Ann Rehabil Med.  2019 Apr;43(2):204-214. 10.5535/arm.2019.43.2.204.

Efficacy and Safety of Intra-articular Injections of Hyaluronic Acid Combined With Polydeoxyribonucleotide in the Treatment of Knee Osteoarthritis

• Yoon S
• Kang JJ
• Kim J
• Park S
• Kim JM

• KMID: 2449003
• DOI: http://doi.org/10.5535/arm.2019.43.2.204

Abstract

OBJECTIVE
To assess the clinical efficacy and safety of intra-articular injection of hyaluronic acid (HA) combined with polydeoxyribonucleotide (PDRN) in patients with knee osteoarthritis in comparison with that of HA alone.
METHODS
The current single-center, prospective, randomized, double-blind, controlled study was conducted in 36 patients with knee osteoarthritis at our medical institution. All the eligible patients (n=30) were equally assigned to two treatment arms (trial group "˜HA+PDRN' and control group "˜HA'). For efficacy assessment, the patients were evaluated for the visual analogue scale (VAS) scores, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Knee Society Scores (KSS), all of which served as efficacy outcome measures. We monitored time-dependent changes in efficacy outcome measures at baseline and 1, 3 and 6 months. Subsequently, we compared differences in changes in efficacy outcome measures at 6 months from baseline between the two groups. Moreover, we assessed the safety based on the treatment-emergent adverse events (TEAEs), adverse drug reactions (ADRs) and any other complications serving as safety outcome measures.
RESULTS
There were significant differences in changes in the VAS scores, the WOMAC scores in all domains, except "˜Stiffness', the total WOMAC scores, and the KSS scores in all the domains at 6 months from baseline between the two groups (p<0.05). In our series, there were no TEAEs, ADRs, and any other complications.
CONCLUSION
Intra-articular injections of HA combined with PDRN can also be considered in the treatment of knee osteoarthritis. However, further large-scale and multi-center studies are required to demonstrate the potential of the proposed combination.

Keyword

Knee osteoarthritis; Intra-articular injections; Hyaluronic acid; Polydeoxyribonucleotides

MeSH Terms

Arm
Drug-Related Side Effects and Adverse Reactions
Humans
Hyaluronic Acid*
Injections, Intra-Articular*
Knee*
Ontario
Osteoarthritis
Osteoarthritis, Knee*
Outcome Assessment (Health Care)
Polydeoxyribonucleotides
Prospective Studies
Treatment Outcome
Hyaluronic Acid
Polydeoxyribonucleotides

Figure

• 

  Fig. 1. The study flow chart. A total of 30 enrolled patients were randomized to two treatment arms. With the exclusion of one case of lost-to-follow-up in the control group, the remaining 29 patients completed the entire study.

Reference

1. Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull. 2013; 105:185–99.

2. Rosemann T, Laux G, Kuehlein T. Osteoarthritis and functional disability: results of a cross sectional study among primary care patients in Germany. BMC Musculoskelet Disord. 2007; 8:79.

3. Bhatia D, Bejarano T, Novo M. Current interventions in the management of knee osteoarthritis. J Pharm Bioallied Sci. 2013; 5:30–8.

4. Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. Arthritis Rheum. 2008; 58:26–35.

5. Felson DT, Lawrence RC, Dieppe PA, Hirsch R, Helmick CG, Jordan JM, et al. Osteoarthritis: new insights. Part 1. The disease and its risk factors. Ann Intern Med. 2000; 133:635–46.

6. Le TK, Montejano LB, Cao Z, Zhao Y, Ang D. Health care costs in US patients with and without a diagnosis of osteoarthritis. J Pain Res. 2012; 5:23–30.

7. Iannitti T, Lodi D, Palmieri B. Intra-articular injections for the treatment of osteoarthritis: focus on the clinical use of hyaluronic acid. Drugs R D. 2011; 11:13–27.

8. Chard J, Dieppe P. Update: treatment of osteoarthritis. Arthritis Rheum. 2002; 47:686–90.

9. Bannuru RR, Natov NS, Obadan IE, Price LL, Schmid CH, McAlindon TE. Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: a systematic review and metaanalysis. Arthritis Rheum. 2009; 61:1704–11.

10. Bellamy N, Campbell J, Robinson V, Gee T, Bourne R, Wells G. Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev. 2006; (2):CD005321.

11. Hashizume M, Mihara M. Desirable effect of combination therapy with high molecular weight hyaluronate and NSAIDs on MMP production. Osteoarthritis Cartilage. 2009; 17:1513–8.

