Meenakshi, B (2008) A Randomised, Open Label, Comparative, Prospective, Parallel Group study of Atorvastatin as an Add On Therapy to Standard Therapy in Reducing Disease Activity of Rheumatoid Arthritis. Masters thesis, Madras Medical College, Chennai.
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Abstract
INTRODUCTION Rheumatoid arthritis (RA) is the most common inflammatory arthritis affecting 0.5 to 1% of the general population worldwide. Women are affected approximately three times more than men. The onset is most frequent during the fourth decade of life with 80% of all patients developing the disease between the ages of 35 and 50. Rheumatoid arthritis is not a benign disease. A 25-year-old prospective study showed that median life expectancy is shortened by 7 years in males and 3 years in females. Rheumatoid arthritis typically presents as symmetric arthritis principally affecting the small joints of hands and feet, ankles, knees, wrists, elbows and shoulders. It is proposed that the disease is initiated in a genetically predisposed individual by activation of helper T cells responding to some arthritogenic agents possibly microbials. In turn, the activated CD4+ cells produce cytokines that will activate macrophages and other cells in the joint space, releasing degradative enzymes and other factors that perpetuate inflammation and activate B cells, resulting in the production of antibodies, some of which are directed against self constituents. The rheumatoid synovium is rich in both lymphocyte and macrophage derived cytokines. The activity of these cytokines accounts for many features of RA. They are not only proinflammatory, some, such as interleukin 1 (IL-1) and transforming growth factor alpha (TGF α) also cause synovial cell and fibroblast proliferation. They also stimulate synovial cell and chondrocyte secretion of proteolytic and matrix degrading enzymes. OBJECTIVES: 1. To assess the beneficial effects of atorvastatin in different doses as an add on therapy to the standard regimen in active rheumatoid arthritis. 2. To find out the minimum effective dose of atorvastatin in rheumatoid arthritis. 3. To evaluate the tolerability of atorvastatin. METHODOLOGY: STUDY DESIGN: Open label, randomized comparative, parallel group prospective study. STUDY CENTRE: Department of Rheumatology, Govt. General Hospital, Chennai. STUDY PERIOD: May 2006 to August 2007. STUDY DURATION: 6 months for every patient. STUDY POPULATION: Patients attending Rheumatology Out Patient Department with active rheumatoid arthritis. STUDY SAMPLE: 80 Patients. INCLUSION CRITERIA: 1. Age 18 – 60 years. 2. Both genders. 3. Active rheumatoid arthritis in spite of taking standard regimen for more than 6 months (Active rheumatoid arthritis- at least six swollen joints accompanied by two of the following; six tender joints, early morning stiffness lasting at least 30 minutes, and having ESR of at least 28 mm/hr). 4. Rheumatoid factor positive. 5. Disease activity score > 6. 6. C- reactive protein positive (> 6 mg/ lit.). EXCLUSION CRITERIA: 1. Patients with BMI less than 18. 2. Pregnant and lactating women. 3. Patients with diabetes mellitus. 4. Patients with the history of renal disorders, liver diseases, hypercholesterolemia and hypothyroidism. 5. Patients who have undergone any surgery within 3 months. 6. Patients who are taking prednisolone > 10 mg /day. 7. Patients already taking lipid lowering drugs 8. Patients who are on amiodarone, digoxin, warfarin, cyclosporine, macrolide antibiotics, azole antifungals, nefazodone, protease inhibitors. 10. Patients who are not willing to give informed consent. RESULTS: The study was taken up to assess the efficacy and tolerability of atorvastatin in different doses as an add on therapy to standard therapy in reducing disease activity of rheumatoid arthritis. Out of 221 patients screened, 83 patients were found to have hypercholesterolemia, 12 patients had diabetes mellitus, 18 patients were CRP negative, 9 patients had elevated liver enzymes, 19 patients had their ESR < 28 mm and 2 patients had increased serum creatinine levels. They were excluded from the study. 80 patients who fulfilled the inclusion criteria were recruited for the study. They were randomly allocated into 4 groups (A, B, C& D) each containing 20 patients by simple randomization method. Group A received the standard treatment with tablet methotrexate 10 mg weekly once on the same day of the week, tablet folic acid 5 mg weekly once, tablet diclofenac 50 mg twice daily after food, tablet prednisolone 5mg daily in the morning and tablet calcium 1gm daily at night. Group B, Group C & Group D in addition received atorvastatin 5mg, 10mg, and 20mg once daily respectively. Each patient was under treatment for six months. Clinical and laboratory parameters were assessed at the baseline and at the end of 3rd & 6th month. Only 64 patients (15 in group A, 16 in group B, 16 in group C and 17 in group D) completed the study. Statistical analysis was done with one-way ANOVA and multiple comparisons with Bonferroni T test. Sex distribution was analyzed with chi-square test. CONCLUSION: Based on the results of our study we conclude that 1. Atorvastatin produces beneficial effects in rheumatoid arthritis. 2. Atorvastatin 5mg is not effective. Atorvastatin 10mg is effective and atorvastatin 20mg is more effective in reducing the disease activity in rheumatoid arthritis. 3. Atorvastatin 20 mg is well tolerated in rheumatoid arthritis.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Atorvastatin, Add On Therapy, Standard Therapy, Reducing Disease Activity, Rheumatoid Arthritis, Randomised, Open Label, Comparative, Prospective, Parallel Group study. |
| Subjects: | MEDICAL > Pharmacology |
| Depositing User: | Subramani R |
| Date Deposited: | 31 Jul 2020 18:02 |
| Last Modified: | 01 Aug 2020 10:01 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/12689 |
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