Rheumatoid Arthritis: Thompson A

Tugwell P, Wells G, Strand V, Maetzel A, Bombardier C, Crawford B, Dorrier C, Thompson A. · Department of Medicine, Ottawa Hospital, Ontario, Canada. · Arthritis Rheum. · Pubmed #10728742 links to  free full text

Abstract: OBJECTIVE: To examine correlations between clinical improvement as defined by the American College of Rheumatology (ACR) responder analysis and clinical improvement as determined by 4 function and/or health-related quality of life measures, and to estimate the sensitivity and relative efficiency of these measures compared with changes in the tender joint count in patients with rheumatoid arthritis (RA). METHODS: A 52-week, multicenter, double-blind controlled trial was conducted to compare treatment with leflunomide (n = 182), methotrexate (n = 180), or placebo (n = 118) in patients with active RA. ACR response rates and improvement in scores on the Health Assessment Questionnaire (HAQ), Problem Elicitation Technique (PET), and Medical Outcomes Survey Short Form 36 (SF-36) were compared in 438 of the patients. RESULTS: In comparing leflunomide with placebo, the patient global assessment, HAQ disability index, and SF-36 bodily pain scale were most responsive to treatment group differences. The modified HAQ (M-HAQ), PET Top 5, SF-36 physical component score, physician global assessment, pain intensity scale, and SF-36 physical functioning scale were more responsive to treatment group differences than was the tender joint count. In comparing methotrexate with placebo, the patient and physician global assessments were most responsive. These 2 measures, as well as the pain intensity scale and the C-reactive protein level, were more responsive to treatment group differences than was the tender joint count, while the SF-36 mental health component score was least responsive. A close correlation between changes in the M-HAQ and HAQ scores indicated that the M-HAQ was similarly responsive to change over time. Improvements in the PET, SF-36 physical component score, bodily pain, and physical functioning scales correlated with the ACR responder status. CONCLUSION: Both disease-specific and generic measures of function and health-related quality of life detect improvements in RA patients. Using both types of measures for evaluating therapies will identify discernible changes that are important to patients, and will facilitate comparisons across different disease states.

Strand V, Tugwell P, Bombardier C, Maetzel A, Crawford B, Dorrier C, Thompson A, Wells G. · University of Toronto, Ontario, Canada. · Arthritis Rheum. · Pubmed #10513801 links to  free full text

Abstract: OBJECTIVE: To assess the efficacy of leflunomide or methotrexate compared with placebo in improving function and health-related quality of life in patients with active rheumatoid arthritis (RA), and to examine correlations between response status (as defined by the American College of Rheumatology [ACR] response criteria) and improvement in these measures. METHODS: This 52-week, multicenter, doubleblind, controlled trial compared responses to the Health Assessment Questionnaire (HAQ), modified Health Assessment Questionnaire (MHAQ), Problem Elicitation Technique (PET), Medical Outcomes Study Short Form 36 (SF-36), and questions regarding work productivity among 3 treatment groups (leflunomide, methotrexate, and placebo). Improvement in the PET top 5 and SF-36 scales and component scores were compared with ACR response rates. RESULTS: Clinically meaningful and statistically significant (P<0.0001) improvement in measures of function and heath-related quality of life (MHAQ scores, all scales and disability index of the HAQ, weighted top 5 score of the PET, 5 of 8 scales and physical component score of the SF-36, and work productivity) was seen during treatment with leflunomide in comparison with placebo. Methotrexate administration resulted in significant improvements (P<0.05) in comparison with placebo in the MHAQ scores, HAQ disability index, weighted top 5 score of the PET, physical component score of the SF-36, and bodily pain scale. Compared with methotrexate, leflunomide administration resulted in significantly (P<0.01) more improvement in the MHAQ scores, 5 of 8 scales and disability index of the HAQ, weighted top 5 score of the PET, and 2 of 8 scales and physical component score of the SF-36. Improvements in the PET score, SF-36 physical component score, and work productivity correlated with the ACR responder rates of > or =20% and > or =50% improvement. CONCLUSION: Significant improvements in function and health-related quality of life occurred in patients with RA during treatment with leflunomide or methotrexate. These findings were clinically meaningful and correlated with the ACR response status.

Thompson A. · Dr. A. Thompson, PO Box 5777, Station B, London, Ontario N6A 4V2. E-mail: · J Rheumatol Suppl. · Pubmed #19509329 No free full text.

Abstract: With the availability of more effective treatments for the management of rheumatoid arthritis (RA), patients look to their rheumatologist to guide their decision-making. The challenge for rheumatologists is to effectively communicate the risks and benefits related to the many options that are currently available for patients with RA. Physicians must be aware of patient preferences regarding the administration and dosing of their RA medications to help guide their treatment decisions.

van Bergen J, Kooy-Winkelaar EM, van Dongen H, van Gaalen FA, Thompson A, Huizinga TW, Feltkamp MC, Toes RE, Koning F. · Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, the Netherlands. · J Immunol. · Pubmed #19299715 No free full text.

Abstract: Although very few CD4(+) T cells express killer Ig receptors (KIR), a large proportion of CD4(+) T cells with a late memory phenotype, characterized by the absence of CD28, does express KIR. Here, we show that KIR expression on CD4(+) T cells is also associated with memory T cell function, by showing that the frequency of CMV-specific cells is higher in CD4(+)KIR(+) than CD4(+)KIR(-) T cells. In addition, engagement of an inhibitory KIR inhibited the CMV-specific proliferation of these CD4(+)KIR(+) memory T cells, but had no detectable effect on cytokine production. Our data reveal that, in marked contrast with CD8(+) T cells, the activity of a subset of CMV-specific CD4(+) T cells is modulated by HLA class I-specific KIR. Thus, the CMV-induced down-regulation of HLA class I may in fact enhance memory CMV-specific CD4(+) T cell responses restricted by HLA class II.