To assess the response of RA patients to rituximab (RTX) treatment using a sensitive imaging technique for synovitis.
Twenty-three RA patients were treated with two 1000-mg infusions of the B-cell depleting antibody, RTX, in an observational protocol. Clinical response was assessed by the European League Against Rheumatism (EULAR) response criteria. High-resolution grey-scale and colour-coded power Doppler (PD) ultrasonography was performed at baseline and 6 months after RTX. The second to fifth MCP and PIP joints were bilaterally examined with joints in a neutral 0 position from a palmar view and scored from 0 to 3.
Median disease activity score (DAS28) improved from 5.03 to 3.56 (P = 0.001), which corresponded to a EULAR moderate response in 11 of 23 patients and a EULAR good response in another 6 patients. Improved control of disease activity by RTX was also indicated by tapering of median daily corticosteroid doses from 10 to 5 mg, without flare ups. Mean grey-scale scores correlated with the swollen joint count at baseline (r = 0.484, P = 0.022) and month 6 (r = 0.519, P = 0.011). Mean grey-scale scores improved upon RTX from a 0.90 median (range 0.13-1.87) to 0.75 (range 0.19-1.50, P = 0.023). Frequency of PD positive joints was low (6.1%) at baseline and did not significantly change following RTX treatment.
High-resolution grey-scale ultrasonography (US) examination confirmed reduced synovial hyperplasia, but the applied PD method displayed no significant changes. Therefore, only grey-scale US is recommended in follow-up examinations after RTX treatment.
"US follow-up after steroid injection  or other treatments  have been reported in several studies in adult rheumatology, but only in a few studies in children [21,24-26]. All JIA studies have focused on the knee and hip and none on the ankle. "
[Show abstract][Hide abstract] ABSTRACT: The ankle region is frequently involved in juvenile idiopathic arthritis (JIA) but difficult to examine clinically due to its anatomical complexity. The aim of the study was to evaluate the role of ultrasonography (US) of the ankle and midfoot (ankle region) in JIA. Doppler-US detected synovial hypertrophy, effusion and hyperemia and US was used for guidance of steroid injection and to assess treatment efficacy.
Forty swollen ankles regions were studied in 30 patients (median age 6.5 years, range 1-16 years) with JIA. All patients were assessed clinically, by US (synovial hypertrophy, effusion) and by color Doppler (synovial hyperemia) before and 4 weeks after US-guided steroid injection.
US detected 121 compartments with active disease (joints, tendon sheaths and 1 ganglion cyst). Multiple compartments were involved in 80% of the ankle regions. The talo-crural joint, posterior subtalar joint, midfoot joints and tendon sheaths were affected in 78%, 65%, 30% and 55% respectively. Fifty active tendon sheaths were detected, and multiple tendons were involved in 12 of the ankles. US-guidance allowed accurate placement of the corticosteroid in all 85 injected compartments, with a low rate of subcutaneous atrophy (4,7%). Normalization or regression of synovial hypertrophy was obtained in 89%, and normalization of synovial hyperemia in 89%. Clinical resolution of active arthritis was noted in 72% of the ankles.
US enabled exact anatomical location of synovial inflammation in the ankle region of JIA patients. The talo-crural joint was not always involved. Disease was frequently found in compartments difficult to evaluate clinically. US enabled exact guidance of steroid injections, gave a low rate of subcutaneous atrophy and was proved valuable for follow-up examinations. Normalization or regression of synovial hypertrophy and hyperemia was achieved in most cases, which supports the notion that US is an important tool in the management of ankle involvement in JIA.
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is characterized by the presence of circulating rheumatoid factor (RF) and anticitrullinated peptide
antibodies (ACPA), which are positive in about 70–80% of patients. APCA have a higher specificity and therefore a higher diagnostic
power than RF, but are less informative than RF in monitoring the course of the disease in patients under treatment. Recently,
it has been reported that the anticitrullinated vimentin (a-MCV) antibody test can identify a particular subgroup of APCA
that may be negative for anticyclic citrullinated peptide (a-CCP) antibodies. Concerning RF, the RF IgA isotype has been described
as a more specific marker of erosive joint damage than total RF. The aim of our study was to monitor the levels of a-CCP,
a-MCV, total RF and RF IgA in the follow-up of patients with RA treated with B-lymphocytedepletive rituximab (RTX), to detect
any differences or peculiarities in patterns of these autoantibodies, especially in relation to their potential use as predictive
markers of therapeutic response. We studied 30 patients with RA treated with RTX. All patients were previously unresponsive
to at least 6 months of therapy with disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide, cyclosporine,
chloroquine) and/or at least 6 months of therapy with anti-TNF biologics. The evaluation of response to RTX was made at month
+6 using the EULAR criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline (before the first infusion
of RTX) and after 1, 3 and 6 months. In serum samples obtained before treatment two cytokines essential for Blymphocyte proliferation,
interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In all patients a significant and consistent
reduction in all the tested antibodies was found during follow-up, with no differences in respect of the degree of response
to RTX. Of note, at baseline, generally a higher titre of all autoantibodies was seen in patients who then showed a better
response to RTX. Finally, there were no differences in serum concentrations of IL-6 and BLyS in patients in relation to the
presence or absence of the autoantibodies investigated, nor was there any significant correlation between the serum concentrations
of the cytokines and the titres of the autoantibodies. Thus, neither a-MCV compared to a- CCP, nor RF IgA compared to routine
total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.
KeywordsAnticitrullinated peptide antibodies-Antimodified citrullinated vimentin antibodies-Rheumatoid factor-Rheumatoid arthritis-Rituximab
[Show abstract][Hide abstract] ABSTRACT: Rheumatoid arthritis (RA) is an aggressive disease that needs to be treated effectively if subsequent deformity and disability are to be reduced. A recent advance in the management of RA is the use of biological agents which block certain key molecules involved in the pathogenesis of the illness. They include tumor necrosis factor (TNF-) -blocking agents, Anti-Interleukin-1receptor (IL-1) antagonist, anti-CD-20 agents, CTLA-4 Ig, anti IL-6 etc. These newer agents proved to be useful for alleviating symptoms and slowing the disease progression in the patients with RA who have failed to respond to conventional disease modifying anti-rheumatic drugs (DMARDs). DMARDs are nonspecific immunomodulators, each of which has substantial drawbacks in terms of effectiveness or adverse effects (AEs). The development of biologic agents has provided more effective therapeutic options. The terms biologic therapies and biologics have emerged to describe agents with biologic properties, including monoclonal antibodies and soluble cytokine receptors etc. The advent of effective biological agents has certainly been a major advance in the treatment of inflammatory arthritis, heralding a new era for rheumatology. In this review the focus is only on pathophysiology of the disease process as well as the recent advances with Biological response modifiers (BRMs) and its impact on current clinical practice in the treatment of RA.
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