knee CR Apex Knee 3 1016 0.1 (0.0, 0.7) 0.7 (0.2, 2.2) Apex Knee PS Apex Knee 25 1953 0.7 (0.4, 1.2) 3.4 (1.9, 5.9) Attune CR Attune 49 5691 0.6 (0.4, 0.9) 2.1 (1.4, 3.1) Attune PS Attune 18 2693 0.4 (0.2, 0.8) 1.1 (0.6, 1.9) BalanSys BalanSys 27 1636 0.3 (0.1, 0.7) 1.6 (1.0, 2.5) 2.1 (1.3, 3.2) 4.2 (2.5, 7.0) Columbus Columbus 8 403 0.8 (0.3, 2.5) 2.5 (1.2, 5.4) 2.5 (1.2, 5.4) Duracon Duracon* 453 8968 1.0 (0.8, 1.2) 2.4 (2.1, 2.8) 3.3 (2.9, 3.7) 4.9 (4.4, 5.4) 7.0 (6.3, 7.9) 7.2 (6.4, 8.2) E.Motion E.Motion 23 519 2.0 (1.1, 3.7) 4.9 (3.2, 7.4) 5.4 (3.6, 8.1) Evolis Evolis 14 797 0.3 (0.1, 1.1) 1.0 (0.5, 2.1) 1.6 (0.9, 3.0) Evolution Evolution 32 3107 0.7 (0.4, 1.2) 2.3 (1.5, 3.5) GMK Primary GMK Primary 17 587 1.1 (0.5, 2.3) 2.8 (1.7, 4.7) 5.1 (2.6, 9.8) GMK Sphere Primary GMK Primary 49 3417 1.2 (0.8, 1.7) 2.7 (2.0, 3.7)

Genesis II CR Genesis II 466 13669 0.9 (0.8, 1.1) 2.4 (2.1, 2.7) 3.1 (2.8, 3.4) 4.3 (3.9, 4.7) 5.6 (4.9, 6.5) 6.0 (5.0, 7.1) Genesis II CR Profix Mobile* 35 490 1.7 (0.8, 3.3) 3.4 (2.1, 5.4) 5.4 (3.7, 8.0) 9.0 (6.3, 12.9) Genesis II Oxinium CR Genesis II 347 7488 1.0 (0.8, 1.3) 2.8 (2.4, 3.2) 3.7 (3.2, 4.2) 6.1 (5.5, 6.9) 10.9 (8.3, 14.2)

Genesis II Oxinium PS Genesis II 785 15823 1.5 (1.3, 1.7) 3.8 (3.5, 4.1) 5.2 (4.8, 5.6) 7.5 (6.9, 8.1)

Genesis II PS Genesis II 571 15816 1.2 (1.1, 1.4) 2.8 (2.6, 3.1) 3.7 (3.4, 4.0) 5.0 (4.5, 5.5) 6.2 (5.2, 7.3) Journey Oxinium Journey* 245 3032 1.4 (1.0, 1.9) 4.6 (3.9, 5.4) 6.4 (5.6, 7.4) 10.9 (9.4, 12.7)

Kinemax Plus Kinemax Plus* 111 1826 0.9 (0.6, 1.5) 2.4 (1.8, 3.3) 3.1 (2.4, 4.0) 4.6 (3.7, 5.7) 8.5 (6.9, 10.4) 9.3 (7.2, 12.0) LCS CR LCS 299 3939 1.0 (0.7, 1.4) 3.8 (3.2, 4.4) 5.0 (4.4, 5.8) 7.2 (6.4, 8.1) 9.1 (8.1, 10.2) 9.4 (8.2, 10.8)

516 different femoral and tibial prosthesis combinations have been reported to the Registry. Outcomes at 16 years are being

reported for the first time.

AOANJRR | 2017 ANNUAL REPORT

192 aoa.org.au Data Per iod 1 September 1999 – 31 December 2016

PROSTHESIS TYPES

There have been 516 femoral and tibial prosthesis combinations used in primary total knee replacement reported to the Registry. In 2016, 119 femoral and tibial combinations were used. This is eight less than in 2015. The cumulative percent revision of the 144 combinations with more than 400 procedures per combination are listed in Tables KT7 to KT9. Although the listed combinations are a small proportion of all possible combinations, they represent 96.4% of all primary total knee replacement. The ‘Other’ group is the combined outcome of the remaining 372 prosthesis combinations with less than 400 procedures reported per combination. There are 63 cemented femoral and tibial prosthesis combinations with more than 400 procedures. Of those with a 16 year cumulative percent revision, the Nexgen CR/Nexgen is the

lowest at 5.1% (Table KT7). There are 39 cementless femoral and tibial prosthesis combinations with more than 400 procedures. Of those with a 16 year cumulative percent revision, the Nexgen CR/Nexgen is the lowest at 4.4% (Table KT8).

There are 42 combinations of primary total knee replacement using hybrid fixation and with more than 400 procedures. The PFC Sigma CR/PFC Sigma has the lowest 16 year cumulative percent revision (4.8%) (Table KT9).

