Tumour necrosis factor alpha blockade in treatment resistant pigmented villonodular synovitis

BACKGROUND: Pigmented villonodular synovitis (PVNS) is considered to be a neoplastic-like disorder of the synovium histologically characterised by villonodular hyperplasia, resulting in dense fibrosis and haemosiderin deposition. The pathogenesis of the disease is still unknown. CASE REPORT: A patient presented with severe treatment resistant PVNS of the right knee joint. Several conventional treatment regimens, including open surgical synovectomy and intra-articular injections of yttrium-90 ((90)Y) failed to control the disease. After finding marked tumour necrosis factor alpha (TNF alpha) expression in arthroscopic synovial tissue samples, treatment with an anti-TNF alpha monoclonal antibody (infliximab) at a dose of 5 mg/kg was started. Additional courses with the same dose given 2, 6, 14, and 20 weeks later, and bimonthly thereafter up to 54 weeks, controlled the signs and symptoms. Immunohistological analysis at follow up identified a marked reduction in macrophage numbers and TNF alpha expression in the synovium. DISCUSSION: This is probably the first case which describes treatment with TNF alpha blockade of PVNS in a patient who is refractory to conventional treatment. It provides the rationale for larger controlled studies to elucidate further the efficacy of TNFalpha blockade treatment in refractory PVNS

Fatique in rheumatoid arthritis: The role of self-efficacy and problematic social support

OBJECTIVE: To examine the relationship of fatigue in people with rheumatoid arthritis (RA) with self-efficacy, positive and problematic aspects of social support, and demographic and disease-related variables. METHOD: Out-patients with at least 5 yr RA were studied. Fatigue was measured with a visual analogue scale. Other variables included were: positive social support [Social Support List- Interactions (SSL12-I)] and problematic social support; self-efficacy towards coping with RA and towards mobilizing support; health status (Dutch-AIMS2); and laboratory tests: erythrocyte sedimentation rate (ESR), haemoglobin (Hb) and rheumatoid factor (RF); and disease duration. RESULTS: A total of 229 out-patients were included. Fatigue correlated with all scales of the Dutch-AIMS2: with pain, physical function and affect (P < 0.001). There was no significant correlation with social support, but there was a highly significant correlation of fatigue with problematic social support (P < 0.001). Both forms of self- efficacy correlated strongly with fatigue: patients with high self- efficacy expectations towards coping with RA, and towards mobilizing the social network (P < 0.001), had less fatigue. In the regression analysis to explain the variation in fatigue, only pain, self-efficacy expectations towards coping with RA, and towards asking for help and problematic social support remained significant. CONCLUSIONS: Fatigue can to a large extent (37%) be explained by pain, self-efficacy towards coping with RA, and towards asking for help and problematic social support. It is known that self-efficacy can be enhanced by self- management courses and it may thus be possible to improve fatigue

Effect of anakinra on functional status in patients with active rheumatoid arthritis receiving concomitant therapy with traditional disease modifying antirheumatic drugs: evidence from the OMEGA Trial

Objective. To assess changes in functional status in patients with rheumatoid arthritis (RA) receiving the interleukin-1 receptor antagonist anakinra in addition to a disease modifying antirheumatic drug (DMARD). Methods. In this large, multicenter, open-label, single-arm study, adult patients with RA receiving methotrexate, sulfasalazine, or hydroxychloroquine for &gt;= 3 months were given anakinra 100 mg once daily for up to 36 weeks. The primary objective was to evaluate changes from baseline to week 36 in the Health Assessment Questionnaire (HAQ) disability index and subscales. Changes in the 28-joint Disease Activity Score (DAS28), proportion of patients meeting European League Against Rheumatism (EULAR) response criteria, and the safety of each combination regimen were also assessed. Results. A total of 1207 patients were enrolled, received &gt;= 1 dose of anakinra, and were included in the efficacy and safety analyses. A statistically significant change in the HAQ disability index was observed (p = 0.0001); no significant differences were seen among the 3 DMARD groups. A clinically meaningful improvement in HAQ (&gt; 0.22) was observed in 51% of patients. Mean improvement in DAS28 was 1.5 (p &lt; 0.0001), and 64% of patients achieved a good or moderate EULAR response score. Injection site reaction was the most frequently (62%) reported adverse event. The incidence of infections (24%), most commonly respiratory infection, was similar across treatment groups. No notable changes were observed in laboratory findings and vital signs. Conclusion. These findings indicate that anakinra 100 mg/day in combination with DMARD therapy safely improved functional status in patients with active RA

Intranasal administration of recombinant human cartilage glycoprotein-39 as a treatment for rheumatoid arthritis: a phase II, multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding trial

Background: Autoantigen-specific immunotherapy by mucosal tolerance induction via the intranasal route is an attractive therapeutic option for the treatment of autoimmune diseases, including rheumatoid arthritis (RA). Human cartilage glycoprotein-39 (HC gp-39) has been identified as a potential key autoantigen in RA. Based on animal studies, intranasal administration of the autoantigen is hypothesised to induce immunological tolerance in patients with RA and to ameliorate disease activity. In a phase I/IIA clinical trial in patients with RA, intranasal application of HC gp-39 was safe and well tolerated. Objective: To investigate the efficacy of intranasally administered fully human, recombinant HC gp-39 (Org 39141) by a large clinical study. Methods: In a 13-week multicentre, double-blind, randomised, placebo-controlled, parallel-group, dose-finding, proof-of-concept trial, patients with RA (disease-modifying antirheumatic drug (DMARD) naive or after washout of DMARD treatment) were randomised to receive either intranasal applications of placebo or HC gp-39 in doses of 30, 150, 300 or 600 mu g, once a week. The primary efficacy variable was the 28 joint count Disease Activity Score (DAS28). Results: During the treatment period the DAS28 decreased similarly for all treatment groups-including placebo-indicating lack of efficacy of intranasal HC gp-39 treatment in the current setting. Safety variables were similar for all study groups. Conclusion: It was concluded that with the treatment protocol used (dose levels and frequency of dosing), intranasal treatment with Org 39141 was safe but did not result in more clinical improvement than in placebo-treated patients