Rheumatoid Arthritis: Osiri M

Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. · Medicine, Chulalongkorn University Hospital, Division of Rheumatology, Department of Medicine, Chulalongkorn University Hospital, Rama IV Road, Pathumwan, Bangkok, Thailand, 10330. · Cochrane Database Syst Rev. · Pubmed #12535423 No free full text.

Abstract: BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. Leflunomide, as an inhibitor of pyrimidine synthesis, has a different mechanism of action than other existing disease modifying anti-rheumatic drugs (DMARD). OBJECTIVES: To determine the efficacy and toxicity of leflunomide compared to placebo or other DMARDs in the treatment of RA. SEARCH STRATEGY: We conducted a search in MEDLINE, EMBASE, Current Contents and the Cochrane Controlled Trial Register for trials up to December 2001. We also hand-searched reference lists and consulted content experts. SELECTION CRITERIA: Two independent reviewers selected the trials that met predetermined inclusion criteria. DATA COLLECTION AND ANALYSIS: Two independent reviewers extracted data and assessed methodologic quality using standardized forms. MAIN RESULTS: Six trials were included in this review. Using the ACR20 improvement criteria, there was an absolute difference in improvement of 28% (95% confidence interval: 21 - 35%) favouring leflunomide (232 out of 413 leflunomide treated patients compared to 89 out of 311 placebo patients met the criteria). There was no difference in ACR20 response rate between the patients treated with leflunomide and SSZ or MTX at 6 and 12 months. Other clinical outcomes were improved significantly in the leflunomide group compared to placebo but not different from SSZ or MTX. Withdrawals due to adverse events with leflunomide were 10% greater than placebo (70 out of 416 compared to 18 out of 311 respectively). Important adverse events included gastrointestinal symptoms, elevated liver function tests, alopecia, and infections. Overall adverse events and withdrawals in the leflunomide group were not significantly different from SSZ or MTX. REVIEWER'S CONCLUSIONS: Leflunomide appears to improve all clinical outcomes and delay radiologic progression at both 6 and 12 months of treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Long-term efficacy and toxicity remains to be established.

Osiri M, Deesomchok U, Tugwell P. · Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Pathumwan, Bangkok, 10330, Thailand. · Clin Rheumatol. · Pubmed #16365685 No free full text.

Abstract: The aim of this study was to compare the effectiveness of different disease-modifying anti-rheumatic drugs (DMARDs) in improving disease activity and functional status in patients with rheumatoid arthritis (RA). One hundred and fifty-two Thai RA patients treated with at least one DMARD were enrolled in this 1-year cohort. Demographic characteristics, baseline and end-of-study data on disease activity and Health Assessment Questionnaire (HAQ) Disability Index of the subjects were compared among different DMARD options. Predictors of HAQ score were investigated using regression analysis. The results showed that the studied patients had established RA with mild to moderate activity. More than 85% were prescribed methotrexate (MTX) as single or combined DMARDs. At 1 year, improvement in most activity measures was experienced. However, all patients had functional declines. Patients taking antimalarial agents had the maximal rate of functional deterioration. Patients taking MTX-based DMARDs had significantly lower rate of functional decline than patients taking DMARDs without MTX (p=0.018). Only patients receiving MTX-based DMARDs had clinically meaningful improvement in HAQ score. The predictors of HAQ score at 1 year included baseline HAQ score and patient global assessment at end of study. In conclusion, although DMARD treatment was shown to improve disease activity in RA patients, functional deterioration was evident in our cohort. Thus, measures of functional status are more appropriate than measures of disease activity to evaluate treatment effects of DMARDs in established RA in clinical practice. MTX-based DMARDs should be prescribed where possible in RA patients with persisting activity due to their ability to delay functional deterioration.

Osiri M, Kamolratanakul P, Maetzel A, Tugwell P. · Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Rama IV Road, Pathumwan, Bangkok 10330, Thailand. · Rheumatol Int. · Pubmed #17440729 No free full text.

