M. A. van Leeuwen

OBJECTIVE: The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts. METHODS: These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated. RESULTS: No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists). CONCLUSION: The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.

OBJECTIVE: To study the predictive value of anticyclic citrullinated peptide antibody (anti-CCP) in patients with recent-onset rheumatoid arthritis (RA). METHODS: Outcome in terms of physical disability (Health Assessment Questionnaire) and radiologic damage (modified Sharp method) over 3-year and 6-year periods was determined in an inception cohort of 273 RA patients who had had disease symptoms for <1 year at study entry. Anti-CCP titers were determined at baseline and considered positive as recently described. Their prognostic value was studied by means of multiple regression analysis, in which anti-CCP positivity, sex, age at study entry, IgM rheumatoid factor (IgM-RF) status, Disease Activity Score (DAS), HLA-DR4 status, and (in a separate group of patients) shared epitope status were used as independent variables, and radiologic damage and functional disability as dependent variables. RESULTS: Patients with anti-CCP had developed significantly more severe radiologic damage after 6 years of followup. In multiple regression analysis, radiologic damage after 6 years followup was significantly predicted by IgM-RF status, radiologic score at entry, and anti-CCP status. Functional disability was significantly predicted by sex, age at entry, IgM-RF status, and DAS. CONCLUSION: Our data show that in almost 70% of RA patients, anti-CCP antibody is present at the early stages of disease. Anti-CCP-positive patients developed significantly more severe radiologic damage than patients who were anti-CCP negative, although in multiple regression analysis the additional predictive value was rather moderate.

In a prospective followup study of 147 patients with rheumatoid arthritis of recent onset, we assessed the progression of radiographic evidence of joint damage on films of the patients' hands and feet obtained biannually. Patients were receiving first-line and second-line treatment. Ninety patients were followed up for 3 years, and 57 were followed up for only 2 years. Radiographic damage was determined by a modification of the method described by Sharp, and to ensure comparability of findings, we determined the percentage of damage per joint group (actual score divided by the maximum possible score). After 3 years, radiographic damage was present in 70% of the patients, all of whom could be identified after 1 year of study. Overall, 18-20% of the joints of the hands and feet were affected after 3 years, with relatively little abnormality per joint (approximately 8% of maximum possible score). During the entire followup, more foot joints than hand joints were affected. The rate of progression in the first year was significantly higher than in the second and third years of study, indicating a flattening of the curve of radiographic progression of joint damage.

OBJECTIVE: For patients with rheumatoid arthritis (RA), yearly influenza vaccination is recommended. However, its efficacy in patients treated with rituximab is unknown. The objectives of this study were to investigate the efficacy of influenza vaccination in RA patients treated with rituximab and to investigate the duration of the possible suppression of the humoral immune response following rituximab treatment. We also undertook to assess the safety of influenza vaccination and the effects of previous influenza vaccination. METHODS: Trivalent influenza subunit vaccine was administered to 23 RA patients who had received rituximab (4-8 weeks after rituximab for 11 patients [the early rituximab subgroup] and 6-10 months after rituximab for 12 patients [the late rituximab subgroup]), 20 RA patients receiving methotrexate (MTX), and 29 healthy controls. Levels of antibodies against the 3 vaccine strains were measured before and 28 days after vaccination using hemagglutination inhibition assay. The Disease Activity Score in 28 joints (DAS28) was used to assess RA activity. RESULTS: Following vaccination, geometric mean titers (GMTs) of antiinfluenza antibodies significantly increased for all influenza strains in the MTX-treated group and in healthy controls, but for no strains in the rituximab-treated group. However, in the late rituximab subgroup, a rise in GMT for the A/H3N2 and A/H1N1 strains was demonstrated, in the absence of a repopulation of CD19+ cells at the time of vaccination. Seroconversion and seroprotection occurred less often in the rituximab-treated group than in the MTX-treated group for the A/H3N2 and A/H1N1 strains, while seroprotection occurred less often in the rituximab-treated group than in the healthy controls for the A/H1N1 strain. Compared with unvaccinated patients in the rituximab-treated group, previously vaccinated patients in the rituximab-treated group had higher pre- and postvaccination GMTs for the A/H1N1 strain. The DAS28 did not change after vaccination. CONCLUSION: Rituximab reduces humoral responses following influenza vaccination in RA patients, with a modestly restored response 6-10 months after rituximab administration. Previous influenza vaccination in rituximab-treated patients increases pre- and postvaccination titers. RA activity was not influenced.