IRACON 2016

Dr. Arjun MN, Dr Vivek VasdevDepartment of RheumatolgyArmy Hospital (Research & Referral), Delhi Cantt

Title

Comparative analysis of efficacy of intra articular autologous

platelet rich plasma (PRP) with steroids in osteoarthritis kneeA Prospective randomized comparative interventional study

Introduction

Osteoarthritis (OA) of the knee is one the most prevalent degenerative joint disease in the world affecting almost 13 % of patients aged >60 yrs

In India, the prevalence of OA knee ranges from 28.7-31.4 %

Main treatment option is surgery Cumbersome Associated with significant cost and potential morbidity.

Ref: Neogi T. The epidemiology and impact of pain in osteoarthritis. Osteoarthritis Cartilage. 2013;21:1145–1153 Pal CP, Singh P, Chaturvedi S, Epidemiology of knee osteoarthritis in India and related factors. Indian J Orthop

2016;50:518-22

Background:

Evidence lacking regarding the amount and duration of efficacy of PRP

No consensus worldwide about standardization of PRP dosing or regimes

Weekly PRP injections require frequent visits to hospital and repeated

injections is inconvenient and have potential related side effects

Two 6 ml injection at 03 monthly intervals, represent an attractive

alternative to the current treatment regimen, reducing the number of

intra-articular injections and offers potential comfort and safety benefits

Patel S, Dhillon MS, Aggarwal S, Marwaha N, Jain A. Treatment with platelet-rich plasma is more effective than placebo for knee osteoarthritis: a prospective, double-blind, randomized trial. Am J Sports Med. 2013; 41(2):356–364

Platelet Rich Plasma (PRP)

PRP is an autologous concentration of a high number of platelets in a small volume of plasma prepared by centrifugation of blood

PRP has been used in maxillofacial and plastic surgery > a decade. Presently, accepted in orthopaedics and sports medicine for treatment of tendinopathy and capsular relaxation in the shoulder.

Rationale for the use of PRP is to stimulate natural healing cascade and tissue regeneration by a “supraphysiologic” release of platelet-derived growth factors directly at the site of treatment

Ref: • Cerza F, Carni S, Carcangiu A, et al. Comparison between hyaluronic acid and platelet-rich plasma, intra-articular infiltration in the treatment of gonarthrosis. Am J Sports Med. 2012; 40(12):2822–2827• Linda Mundy HealthPACT “ Brief Platelet-rich plasma for the treatment of knee osteoarthritis “ August 2013

Platelets structure and activation: Platelets contain significant amounts of cytokines and growth factors which are capable of stimulating cellular growth, vascularization, proliferation, tissue regeneration, and collagen synthesis.

Ref: Ryosuke Sakata, MD, and A. Hari Reddi, PhD REVIEW ARTICLE Platelet-Rich Plasma Modulates Actions on Articular Cartilage Lubrication and Regeneration TISSUE ENGINEERING: Part B Volume 22, Number 5, 2016

Aim of study

Primary Objective: To compare the efficacy of Intra Articular(IA)

autologous platelet rich plasma (PRP) and steroids in a subset of

patients with early OA of the knee

Secondary Objective: Assess the effect of PRP on pain, joint

stiffness, and physical function and to compare it with steroids

Materials & Method Study design

Open label Prospective Simple randomized Comparative interventional study with a follow up till 24 weeks

All patients gave their informed consent and the study was approved by the Institutional Ethical and Scientific Committee

Study population:

Comprised 60 adult patients, attending the Rheumatology/ Ortho OPD at

Army Hospital (R&R), Delhi Cantt, between Sep 2015 -Mar 2016

Symptomatic OA knee for at least 6 months with a prespecified pain of ≥ 40 mm on a 100 mm visual analogue scale (VAS) despite standard of care

Inclusion Criteria

Fulfilled the ACR clinical/radiographic criteria for OA knee

Symptomatic for atleast 6 months with a prespecified pain of ≥40 mm on a 100 mm visual analogue scale (VAS)

Contraindications to regular NSAIDS or weak opioids.

Patients gave informed consent

Exclusion criteria:

Received either oral, injectable (IM/ IV) or IA steroid during 3 months prior to the study.

Received an IA Hyaluronic Acid injection within the past 1 year prior to the study.

Platelet counts < 1.5 lakhs/cumm

Uni-compartment knee OA/ Grade 4 OA /Concomitant symptomatic hip OA / secondary OA

Prosthetic joint or having had arthroscopy surgery

Inclusion and Exclusion Criteria

Sample size was calculated using PS software 3.1.2, 2014

Sample size was calculated out to be 23. With loss to follow up taking up to

20%, it was rounded off to 30

Sample size & sample technique:

PRP Preparation

Sampling and the centrifugation of the PRP preparation were performed

according to criteria established by the Authority Operational Office of

Armed Forces Transfusion Centre (AFTC), Delhi

Preparation of platelet Rich Plsma

Interventional Procedure:

Patient is placed in supine position with knee in full extension

Under aseptic conditions, 6 mL of either platelet concentrate or 2 ml of Depomedrol is injected through a supralateral approach with an 18- gauge needle under ultrasound guidance

