The Features of the Synovium in Early Rheumatoid Arthritis According to the 2010 ACR/EULAR Classification Criteria

OBJECTIVES: It has been shown in early arthritis cohorts that the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) enable an earlier diagnosis, perhaps at the cost of a somewhat more heterogeneous patient population. We describe the features of synovial inflammation in RA patients classified according to these new criteria. METHODS: At baseline, synovial tissue biopsy samples were obtained from disease-modifying antirheumatic drug (DMARD)-naïve early RA patients (clinical signs and symptoms <1 year). Synovial tissue was analyzed for cell infiltration, vascularity, and expression of adhesion molecules. Stained sections were evaluated by digital image analysis. Patients were classified according to the two different sets of classification criteria, autoantibody status, and outcome. FINDINGS: Synovial tissue of 69 RA patients according to 2010 ACR/EULAR criteria was analyzed: 56 patients who fulfilled the criteria for RA at baseline and 13 who were initially diagnosed as undifferentiated arthritis but fulfilled criteria for RA upon follow up. The synovium at baseline was infiltrated by plasma cells, macrophages, and T cells as well as other cells, and findings were comparable to those when patients were selected based on the 1987 ACR criteria for RA. There was no clear cut difference in the characteristics of the synovium between RA patients initially diagnosed as undifferentiated arthritis and those who already fulfilled classification criteria at baseline. CONCLUSION: The features of synovial inflammation are similar when the 2010 ACR/EULAR classification criteria are used compared to the 1987 ACR criteria

Progression of radiologic damage in patients with rheumatoid arthritis in clinical remission

To assess whether radiologic progression occurs during clinical remission in patients with rheumatoid arthritis (RA). One hundred eighty-seven patients with RA in clinical remission were followed up clinically and radiologically for 2 years. Clinical remission was defined according to a modification of the American College of Rheumatology criteria (i.e., the criterion of fatigue was omitted, and patients had to fulfill 4 of the 5 remaining criteria). Radiologic joint damage was assessed by the Sharp/van der Heijde method. After 2 years of followup, remission persisted in 52% of patients. The median radiologic score for the total group of patients increased from 21 (interquartile range [IQR] 5, 65) at the time of entry to 25 (IQR 7, 72) after 2 years (P <0.001). The median score for radiologic progression between baseline and 2 years was 0.5 (IQR 0, 2.5). Among patients with an exacerbation of RA (n = 86), the median score for progression over 2 years was 1.0 (IQR 0, 4.5) (P <0.001), and in patients with a persistent remission (n = 93) it was 0 (IQR -0.5, 2.0) (P <0.001). Clinically relevant progression of damage was more frequent in patients with exacerbation (23%) than in those with persistent remission (7%) (P = 0.001). However, in 15% of patients with persistent remission, an erosion developed in a previously unaffected joint. In the logistic regression analysis, the area under the curve of the Disease Activity Score, a continuous measure, was related to the chance of radiologic progression, regardless of the absolute disease activity level. Results were similar when other definitions of remission were used. Although rare, clinically relevant progression of joint damage does occur in patients with RA in prolonged remission. This suggests the need for markers that predict progression during periods of low disease activity and for drugs that prevent damage that is independent of disease activit

Efficacy and safety of adalimumab for the treatment of peripheral arthritis in spondyloarthritis patients without ankylosing spondylitis or psoriatic arthritis

To evaluate the efficacy and safety of adalimumab in patients with peripheral spondyloarthritis (SpA) not fulfilling the criteria for ankylosing spondylitis (AS) or psoriatic arthritis (PsA). 40 patients with active peripheral SpA fulfilling the European Spondyloarthropathy Study Group or Amor criteria but not the criteria for AS or PsA were included in a randomised, double-blind, placebo-controlled clinical trial. Patients were treated 1 : 1 with adalimumab or placebo for 12 weeks, followed by an open label extension up to week 24. Safety and efficacy measurements were performed every 6 weeks, with the patient's global assessment of disease activity at week 12 as the primary endpoint. At week 12, the patient's and physician's global assessment of disease activity, swollen joint count, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and erythrocyte sedimentation rate improved significantly in the adalimumab group compared with the baseline values and compared with placebo. A similar improvement was seen upon adalimumab treatment from weeks 12 to 24 in the patients originally randomised to placebo, whereas the clinical response was maintained or even augmented at week 24 in the patients who received adalimumab from the start. ASDAS inactive disease and BASDAI50 responses were met in 42% of the adalimumab group versus 0%-5% in the placebo group at week 12 (p=0.001 and p=0.008, respectively), and were further increased at week 24. The number of adverse events was not different between the adalimumab and placebo groups. Adalimumab appears to be effective and well tolerated in SpA patients with peripheral arthritis, also in those patients not fulfilling the AS or PsA criteri

Burden of caregiving: Evidence of objective burden, subjective burden, and quality of life impacts on informal caregivers of patients with rheumatoid arthritis

Objective. To improve understanding of the nature and magnitude of the burden of informal care and also to indicate important areas for improving the current ways in which informal care is investigated. Methods. Information on objective burden (such as care tasks performed and time investment), subjective burden (using the Caregiver Reaction Assessment instrument and a self-rated burden score), and quality of life (using the EuroQoL instrument) were collected in a postal questionnaire of 153 informal caregivers who provide care for rheumatoid arthritis (RA) patients. Results. Caregivers had been caring for the RA patients on average for >11 years, reflecting the chronic nature of RA. They provide a substantial amount of care (27.4 hours per week) and are moderately strained (24.6 on the self-rated burden scale). Caregivers are relatively healthy on average but caregivers of more severe RA patients are relatively unhealthy, which may indicate health losses due to caregiving. Conclusion. Informal care can be burdensome in the context of RA. More information may help assist informal caregivers in caring for RA patients and help to avoid health problems and high subjective burde

