Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects approximately 1% of the worldwide population. It primarily targets the synovial membrane of joints, leading to a synovial proliferation, joint cartilage lesion and erosions in the adjacent bone tissue. The disease is usually progressive and if the inflammatory process is not adequately suppressed, joint deformity takes place, leading to a significant functional disability and work incapacity. Over the last decade, biological therapy was established as a major step towards disease control in those patients who experienced failure after treatment with disease-modifying antirheumatic drugs. Despite the growing number of biological agents with different immunological targets, a significant number of patients do not receive appropriate disease control, or have the use of these agents limited because of adverse events. As such, the search for new molecules with a higher efficacy and better safety profile is ongoing. This article focuses on a new drug, tofacitinib, which is a synthetic disease-modifying antirheumatic drug for treatment of RA. Preclinical studies in arthritis and transplantation animal models are reviewed as a background for the possible use of tofacitinib treatment in humans. Four Phase II (one A and three B dose-ranging) trials lasting from 6 to 24 weeks in RA patients showed significant American College of Rheumatology 20 improvements as early as week 2 and sustained at week 24 in two studies. Tofacitinib Phase III studies in RA are included in a clinical program called 'ORAL Trials'. Long-term follow-up from ongoing studies will contribute to a more accurate tofacitinib efficacy and safety profile. Trials in other illness such as psoriasis, psoriatic arthritis, renal transplant rejection prevention, inflammatory bowel diseases and dry eye are underway.

OBJECTIVE: To determine the efficacy and safety of ocrelizumab (OCR) with methotrexate (MTX) in MTX-naive rheumatoid arthritis (RA) patients.METHODS: In a randomised, double-blind, controlled trial, patients received placebo+MTX (MTX; n=210), OCR 200 mg×2+MTX (OCR 200; n=200) or OCR 500 mg×2+MTX (OCR 500; n=203). OCR/placebo (two intravenous infusions) was given on days 1 and 15, with fixed re-treatment scheduled at weeks 24/26, 52/54 and 76/78. Due to early termination of OCR dosing, there was no formal primary end point analysis (change from baseline in modified total Sharp score (ΔmTSS) at week 104). Analyses are reported for week 52 outcomes.RESULTS: At week 52, treatment with OCR+MTX compared with MTX alone reduced progression of joint damage (mean (SD) change in ΔmTSS: OCR 200, 0.66 (4.51); OCR 500, 0.27 (2.91); MTX alone, 1.59 (4.82); p=0.001 and p=0.003, respectively vs MTX alone) and improved clinical signs and symptoms (American College of Rheumatology 20 response: OCR 200, 73.0%; OCR 500, 71.0%; MTX alone, 57.5%; p<0.005 for each OCR vs MTX alone). Serious infection rates per 100 patient-years were similar with OCR 200 and MTX alone (2.6 (95% CI 0.9 to 6.1) and 3.0 (1.1 to 6.5), respectively), but higher with OCR 500 (7.1 (3.9 to 11.9)).CONCLUSIONS: OCR 200 mg and 500 mg with MTX in MTX-naive patients with RA were effective in inhibiting joint damage progression and improving RA signs and symptoms. OCR 500 mg with MTX was associated with an increased rate of serious infections.

Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score <-2.5 and not <-4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68%(p < 0.0001) and nonvertebral fracture by 20%(p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35%[95% confidence interval (CI): 20%-61%] and 51%[95% CI: 39%-66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87%[95% CI: 35%->100%] and 72%[95% CI: 24%->100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab.

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CONTEXT AND OBJECTIVES: Osteoporosis has frequently been observed in patients with rheumatoid arthritis. The present study was undertaken in order to evaluate factors associated with osteoporosis among women with rheumatoid arthritis. DESIGN AND SETTING: Cross-sectional study, carried out in a public hospital in São Paulo. METHODS: The participants were 83 women with rheumatoid arthritis (53.7 +/- 10.0 years old). Bone mineral density (BMD) and body composition were measured by dual energy X-ray absorptiometry. The patients were divided into three groups according to BMD: group 1, normal BMD (n = 24); group 2, osteopenia (n = 38); and group 3, osteoporosis (n = 21). Tests were performed to compare differences in means and correlations, with adjustments for age, duration of disease and cumulative corticosteroid. The relationships between clinical factors, physical activity score, dietary intake, body composition and biochemical parameters were analyzed using linear regression models. RESULTS: Mean calcium, vitamin D and omega-6 intakes were lower than the recommendations. Associations were found between BMD and age, disease duration, parathyroid hormone concentration and fat intake. The linear regression model showed that being older, with more years of disease and lower weight were negatively correlated with BMD [Total femur = 0.552 + 0.06 (weight)+ 0.019 (total physical activity)- 0.05 (age)- 0.003 (disease duration); R(2)= 48.1; P < 0.001]. CONCLUSION: The present study indicates that nutritional factors and body composition are associated with bone mass in women with rheumatoid arthritis.

