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.

Cyclooxygenase (COX), the key enzyme required for the conversion of arachidonic acid to prostaglandins was first identified over 20 years ago. Drugs, like aspirin, that inhibit cyclooxygenase activity have been available to the public for about 100 years. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in biology and disease than at any other time in history. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. Under many circumstances the COX-1 enzyme is produced constitutively (i.e., gastric mucosa) whereas COX-2 is inducible (i.e., sites of inflammation). Here, we summarize the current understanding of the role of cyclooxygenase-1 and -2 in different physiological situations and disease processes ranging from inflammation to cancer. We have attempted to include all of the most relevant material in the field, but due to the rapid progress in this area of research we apologize that certain recent findings may have been left out.

Only a few autoantibodies that are more or less specific for RA have been described so far. The rheumatoid factor most often tested for is not very specific for RA, while the more specific antiperinuclear factor for several reasons is not routinely used as a serological parameter. Here we show that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients. Using several citrulline-containing peptide variants in ELISA, antibodies could be detected in 76% of RA sera with a specificity of 96%. Sera showed a remarkable variety in the reactivity pattern towards different citrulline-containing peptides. Affinity-purified antibodies were shown to be positive in the immunofluorescence-based antiperinuclear factor test, and in the so-called antikeratin antibody test, and were reactive towards filaggrin extracted from human epidermis. The specific nature of these antibodies and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulline-containing epitopes in the pathogenesis of RA.

Objective. To validate the European League Against Rheumatism (EULAR), the American College of Rheumatology (ACR), and the World Health Organization (WH0)hnternational League Against Rheumatism (ILAR) response criteria for rheumatoid arthritis (RA).Methods. EULAR response criteria were developed combining change from baseline and level of disease activity attained during followup. In a trial comparing hydroxychloroquine and sulfasalazine, we studied construct (radiographic progression), criterion (functional capacity), and discriminant validity.Results. EULAR response criteria had good construct, criterion, and discriminant validity. ACR and WHO/ILAR criteria showed only good criterion validity.Conclusion. EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHOIILAR response criteria for RA.

Objective: To develop and validate an extensive radiographic scoring system for ankylosing spondylitis (AS). Methods: The Stoke Ankylosing Spondylitis Spinal Score (SASSS) was modified by adding a score for the cervical spine and defining squaring. This modified SASSS (mSASSS) is the sum of the lumbar and cervical spine score (range 0-72). 370 lateral views of the lumbar and cervical spine were used for development of the mSASSS, standardisation of observers, and for studying reliability. In a 48 week NSAID study of 57 patients, change over time and construct validity were studied. Results: Interobserver correlations of the lumbar and cervical spine scores were good (r.0.95). The interobserver duplicate error was 0.55 in a range from 0 to 36. The mean change in the cervical and lumbar spine scores between weeks 0 and 48 of all patients was 1.45 (range 0-6.0) and 1.06 (0-5.0), respectively (paired t testing, p,0.001). Change in radiological score was seen in 36/57 (63%) patients (lumbar and cervical spine 11, cervical spine 12, lumbar spine 13 patients). Conclusion: The mSASSS is useful for assessing extensive radiographic damage in AS. It is reliable, detects changes over 48 weeks, and shows a satisfactory face and construct validity.

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.

Objective: To evaluate the efficacy and safety of monotherapy with adalimumab in patients with RA for whom previous DMARD treatment has failed. Methods: In a 26 week, double blind, placebo controlled, phase III trial, 544 patients with RA were randomised to monotherapy with adalimumab 20 mg every other week, 20 mg weekly, 40 mg every other week, 40 mg weekly, or placebo. The primary efficacy end point was >20% improvement in the ACR core criteria (ACR20 response). Secondary efficacy end points included ACR50, ACR70, EULAR responses, and the Disability Index of the Health Assessment Questionnaire (HAQ DI

In a prospective Ibllow-up study of patients with early-onset rheumatoid arthritis, the prevalence of remission according to the 1981 American Rheumatism Association (ARA) preliminary criteria was evaluated. A total of 227 patients with a median follow-up of 3.9 yr and a total of 2832 follow-up visits were studied. The ARA remission criteria were fulfilled in 9.5% of these visits. The percentage of patients with at least one visit fulfilling the ARA criteria was for years 2 6 ~ 25%. Each year, 15% of the patients were in remission for at least two consecutive visits. A comparison was made between the ARA remission criteria and the Disease Activity Score (DAS). DAS <1.6 corresponded with being in remission according to the ARA criteria. The DAS is being proposed as a tool to define remission because absence of disease activity should be measured using the same method as for higher levels of disease activity, preferably on a continuous scale.