Rheumatoid Arthritis: Westedt ML

Landewé RB, Boers M, Verhoeven AC, Westhovens R, van de Laar MA, Markusse HM, van Denderen JC, Westedt ML, Peeters AJ, Dijkmans BA, Jacobs P, Boonen A, van der Heijde DM, van der Linden S. · Department of Internal Medicine/Rheumatology, PO Box 5800, University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands. · Arthritis Rheum. · Pubmed #11840436 No free full text.

Abstract: OBJECTIVE: The Combinatietherapie Bij Reumatoide Artritis (COBRA) trial demonstrated that step-down combination therapy with prednisolone, methotrexate, and sulfasalazine (SSZ) was superior to SSZ monotherapy for suppressing disease activity and radiologic progression of rheumatoid arthritis (RA). The current study was conducted to investigate whether the benefits of COBRA therapy were sustained over time, and to determine which baseline factors could predict outcome. METHODS: All patients had participated in the 56-week COBRA trial. During followup, they were seen by their own rheumatologists and were also assessed regularly by study nurses; no treatment protocol was specified. Disease activity, radiologic damage, and functional ability were the primary outcome domains. Two independent assessors scored radiographs in sequence according to the Sharp/van der Heijde method. Outcomes were analyzed by generalized estimating equations on the basis of intent-to-treat, starting with data obtained at the last visit of the COBRA trial (56 weeks after baseline). RESULTS: At the beginning of followup, patients in the COBRA group had a significantly lower mean time-averaged 28-joint disease activity score (DAS28) and a significantly lower median radiologic damage (Sharp) score compared with those in the SSZ monotherapy group. The functional ability score (Health Assessment Questionnaire [HAQ]) was similar in both groups. During the 4-5 year followup period, the time-averaged DAS28 decreased 0.17 points per year in the SSZ group and 0.07 in the COBRA group. The Sharp progression rate was 8.6 points per year in the SSZ group and 5.6 in the COBRA group. After adjustment for differences in treatment and disease activity during followup, the between-group difference in the rate of radiologic progression was 3.7 points per year. The HAQ score did not change significantly over time. Independent baseline predictors of radiologic progression over time (apart from treatment allocation) were rheumatoid factor positivity, Sharp score, and DAS28. CONCLUSION: An initial 6-month cycle of intensive combination treatment that includes high-dose corticosteroids results in sustained suppression of the rate of radiologic progression in patients with early RA, independent of subsequent antirheumatic therapy.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA. · Leiden University Medical Center, Leiden, The Netherlands. · Arthritis Rheum. · Pubmed #18240203 links to  free full text

Abstract: OBJECTIVE: Several treatment strategies have proven value in the amelioration of rheumatoid arthritis (RA), but the optimal strategy for preventing long-term joint damage and functional decline is unclear. We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies, with intense monitoring in all patients. METHODS: In a multicenter, randomized clinical trial, 508 patients were allocated to 1 of 4 treatment strategies: sequential disease-modifying antirheumatic drug monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with the tumor necrosis factor antagonist infliximab (group 4). Treatment adjustments were made every 3 months in an effort to obtain low disease activity (a Disease Activity Score in 44 joints of < or =2.4). RESULTS: Initial combination therapy including either prednisone (group 3) or infliximab (group 4) resulted in earlier functional improvement than did sequential monotherapy (group 1) and step-up combination therapy (group 2), with mean scores at 3 months on the Dutch version of the Health Assessment Questionnaire (D-HAQ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 (P < 0.001). After 1 year, mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4 (P = 0.009). The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0, 2.5, 1.0, and 0.5 in groups 1-4, respectively (P < 0.001). There were no significant differences in the number of adverse events and withdrawals between the groups. CONCLUSION: In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.

Zirkzee EJ, Sneep AC, de Buck PD, Allaart CF, Peeters AJ, Ronday HK, Westedt ML, le Cessie S, Vliet Vlieland TP. · Department of Rheumatology C1-R, Leiden University Medical Center, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. · Clin Rheumatol. · Pubmed #17492248 links to  free full text