12. Onur TS, Sitron CS, Dang A. Co-administration of hyaluronic acid with local anaesthetics shows lower cytotoxicity than local anaesthetic treatment alone in bovine articular chondrocytes. Bone Joint Res. 2013; 2:270–5.

13. Euppayo T, Punyapornwithaya V, Chomdej S, Ongchai S, Nganvongpanit K. Effects of hyaluronic acid combined with anti-inflammatory drugs compared with hyaluronic acid alone, in clinical trials and experiments in osteoarthritis: a systematic review and metaanalysis. BMC Musculoskelet Disord. 2017; 18:387.

14. Zazgyva A, Gergely I, Russu OM, Roman C, Pop TS. Polynucleotides versus sodium hyaluronate in the local treatment of knee osteoarthritis. Acta Medica Transilvanica. 2013; 2:260–3.

15. Vanelli R, Costa P, Rossi SM, Benazzo F. Efficacy of intra-articular polynucleotides in the treatment of knee osteoarthritis: a randomized, double-blind clinical trial. Knee Surg Sports Traumatol Arthrosc. 2010; 18:901–7.

16. Dallari D, Sabbioni G, Del Piccolo N, Carubbi C, Veronesi F, Torricelli P, et al. Efficacy of intra-articular polynucleotides associated with hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis: a randomized, double-blind, controlled clinical trial. Clin J Sport Med. 2018; Apr. 10. [Epub]. http://doi.org/10.1097/JSM.0000000000000569.

17. Kim JK, Chung JY. Effectiveness of polydeoxyribonucleotide injection versus normal saline injection for treatment of chronic plantar fasciitis: a prospective randomised clinical trial. Int Orthop. 2015; 39:1329–34.

18. Kang KN, Kim TW, Koh JW, Oh HB, Mun JU, Seo MS, et al. Effect of transforaminal epidural polydeoxyribonucleotide injections on lumbosacral radiculopathy: a case report. Medicine (Baltimore). 2017; 96:e7174.

19. Yoon YC, Lee DH, Lee MY, Yoon SH. Polydeoxyribonucleotide injection in the treatment of chronic supraspinatus tendinopathy: a case-controlled, retrospective, comparative study with 6-month follow-up. Arch Phys Med Rehabil. 2017; 98:874–80.

20. Bitto A, Polito F, Irrera N, D’Ascola A, Avenoso A, Nastasi G, et al. Polydeoxyribonucleotide reduces cytokine production and the severity of collagen-induced arthritis by stimulation of adenosine A(₂A) receptor. Arthritis Rheum. 2011; 63:3364–71.

21. Dougados M, Leclaire P, van der Heijde D, Bloch DA, Bellamy N, Altman RD. Response criteria for clinical trials on osteoarthritis of the knee and hip: a report of the Osteoarthritis Research Society International Standing Committee for Clinical Trials response criteria initiative. Osteoarthritis Cartilage. 2000; 8:395–403.

22. Lee JK, Lee BY, Shin WY, An MJ, Jung KI, Yoon SR. Effect of extracorporeal shockwave therapy versus intraarticular injections of hyaluronic acid for the treatment of knee osteoarthritis. Ann Rehabil Med. 2017; 41:828–35.

23. Haefeli M, Elfering A. Pain assessment. Eur Spine J. 2006; 15 Suppl 1:S17–24.

24. Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988; 15:1833–40.

25. Bae SC, Lee HS, Yun HR, Kim TH, Yoo DH, Kim SY. Cross-cultural adaptation and validation of Korean Western Ontario and McMaster Universities (WOMAC) and Lequesne osteoarthritis indices for clinical research. Osteoarthritis Cartilage. 2001; 9:746–50.

26. Insall JN, Dorr LD, Scott RD, Scott WN. Rationale of the Knee Society clinical rating system. Clin Orthop Relat Res. 1989; (248):13–4.

27. Scuderi GR, Bourne RB, Noble PC, Benjamin JB, Lonner JH, Scott WN. The new Knee Society Knee Scoring System. Clin Orthop Relat Res. 2012; 470:3–19.

28. Kim SJ, Basur MS, Park CK, Chong S, Kang YG, Kim MJ, et al. Crosscultural adaptation and validation of the Korean version of the New Knee Society Knee Scoring System. Clin Orthop Relat Res. 2017; 475:1629–39.

29. Gennero L, Denysenko T, Calisti GF, Vercelli A, Vercelli CM, Amedeo S, et al. Protective effects of polydeoxyribonucleotides on cartilage degradation in experimental cultures. Cell Biochem Funct. 2013; 31:214–27.