Rheumatoid Arthritis: Choi H

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.

Kim HL, Cho YS, Choi H, Chun YS, Lee ZH, Park JW. · Department of Pharmacology, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea. · Biochem Biophys Res Commun. · Pubmed #19013431 No free full text.

Abstract: Rheumatoid arthritis (RA) is known to be associated with increased risks of hypoxia-related diseases, whose progresses are critically determined by HIF-1alpha. The authors hypothesized that the hypoxia-related complications of RA are associated with HIF-1alpha deregulation by some factor(s) in RA serum. Arthritis was induced in female Lewis rats by injecting complete Freund's adjuvant. The effects of arthritic rat serum (ARS) on hypoxic responses were investigated by incubating Hep3B cells in ARS. In the presence of ARS, HIF-1alpha was down-regulated and inactivated under hypoxic conditions. ARS inactivated AKT and mTOR, which led to impaired HIF-1alpha protein synthesis. Furthermore, insulin was found to be deficient in ARS and insulin supplementation fully recovered HIF-1alpha synthesis with AKT and mTOR activation. These results suggest that HIF-1alpha deregulation by components in serum is responsible for the RA-associated aggravation of hypoxic diseases in extra-articular tissues.

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.

Jick SS, Choi H, Li L, McInnes IB, Sattar N. · Boston Collaborative Drug Surveillance Program, Boston University School of Medicine, Lexington, Massachusetts 02421, USA. · Ann Rheum Dis. · Pubmed #18662929 No free full text.

Abstract: OBJECTIVE: To evaluate whether statins are associated with a protective effect on the development of rheumatoid arthritis (RA). METHODS: A nested case-control study was conducted using data from the General Practice Research Database. A study population consisting of three groups of subjects aged 40-89 years was identified: (1) patients exposed to a statin or other lipid-lowering agent (LLA); (2) patients with a diagnosis of hyperlipidaemia in the absence of lipid-lowering drug treatment and (3) a random sample of 25 000 individuals with no diagnosis of hyperlipidaemia nor a prescription for a LLA. From this population incident cases of RA and up to four controls for each case were identified, matched on age, sex, general practice, number of years of recorded history in the database and index date. The independent effects of hyperlipidaemia and statins on the development of RA were evaluated using conditional logistic regression. RESULTS: 313 cases of RA and 1252 matched controls were identified. Compared with patients with untreated hyperlipidaemia, or hyperlipidaemia treated with LLA other than statins, the adjusted odds ratio for patients with no hyperlipidaemia was 0.68 (95% CI 0.50 to 0.91). When those with hyperlipidaemia who received statins were compared with those with hyperlipidaemia who did not use statins (ie, untreated hyperlipidaemia patients or those treated with non-statin LLA) the OR was 0.59 (95% CI 0.37 to 0.96). CONCLUSION: These data provide evidence to support the hypothesis that statins may be protective against the development of RA in patients with hyperlipidaemia.

Ang DC, Choi H, Kroenke K, Wolfe F. · Division of Rheumatology, Indiana University School of Medicine, Indianapolis, Indiana, USA. · J Rheumatol. · Pubmed #15940760 No free full text.

Abstract: OBJECTIVE: Whether comorbid depression increases mortality in patients with rheumatoid arthritis (RA) is unknown. Our objective was to determine whether the presence of depression predicted mortality in patients with RA. METHODS: We followed 1290 consecutive outpatients with RA who met our stringent inclusion criteria during an 18-year observation period. Since 1981, demographic, clinic, and self-report data were collected and entered into a computer database at the time of each clinic visit. The comorbidity data were consistently recorded beginning in 1991. Our primary independent variable was the mean of the Arthritis Impact Measurement Scales (AIMS) depression scores during the first 4 years of entry into the clinic cohort (average 4-year depression). Data were analyzed using Cox proportional hazard models. RESULTS: After adjusting for covariates, the hazard ratio (HR) for each unit increase in the average 4-year depression score on mortality was 1.14 (p < 0.0001). Using only the data obtained from 1991 to 2003, the mortality risk was slightly increased (HR 1.35, p < 0.0001). To reduce residual confounding due to RA disease activity and/or comorbid medical conditions, we then excluded deaths during the first 2 years after study onset. With this method, the HR for the average 4-year depression remained significant (HR 1.35, p < 0.0001). Because an AIMS depression score > or = 4 is consistent with clinical depression, we analyzed the dataset using the average 4-year depression score as a dichotomous variable (score < 4 or > or = 4). The HR of clinical depression on mortality was 2.2 (95% CI 1.2- 3.9, p = 0.01). CONCLUSION: Depression increases the risk of mortality in RA. Our study highlights the importance of comorbid depression in patients with RA.