Alefacept therapy reduces the effector T-cell population in lesional psoriatic epidermis

Alefacept, a LFA-3/IgG1 fusion protein, interferes with the activation and proliferation of T cells by binding to the CD2 receptor on their surfaces. The clinical efficacy of this drug has been demonstrated in chronic plaque psoriasis. We performed a single-center, open-label study to investigate the immunohistochemical effects in psoriatic lesional skin. A group of 11 patients with plaque psoriasis all received 12 weekly doses of 7.5 mg alefacept intravenously. Skin biopsies were obtained at baseline and on days 8, 43 and 92, and were evaluated by digital image analysis after immunohistochemical staining. After completion of treatment, 8 out of the 11 patients experienced a reduction in PASI of 50% or more compared to baseline. Immunohistochemical analysis displayed a gradual decrease in the number of cutaneous T cells during therapy, with a significant reduction in epidermal CD8(+) cells and dermal CD4(+) cells on day 92. Patients with a reduction in PASI of 50% or more after therapy had a clearance of effector/memory T cells from the epidermis, in contrast to patients with a reduction in PASI of less than 50%. These findings support the hypothesis that effector/memory T cells play a prominent role in the pathogenesis of psoriasis, and that alefacept is capable of reducing these cells in lesional psoriatic ski

A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis

OBJECTIVE: Chemokines such as CCL2/monocyte chemotactic protein 1 (MCP-1) play a key role in leukocyte migration and are potential targets in the treatment of chronic inflammatory disorders. The objective of this study was to evaluate the effects of human anti-CCL2/MCP-1 monoclonal antibody (ABN912) treatment in patients with rheumatoid arthritis (RA). METHODS: Patients with active RA were enrolled in a randomized, placebo-controlled, dose-escalation study of ABN912. Infusions were administered on day 1 and day 15. In the dose-escalation phase, 4 cohorts of 8 patients each underwent serial arthroscopic biopsy of synovial tissue. Immunohistochemistry and digital image analysis were used to characterize biomarkers in synovial tissue. Laboratory evaluation included pharmacokinetic analysis and immunotypic studies of peripheral blood mononuclear cells. To assess the clinical effects of treatment with ABN912, an additional 21 patients were treated with the highest dose tolerated. RESULTS: The total study population comprised 45 patients: 33 patients received ABN912, and 12 patients received placebo. ABN912 treatment was well tolerated. Unexpectedly, there was a dose-related increase in ABN912-complexed total CCL2/MCP-1 levels in peripheral blood, up to 2,000-fold. There was no detectable clinical benefit of ABN912 compared with placebo, nor did treatment with the study drug result in a significant change in the levels of biomarkers in synovial tissue and peripheral blood. CONCLUSION: ABN912 treatment did not result in clinical or immunohistologic improvement and may have been associated with worsening of RA in patients treated with the highest dose. The results might be related to the greatly increased level of total CCL2/MCP-1 in serum that was observed following treatment with ABN912. This observation may be relevant for a variety of antibody-based therapie

Expression of synovial phenotypic and vascular markers in patients who fulfilled 2010 ACR/EULAR criteria for RA at baseline after follow up and in the patients who fulfilled1987 ACR criteria.

<p>Values are presented as median (interquartile range). A Mann-Whitney U test was used to compare the different diagnostic groups; a <i>P</i>-value of <0.05 was considered statistically significant. RA = rheumatoid arthritis. CD3 refers to T cells; CD55– fibroblast-like synoviocytes; CD68– macrophages; CD22– B cells; CD138– plasma cells; tryptase – mast cells. L = intimal lining layer; SL = synovial sublining; vWF = von Willebrand factor; VEGF = vascular endothelial growth factor; VCAM-1 = vascular cell adhesion molecule-1. IOD = integrated optical density.</p

Synovial tissue expression of different cellular markers.

<p>Synovial tissue expression of, CD55+ fibroblast-like synoviocytes (FLS), CD3+ T CD68+ macrophages, CD3+ T cells, CD22+ B cells, CD138+ plasma cells. A:RA patient according to the 1987 ACR criteria, B:RA patient according to the 2010 ACR/EULAR criteria.</p

Baseline patient characteristics.

<p>Data are presented as median (interquartile range) or number (n [%]), as appropriate. Baseline characteristics were compared between the two diagnostic groups using a Mann-Whitney U test or a Chi2-test (sex, RF pos, ACPA pos). A <i>P</i>-value of <0.05 was considered statistically significant (bold). RA = rheumatoid arthritis; RA (all) = all patients with RA diagnosis after 2 years of follow up; RA−RA = RA at baseline and follow up; UA−RA = initially UA, but definitive diagnosis of RA at follow up; dis.dur. = disease duration; VAS = visual analog scale; MS = morning stiffness; ESR = erythrocyte sedimentation rate; CRP = C-reactive protein; TJC68 = tender joint count; SJC66 = swollen joint count; RF = IgM rheumatoid factor; ACPA = anti-citrullinated protein antibodies; pos = serum positive.</p

Expression of phenotypic and vascular markers in synovial tissue of RA patients with self-limiting, persistent non-erosive or persistent erosive disease.

<p>Values are presented as median (interquartile range). A Kruskal-Wallis test was used to compare the different diagnostic groups; a <i>P</i>-value of <0.05 was considered statistically significant (bold). CD3 refers to T cells; CD55– fibroblast-like synoviocytes; CD68– macrophages; CD22– B cells; CD138– plasma cells; tryptase – mast cells. L = lining; SL = sublining; vWF = von Willebrand factor; VEGF = vascular endothelial growth factor; VCAM-1 = vascular cell adhesion molecule-1. IOD = integrated optical density.</p