Rheumatoid Arthritis: White B

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.

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.

Goldman JA, Xia HA, White B, Paulus H. · Division of Rheumatology, Emory University School of Medicine, Medical Quarters 5555 Peachtree-Dunwoody Road, Atlanta, GA 30342-1711, USA. · Ann Rheum Dis. · Pubmed #17105853 No free full text.

Abstract: OBJECTIVE: To evaluate a modified American College of Rheumatology 20 (mACR20) scoring system for patients with rheumatoid arthritis. METHODS: The data were evaluated from one study on patients with methotrexate (MTX)-naive early rheumatoid arthritis (ERA) and another study on patients with DMARD-refractory late rheumatoid arthritis (LRA). For mACR20 scoring, acute-phase reactant measurements were excluded, and 20% improvement from baseline was determined by 2 or 3 of the 4 remaining ACR components. RESULTS: For full joint counts with data from patients with ERA, marked differences favoured 25 mg etanercept (ETN) over 10 mg ETN by using the unmodified ACR20 (69% v 55%), the mACR20(3 of 4) (63% v 49%) and the mACR20(2 of 4) (72% v 58%). An assessment of 28 joints showed similar findings. In the trial on patients with LRA, considerably more patients in both ETN groups achieved a clinical response compared with placebo by using the ACR20, the mACR20(3 of 4) and the mACR20(2 of 4), whether using full or 28 joint counts. The mACR20(3 of 4) and full joint counts with data on patients with ERA showed a marked difference between the MTX and 10 mg ETN groups (63% v 49%), which was not observed with the ACR20. CONCLUSION: Patterns of improvement indicated by mACR20 scores were consistent with standard ACR20 scores.

Sibley A, Kersten P, Ward CD, White B, Mehta R, George S. · School of Nursing & Midwifery, University of Southampton, Southampton, UK. · Clin Rehabil. · Pubmed #17005503 No free full text.

Abstract: OBJECTIVE: To evaluate the validity and reliability of an English version of the Impact on Participation and Autonomy Questionnaire (IPA). The original Dutch IPA has been shown to load onto five factors. DESIGN: A validation study. SETTING: Outpatients clinics and people's homes. SUBJECTS: Two hundred and thirteen people with multiple sclerosis, rheumatoid arthritis, spinal cord injury, and general practice attendees, stratified by level of disability (median age 54, 42% male, 58% female). Inclusion criteria: English as first language, aged 18-75, Mental Status Questionnaire score >6. INTERVENTIONS: Self- and interviewer-administered outcome measures. MAIN MEASURES: IPA, including one new item (66 participants completed the IPA on a second occasion). OTHER MEASURES: Short Form-36 Health Survey (SF-36), London Handicap Scale, three domains of the Functional Limitations Profile (FLP): household management, social integration, emotion. RESULTS: Confirmatory factor analysis confirmed the construct validity of the IPA (Normal Fit Index = 0.98, Comparative Fit Index = 0.99), indicating a good fit to the model. Convergent and discriminant validity were confirmed by the predicted associations, or lack of, with the exception of a poor association between the 'social life/relationships' IPA subscale and FLP-emotion. Internal reliability of the IPA was confirmed (Cronbach alphas >0.8; item-total correlations for all subscales >0.5). Test-retest reliability was confirmed for all items (weighted kappas >0.6) and subscales (intraclass correlation coefficients >0.90). CONCLUSIONS: The English IPA is a valid, reliable and acceptable measure of participation and autonomy in people with a range of conditions and can make a unique and fundamental contribution to outcome assessment. Further research is required to examine the responsiveness of the IPA to change over time, its clinical utility and suitability for use with people from ethnic minorities and with older people.

Lovell DJ, Reiff A, Jones OY, Schneider R, Nocton J, Stein LD, Gedalia A, Ilowite NT, Wallace CA, Whitmore JB, White B, Giannini EH, Anonymous00068. · Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. · Arthritis Rheum. · Pubmed #16732547 links to  free full text

