OA Knee Treatment: Ayurvedic Medicine Offers a Good Alternative to Glucosamine and Celecoxib
Rheumatology. 2013;52(8):1408-1417.
Abstract
Objective. To demonstrate clinical equivalence between two standardized Ayurveda (India) formulations (SGCG and SGC), glucosamine and celecoxib (NSAID).
Methods. Ayurvedic formulations (extracts of Tinospora cordifolia, Zingiber officinale, Emblica officinalis, Boswellia serrata), glucosamine sulphate (2 g daily) and celecoxib (200 mg daily) were evaluated in a randomized, double-blind, parallel-efficacy, four-arm, multicentre equivalence drug trial of 24 weeks duration. A total of 440 eligible patients suffering from symptomatic knee OA were enrolled and monitored as per protocol. Primary efficacy variables were active body weight-bearing pain (visual analogue scale) and modified WOMAC pain and functional difficulty Likert score (for knee and hip); the corresponding a priori equivalence ranges were ±1.5 cm, ±2.5 and ±8.5.
Results. Differences between the intervention arms for mean changes in primary efficacy variables were within the equivalence range by intent-to-treat and per protocol analysis. Twenty-six patients showed asymptomatic increased serum glutamic pyruvic transaminase (SGPT) with otherwise normal liver function; seven patients (Ayurvedic intervention) were withdrawn and SGPT normalized after stopping the drug. Other adverse events were mild and did not differ by intervention. Overall, 28% of patients withdrew from the study.
Conclusion. In this 6-month controlled study of knee OA, Ayurvedic formulations (especially SGCG) significantly reduced knee pain and improved knee function and were equivalent to glucosamine and celecoxib. The unexpected SGPT rise requires further safety assessment.
Introduction
Therapeutic options for chronic knee OA, a ubiquitous disorder.[1, 2] are grossly limited to principally providing symptomatic long-term pain relief that exposes patients to potentially serious toxicity.[3] Glucosamine is widely used to treat OA and is allegedly a chondroprotective drug, but its efficacy remains contentious.[4, 5] Eventually patients may deteriorate to end-stage arthritis requiring joint replacement surgery, which is expensive and not universally accessible.
The ancient Ayurveda medicinal system [6, 7] is popularly practiced in the Indian subcontinent. The government of India recently launched the New Millennium Indian Technology Leadership Initiative (NMITLI) program [8] and included Ayurveda. Knee OA was chosen as a key therapeutic target to validate some potential Ayurvedic drugs. We carried out several experimental studies and drug trials. The results of the final drug trial are presented.
Results
A total of 440 eligible patients were randomized and allotted to treatment (Fig. 1). The groups were well matched (Table 2). A total of 126 (28.6%) patients withdrew from the study (Fig. 1). There were no significant differences between the groups except for 12 patients (5 SGCG, 4 SGC and 3 glucosamine) who withdrew due to a study drug-related adverse event (AE) [pruritus, epigastric discomfort, nausea, oral ulcers and elevated serum glutamic pyruvic transaminase (SGPT)/alanine aminotransaminase (ALT)]. Seven patients in the Ayurvedic intervention groups (3 SGC and 4 SGCG) were withdrawn due to a > 3-fold rise above the upper limit of normal (ULN) in SGPT, which was accompanied by a mild rise in other liver enzymes and normal serum bilirubin and albumen; three had concealed a past history of chronic compensated hepatitis (two seropositive for hepatitis B virus).
Adverse Events
There were no significant differences between the groups except for raising SGPT (Table 3). Clinically the AEs were predominantly mild and required only symptomatic treatment. None required hospitalization or any special/invasive intervention.
Twenty-six patients (11 SGCG, 4 glucosamine, 9 SGC and 2 celecoxib) in the study cohort showed an asymptomatic elevation in SGPT that was often accompanied by a proportionately smaller increase (<3 ULN) in other liver serum enzymes [aspartate aminotransaminase/serum glutamic oxalacetic transaminase (SGOT) and alkaline phosphatase (ALP)] and all other normal liver functions including serum bilirubin and normal eosinophil count. None reported a concurrent febrile illness and/or symptoms that could be related to a hepatic, biliary or pancreatic disorder. We could not screen all patients for hepatitis viruses. Altogether, an SGPT increase of > 3-fold (but <6 times) ULN was observed in 10 patients in the Ayurvedic interventional groups at the 4-week follow-up. In all patients (withdrawals and those continued) with >3-fold rise, SGPT returned to normal by 8–12 weeks of follow-up.
Efficacy
Significant improvement was seen in each of the intervention groups (Table 4). The differences between any two intervention groups for the mean change from baseline to completion for primary efficacy measure was within the equivalence range, both for intent-to-treat analysis (Table 5) and completers (Table 1). Pairwise comparison (ANCOVA with adjustment for baseline parameter values) of primary efficacy variables did not show consistent significant differences (supplementary Table 3, available at Rheumatology Online). Oral paracetamol consumption in the completers was negligible and did not differ by study groups (data not shown).
A significant reduction in urinary CTX-II was only observed in the SGCG Interventional group (95% CI 1.04, 2.54). The study groups did not differ for serum hyaluronic acid or CTX-II (supplementary Table 4, available at Rheumatology Online).
Discussion
In this first-ever head-to-head comparison, Ayurvedic drugs (SGCG and SGC) were found equivalent to oral glucosamine sulphate and celecoxib in reducing knee pain and improving knee function in patients with knee OA over 24 weeks of treatment. The AEs in each of the intervention study groups were mild and comparable ( Table 3 ) except for an unexpected increased incidence of asymptomatic high SGPT/ALT in patients treated with Ayurvedic drugs.
via Blogger http://chiropractic-lane.blogspot.com/2013/08/oa-knee-treatment-ayurvedic-medicine.html
Recent Comments