Objective. To determine the efficacy and safety of treatment with rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to anti-tumor necrosis factor (anti-TNF) therapies and to explore the pharmacokinetics and pharmacodynamics of rituximab in this population.Methods. We evaluated primary efficacy and safety at 24 weeks in patients enrolled in the Random- Results. Patients assigned to placebo (n ‫؍‬ 209) and rituximab (n ‫؍‬ 311) had active, longstanding RA. At week 24, significantly more (P < 0.0001) rituximabtreated patients than placebo-treated patients demonstrated ACR20 (51% versus 18%), ACR50 (27% versus 5%), and ACR70 (12% versus 1%) responses and moderate-to-good EULAR responses (65% versus 22%).

Risedronate significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis but not among elderly women selected primarily on the basis of risk factors other than low bone mineral density.

BackgroundBaricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor.MethodsIn this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3.ResultsMore patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein.ConclusionsIn patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage.Trial registration numberNCT01721057; Results.

Objective. To examine immunization responses in patients with rheumatoid arthritis (RA) treated with rituximab and to investigate the effects of rituximabinduced CD20؉ B cell depletion on immune responses to tetanus toxoid (T cell-dependent antigen), pneumococcal polysaccharide (T cell-independent antigen), and keyhole limpet hemocyanin (KLH) (neoantigen) and on delayed-type hypersensitivity (DTH).Methods. In a controlled trial, we enrolled 103 patients with active RA receiving a stable dose of methotrexate (MTX). Tetanus toxoid, pneumococcal polysaccharide, and KLH vaccines as well as a Candida albicans skin test were administered to 1 group of patients receiving rituximab plus MTX (called rituximab-treated patients) for 36 weeks and to 1 group of patients receiving MTX alone for 12 weeks. The primary end point was the proportion of patients with a Ն4-fold rise in antitetanus IgG levels. Antitetanus, antipneumococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following vaccine administration. The DTH response to C albicans was measured 2-3 days following placement.Results. Responses to tetanus toxoid vaccine (Ն4-fold rise) were similar in both groups (39.1% of rituximab-treated patients and 42.3% of patients treated with MTX alone). The ability to maintain a positive DTH response to the C albicans skin test was comparable in both groups (77.4% of rituximab-treated patients and 70% of patients treated with MTX alone), showing no effect of rituximab treatment. Rituximab-treated patients had decreased responses to pneumococcal polysaccharide vaccine (57% of patients had a 2-fold rise in titer in response to >1 serotype, compared with 82% of patients treated with MTX alone) and to KLH vaccine (47% of patients had detectable anti-KLH IgG, compared with 93% of patients treated with MTX alone).Conclusion. Recall responses to the T celldependent protein antigen tetanus toxoid as well as DTH responses were preserved in rituximab-treated RA patients 24 weeks after treatment. Responses to neoantigen (KLH) and T cell-independent responses to pneumococcal vaccine were decreased, but many patients were able to mount responses. These data suggest that polysaccharide and primary immunizations should be administered prior to rituximab infusions to maximize responses.ClinicalTrials.gov identifier: NCT00282308.

Objective. Risedronate, a new pyridinyl bisphos-phonate, is a potent antiresorptive bone agent. This study examines the safety and efficacy of daily, oral risedronate therapy for the prevention of corticosteroid-induced bone loss. Methods. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study was conducted in 224 men and women who were initiating long-term corticosteroid treatment. Patients received either risedronate (2.5 mg or 5 mg) or placebo daily for 12 months. Each patient also received 500 mg of elemental calcium daily. The primary outcome measure was the percentage of change in lumbar spine bone mineral density (BMD). Secondary measures included proximal femur BMD and incidence of vertebral fractures. Results. After 12 months, the lumbar spine BMD (mean SEM) did not change significantly compared with baseline in the 5-mg (0.6 0.5%) or the 2.5-mg (0.1 0.7%) risedronate groups, while it decreased in the placebo group (2.8 0.5%; P < 0.05). The mean differences in BMD between the 5-mg risedronate and the placebo groups were 3.8 0.8% at the lumbar spine (P < 0.001), 4.1 1.0% at the femoral neck (P < 0.001), and 4.6 0.8% at the femoral trochanter (P < 0.001). A trend toward a decrease in the incidence of vertebral fracture was observed in the 5-mg risedronate group compared with the placebo group (5.7% versus 17.3%; P 0.072). Risedronate was well tolerated, and the incidence of upper gastrointestinal adverse events was comparable among the 3 groups. Conclusion. Risedronate therapy prevents bone loss in patients initiating long-term corticosteroid treatment. Corticosteroid therapy is used extensively to treat patients with a variety of medical conditions, most of whom require corticosteroid therapy for its potent anti-inflammatory and immunosuppressive properties. Although this therapy is valuable and necessary for many patients, the administration of corticosteroids for prolonged periods is associated with a number of adverse effects, one of the most debilitating of which is bone loss, which can result in fractures (1,2). Bone loss in patients taking corticosteroids appears to occur as a result of both reduced bone formation , which is attributed to direct inhibition of osteoblas