Abstract: OBJECTIVE: Previous studies showed that etanercept treatment in patients with polyarticular-course juvenile rheumatoid arthritis (JRA) provided rapid clinical improvement that was sustained for up to 2 years. The goal of our study was to provide data on safety and efficacy after 4 years of etanercept treatment in patients with JRA. METHODS: Patients with active polyarticular-course JRA who participated in an efficacy study continued etanercept treatment in an open-label extension. Safety was assessed by measuring rates of serious adverse events (SAEs) and serious infections. Efficacy was assessed using the American College of Rheumatology (ACR) Pediatric 30 criteria for improvement and standard measures of disease activity. (The ACR Pediatric 30 criteria are defined as improvement of > or = 30% in at least 3 of 6 core response variables used to assess disease activity, with no more than 1 variable worsening by > or = 30%.) RESULTS: Of the 69 patients who enrolled in the original efficacy study, 58 patients (84%) enrolled in the extension, 34 patients received etanercept treatment for > or = 4 years, and 32 of these received complete efficacy assessments. The rate of SAEs was 0.13 per patient-year, and the rate of serious infections was 0.04 per patient-year, in a total etanercept exposure of 225 patient-years. Eighty-two percent of patients who received corticosteroids at any time during the extension were able to decrease their dosage to < or = 5 mg/day prednisone equivalent. Of the 32 patients with complete efficacy data who received etanercept for > or = 4 years, 94% achieved an ACR Pediatric 30 response and 78% achieved an ACR Pediatric 70 response at the last study visit. CONCLUSION: Etanercept offers an acceptable safety profile in children with polyarticular-course JRA and provides significant improvement in disease manifestations that are sustained for > or = 4 years.

Schiff MH, Yu EB, Weinblatt ME, Moreland LW, Genovese MC, White B, Singh A, Chon Y, Woolley JM. · Denver Arthritis Clinic, University of Colorado, Denver, Colorado 80230, USA. · Drugs Aging. · Pubmed #16536638 No free full text.

Abstract: BACKGROUND: The impact of long-term therapy for rheumatoid arthritis (RA) in elderly (> or = 65 years of age) and younger (< 65 years of age) patients, especially on patient-reported outcomes, has not been well studied. We evaluated patient-reported outcomes in elderly patients treated with etanercept, in contrast to outcomes in younger patients, using data from multiple controlled and open-label extension studies of patients with early RA (ERA; < or = 3 years) and late RA (LRA; disease-modifying antirheumatic drug [DMARD]-refractory RA). METHODS: This post hoc analysis included adult patients with RA enrolled in controlled, double-blind studies (up to 2 years) and subsequent open-label extension studies (up to 4 years). Patients were evaluated according to age at baseline of the original study. Patients may have received etanercept, placebo or methotrexate during the blinded treatment phases, but all patients had been receiving etanercept 25 mg twice weekly for at least 4 years. Both ERA and LRA extension studies are ongoing. Patient-reported outcome assessments included improvement in Health Assessment Questionnaire-Disability Index (HAQ-DI), proportions of patients achieving an improvement in HAQ-DI > or = 0.22 points, patients exhibiting worsening of HAQ-DI and patients achieving an HAQ-DI score of 0. RESULTS: Elderly patients, with either ERA or LRA, had significantly worse baseline mean HAQ-DI scores than younger patients (p < 0.05, Student's t-test) in most studies, indicating greater disability. Improvement in HAQ-DI was greatest during the first 3 months after starting etanercept treatment in the controlled phase and appeared to be sustained over 3-6 months in patients with early or DMARD-refractory RA. Across the various controlled trials, mean improvements from baseline in HAQ-DI ranged from 0.39 to 0.92 points in elderly patients and from 0.57 to 1.00 points in younger patients. Patients with ERA and LRA, regardless of age group, maintained their improvement in HAQ-DI throughout the open-label extension trials for up to a total of 6 years of etanercept therapy. Change from baseline in HAQ-DI was moderately correlated with 28-joint Disease Activity Score within each age group across the multiple trials. CONCLUSION: Both elderly and younger patients with RA treated with etanercept exhibited similar and rapid improvements in functional status during controlled studies, and these improvements were sustained during open-label extension trials.

Bathon JM, Fleischmann RM, Van der Heijde D, Tesser JR, Peloso PM, Chon Y, White B. · Division of Rheumatology, Johns Hopkins University, Baltimore, MD 21224, USA. · J Rheumatol. · Pubmed #16465653 No free full text.