Abstract: The objective was to assess the cost-effectiveness of various DMARDs compared with antimalarials (AM) for rheumatoid arthritis (RA) treatment. The data on disease activity, functional status and societal costs were collected from a 1-year cohort of 152 patients with RA receiving at least one DMARD for > or = 6 months. Incremental cost effectiveness ratio (ICER) was calculated from the societal costs of DMARD treatment compared with AM per one unit of HAQ improvement. All costs were presented in 2001 US dollars. Mean (SD) societal cost of AM treatment was US$ 2,285 (1,154) per patient per year. MTX + AM was less costly and more effective than AM, as the ICER of this combination would save US$ 834 per 1 U of HAQ improvement. MTX + SSZ, leflunomide, and triple therapy (AM + MTX + SSZ) were more effective than AM with additional costs. RA treatment with non MTX-based DMARDs was not cost-effective.

Osiri M, Maetzel A, Tugwell P. · Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. · J Rheumatol. · Pubmed #17183621 No free full text.

Abstract: OBJECTIVE: To assess annual direct and indirect costs in a prospective cohort of patients with rheumatoid arthritis (RA) in Thailand from the societal perspective. METHODS: Data on costs and intangible losses were prospectively collected at regular intervals over a one-year period from 158 RA patients who attended a major tertiary care facility in Bangkok, Thailand. Direct medical, direct nonmedical, indirect, and total costs were estimated according to patients' respective health insurance conditions and converted to 2001 US dollars using published purchasing power parity estimates. Sensitivity analyses were performed and the predictors of costs and intangible losses were investigated. RESULTS: The average societal cost of RA was estimated to be 2682 US dollars, 41.4% of patients' average annual income. Average direct and indirect costs were estimated to amount to 2135 US dollars and 547 US dollars per patient per year, respectively. Seventy-three patients (46.2%) experienced at least one event of intangible losses and 46 patients (29.1%) had decreased earnings ability because of RA. Poor physical function, joint deformity, high number of disease modifying antirheumatic drugs, and steroid use contributed to higher costs and presence of intangible losses. CONCLUSION: RA consumes a significant proportion of patients' annual average incomes and poses a significant economic burden to society. Since RA mainly affects a working-age population, early and timely treatment of this disease can improve both the suffering and the economic productivity of patients in Thailand.

Osiri M, Shea B, Robinson V, Suarez-Almazor M, Strand V, Tugwell P, Wells G. · Department of Medicine, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand. · J Rheumatol. · Pubmed #12784387 No free full text.

Abstract: OBJECTIVE: To systematically review the evidence from clinical trials on the efficacy and toxicity of leflunomide for the treatment of active rheumatoid arthritis (RA). METHODS: We searched Medline, Embase, Current Contents, and the Cochrane Controlled Trial Register for human randomized controlled trials (RCT) and controlled clinical trials up to December 2001. We also hand-searched reference lists and conference proceedings and consulted content experts. Relative benefit (RB), and weighted mean differences or standardized mean differences with their 95% confidence interval (95% CI) were calculated. RESULTS: Six RCT totaling 2044 patients with RA were included in this review. Using specific criteria, all trials were considered of high methodological quality. Leflunomide improved the ACR20 response rate roughly 2 times over placebo both at 6 months (RB = 1.93, 95% CI 1.51, 2.47) and at 12 months (RB = 1.99, 95% CI 1.42, 2.77). Other clinical outcomes of disease activity and function and radiological scores were also significantly better for leflunomide patients than those taking placebo. No significant differences for most of the outcomes were observed between leflunomide and sulfasalazine (SSZ) or methotrexate (MTX). Adverse events were more common in the leflunomide group, but withdrawal rates were fewer than for placebo. Overall, withdrawal rates and adverse events in the leflunomide group were not different from SSZ or MTX. CONCLUSION: Leflunomide improves all clinical outcomes and delays radiographic progression at 6 and 12 months of RA treatment compared to placebo. Its efficacy and adverse events at 2 years of treatment are comparable to SSZ and MTX. Longterm efficacy and toxicity remain to be established.

Osiri M, Suarez-Almazor ME, Wells GA, Robinson V, Tugwell P. · Department of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand. · Ann Rheum Dis. · Pubmed #12634229 links to  free full text

