Glucocorticoids in early rheumatoid arthritis

For 50 years, glucocorticoids (GC) are used for symptomatic treatment of rheumatoid arthritis (RA). In the last decade, results from clinical studies of treatment with GC as additional therapy to long-acting antirheumatic drugs in patients with early RA suggested also disease-modifying properties of GC in RA. The aim of this thesis was to investigate disease-modifying properties and side effects of low-dose GC as monotherapy of patients with previously untreated early active RA in relation to clinical efficacy, general wellbeing and glucocorticoid receptors. All 81 consecutive outpatients who participated in the clinical 2-year study had recently been diagnosed as having early RA (disease duration less than a year). According to randomization 41 patients were allocated to 10 mg prednisone orally daily and 40 to placebo. Additional therapies like analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), physiotherapy were allowed in both groups and recorded. After 6 months sulphasalazine 2 gram daily could be prescribed as rescue medication only if clinically necessary. According to the study protocol clinical, biochemical and radiologic parameters were assessed. Furthermore, health assessment questionnaires for disability and general wellbeing were performed regularly and side effects documented. In general, patients in the prednisone group experienced significant but transient clinical improvement in the first months compared to those in the placebo group. However, patients in the placebo group used twice as much additional therapies compared to those in the prednisone group. To put it the other way around, prednisone had a sparing effect on the use of NSAIDs and other additional therapies. From 12 months on, radiological scores showed significantly less progression of joint damage (erosions and joint space narrowing) in the prednisone group compared to the placebo group. No clinically relevant side effects were observed, except for a higher incidence of new osteoporotic vertebral fractures in the prednisone group. At the time of the design of the study, back in 1989, it was considered ethical to study RA patients with an active drug against placebo; nowadays such a study design would be unethical because we know that joint damage is an early feature of the disease and early and aggressive therapy is now advocated. Moreover, suppletion with only 500 mg calcium daily was prescribed; nowadays potent anti-osteoporotic treatment with biphosphonates inhibits the negative effects of prednisone on bone and reduce fracture rate. In our study, a non-significant reduction of bone mineral density (BMD) was observed in the prednisone group as opposed to a higher vertebral fracture rate: changes in bone structure and strength rather than diminished BMD could explain, at least partially, the higher incidence of fractures. From our results, no significant changes were observed in the GR-expression (number and affinity) and serum cortisol levels in both groups. So, it seems unlikely that GR-expression plays a major role in the aethiopatogenesis of RA. Also, no predictive values could be found for the response on GC treatment. No correlations between GR-number, radiological scores and BMD was found. We were able to study a unique group of early DMARD-naïve patients with RA, treated with a low-dose prednisone without bias, an opportunity not likely to recur. We demonstrated a powerful disease-modifying effect of prednisone in the early phase of RA. This is in concordance with results of other recent studies in early RA. There seems to be a ´window of opportunity´ in the first 2 years of the disease in which aggressive therapy limits joint destruction over time. In this treatment we advocate a low dose prednisone, in combination with other DMARDs. Future studies should concentrate on the lowest possible effective dose in combination therap

Radiographic severity of Rheumatoid Arthritis in African Americans: Results from a multicenter observational study

To describe radiographic changes in African-Americans with rheumatoid arthritis (RA) from the CLEAR (Consortium for the Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis) Registry, a multicenter observational study

Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis

Abstract Introduction To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans. Methods Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors. Results Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score >0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj = 8.08 (95% confidence interval (CI): 1.60-40.89), P = 0.01 and ORadj = 2.97 (95% CI, 1.08 to 8.17), P = 0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj = 8.45 (95% CI, 1.57 to 45.44), P = 0.01, and ORadj = 3.57 (95% CI, 1.18 to 10.76), P = 0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj = 4.52 (95% CI, 1.20 to 17.03), P = 0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls. Conclusions We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations