A COMPARATIVE STUDY ON THE SAFETY AND EFFECTIVENESS OF GLUCOSAMINE-DIACEREIN AND UNIVESTIN – CHONDROITIN IN KNEE OSTEOARTHRITIC PATIENTS IN A TERTIARY CARE HOSPITAL

Background: Knee Osteoarthritis is a progressive disease showing increasing trend of occurrence in a population .It has lead to great morbidity and disability. Combinations which showed anti-inflammatory property and suppression of cartilage degeneration are better options for management of knee osteoarthritis. According to medical practice, quick relief within short period of exposure to drug therapy is preferred. This study was an attempt to compare the safety and effectiveness of diacerein-glucosamine and univestinchondroitin combinations in knee osteoarthritic patients in a tertiary care hospital. These drugs are now prescribed by Indian physicians in the current scenario. Patients and Method: The study began only after getting the approval from Institutional Ethics Committee and obtaining Inform Consent from subjects. The study was conducted in the department of orthopedics in Pushpagiri Medical College hospital, Kerala. From140 patients who arrived at the Orthopedics OPD Pushpagiri medical college hospital, we sorted and selected only 64 patients based on the study criteria. We divided into two groups (32 each) one receiving diacerein-glucosamine and another receiving univestin chondroitin combinations. From these groups grade 1 and 2 patients are subdivided. They were assessed by WOMAC, KOOS, VAS, 6 minute walk test, and Standard ADR questionnaires (Naranjo’s) for measuring safety and effectiveness of drug combinations. Change in the short term effectiveness for both drugs measure was assessed before the start of treatment, and after 30 days of treatment. Conclusion: For Grade 1 patients both drugs were equally effective. But for Grade 2 Patients diacereinglucosamine combination therapy shows more benefit than univestin-chondroitin. However, semi-synthetic drug combination showed more safety profile than synthetic drug combination in the short term treatment of knee osteoarthritis.


INTRODUCTION
OA (Osteoarthritis) may be defined as a heterogeneous group of conditions that lead to joint symptoms and signs which are associated with defective integrity of articular cartilage in addition to related changes in the underlying bone and at the joint margins. OA is usually a progressive disease of synovial joints that represents failed repair of joint damage that results from stresses that may be initiated by an abnormality in any of the synovial joint tissues including articular cartilage, subchondral bone, ligament mensci, periarticular muscles, peripheral nerves or synovium. This ultimately results in the breakdown of cartilage and bone leading to the symptoms of pain, stiffness and functional disability. Abnormal intra-articular stress and failure of repair may rise as a result of biochemical, biomechanical and genetic factors. This process may be localized to as single joint, a few joint or generalized and the factors that initiate OA likely varying depending on the joint site. • Both female and male patients.
• Those who give consent voluntarily to participate in the study.
• Patients between the age of 35-70. Patients with primary knee OA.
• Patients having comorbidities of hypertension or diabetes can be included.
• Patients receiving NSAIDS for one week.

EXCLUSIONCRITERIA:
• Patients who are not willing to give consent.
• Patients who were advised or had undergone knee replacement surgery.
• Patients having Pre-existing deformities of knee.
• Patients having previous history of fracture and trauma. Patients with renal insufficiency.

BRIEF PROCEDURE OF THE STUDY
 A prospective, observational study was conducted in Department of orthopedics at Pushpagiri Medical College Hospital on the topic comparative study on the safety and effectiveness of glucosamine-diacerein and univestin -chondroitin in knee osteoarthritis patients in a tertiary care hospital.
 The entire study was carried out only after getting approval from Institutional Ethics Committee.
 The selection of patients was based upon the inclusion and exclusion criteria. All patients were provided with a brief introduction regarding the study and the confidentiality of the data. A written Informed Consent was obtained from the patient or care-giver. Patients who met inclusion criteria were first divided into two groups.
 Demographic details of the patients were collected and recorded.
 The patients were also prescribed with NSAID for 1 week along with the medication.
 The patients were further divided into 2 groups based on the Kellgren-Lawrence grade 1, 2.
 We used the standard questionnaire including WOMAC, KOOS, VAS, 6 minute walk test, and Standard ADR questionnaires.
 Between the two groups, change in the short term efficacy measure was assessed before the start of treatment, and after 30 days of treatment.

RESULT:
In the prospective observational study 64 patients with grade 1 and 2 knee OA were selected. Among them 32 were received Univestin -chondroitin (DRUG 1) and others received Diacerein -Glucosamine (DRUG 2) combinations respectively.     In grade 2 patients there is decrease in pain by the use of drug 2 compared to drug 1. Thus drug 2 is more effective in case of grade 2 patients.  There is no considerable change of effect in stiffness by the use of drug 1 and 2 in grade 1 patients. Figure:4(b)

WOMACQUESTIONNAIRE
In grade 2 patients there is decrease in stiffness by the use of drug 2 compared to drug 1. Thusdrug 2 is more effective in case of grade 2patients.          In grade 1 patients there is change of effect in symptoms by the use of drug 1 and 2 in grade 1 patients. Here the drug 2 is more effective compared to drug 1.