Abstract: We studied the occurrence of sick leave and work disability, the presence of workplace adaptations and the usage of professional guidance related to working problems in patients with early arthritis. Inclusion criteria were arthritis symptoms of less than 2 years duration and a paid job at the time of diagnosis. Assessments were done in connection with an early arthritis clinic (EAC) at entry into the cohort and 12 months thereafter by means of a questionnaire comprising questions on sick leave (absenteeism from work reported to the employer), work disability (receiving a full or partial work disability pension), unemployment, work adaptations and professional guidance related to working problems. Fifty-seven of the 69 participants (83%) had an arthritis symptom duration of <6 months. The number of patients with sick leave due to arthritis in the past 12 months decreased from 28 (41%) at study entry to 18 (26%) after 12 months of follow-up. The number of patients receiving a work disability pension increased from 5 (7%) at study entry to 13 (19%) after 12 months of follow-up (10 partial and 3 full). Sick leave in the 12 months before study entry appeared to be the most important predictor of the institution or increase in a work disability pension (odds ratio, 16.1; 95%CI, 1.8-142.8). Between study entry and follow-up, the number of patients with workplace adaptations increased from 20 (29%) to 28 (42%), whereas the number of patients receiving vocational guidance decreased from 48 (70%) to 36 (52%). In patients with early arthritis and a paid job, arthritis-related sick leave was common and occurred in part before patients entered the EAC and a diagnosis was made. About 20% of the patients became permanently work disabled, with partial work disability being more common than full work disability. Considerable proportions of patients received workplace adaptations and professional guidance with working problems.

van Dongen H, van Aken J, Lard LR, Visser K, Ronday HK, Hulsmans HM, Speyer I, Westedt ML, Peeters AJ, Allaart CF, Toes RE, Breedveld FC, Huizinga TW. · Leiden University Medical Center, Leiden, The Netherlands. · Arthritis Rheum. · Pubmed #17469099 links to  free full text

Abstract: OBJECTIVE: To determine whether patients with undifferentiated arthritis (UA; inflammatory, nontraumatic arthritis that cannot be diagnosed using current classification criteria) benefit from treatment with methotrexate (MTX). METHODS: The PRObable rheumatoid arthritis: Methotrexate versus Placebo Treatment (PROMPT) study was a double-blind, placebo-controlled, randomized, multicenter trial involving 110 patients with UA who fulfilled the American College of Rheumatology (ACR) 1958 criteria for probable RA. Treatment started with MTX (15 mg/week) or placebo tablets, and every 3 months the dosage was increased if the Disease Activity Score was >2.4. After 12 months, the study medication was tapered and discontinued. Patients were followed up for 30 months. When a patient fulfilled the ACR criteria for RA (primary end point), the study medication was changed to MTX. Joint damage was scored on radiographs of the hands and feet. RESULTS: In 22 of the 55 patients (40%) in the MTX group, UA progressed to RA compared with 29 of 55 patients (53%) in the placebo group. However, in the MTX group, patients fulfilled the ACR criteria for RA at a later time point than in the placebo group (P = 0.04), and fewer patients showed radiographic progression over 18 months (P = 0.046). CONCLUSION: This study provides evidence for the efficacy of MTX treatment in postponing the diagnosis of RA, as defined by the ACR 1987 criteria, and retarding radiographic joint damage in UA patients.

Goekoop-Ruiterman YP, de Vries-Bouwstra JK, Allaart CF, van Zeben D, Kerstens PJ, Hazes JM, Zwinderman AH, Ronday HK, Han KH, Westedt ML, Gerards AH, van Groenendael JH, Lems WF, van Krugten MV, Breedveld FC, Dijkmans BA. · Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. · Arthritis Rheum. · Pubmed #16258899 links to  free full text

Abstract: OBJECTIVE: Several treatment strategies have proven value in the amelioration of rheumatoid arthritis (RA), but the optimal strategy for preventing long-term joint damage and functional decline is unclear. We undertook this study to compare clinical and radiographic outcomes of 4 different treatment strategies, with intense monitoring in all patients. METHODS: In a multicenter, randomized clinical trial, 508 patients were allocated to 1 of 4 treatment strategies: sequential disease-modifying antirheumatic drug monotherapy (group 1), step-up combination therapy (group 2), initial combination therapy with tapered high-dose prednisone (group 3), and initial combination therapy with the tumor necrosis factor antagonist infliximab (group 4). Treatment adjustments were made every 3 months in an effort to obtain low disease activity (a Disease Activity Score in 44 joints of < or =2.4). RESULTS: Initial combination therapy including either prednisone (group 3) or infliximab (group 4) resulted in earlier functional improvement than did sequential monotherapy (group 1) and step-up combination therapy (group 2), with mean scores at 3 months on the Dutch version of the Health Assessment Questionnaire (D-HAQ) of 1.0 in groups 1 and 2 and 0.6 in groups 3 and 4 (P < 0.001). After 1 year, mean D-HAQ scores were 0.7 in groups 1 and 2 and 0.5 in groups 3 and 4 (P = 0.009). The median increases in total Sharp/Van der Heijde radiographic joint score were 2.0, 2.5, 1.0, and 0.5 in groups 1-4, respectively (P < 0.001). There were no significant differences in the number of adverse events and withdrawals between the groups. CONCLUSION: In patients with early RA, initial combination therapy including either prednisone or infliximab resulted in earlier functional improvement and less radiographic damage after 1 year than did sequential monotherapy or step-up combination therapy.