Objective. Etanercept has been shown to improve the articular and cutaneous manifestations of psoriatic arthritis (PsA). In this study, we further evaluated the safety, efficacy, and effect on radiographic progression of etanercept in patients with PsA.Methods. Patients with PsA (n ؍ 205) were randomized to receive placebo or 25 mg etanercept subcutaneously twice weekly for 24 weeks. Patients continued to receive blind-labeled therapy in a maintenance phase until all had completed the 24-week phase, then could receive open-label etanercept in a 48-week extension. Efficacy and safety were evaluated at 4, 12, and 24 weeks and at 12-week intervals thereafter. Radiographs of the hands and wrists were assessed at baseline and 24 weeks, at entry to the open-label phase, and after 48 weeks in the study.Results. Etanercept significantly reduced the signs and symptoms of PsA and psoriasis. At 12 weeks, 59% of etanercept patients met the American College of Rheumatology 20% improvement criteria for joint response, compared with 15% of placebo patients (P < 0.0001), and results were sustained at 24 and 48 weeks. At 24 weeks, 23% of etanercept patients eligible for psoriasis evaluation achieved at least 75% improvement in the Psoriasis Area and Severity Index, compared with 3% of placebo patients (P ؍ 0.001). Radiographic disease progression was inhibited in the etanercept group at 12 months; the mean annualized rate of change in the modified total Sharp score was ؊0.03 unit, compared with ؉1.00 unit in the placebo group (P ؍ 0.0001). Etanercept was well tolerated.Conclusion. Etanercept reduced joint symptoms, improved psoriatic lesions, inhibited radiographic progression, and was well tolerated in patients with PsA.
Results. Treatment with etanercept resulted in dramatic improvement. The ASAS20 was achieved by 59% of patients in the etanercept group and by 28% of patients in the placebo group (P < 0.0001) at week 12, and by 57% and 22% of patients, respectively, at week 24 (P < 0.0001). All individual ASAS components, acutephase reactant levels, and spinal mobility measures were also significantly improved. The safety profile of etanercept was similar to that reported in studies of patients with rheumatoid arthritis or psoriatic arthritis. The only adverse events that occurred significantly more often in the etanercept group were injection-site reactions, accidental injuries, and upper respiratory tract infections.Conclusion. Etanercept is a highly effective and well tolerated treatment in patients with active AS.Ankylosing spondylitis (AS) is an inflammatory arthritis and enthesitis involving the spine and periSupported by Immunex Corporation, Seattle, Washington, a wholly owned subsidiary
Objective. RANKL is essential for osteoclast development, activation, and survival. Denosumab is a fully human monoclonal IgG2 antibody that binds RANKL, inhibiting its activity. The aim of this multicenter, randomized, double-blind, placebo-controlled, phase II study was to evaluate the effects of denosumab on structural damage in patients with rheumatoid arthritis (RA) receiving methotrexate treatment.Methods. RA patients received subcutaneous placebo (n ؍ 75), denosumab 60 mg (n ؍ 71), or denosumab 180 mg (n ؍ 72) injections every 6 months for 12 months. The primary end point was the change from baseline in the magnetic resonance imaging (MRI) erosion score at 6 months.Results. At 6 months, the increase in the MRI erosion score from baseline was lower in the 60-mg denosumab group (mean change 0.13; P ؍ 0.118) and significantly lower in the 180-mg denosumab group (mean change 0.06; P ؍ 0.007) than in the placebo group (mean change 1.75). A significant difference in the modified Sharp erosion score was observed as early as 6 months in the 180-mg denosumab group (P ؍ 0.019) as compared with placebo, and at 12 months, both the 60-mg (P ؍ 0.012) and the 180-mg (P ؍ 0.007) denosumab groups were significantly different from the placebo group. Denosumab caused sustained suppression of markers of bone turnover. There was no evidence of an effect of denosumab on joint space narrowing or on measures of RA disease activity. Rates of adverse events were comparable between the denosumab and placebo groups.ClinicalTrials.gov identifier: NCT00095498.
Objective. To investigate the effect of etanercept therapy on radiographic progression in patients with ankylosing spondylitis (AS).Methods Conclusion. Unlike other inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis, structural progression in AS seems to be independent of TNF, despite the fact that TNF is responsible for the signs and symptoms due to inflammation in this disease.Ankylosing spondylitis (AS) belongs to a family of rheumatic diseases known as spondylarthritides that characteristically cause spinal joint inflammation and bony fusion of the spine. AS is the prototype of the spondylarthritides and is typified by ankylosis of the axial skeleton. Radiographic damage known to result from AS primarily includes fusion of entheses of the sacroiliac joints and of the posterior articulations and ligaments of the spine. These fusions can lead to impaired spinal mobility and in turn decreased ability to perform daily activities and severely reduced healthrelated quality of life (1).Tumor necrosis factor ␣ (TNF␣) has been shown to play an important role in the inflammatory response observed in AS. It has been found at increased levels in the serum and synovium of patients with AS (2,3), and treatment with TNF␣-blocking agents (etanercept, adalimumab, and infliximab) has been shown to safely and effectively reduce the signs and symptoms of AS (4-6) and significantly improve health-related quality of life (1). In addition, these agents have been shown to ClinicalTrials.gov identifier: NCT00356356.
The design and conduct of clinical trials for new OA treatments should address the heterogeneity of the disease, treatment-associated structural changes in target joints and patient-reported outcomes.
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