Figure8(b)
In grade 2 patients there is effective change in symptoms by the use of drug 1 and 2 in grade 1 patients. Here the drug 2 is more effective compared to drug1.   . There is no considerable change or effect in stiffness by the use of drug 1 and 2 in grade 1 patients Figure 9(b) In grade 2 patients there is effective change in stiffness by the use of drug 2 compared to drug 1. Thus drug 2 is more effective in case of grade 2 patients.   There is no considerable change or effect in pain by the use of drug 1 and 2 in grade 1 patients.

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In grade 2 patients there is decrease in pain by the use of drug 2 compared to drug 1. Thus drug 2 is more effective in case of grade 2 patients.

Figure11(a)
There is no considerable change or effect in daily activities by the use of drug 1 and 2 in grade 1patients.

Figure11(b)
In grade 2 patients there is decrease in daily activities by the use of drug 2 compared to drug1 Thus drug 2 is more effective in case of grade 2patients.  There is no considerable change of effect in entertainment by the use of drug 1 and 2 in grade 1 patients.

Figure 12(b)
In grade 2 patients there is effective change in entertainment by the use of drug 2 compared to drug 1. Thus drug 2 is more effective in case of grade 2patients.

Figure 13(a)
There is no considerable change or effect in the use of drug 1 and drug 2.

Figure 13(b)
In grade 2 patients there is effective change in quality of life by the use of drug 2 compared to drug 1. Thus drug 2 is more effective in case of grade 2patients.   In grade 2 patients there is decrease in pain by the use of drug 2 compared to drug 1. Thus drug 2 is more effective in case of grade 2 patients.   In grade 2 patients there is effective change in six minute walk of patients by the use of drug 2 compared to drug 1. Thus drug 2 is more effective in case of grade 2 patients. • Female are more prone to knee osteoarthritis than males. Gender has no direct relationship with effectiveness of drugs.

NARANJO's SCALE
• Diarrhoea, gastritis and dark yellow coloured urine are adverse drug reactions that are reported by 3 of the patients within one month of therapy using diacerein-glucosamine combination. There are no observed adverse drug reactions reported for univestinchondroitin for short period of time.
• Both drug combinations showed reduction in WOMAC AND KOOS pain scores. Both the drugs showed anti-nociceptive property by reducing pain within short period of therapy. In grade 1 patients there is no considerable change in antinociceptive effect for both drugs. In grade 2 patients there is significant reduction in pain by use of drug 2 as compared todrug1.
• Both drug combinations showed reduction in WOMAC AND KOOS stiffness scores. Both the drugs showed anti-inflammatory property by reducing stiffness within short period of therapy. In grade1 patients there is no considerable change in anti-inflammatory effect for both drugs. In grade 2 patients there is significant reduction in stiffness by use of drug 2 as compared to drug1.
• The difficulty in performing daily activities and entertainment activities decreased with use of both drugs. In grade 1, both drugs showed similar effect. However Diacerein-glucosamine combination is more beneficial forgrade2.
• The 6-min walking score increased for those taking diacerein-glucosamine than those patients taking univestin-chondroitin combination.
• The Quality of Life was found to be more improved for patients taking diacereinglucosamine than univestin; chondroitin combinations.
• Among 64 populations, diacerein-glucosamine combination was found to bemore effective in knee osteoarthritis patients of grade 1 and 2. However univestin-chondroitin was found to have more safety profile in short term therapy.

CONCLUSION
Knee Osteoarthritis is a progressive disease showing increasing trend of occurrence in a population. Females are more prone to this disease than male. This study is an attempt to compare the safety and effectiveness of diacerein-glucosamine and univestin chondroitin combinations which are prescribed by physicians in the current scenario. The current study was conducted in the department of orthopaedics in Pushpagiri medical college hospital. 64 patients having knee OA were selected for the study and they were divided into two groups (32 each) ,one receiving diacerein-glucosamine and another receiving univestin chondroitin combinations.
We can conclude that both drugs are equally effective for grade 1 and grade 2 patients. The study reveals that among these two drugs diacereinglucosamine combination therapy shows more benefit for grade 2 patients than univestinchondroitin. As per AAOS (17) , ARA (18) , NHS (19) guidelines there are no combination of medication that shows ant-inflammatory property and that suppress cartilage degeneration. In this study we found that both the combination therapies showed anti-inflammatory property and that suppress cartilage degeneration. Apart from this, there is 4.7% of possible chance of ADR for diacereinglucosamine combination. However, there are no ADRs reported for the other combination. Hence semi-synthetic drug combination showed more safety profile than synthetic drug combination in the treatment of knee osteoarthritis. Since Univestin is a newer drug for knee OA in the current scenario, supporting studies on its combination therapy was not yet conducted. According to medical practice , quick relievenent within short period of exposure to drug therapy is preferred. Therefore further studies to reveal the short term effectiveness of univestin is needed.