In the PRP group, 0.5 mL of CaCl2 (M/40) is injected for every 6 mL of PRP to activate platelets

The knees immobilized for 10 minutes after injection. The patients were discharged after 30 minutes of observation

Statistical analysis-

Data was analyzed using SPSS version 19

Comparison of demographic variables were done with Chi square test

t- test was carried out to compare mean difference in VAS and WOMAC score at

baseline, 6 weeks, 12 weeks and at 24 weeks

A p value <0.05 was taken as statistically significant

EnrollmentAssessed for eligibility (n=70)

Randomized (n=60)

Excluded (n=10) ♦ Not meeting inclusion criteria (n=5) ♦ Declined to participate (n=2) ♦ Other reasons (n=3)

Allocated to receive PRP infiltration (n=30) ♦ Received allocated intervention (n=30) ♦ Did not receive allocated intervention (n=0)l

Lost to follow-up (n=0)Discontinued intervention (n=0)

Analyzed (n=30)Excluded from analysis (n=0)

Allocated to receive Depomed infiltration (n=30) ♦ Received allocated intervention (n=30) ♦ Did not receive allocated intervention (n=0)

Lost to follow-up (n=0) Discontinued intervention (n=0)

Analyzed (n=30)Excluded from analysis (n=0)

Follow-up

Allocation

Analysis

Flow diagram of the study

PRP (n=30)Mean (SD)

Steroid (n=30)

Mean SDp-value

Age 53.3 ± 7.9 57.0 ± 7.2 0.08

Male 9 11 0.584

Duration of OA in years 7.3 ± 4.0 8.0 ± 4.4 0.505

BMI in Kg/m2 26.0 ± 2.3 25.8 ± 2.4 0.748

Received previous IA Steroids/ HA n= 6 8 0.526

Bony swelling n= 16 11 0.518

Knee effusion n= 4 15 0.002

Demographic and baseline clinical characteristics of study patients (n=60)

PRP group(n= 30)

Steroid(n=30)

P value

Grade 1 0 0

0.677

Grade 2 5 6

Grade 3 25 24

Grade 4 0 0

Kellgren-Lawrence score

Baseline VAS Pain scores and WOMAC scores in study patients (N=60)

PRP (n=30)Mean ±SD)(Baseline)

Steroid (n=30)Mean ± SD(Baseline)

p-value

VAS score 78.4 ± 9.2 77.2± 8.8 0.598

Total WOMAC score 75.6± 9.1 76.6± 7.6 0.524

Pain 16.0± 2.03 16.3± 1.44 0.512

Physical function 53.8± 6.6 54.3± 6.2 0.73

Stiffness 5.8± 1.3 6.3± 0.8 0.1

Results(Contd)

• At final follow-up, mean total WOMAC scores showing significant improvement

from baseline in PRP group (75.6 ± 9.1 - 34.9 ± 17.9) and VAS score ( 78.4 ± 9.2 –

45.5 ± 14.6) ; p <0.001

• In steroid group WOMAC score 76.6 ± 7.6 – 69.1 ± 9.1 and VAS score 77.2 ± 8.8 –

64.3 ± 6.3 in PRP vs Steroid groups respectively; P <0.001)

Baseline 6 Weeks 12 Weeks 24 Weeks0

10

20

30

40

50

60

70

80

90

Changes in WOMAC score from base-line to 24 weeks n(60)

IA PRPIA Steroid

Duration

WO

MAC

Sco

re 48.754.3

34.9

69.1

0.0451

43.5

61.0

Mean Western Ontario and McMaster (WOMAC) /VAS scores for the autologous platelet rich plasma (PRP) and Depomedrol (Steroid) groups.

P <0.0001P < 0.0001

45.547.5

Baseline 6 Weeks 12 Weeks 24 Weeks0

10

20

30

40

50

60

70

80

90

Change in VAS from baseline to 24 weeks N(60)

IA PRPIA Steroid

DurationVA

S Sc

ore 44.7

54.0(p < 0.0004)

64.355.4

Discussion

Summary of studies using PRP for knee osteoarthritis

PRP (n=30)mean ± SD

Steroid (n=30)Mean ± SD

p-value

WOMAC scores

Pain 10.0 ± 3.4 2.2 ± 1.3 <0.0001

Physical function 27.6 ± 11.0 4.8 ± 4.6 <0.0001

stiffness 3.1 ± 1.3 0.7± 0.6 <0.0001

WOMAC total 40.7 ± 14.7 7.5 ± 5.5 <0.0001

VAS Score 32.9 ± 12.1 12.9 ± 5.9 <0.0001

Mean difference in VAS Pain scores at baseline and 24 weeks (N=60) follow up

Conclusion

Treatment with PRP showed significantly better clinical outcomes, with

sustained improvement lasting upto 24 weeks.

PRP is a safe and cost effective mode of therapy for improvement in functional

status in early knee osteoarthritis and a minimum of two injections are

appropriate

Further studies will be required with larger sample size and longer follow up

Thank You…..