Rheumatoid Arthritis: Koch G

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D, Anonymous00358, Anonymous00359. · Medical University of Vienna, Vienna, Austria. · Arthritis Rheum. · Pubmed #18821648 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. CONCLUSION: These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.

Pincus T, Strand V, Koch G, Amara I, Crawford B, Wolfe F, Cohen S, Felson D. · Division of Rheumatology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. · Arthritis Rheum. · Pubmed #12632413 links to  free full text

Abstract: OBJECTIVE: To evaluate the capacity of a pooled index of only the 3 patient self-report questionnaire measures among the 7 American College of Rheumatology (ACR) core data set (Core Data Set) measures to distinguish efficacy of active treatment of rheumatoid arthritis (RA) with leflunomide or methotrexate versus placebo in a randomized, controlled clinical trial, and to compare the results with those obtained using the ACR 20% response criteria (ACR20), Disease Activity Score (DAS), and other pooled indices. METHODS: The 7 ACR Core Data Set measures of 1) joint swelling, 2) joint tenderness, 3) physician global assessment, 4) erythrocyte sedimentation rate (ESR), 5) functional disability, 6) pain, and 7) patient global assessment were combined into the following 5 pooled indices: "All Core Data Set" (all 7 measures), "Assessor Only" (measures 1-3), "Assessor + ESR" (measures 1-4), "Patient Only" (measures 5-7), and "Patient + ESR" (measures 4-7). The capacity of each of these 5 indices to detect differences between active treatment and placebo treatment was compared with that of the ACR20 and the DAS using 4 different analytic methods, each of which presented advantages and limitations. Agreement of the indices with one another and with the ACR20 and the DAS was analyzed according to pairwise kappa statistics and Z scores in multivariate logistic regression models. RESULTS: Each of the 5 indices, including "Patient Only," had a similar capacity to detect greater efficacy of leflunomide and methotrexate versus placebo in this clinical trial, according to each of 4 methods, at similar levels of statistical and clinical significance. CONCLUSION: A pooled index of patient self-report questionnaire Core Data Set measures appears to be as informative as ACR20 responses, DAS scores, and pooled indices of all and assessor-derived Core Data Set measures for distinguishing between active treatment and placebo treatment in this RA clinical trial.

Schlapbach A, Feifel R, Hawtin S, Heng R, Koch G, Moebitz H, Revesz L, Scheufler C, Velcicky J, Waelchli R, Huppertz C. · Novartis Institutes for BioMedical Research, global Discovery Chemistry, WSJ-88.508, CH-4002 Basel, Switzerland. · Bioorg Med Chem Lett. · Pubmed #18945615 No free full text.

Abstract: Pyrrolo-pyrimidones of the general structure 1 were synthesized and evaluated for their potential as MK2 inhibitors. Potent derivatives were discovered which inhibit MK2 in the nanomolar range and show potent inhibition of cytokine release from LPS-stimulated monocytes. These derivatives were shown to inhibit phosphorylation of hsp27, a downstream target of MK2 and are modestly selective in a panel of 28 kinases.

Aletaha D, Landewe R, Karonitsch T, Bathon J, Boers M, Bombardier C, Bombardieri S, Choi H, Combe B, Dougados M, Emery P, Gomez-Reino J, Keystone E, Koch G, Kvien TK, Martin-Mola E, Matucci-Cerinic M, Michaud K, O'Dell J, Paulus H, Pincus T, Richards P, Simon L, Siegel J, Smolen JS, Sokka T, Strand V, Tugwell P, van der Heijde D, van Riel P, Vlad S, van Vollenhoven R, Ward M, Weinblatt M, Wells G, White B, Wolfe F, Zhang B, Zink A, Felson D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Ann Rheum Dis. · Pubmed #18791055 No free full text.

Abstract: OBJECTIVE: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). METHODS: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). RESULTS: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. CONCLUSIONS: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses.