1. DoubleWing Medical Intra-articular Joint Injection Clinical studies

2. ESCEO algorithm – knee OA
European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO) 2014 guidelines
Initial pharmacological treatments (NSAIDs), analgesia….
Injectable corticosteroid
Injectable HA – ‘delivers sustained clinical benefit with effects lasting up to six months after a short course of weekly injections’
Conclusion “Intra-articular HA is an effective and safe treatment for long term management of knee OA and may be a cost effective treatment…”

3. ESCEO taskforce
At a May 2015 review meeting and in their subsequently published paper the ESCEO task force stated: “Real-life evidence for the long-term effectiveness of IA HA is reported in a study of over 300 patients with knee OA who received repeat cycles of IA HA injections (4 cycles of 5 weekly injections).... After 40 months (12 months after the last treatment cycle), significantly more treatment responders were found in the treatment group compared with placebo according to OARSI 2004 criteria for pain, function, and patient global assessment (80.5% of responders with HA vs. 65.8% for placebo; p ¼ 0.004) [81]. Notably, the number of responders to IA HA increased progressively after each treatment cycle, while response to placebo remained fairly stable.”  Similarly, in “other observational studies, IA HA injections in knee OA were highly effective in improving resting and walking pain with duration of symptom control up to 6 months, and a reduction in concomitant analgesia use of 30–50%. Furthermore, IA HA delayed the need for total knee replacement (TKR) surgery by approximately 2 years.” 

4. Viscosupplementation in sports injuries
AMSSM 2100 non surgical sports injury consultants – META analysis of publications 1960 to 2104   
“In light of the aforementioned results of our NMA [Network Meta-analysis], the AMSSM recommends the use of HA for the appropriate patients with knee OA. ...  We RECOMMEND viscosupplementation injections for K-L [Kellgren-Lawrence] grade II-III [mild to moderate] knee osteoarthritis in those patients above the age of 60 years based on HIGH quality evidence demonstrating benefit using OMERACT-OARSI Responder Rating. … We SUGGEST viscosupplementation injections for knee osteoarthritis for those under the age of 60 years based on MODERATE quality evidence due to response of treatment in those over 60 years of age.”   

5. Jazrawi & Rosen (Phys Sportsmed 2011)
Potential treatment of younger patients with knee injury or post traumatic arthritis
Anterior cruciate ligament and meniscal injuries common in athletes & general popn.
In younger patients IA HA may be useful in improving short term outcomes and arresting/slowing OA
Several clinical trials have demonstrated efficacy of IA HA in younger patients with acute knee damage, meniscal tears, ACL damage with chondral injury…
Administration of IA HA shown to improve outcomes in knee arthroscopy
And IA HA also has direct antinociceptive effects that may contribute in patients with acute patellofemoral pain…
There is a need for large scale trials… to further elucidate benefits of IA HA in younger patients with knee damage… which has a substantial need for new treatments…

6. Petrella et al (BMC Sports Science 2010)
Management of tennis elbow with periarticular Na HA injections
Prospective randomised trial in primary care 331 racquet sports players
Chronic (>3 months) lateral epicondylosis given 2 injections one week apart
Assessments at baseline, 7, 14,30, 90, 365 days – patient and physician assessment of pain, grip strength, disability free sport, adverse events
Statistically significant improvement in all measures in HA groups control group declined. Return to disability free sport HA group 18 (+/-11) days
Assessment of patient/physician continued to favour HA at follow up
Conclusion: Peri-articular treatment with HA was significantly better in improving pain/grip and resulted in a better return to pain free sport compared to control

7. Tsvetkova et al (Moscow 2015)
Objectives: Assessment of the effect of single administration of 20mg HA to the carpometacarpal (wrist) joints and metatarsophalangeal (foot) joints vs. placebo
Methods. 120 patients with OA of hand/foot – 24 weeks blind phase after treatment followed by 48 weeks follow up
Results. 79.7% patients experienced reduction of pain by 40% in HA group, 30% in placebo. Pain stiffness and function all improved compared to placebo as measured by AUSCAN scale. Improvement maintained to 48th week as measured by patient and physician. No adverse effects.
Conclusion. High efficacy and 48 weeks duration of after effect demonstrated following single administration of HA compared to placebo

8. Kaux et al (Muscles, ligaments & tendons 2015)
Hyaluronic acid and tendons – a review of it’s use in tendonopathies
28 articles in English/French including in vitro/in vivo and human studies
Preclinical studies demonstrate encouraging results – HA permits tendon gliding, reduced adhesion and better tendon architecture
Clinical studies support these results demonstrating improved pain and function
Meloni: 56 patients. After 12 months 19/28 HA treated patients still satisfied, 28/28 control dissatisfied.
Petrella: already covered.
Blazina: 54% excellent, 40% good results.
Riccio: post surgical adhesions digital flexor. 27:10 and 43:28 improvement HA:placebo at 30;180 days
Merolla: 48 patients rotator cuff tendonopathy – safe and more effective than rehab alone.
Kumai: 61 patients with enthesopathies (bone attachments) – overall decrease in pain confirmed efficacy

9. Leopold et al (Journal bone & joint Surgery 2003)
Comparison of corticosteroid and HA injections for OA knee – prospective randomised study
Synvisc 20mg HA and bethmethasone compared for pain and function patients randomised: either 3 injections Synvisc or 1 or 2 injections steroid.
Improvements measured using WOMAC scale (Western Ontario/McMaster University OA Scale), Knee Society scale and VAS
Both groups showed decrease in WOMAC scores (p<0.01), neither stat sig for Knee Sociely. Scores on VAS improved for HA but not steroid.
No significant differences were found between the two treatment regimens with respect to pain relief or function at 6 month follow up

10. Askari et al (Iran) (SpringerPlus 2016)
Comparison of IA HA with corticosteroids for knee OA
140 patients randomised to two groups followed for 3 months. Both received one injection of HA or steroid.
Progress measured by Western Ontario and McMaster University OA Index (WOMAC), Knee Injury and OA outcome score (KOOS) and a VAS
Results: WOMAC no improvement in either group. KOOS symptoms improved in both groups after 3 months (p<0.05). Daily activity improved in both groups (p<0.05).
Conclusion. The most important difference between the interventions is the duration of effectiveness. HA is superior in delivering pain relief. HA can be given every three months, steroid every 2 months. Therefore it is more convenient to use HA.

11. Murphy et al. (J Foot Ankle Surgery 2017)
Viscosupplementation can provide pain relief and delay the need for surgery in ankle OA patients
Evaluation of 50 subjects undergoing 3 injection protocol HA
Progress assessed by Foot and Ankle Outcomes Score pre and post treatment
Pre-treatment score was 48 +/- 6.3
Post-treatment score was 78 +/- 5.8
The difference was statistically significant p<0.003
Conclusion: Intra-articular injections NA Hyaluronate viscosupplementation is useful conservative therapy for OA of the ankle

12. Posnett et al (DovePress 2015)
Review of treatments for OA knee & patient willingness to pay across 5 EU countries
Internet based survey of 2073 patients with self reported OA knee in UK, Germany, France, Italy and Spain
17.4% rated OA as drastically affecting ability to function normally
39.3% employed patients said they had lost work time
Perceived most effective medical treatments were viscosupplementation 74.1%, narcotics 67.8% and steroid therapy 67.6%
Average patient was willing to pay €35 and co-pay €64 for steroid or viscosupplementation products per knee above OTC oral pain treatments p<0.05
Conclusion patients are willing to pay for treatment that are perceived as more effective even when not routinely offered to them