Abstract: OBJECTIVE: To calculate the number needed to treat (NNT) and number needed to harm (NNH) from the data in rheumatology clinical trials and systematic reviews. METHODS: The NNTs for the clinically important outcome measures in the rheumatology systematic reviews from the Cochrane Library, issue 2, 2000 and in the original randomised, double blind, controlled trials were calculated. The measure used for calculating the NNT in rheumatoid arthritis (RA) interventions was the American College of Rheumatology 20% improvement or Paulus criteria; in osteoarthritis (OA) interventions, the improvement of pain; and in systemic sclerosis (SSc) interventions, the improvement of Raynaud's phenomenon. The NNH was calculated from the rate of withdrawals due to adverse events from the treatment. RESULTS: The data required for the calculation of the NNT were available in 15 systematic reviews and 11 original articles. For RA interventions, etanercept treatment for six months had the smallest NNT (1.6; 95% confidence interval (CI) 1.4 to 2.0), whereas leflunomide had the largest NNH (9.6; 95% CI 6.8 to 16.7). For OA treatment options, only etodolac and tenoxicam produced significant pain relief compared with placebo (NNT=4.4; 95% CI 2.4 to 24.4 and 3.8; 95% CI 2.5 to 7.3, respectively). For SSc interventions, none were shown to be efficacious in improving Raynaud's phenomenon because the 95% CI of the NNT was infinite. CONCLUSIONS: The NNT and NNH are helpful for clinicians, enabling them to translate the results from clinical trials and systematic reviews to use in routine clinical practice. Both NNT and NNH should be accompanied by a limited 95% CI and adjusted for the individual subject's baseline risk.

Osiri M, Deesomchok U, Tugwell P. · Division of Rheumatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. · Rheumatology (Oxford). · Pubmed #11371665 links to  free full text

Abstract: METHODS: The Health Assessment Questionnaire (HAQ) was translated into Thai and its validity and applicability were assessed in 22 Thai patients with active rheumatoid arthritis (RA) before and after 6 months of treatment with disease-modifying anti-rheumatic drugs (DMARDs). The activities in three subcategories of the Thai HAQ were modified, including Eating, Hygiene and ACTIVITIES: Two common activities in Thai people were incorporated into the items in the Grip and Arising domains. RESULTS: Significant improvements in mean HAQ scores and other parameters were observed after DMARD therapy. Mean HAQ scores correlated significantly with tender joint count, patient global and physician global assessments, and grip strength. CONCLUSIONS: The Thai HAQ met validity requirements and can be used in the measurement of functional capacity of Thai RA patients.

Osiri M, Akkasilpa S, Deesomchok U. · Department of Medicine, Chulalongkorn University, Bangkok, Thailand. · J Med Assoc Thai. · Pubmed #10808674 No free full text.

Abstract: OBJECTIVE: To compare patterns and time trends of initial disease-modifying antirheumatic drugs (DMARDs) and prednisolone prescriptions for patients with rheumatoid arthritis (RA) by the rheumatologists at King Chulalongkorn Memorial Hospital, Bangkok, Thailand over a 15-year period, as well as their side effects. METHOD: Medical records of all patients with RA seen at the Rheumatology Clinic from January 1983 to June 1997 with a duration of follow-up of 6 months or more were reviewed. Information on the disease, initial DMARDs prescriptions and their side effects, prednisolone use, dosage and side effect(s) were focused and compared among three 5-year periods (1983-1987, 1988-1992 and 1993-1997). RESULTS: 236 patients were included in this study. There were 44, 82 and 110 patients in the first, second and third period, respectively. Methotrexate (MTX) was the most frequently prescribed DMARD in all time periods. Dapsone and intramuscular (i.m.) gold were prescribed in the first period while antimalarial drugs and sulfasalazine (SSZ) were increasingly used in the second and third periods. Combination treatment of DMARDs was first used in the third period. Side effects from MTX were observed in patients with a longer duration of treatment (p < 0.05). Patients prescribed combined DMARDs did not develop more side effects compared with those who had monotherapy. Prednisolone was prescribed in 57.2 per cent of the patients, most being newly prescribed at the clinic. Mean starting dose of prednisolone was 8.9 mg per day. 64 patients took prednisolone together with non-steroidal antiinflammatory drugs (NSAIDs). Gastrointestinal side effects did not increase in these patients. CONCLUSION: MTX was the most frequently prescribed DMARDs regardless of the time period. Antimalarial drugs, SSZ and combination of DMARDs (most were MTX + chloroquine) have been prescribed more in the last 5 years, while dapsone, auranofin and i.m. gold were rarely used as initial DMARDs. Low dose prednisolone was prescribed in more than half of the patients with RA. Side effects from DMARDs and prednisolone found in this study were comparable to previous reports.

Osiri M, Tantawichien T. · No affiliation provided · Scand J Rheumatol. · Pubmed #17763211 No free full text.

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