Table KT7 Cumulative Percent Revision of Cemented Primary Total Knee Replacement by Prosthesis Combination

Femoral Component

Tibial Component

N Revised

N Total 1 Yr 3 Yrs 5 Yrs 10 Yrs 15 Yrs 16 Yrs

ACS ACS Mobile 12 533 1.0 (0.4, 2.4) 1.9 (0.9, 3.9) AGC AGC 195 3497 0.5 (0.3, 0.9) 2.5 (2.0, 3.0) 3.6 (3.0, 4.3) 5.6 (4.8, 6.5) 8.8 (7.4, 10.4) 9.6 (7.6, 12.1) Active Knee Active Knee 48 1698 0.9 (0.5, 1.5) 2.4 (1.7, 3.4) 3.7 (2.7, 5.0) 4.8 (3.4, 6.6) Advance Advance II 56 918 1.5 (0.9, 2.6) 4.2 (3.1, 5.7) 4.8 (3.6, 6.4) 7.1 (5.4, 9.4) Apex Knee CR Apex Knee 3 1016 0.1 (0.0, 0.7) 0.7 (0.2, 2.2) Apex Knee PS Apex Knee 25 1953 0.7 (0.4, 1.2) 3.4 (1.9, 5.9) Attune CR Attune 49 5691 0.6 (0.4, 0.9) 2.1 (1.4, 3.1) Attune PS Attune 18 2693 0.4 (0.2, 0.8) 1.1 (0.6, 1.9) BalanSys BalanSys 27 1636 0.3 (0.1, 0.7) 1.6 (1.0, 2.5) 2.1 (1.3, 3.2) 4.2 (2.5, 7.0) Columbus Columbus 8 403 0.8 (0.3, 2.5) 2.5 (1.2, 5.4) 2.5 (1.2, 5.4) Duracon Duracon* 453 8968 1.0 (0.8, 1.2) 2.4 (2.1, 2.8) 3.3 (2.9, 3.7) 4.9 (4.4, 5.4) 7.0 (6.3, 7.9) 7.2 (6.4, 8.2) E.Motion E.Motion 23 519 2.0 (1.1, 3.7) 4.9 (3.2, 7.4) 5.4 (3.6, 8.1) Evolis Evolis 14 797 0.3 (0.1, 1.1) 1.0 (0.5, 2.1) 1.6 (0.9, 3.0) Evolution Evolution 32 3107 0.7 (0.4, 1.2) 2.3 (1.5, 3.5) GMK Primary GMK Primary 17 587 1.1 (0.5, 2.3) 2.8 (1.7, 4.7) 5.1 (2.6, 9.8) GMK Sphere Primary GMK Primary 49 3417 1.2 (0.8, 1.7) 2.7 (2.0, 3.7)

Genesis II CR Genesis II 466 13669 0.9 (0.8, 1.1) 2.4 (2.1, 2.7) 3.1 (2.8, 3.4) 4.3 (3.9, 4.7) 5.6 (4.9, 6.5) 6.0 (5.0, 7.1) Genesis II CR Profix Mobile* 35 490 1.7 (0.8, 3.3) 3.4 (2.1, 5.4) 5.4 (3.7, 8.0) 9.0 (6.3, 12.9) Genesis II Oxinium CR Genesis II 347 7488 1.0 (0.8, 1.3) 2.8 (2.4, 3.2) 3.7 (3.2, 4.2) 6.1 (5.5, 6.9) 10.9 (8.3, 14.2)

Genesis II Oxinium PS Genesis II 785 15823 1.5 (1.3, 1.7) 3.8 (3.5, 4.1) 5.2 (4.8, 5.6) 7.5 (6.9, 8.1)

Genesis II PS Genesis II 571 15816 1.2 (1.1, 1.4) 2.8 (2.6, 3.1) 3.7 (3.4, 4.0) 5.0 (4.5, 5.5) 6.2 (5.2, 7.3) Journey Oxinium Journey* 245 3032 1.4 (1.0, 1.9) 4.6 (3.9, 5.4) 6.4 (5.6, 7.4) 10.9 (9.4, 12.7)

Kinemax Plus Kinemax Plus* 111 1826 0.9 (0.6, 1.5) 2.4 (1.8, 3.3) 3.1 (2.4, 4.0) 4.6 (3.7, 5.7) 8.5 (6.9, 10.4) 9.3 (7.2, 12.0) LCS CR LCS 299 3939 1.0 (0.7, 1.4) 3.8 (3.2, 4.4) 5.0 (4.4, 5.8) 7.2 (6.4, 8.1) 9.1 (8.1, 10.2) 9.4 (8.2, 10.8)

516 different femoral and tibial prosthesis combinations have been reported to the Registry. Outcomes at 16 years are being

reported for the first time. AOANJRR | 2017 ANNUAL REPORT

aoa.org.au 213Data Per iod 1 September 1999 – 31 December 2016

Fixation

The effect of fixation varies depending on implant stability. With a minimally stabilised prosthesis, there is no difference between cemented and hybrid fixation and both have a lower rate of revision compared to cementless fixation (Table KT22 and Figure KT24). When a posterior stabilised knee is used, cemented fixation has a lower rate of revision compared to hybrid fixation and when compared to cementless fixation within the first 1.5 years. Hybrid fixation has a higher rate of revision compared to both cemented and cementless fixation (Table KT23 and Figure KT25).

