Efficacy of Single Intra-articular Injection of Hyaluronic Acid for Osteoarthritis of the Knee Joint in South Indian Population
Corresponding Author: Vetrivel Chezian Sengodan, Institute of Orthopaedics and Traumatology, Coimbatore Medical College and Hospital, Coimbatore, Tamil Nadu, India; The Tamil Nadu Dr MGR Medical University, Chennai, Tamil Nadu, India, Phone: +91 9843028096, e-mail: firstname.lastname@example.org
Background: Intra-articular viscosupplements are one of the effective and safe approaches for clinical management of osteoarthritis (OA). Hyaluronic acid is one such viscosupplement which results in pain relief, reduces use of NSAIDS and delays joint-replacement surgeries.
Methods: This study evaluated the efficacy of Hylan GF 20 which is approved for use in India since 2010, in a south Indian population under public health care system. Patients above 40 years of age with osteoarthritis of grade 2, 3, 4 based on KL classification were included. WOMAC score (Western Ontario and McMaster Osteoarthritis Index) was used to evaluate pain, stiffness and functioning of the knee joint.
Results: Single intra articular administration of hyaluronic acid progressively decreased the WOMAC score as early as 2 weeks, with the score continued to decline until 6 months of follow up. Compared to the baseline, a 43 percent improvement in WOMAC score was observed at 6 months, reflecting a significant clinical efficacy of Hylan GF 20. Most drastic reduction in the WOMAC score observed in the grade 2 OA subgroup followed by grade 3 and 4 OA subgroups.
Conclusion: The results of this study supports the use of Hylan GF 20 for the treatment osteoarthritis of knee as a single injection which can be easily adopted to public health service measures as a day care procedure.
How to cite this article: Sengodan VC, Pynadath JJ. Efficacy of Single Intra-articular Injection of Hyaluronic Acid for Osteoarthritis of the Knee Joint in South Indian Population. J Orth Joint Surg 2022;4(2):61-65.
Source of support: Nil
Conflict of interest: None
Keywords: Hyaluronic acid, Inflammation, Joint pain, Mobility, Osteoarthritis
Osteoarthritis (OA) is a chronic progressively degenerative disease with slow and gradual development of fluctuating symptoms like joint pain, swelling, stiffness and reduced joint movement, which eventually lead to disabilities associated with functional and social activities, socioeconomic status, relationships, emotional well-being and body image.1 In India, osteoarthritis is the second most common rheumatological disorder with a prevalence of 28.7%,2 while globally, it is the eighth leading cause of disability with the knee joint being the most commonly affected joint.3,4 Despite this crippling condition and increasing disease burden, currently an established disease modifying treatment is lacking although a few non-pharmacological treatments are recommended by the American College of Rheumatology.5,6 While patient education, physiotherapy, weight loss, ambulatory assistance devices and orthoses are some of the non-pharmacological therapy recommended, pharmacological therapy includes use of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, muscle relaxants, antidepressants and intraarticular injections of steroids, platelet-rich plasma and viscosupplements. The current treatment mainly aims at controlling symptoms but as osteoarthritis advances, this conservative management fails, and total knee replacement becomes inevitable. Intra-articular viscosupplements are one of the effective and safe alternatives for the management of osteoarthritis. Hyaluronic acid is one such viscosupplement that results in pain relief, reduces the use of NSAIDs and delays joint-replacement surgeries.
Hyaluronic acid is a polysaccharide that forms the primary chemical component of synovial fluid and is produced by the synoviocytes, fibroblasts and chondrocytes.7 In a healthy knee joint, approximately 2 ml of synovial fluid is present with hyaluronic acid concentration of around 0.35 g/dl, where it functions as a lubricant, shock absorber, regulatory of biochemical milieu to protect the articular cartilage and joint structures against the mechanical forces.8,9 Additionally it also has anti-inflammatory properties and protects the subchondral bone from damage.10 The viscoelastic properties of the hyaluronic acid depend on its molecular weight, concentration and sheer dependence. In the osteoarthritic joint, the hyaluronate depolymerizes (2,700–4,500 k Da), consequently it is cleared at a faster rate than normal (normal half-life of 20 hours is reduced to 11–12 hours)11 making the joint more susceptible to damage by biomechanical forces. Due to poor gastrointestinal absorption12 exogenous hyaluronic acid is directly injected into intra-articular space to augment the viscoelastic property of the synovial fluid.
Hylan GF 20 (Synvisc One, Sanofi-Aventis; 48 mg/6 ml hyaluronic acid with Hylan A and Hylan B13-15 is a FDA approved class III medical device used for osteoarthritis of the knee joint as a single intraarticular injection.16,17 Although Hylan GF 20 is approved for use in India since 2010, studies examining the efficacy of Hylan GF 20 in the south Indian population are limited. Hence this study was designed to evaluate the efficacy of Hylan GF 20 in patients with osteoarthritis of grades 2, 3, 4 based on Kellgren-Lawrence classification.
