Abstract: OBJECTIVE: To evaluate the efficacy of etanercept, a recombinant human soluble fusion protein of tumor necrosis factor-alpha (TNF-alpha) type II receptor and IgG1, in patients with adult dermatomyositis (DM). METHODS: Five patients with active DM were studied. All patients reported muscle weakness and had elevated muscle enzymes creatine kinase and lactate dehydrogenase. Because of lack of response to steroid and cytotoxic therapy, etanercept was given at a dose of 25 mg subcutaneously twice a week for at least 3 months. RESULTS: All patients experienced an exacerbation of disease, with increase of muscle weakness, elevation of muscle enzyme levels, and unchanged rash. Treatment with etanercept was stopped. After receiving a combination of methotrexate (MTX) and azathioprine, disease manifestations improved in all patients. CONCLUSIONS: In our case series, TNF-alpha inhibition by etanercept was not effective, suggesting that a broad immunosuppressive therapy is needed to treat DM.
Abstract: OBJECTIVE: To determine whether Bcl-2, p53, and Fas/CD95 help to control cartilage metabolism. METHODS: Six normal and 14 osteoarthritic (OA) cartilage samples were examined, and two zones from each sample showing the least (Min) and most (Max) anatomical damage were selected. Chondrocytes were isolated by sequential enzymatic digestion and freshly processed. Bcl-2, p53, and Fas/CD95 expression was evaluated by immunofluorescence and FACS analysis; the cell cycle was analysed using propidium iodide, and chondrocyte proliferation assessed by [(3)H]thymidine incorporation. RESULTS: Intracellular levels of Bcl-2 were significantly higher in Max (27.5%) than in Min (21%, p<0.01) OA or normal chondrocytes (18.5%, p<0.01). Intracellular p53 expression was significantly decreased in Max (25.5%) compared with Min (37%, p<0.01) OA or normal cartilage (41.5%, p<0.05). Fas/CD95 receptor expression on surface chondrocytes did not significantly differ between OA and normal cartilage. Cell cycle analysis showed that the proportion of activated chondrocytes in the S phase was significantly higher in Max (69%) than in Min (49%) OA or normal cartilage (43%). The prevalence of proliferating chondrocytes progressively increased according to the degree of OA damage (mean (SEM) Min 1247 (260), Max 2423 (460), p<0.05). Chondrocyte [(3)H]thymidine uptake correlated positively with Bcl-2 (r(s) = 0.62, p = 0.009) and correlated inversely with p53 levels (r(s) = -0.55, p = 0.02). CONCLUSIONS: Bcl-2 and p53 play a part in apoptosis, but also help to regulate chondrocyte growth and differentiation. Whereas Bcl-2 promotes cell survival, p53 can arrest cell cycle. The data confirm that chondrocyte activity is enhanced in OA and suggest that the increased Bcl-2/p53 ratio sustains the metabolic boost of chondrocytes.
Abstract: OBJECTIVE: To assess the long-term efficacy and tolerability of a therapy consisting of infliximab at low dosage plus methotrexate in patients with psoriatic arthritis (PsA). As a second objective, we assessed whether the improvement obtained after 54 weeks of infliximab could be maintained with methotrexate alone. METHODS: A group of 26 patients with peripheral PsA resistant to various DMARDs were treated with infliximab + methotrexate for 54 weeks. RESULTS: The clinical response after the induction period was constant and progressive, with a high percentage of patients achieving an ACR50 response. The ESR and CRP values also declined continuously and gradually, but only CRP returned to normal values. During the follow-up period after 54 weeks, infliximab was stopped and the improvement obtained lasted for 2-6 months. The secondary end point was not achieved, and an extension period was designed. Results at 78 weeks are presented. CONCLUSIONS: Open questions for treating patients with infliximab and methotrexate are the schedule and the length of the administration and how to preserve the improvement obtained after the drug discontinuation.
Abstract: OBJECTIVE: Uveitis is a severe manifestation of rheumatic diseases since it can lead to visual impairment and even blindness. Ocular involvement is frequently a clinical challenge because its occurrence often requires changes of the therapeutic strategy. There are growing evidence that tumor necrosis factor alpha (TNFalpha) inhibitors may be an effective treatment of refractory uveitis. Purpose of this study was to evaluate the efficacy and safety of TNFalpha blocking agents in patients with seronegative spondylo-arthropathies (SNSA) and Behcet disease (BD) associated relapsing uveitis. METHODS: Five consecutive patients with chronic or relapsing uveitis were prospectively studied. Two patients with SNSA had recurrent anterior uveitis and three patients had BD associated uveitis (one anterior, two posterior uveitis). All of the patients were taking systemic and topical corticosteroids and three of them were also treated with DMARDs (methotrexate, cyclosporine, sulphasalazine) without clinical benefit. Four patients received infliximab, an anti-TNFalpha monoclonal antibody, at a dosage of 5 mg/kg body weight and one patient was treated with etanercept, a TNFalpha receptor p75-Fc fusion protein, at a dosage of 25 mg twice weekly. RESULTS: Both infliximab and etanercept induced a marked improvement in uveitis and none relapse was observed throughout all the study. Systemic corticosteroids were progressively tapered and stopped in all patients. Also methotrexate and sulphasalazine were discontinued, while cyclosporine dose has been reduced by 30%. No side effects were observed. CONCLUSIONS: Therapy with TNFalpha blockers, infliximab and etanercept, was effective and safe in the treatment of rheumatic disease associated uveitis. A complete remission was achieved even in patients with severe steroid resistant uveitis. Further controlled studies on larger number of patients are needed to better define the different forms of ocular involvement that can benefit from the therapy with TNFalpha inhibitors.