When a medial pivot prosthesis is used there is a similar outcome to minimally stabilised prostheses with respect to fixation. There is no difference between cemented and hybrid fixation and both have a lower rate of revision compared to cementless fixation (Table KT24 and Figure KT26).

Table KT22 Cumulative Percent Revision of Minimally Stabilised Primary Total Knee Replacement by Fixation (Primary

Diagnosis OA)

Fixation N Revised

N Total 1 Yr 3 Yrs 5 Yrs 10 Yrs 15 Yrs 16 Yrs

Cemented 4712 157680 0.8 (0.8, 0.9) 2.2 (2.1, 2.3) 2.9 (2.9, 3.0) 4.5 (4.3, 4.6) 6.5 (6.2, 6.9) 6.9 (6.5, 7.3) Cementless 4795 102625 1.2 (1.1, 1.2) 3.2 (3.0, 3.3) 4.2 (4.1, 4.4) 6.1 (5.9, 6.3) 8.5 (8.1, 8.9) 9.6 (8.9, 10.3) Hybrid 3804 118721 0.8 (0.8, 0.9) 2.3 (2.2, 2.4) 3.1 (3.0, 3.2) 4.6 (4.4, 4.7) 6.4 (6.1, 6.7) 7.0 (6.4, 7.6) TOTAL 13311 379026

Note: Excluding cementless Genesis Oxinium and Profix Oxinium femoral prostheses Figure KT24 Cumulative Percent Revision of Minimally Stabilised Primary Total Knee Replacement by Fixation (Primary

Diagnosis OA)

Number at Risk 0 Yr 1 Yr 3 Yrs 5 Yrs 10 Yrs 15 Yrs 16 Yrs Cemented 157680 137324 102690 75175 27902 2835 658 Cementless 102625 95177 78385 60395 22089 1754 451 Hybrid 118721 106395 81421 59789 23799 2381 546

Cum

ulat

ive

Perc

ent R

evisi

on

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

22%

24%

Years Since Primary Procedure0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Cementless vs CementedEntire Period: HR=1.26 (1.21, 1.32),p<0.001

Hybrid vs CementedEntire Period: HR=0.99 (0.95, 1.04),p=0.775

Cementless vs HybridEntire Period: HR=1.27 (1.22, 1.33),p<0.001

HR - adjusted for age and genderCementedCementlessHybrid

Cementing the tibial component gives the best outcome for minimally stabilised and medial pivot prostheses. Cementing both tibial and femoral components gives the

best outcome for posterior stabilised prostheses.

AOANJRR | 2017 ANNUAL REPORT

214 aoa.org.au Data Per iod 1 September 1999 – 31 December 2016

Table KT23 Cumulative Percent Revision of Posterior Stabilised Primary Total Knee Replacement by Fixation (Primary Diagnosis OA)

Fixation N Revised

N Total 1 Yr 3 Yrs 5 Yrs 10 Yrs 15 Yrs 16 Yrs

Cemented 4774 124375 1.1 (1.1, 1.2) 2.9 (2.8, 3.0) 3.9 (3.8, 4.1) 5.9 (5.8, 6.1) 7.8 (7.3, 8.3) 8.0 (7.3, 8.8) Cementless 337 6947 1.9 (1.6, 2.2) 4.0 (3.5, 4.5) 5.0 (4.5, 5.6) 6.3 (5.6, 7.1) Hybrid 675 11458 1.6 (1.4, 1.8) 4.2 (3.8, 4.6) 5.5 (5.1, 6.0) 7.3 (6.7, 7.9) 10.3 (9.0, 11.8) 10.9 (9.3, 12.8) TOTAL 5786 142780

Figure KT25 Cumulative Percent Revision of Posterior Stabilised Primary Total Knee Replacement by Fixation (Primary Diagnosis

OA)

Number at Risk 0 Yr 1 Yr 3 Yrs 5 Yrs 10 Yrs 15 Yrs 16 Yrs Cemented 124375 110276 83217 59991 15594 689 140 Cementless 6947 6351 5132 3930 769 12 2 Hybrid 11458 10570 8814 7016 2276 174 54

Cum

ulat

ive

Perc

ent R

evisi

on

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

22%

24%

Years Since Primary Procedure0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

Cementless vs Cemented0 - 1.5Yr: HR=1.36 (1.17, 1.59),p<0.001

1.5Yr+: HR=0.89 (0.76, 1.05),p=0.163

Hybrid vs CementedEntire Period: HR=1.28 (1.18, 1.39),p<0.001

Hybrid vs CementlessEntire Period: HR=1.20 (1.05, 1.36),p=0.007

HR - adjusted for age and genderCementedCementlessHybrid