A prospective multi-centre, open study of the safety and efficacy of hylan G-F 20 (Synvisc®) in patients with symptomatic ankle (talo-crural) osteoarthritis
Introduction
Osteoarthritis (OA) is a chronic, degenerative disorder associated with joint pain and loss of joint function. It is the most common disease to affect synovial joints and is one of the most frequently occurring chronic conditions.
OA can affect any synovial joint but is most frequently found in the knee, hip and hand, and the majority of these patients present with primary (idiopathic) disease [1]. Reliable figures on the prevalence of OA in other joints are not readily available but estimates suggest that symptomatic ankle OA is found in <1% of the adult population [2]. In contrast to knee and hip OA, about 70% of patients with ankle OA present with secondary, post-traumatic disease [3]. As ankle trauma is often sports-related, patients suffering from OA are, on average, relatively young. Ankle OA can often prevent these young, otherwise healthy patients from working or participating in sports activities [3], [4].
The choice of treatment of ankle OA depends on the severity of the disease, the patient's age, medical and social history and the level of physical activity expected to be demanded of the joint.
A group that is difficult to treat are those patients suffering from milder, Grade II [5] ankle OA (joint space narrowing ≤50%). Although, usually, these patients are not yet surgical candidates, they are often relatively young and wish to be active without the burden of chronic pain medications with their associated adverse side-effects. Viscosupplementation (intra-articular supplementation of hyaluronic acid) could potentially provide a useful alternative in treating such patients with painful ankle OA.
Viscosupplementation is a well-established treatment option in knee OA and is included in the professional guidelines for treatment of the disease in this joint [6], [7]. The potential for treating osteoarthritis of the ankle joint by viscosupplementation has been suggested in the literature [8], [9]. Evidence for efficacy and safety in this setting is limited but two recent studies showed that five weekly HA injections in the ankle joint seem to be well-tolerated and can improve pain and function [10], [11].
Dosing in the ankle joint remains an area for discussion as no dosing studies have been published to date. Anecdotal evidence suggests that some clinicians simply follow the dosing regimen for knee OA, which varies from 3 to 5 weekly injections of 1–2 ml. However, published evidence on the use of hylan G-F 20 in hip OA shows that a single, 2 ml injection, with an optional second injection between 1 and 3 months after the first, can be safe and effective [12], [13].
The aim of this study was therefore to evaluate the safety and efficacy of a single, 2 ml injection of hylan G-F 20, with an optional, second injection between 1 and 3 months after the first, in patients with symptomatic ankle (talo-crural) OA.
Section snippets
Trial design
This was a prospective, multi-centre, open study conducted in adult patients with symptomatic ankle OA between November 2003 and January 2006. To be considered symptomatic patients had to score ≥50 and ≤90 mm on the Ankle OA Pain visual analogue scale (VAS) (0–100 mm) at the baseline visit. Patients must have undergone at least 6 months of conservative treatment modalities (rest, physical therapy, NSAIDs etc.), and failed to achieve adequate symptomatic relief from these treatments, to be
Patients
Patient disposition for the study is shown in Fig. 1. The ITT population consisted of 55 patients. Fifty-one of the 55 patients (93%) completed the study. Baseline demographics for the ITT population are presented in Table 1. Patients were predominantly male (60%) and the mean age was 41 years.
Safety
Thirty-five patients (63.6%) experienced a total of 89 study ankle AEs during the study (Table 2). Of these, 17 patients (30.9%) experienced 28 treatment-related AEs of the study ankle. The majority
Discussion
Although osteoarthritis of the ankle occurs infrequently in the general population, it remains of major clinical significance due to the limitations that the disease places on the everyday activities of affected individuals. These patients could benefit from additional non-surgical treatment options if the need for subsequent surgical intervention could be delayed or negated.
The objective of this study was therefore to evaluate the safety and efficacy (including duration of action) of
Conflict of interest statement
This study was sponsored by Genzyme Europe B.V. There are no conflicts of interest.
Acknowledgement
The authors acknowledge the writing assistance of Anna Porter, funded by Genzyme Europe B.V.
References (23)
- et al.
The impact of osteoarthritis
Clin Orthop Relat Res
(2004) - et al.
Study of 500 patients with limb joint osteoarthritis. I. Analysis by age, sex, and distribution of symptomatic joint sites
Ann Rheum Dis
(1991) - et al.
Epidemiology of ankle arthritis: report of a consecutive series of 639 patients from a tertiary orthopedic center
Iowa Orthop J
(2005) - et al.
Functional limitations of patients with end-stage ankle arthrosis
Foot Ankle Int
(2005) - et al.
A prospective study of prognostic factors concerning the outcome of arthroscopic surgery for anterior ankle impingement
Am J Sports Med
(1997) Recommendations for the medical management of osteoarthritis of the hip and the knee: 2000 update
Arthritis Rheum
(2000)- et al.
EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies including Therapeutic Trials (ESCISIT)
Ann Rheum Dis
(2000) - et al.
The pathophysiology of osteoarthritis and the implication of the use of hyaluronan and hylan as therapeutic agents in viscosupplementation
J Rheumatol Suppl
(1993) - et al.
Musculoskeletal applications of hyaluronan and hylan. Potential uses in the foot and ankle
Clin Podiatr Med Surg
(1995) - et al.
Sodium hyaluronate in the treatment of osteoarthritis of the ankle: a controlled, randomized, double-blind pilot study
J Bone Joint Surg Am
(2006)
Efficacy of intra-articular hyaluronic acid in patients with osteoarthritis of the ankle: a prospective study
Osteoarthritis Cartilage
Cited by (58)
Effects and Safety of Intra-Articular Sodium Hyaluronate Injection for the Treatment of Ankle Osteoarthritis: A Prospective Clinical Trial
2022, Journal of Foot and Ankle SurgeryCitation Excerpt :DeGroot et al performed a single injection of low-molecular-weight HA and did not find any superiority of HA injection to saline solution injection (49). However, Witteveen et al reported that a single intra-articular injection of high-molecular-weight HA (2 mL Synvisc®; Wyeth) was well tolerated and effective in the treatment of ankle osteoarthritis (50). A recent Cochrane review demonstrated the efficacy of intra-articular HA injection as a conservative treatment for symptomatic ankle arthritis.
Orthobiologics in Foot and Ankle Applications
2020, Baxter’s The Foot And Ankle In SportNonanimal Hyaluronic Acid for the Treatment of Ankle Osteoarthritis: AProspective, Single-Arm Cohort Study
2019, Journal of Foot and Ankle SurgeryCorticosteroids and Hyaluronic Acid Injections
2019, Clinics in Sports MedicineProspective Evaluation of Intra-Articular Sodium Hyaluronate Injection in the Ankle
2017, Journal of Foot and Ankle Surgery