OBJECTIVES: To determine the efficacy of CP-690,550 in improving pain, function, and health status in patients with moderate to severe active rheumatoid arthritis (RA) and an inadequate response to methotrexate or a TNF-alpha inhibitor. METHODS: Patients were randomized equally to placebo, CP 690,550 5, 15, or 30 mg BID for 6 weeks, with 6 weeks' follow-up. Patient's Assessment of Arthritis Pain (Pain), Patient's Assessment of Disease Activity, HAQ-DI, and SF-36 were recorded. RESULTS: At Week 6, significantly more patients in the CP-690,550 5, 15, and 30 mg BID groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78%, and 14%, respectively), clinically meaningful reductions in HAQ-DI (>/=0.3 units)[57%, 75%, 76%, and 36%, respectively], and clinically meaningful improvements in SF-36 domains and physical and mental components. CONCLUSIONS: CP-690,550 was efficacious in improving the pain, function, and health status of patients with RA, from Week 1 to Week 6.

OBJECTIVE: To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response. METHODS: Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks. RESULTS: By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4%(versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all CP-690,550 treatment arms. CONCLUSION: Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.

Background: The MOTION (Monthly Oral Therapy with Ibandronate for Osteoporosis Intervention) study reported that once-monthly ibandronate was noninferior to once-weekly alendronate in terms of increasing bone mineral density (BMD) at the lumbar spine and total hip over 12 months. On analysis of secondary and exploratory end points in MOTION, which included trochanter and femoral neck BMD, monthly ibandronate was found to be noninferior to weekly alendronate. The coprimary, secondary, and exploratory BMD end points from MOTION have been previously reported. Objective: This report presents additional results from the MOTION study, including response rates in terms of lumbar spine and total hip BMD gains above baseline; findings from a comparison of serum concentrations of bone turnover markers; and tolerability analysis, including adverse events that led to withdrawal and gastrointestinal (GI) adverse events. Methods: MOTION was a 12-month (with 15-day follow-up), randomized, multinational, multicenter, double-blind, double-dummy, parallel-group, nonin-feriority study in postmenopausal women aged 55 to <85 years with osteoporosis. Patients were randomly assigned to receive 150-mg-monthly oral ibandronate and weekly alendronate-matched placebo, or 70-mg-weekly oral alendronate and monthly ibandronate-matched placebo, for 12 months. At baseline, day 7 of treatment, 3 and 6 months, 6 months + 7 days, and 12 months, serum concentrations of markers of bone resorption (C-telopeptide of the a chain of type 1 collagen [sCTX]) and bone formation (serum N-terminal propeptides of type 1 collagen) were measured in a subset of the total trial population. At baseline and month 12, BMD was measured using dual-energy x-ray absorptiometry. Exploratory analyses of patients whose spine, total hip, and trochanter BMD at 12 months were above baseline (responders) were also performed. Results: A total of 1760 women were enrolled (ibandronate, 887 patients; alendronate, 873). The median changes in the trough concentrations of sCTX were -75.5% with monthly ibandronate and -81.2% with weekly alendronate. The percentage of patients with mean lumbar spine and total hip BMD gains above baseline (responders) were 90% and 87%, respectively, for ibandronate and 92% and 90%, respectively, for alendronate. GI adverse events were reported in </=30% of patients per group during this 1-year study. Conclusion: The data from these postmenopausal women with osteoporosis suggest that once-monthly 150-mg ibandronate therapy provided clinically comparable efficacy in terms of BMD response, reductions in bone turnover, and GI tolerability similar to that of weekly 70-mg alendronate.

OBJECTIVE: To determine the efficacy and safety of pamapimod in adult patients with active rheumatoid arthritis (RA) who had an inadequate clinical response to methotrexate (MTX). METHODS:/B> Patients receiving stable doses of MTX were randomized to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily [qd]) or matching placebo. The primary efficacy measure was the proportion of patients with >/= 20% improvement in RA based on the American College of Rheumatology criteria (ACR20) at 12 weeks. Secondary measures were ACR50, DAS/EULAR response, and individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing, and immunology assessments. RESULTS:/B> On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31-43%) was not significantly different from placebo (34%). Secondary efficacy end points showed a similar pattern. AEs were typically mild and included infections, gastrointestinal disturbances, dizziness and rashes; AEs resulting in discontinuation of study drug were primarily attributed to infections. CONCLUSION: In patients with active RA receiving stable doses of MTX, pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.

With the evolution of bone densitometry, differences in technologies, acquisition techniques, reference databases, reporting methods, diagnostic criteria and terminology have developed and the International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences, the latest in 2007. The Brazilian Society for Clinical Densitometry (SBDens), with support from many Brazilian societies interested in bone health, gathered numerous specialists to discuss the ISCD proposals and to evaluate the validity of the extension of those norms to Brazilian population. The SBDens reunion of consensus made a very useful document to help the understanding and interpretation of bone densitometry and other methods of bone assessment.