MATERIALS AND METHODS
The study was conducted at the Institute of Orthopedics and Traumatology, Government Coimbatore Medical College and Hospital, Tamil Nadu, India. Informed consent was obtained from all the patients enrolled for the study. Radiographs (weight-bearing anteroposterior, lateral and skyline views) were used to grade the osteoarthritic changes based on Kellgren-Lawrence (KL) classification.18,19 Patients above 40 years of age with osteoarthritis of grade 2, 3, 4 based on KL classification were included. In bilateral osteoarthritis, the worst side was considered as the target knee. Patients below 40 years of age, grade 1 of KL classification, septic arthritis, hypersensitivity to any components of Hylan, inflammatory arthritis, history of any intra-articular injections within the past 3 months were excluded. The study enrolled a total of 255 patients with 108 males and 147 female patients. All the patients were assessed using WOMAC score (Western Ontario and McMaster Osteoarthritis Index) which is a standardized questionnaire to evaluate pain, stiffness and functioning of the knee joint (Fig. 1).
A single prefilled dose of 6 ml Hylan GF 20 was injected using a 22-gauge, 1.5-inch needle into medial and lateral compartments of the knee joint under C-arm guidance and passive range of movements were performed to facilitate even distribution of the agent inside the joint. Patients were advised to rest for 24 hours following injection as a daycare procedure and the use of NSAIDs was avoided. Patients were followed at various intervals (2 weeks, 1, 3 and 6 months) and WOMAC scoring was recorded at each visit (Fig. 2). Safety was assessed by physical examination, vital signs monitoring and recording of all adverse effects reported by the patients.
The WOMAC score were tabulated for each time point for all patient cohorts and the descriptive statistics (mean, SEM, median, min and max value) were estimated and analysed by one-way ANOVA. The patient data was further subgrouped into three categories (grade 2, 3, 4 based on KL classification) and the data was analyzed using repeated measures ANOVA. Statistical significant preset at p < 0.05 was compared for repeated measures ANOVA F ratio values.
A total of 255 patients were recruited for this study, with 108 males and 147 female patients. Of these patients’ cohorts, 27 participants were classified as grade 2 OA, 126 were classified as grade 3 OA while 106 were classified as grade 4 OA. All the patients successfully completed the study evaluation up to 6 months follow up, hence achieving a 100% compliance rate.
Intra-articular administration of hyaluronic acid progressively decreased the WOMAC score as early as 2 weeks, with the score continuing to decline until 6 months of follow-up and was statistically significant (Table 1). Compared to the baseline, a 43% improvement in WOMAC score was observed at 6 months, reflecting a significant clinical efficacy of Hylan GF 20.
|At 2 weeks||59.39||0.67||60||28||86|
|At 1 month||52.34||0.67||52||26||80|
|At 3 months||43.75||0.73||42||20||80|
|At 6 months||34.50||0.81||32||14||80|
The patients cohorts subgrouped based on grade 2, 3, 4 OA classification were further analysed using repeated measures ANOVA (Fig. 3). The reduction in WOMAC score was specific to OA grade type, with most drastic reduction in the WOMAC score observed in the grade 2 OA subgroup followed by grade 3 and 4 OA subgroups. The difference in WOMAC score between the grade 2, 3 and 4 OA subgroups persisted at each time point of clinical assessment until 6 months of study follow up (Table 2 and Fig. 3).
|Source||F ratio||p value|
|Between grade’s||19.37||p < 0.01|
|Between duration’s||1778.95||p < 0.01|
|Interaction-duration’s and grades||3.63||p < 0.01|
Intra-articular viscosupplementation is a safe and efficacious treatment modality for osteoarthritis20,21 and this study further supports the merit of using a single intra-articular injection of Hylan GF 20 for primary osteoarthritis of the knee joint in a cohort of the south Indian population.
The pathogenesis of osteoarthritis is characterized by an imbalance between synthesis and degradation of cartilage matrix resulting in the slow degradation of cartilage, subchondral bone remodeling, osteophyte formation and inflammation of the synovium.6 These changes are influenced by several biochemical factors7 including reduced hyaluronic acid content in synovium resulting in acute as well as chronic pain.8 The viscoelasticity of hyaluronic acid is a critical regulator of osteoarthritis pathology, as it directly influences the pharmacokinetics of hyaluronic acid in synovium.17,22 This is perhaps the reason for the superior efficacy of high molecular weight hyaluronic acid, which has led to making available of intra-articular viscosupplementation in all the public hospitals in the Tamil Nadu state of India under the CMCHISTN scheme as a public healthcare measure. The measure of benefits to patients under the CMCHISTN scheme is directly demonstrated in this study and is evident from a significant improvement in patients’ clinical condition as early as 2 weeks following treatment with the benefits observed showing progressive improvement up to 6 months.
Although this study didn’t directly compare the clinical efficacy of viscosupplementation with other treatment modalities such as NSAIDs, corticosteroids, sodium hyaluronate and physiotherapy, several previous studies have shown viscosupplementation such as Hylan GF 20 to have superior efficacy.22-24 This study while further adding to the growing literature on the merit of Hylan GF 20 therapy for osteoarthritis, also established its safety in South Indian population cohorts throughout the 6 months clinical follow-up period.
The use of Hylan GF 20 injection has several advantages over management of osteoarthritis using NSAIDs, as the increased adverse effects such as gastrointestinal complications and cerebrovascular accidents especially among elderly patients can be prevented, besides the risk of non-compliance in daily intake of NSAIDs can be avoided.
Single intra-articular injection of 6ml Hylan GF 20 was efficacious and safe in the primary osteoarthritic knee as evident from a statistically significant improvement in WOMAC score among 255 patients with grade 2, 3 and 4 osteoarthritis for up to 6 months. The results of this study support the use of Hylan GF 20 for the treatment of osteoarthritis of the knee as a single injection which can be easily adopted to public health service measures as a daycare procedure.
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