Abstract: OBJECTIVE: To evaluate safety and efficacy of etanercept treatment in elderly (age > or = 65 yrs) and younger adult subjects (age < 65 yrs) with rheumatoid arthritis (RA). METHODS: Subset analyses were used to describe the safety and efficacy of etanercept in elderly and younger subjects treated for early and disease modifying antirheumatic drug-resistant or late-stage RA (ERA and LRA) in one of 4 randomized controlled clinical studies (N = 1353) or 2 longterm extensions (N = 1049). RESULTS: Rates of serious adverse events tended to be higher in elderly than younger subjects; however, rates of safety events observed in elderly etanercept-treated subjects did not exceed rates in elderly placebo or methotrexate (MTX)-treated subjects. With regard to efficacy measures [American College of Rheumatology 20% response (ACR20), ACR50, and ACR70], elderly subjects tended to have somewhat less robust responses to treatment than younger subjects. However, for both age groups, treatment with etanercept resulted in improved efficacy and function compared with control treatment, and combination therapy with etanercept plus MTX resulted in greater efficacy than either etanercept or MTX used alone. Efficacy responses of elderly subjects were sustained for up to 6 years. Radiographic progression (measured using modified Sharp Score) after one year of treatment was lower in subjects treated with both etanercept and MTX compared with subjects treated with either agent used alone, and this pattern was similar in both age groups. CONCLUSION: Consistent with responses in younger subjects, elderly subjects with RA treated with etanercept experienced significant improvement in disease activity and function without incurring additional safety concerns.

Haraoui B, Cameron L, Ouellet M, White B. · Department of Rheumatology, Centre Hospitalier de l'Université de Montréal, and Groupe de recherche des maladies rhumatismales du Québec, Montréal, Quebec, Canada. · J Rheumatol. · Pubmed #16395747 No free full text.

Abstract: OBJECTIVE: To determine whether the need to use doses of infliximab greater than 3 mg/kg every 8 weeks to achieve or maintain clinical response in patients with rheumatoid arthritis (RA) is associated with differences in baseline clinical characteristics or anti-infliximab antibodies. METHODS: Baseline clinical characteristics and anti-infliximab levels were evaluated retrospectively in a cohort of 51 consecutive patients with RA treated with infliximab at a single center. Patients were divided into 2 groups for comparison: Group 1 patients achieved and maintained clinical responses with infliximab 3 mg/kg every 8 weeks; Group 2 patients required higher doses. RESULTS: Thirty-two (63%) patients required infliximab dose escalation (Group 2). There were no statistically significant differences in baseline or clinical characteristics between Group 1 and Group 2 patients. Anti-infliximab antibodies occurred in 47% of Group 2 versus 27% of Group 1 patients, with higher anti-infliximab antibody concentrations in Group 2 patients (mean +/- SD: 18.3 +/- 8.9 g/ml vs 7.5 +/- 4.8 g/ml; p = 0.02). Patients who developed anti-infliximab antibodies were younger and receiving less prednisone at the time of infliximab initiation than patients who did not. CONCLUSION: Finding higher anti-infliximab antibody concentrations in patients who needed dose escalation of infliximab to achieve or maintain clinical responses with lower serum trough levels of infliximab suggests that development of anti-infliximab antibodies may reduce clinical efficacy of infliximab in some patients with RA.

Fleischmann R, Baumgartner SW, Weisman MH, Liu T, White B, Peloso P. · University of Texas Southwestern Medical Center at Dallas, 5939 Harry Hines Boulevard, Dallas, Texas 75235, USA. · Ann Rheum Dis. · Pubmed #16150792 links to  free full text

Abstract: OBJECTIVES: To determine the long term safety profile of the tumour necrosis factor (TNF) antagonist etanercept in subjects with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or ankylosing spondylitis (AS) aged > or =65 years in comparison with subjects aged <65 years. METHODS: Safety data from an integrated database of 4322 subjects enrolled in 18 RA trials, 2 PsA trials, and 2 AS trials were analysed. Safety end points included subject incidence of all adverse events (AE), serious adverse events (SAE), infectious events (IE), medically important infections (MII), and deaths. Events of particular interest in subjects treated with TNF modulating biological treatments, including demyelinating diseases, tuberculosis, lymphomas, and cardiovascular diseases, were also evaluated. RESULTS: The incidence of AE, SAE, IE, MII, and malignancies was not significantly raised in elderly subjects in comparison with subjects aged <65 years. No cases of tuberculosis were reported in the trials. Demyelinating diseases were seen only in subjects aged <65 years. The incidence and types of death in the elderly subjects were consistent with the expected rates for subjects of comparable age. CONCLUSIONS: Etanercept is a generally safe and well tolerated biological agent for treatment of rheumatological diseases in the elderly, and the risk of AE in these studies was no greater in subjects aged > or =65 years than in younger subjects.

White B. · University of Maryland, Research Service (151), Baltimore VA Medical Center, 21201, USA. · Inflamm Res. · Pubmed #11926314 No free full text.

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