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.

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.

Objective. To evaluate the efficacy and safety of treatment with adalimumab, a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody, over 48 weeks in patients with moderate to severe psoriatic arthritis (PsA).Methods. Patients who completed the Adalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT), a 24-week, double-blind study of adalimumab versus placebo in PsA, could elect to receive open-label adalimumab, 40 mg subcutaneously every other week after week 24. Radiographs were obtained at week 48 and were read with radiographs obtained previously. Clinical and radiographic efficacy data were analyzed overall and in patient subsets. Safety data were collected over 48 weeks.Results. At week 48, patients from the adalimumab arm of ADEPT (n ‫؍‬ 151) had achieved American College of Rheumatology 20% improvement (ACR20), ACR50, and ACR70 response rates of 56%, 44%, and 30%, respectively. Among those evaluated with the Psoriasis Area and Severity Index (PASI) (n ‫؍‬ 69), PASI50, PASI75, PASI90, and PASI100 response rates (>50%, >75%, >90%, and 100% reduction in PASI scores, respectively) were 67%, 58%, 46%, and 33%, respectively (ACR and PASI response rates were analyzed using nonresponder imputation). Improvements in disability, as measured by the Disability Index of the Health Assessment Questionnaire (mean change in score -0.4) were sustained from week 24 to week 48. At week 24 and week 48, the mean changes from baseline in the modified total Sharp score were -0.1 and 0.1, respectively, for patients who received adalimumab for 48 weeks (n ‫؍‬ 133), and 0.9 and 1.0, respectively, for patients who received placebo for 24 weeks followed by adalimumab for 24 weeks (n ‫؍‬ 141). Adalimumab demonstrated clinical and radiographic efficacy regardless of whether patients were receiving methotrexate (MTX) at baseline. Adalimumab was generally safe and well tolerated through week 48.Conclusion. Adalimumab improved joint and skin manifestations, reduced disability, and inhibited radiographic progression over 48 weeks in patients with PsA who were participants in ADEPT. MTX use at baseline was not required for clinical or radiographic efficacy. Adalimumab had a good safety profile through week 48.Psoriatic arthritis (PsA) is an inflammatory arthritis that occurs in up to one-third of patients with Supported by Abbott Laboratories.

Objective:To evaluate the long-term effectiveness and tolerability of adalimumab in the treatment of psoriatic arthritis (PsA).Methods:Patients with PsA who completed a 24-week, double-blind study of adalimumab versus placebo were eligible to enroll in an open-label extension study and receive adalimumab 40 mg subcutaneously every other week for up to an additional 120 weeks. At the time of this analysis, available efficacy evaluations throughout 2 years of treatment (n  =  245) included American College of Rheumatology (ACR) 20%, 50% and 70% improvement scores, measures of joint disease and skin disease, disability and quality of life; modified total Sharp scores (mTSS) were available for 2.75 years of treatment for patients who received adalimumab in the 24-week study.Results:After 24 weeks of double-blind treatment, the mean change in mTSS was −0.2 for the adalimumab group (N  =  144) and 1.0 for the placebo group (N  =  152; p<0.001), and outcomes for all individual ACR component variables were significantly improved in adalimumab compared with placebo-treated patients. Compared with 24-week responses, inhibition of radiographic progression and improvements in joint disease were maintained in most patients during long-term, open-label adalimumab treatment. Also, improvements in skin disease were maintained, with >20% of patients achieving the strict criterion of psoriasis area and severity index 100. The nature and frequency of adverse events during long-term adalimumab treatment were consistent with the safety profile during short-term treatment.Conclusions:The clinical and radiographic efficacy of adalimumab demonstrated during short-term treatment was sustained during long-term treatment. Adalimumab has a favourable risk–benefit profile in patients with PsA.Trial registration number:NCT00195689.