Safety profile of biological therapies for treating rheumatoid arthritis.

INTRODUCTION: Biological agents such as tumor necrosis factor inhibitors (TNFi), abatacept, rituximab and tocilizumab have proven efficacy in RA. However, these agents are also associated with adverse events so further data is essential to detect them at the earliest stage possible. Areas covered: Herein, the authors review the safety profile of biological therapy, including TNFi and non-TNF agents including abatacept (ABA), rituximab (RTX) and tocilizumab (TCZ). The authors analyze both published articles and congress communications including clinical trials, meta-analyses, observational studies, data from registries and spontaneous clinical reports. The authors classify studies according to the most common and relevant adverse events associated with biological agents. Expert opinion: Biological therapies have a reasonable safety profile and, globally, the benefits far outweigh the possible risk of adverse events. Currently, the risk of serious infections is low and no increased risk in solid malignancies or cardiovascular events have been found after a long clinical experience with these therapies. However, there are still potential risks as well as concerns of immunogenicity induced by TNFi. More studies are required to understand these risks, design safer drugs, and implement pharmacogenomics into the clinic. This will lead to a more personalized medicine in the future.

Ciprofibrate therapy in patients with hypertriglyceridemia and low high density lipoprotein (HDL)-cholesterol: greater reduction of non-HDL cholesterol in subjects with excess body weight (The CIPROAMLAT study).

BACKGROUND: Hypertriglyceridemia in combination with low HDL cholesterol levels is a risk factor for cardiovascular disease. Our objective was to evaluate the efficacy of ciprofibrate for the treatment of this form of dyslipidemia and to identify factors associated with better treatment response. METHODS: Multicenter, international, open-label study. Four hundred and thirty seven patients were included. The plasma lipid levels at inclusion were fasting triglyceride concentrations between 1.6-3.9 mM/l and HDL cholesterol < or = 1.05 mM/l for women and < or = 0.9 mM/l for men. The LDL cholesterol was below 4.2 mM/l. All patients received ciprofibrate 100 mg/d. Efficacy and safety parameters were assessed at baseline and at the end of the treatment. The primary efficacy parameter of the study was percentage change in triglycerides from baseline. RESULTS: After 4 months, plasma triglyceride concentrations were decreased by 44% (p < 0.001). HDL cholesterol concentrations were increased by 10% (p < 0.001). Non-HDL cholesterol was decreased by 19%. A greater HDL cholesterol response was observed in lean patients (body mass index < 25 kg/m2) compared to the rest of the population (8.2 vs 19.7%, p < 0.001). In contrast, cases with excess body weight had a larger decrease in non-HDL cholesterol levels (-20.8 vs -10.8%, p < 0.001). There were no significant complications resulting from treatment with ciprofibrate. CONCLUSIONS: Ciprofibrate is efficacious for the correction of hypertriglyceridemia / low HDL cholesterol. A greater decrease in non-HDL cholesterol was found among cases with excess body weight. The mechanism of action of ciprofibrate may be influenced by the pathophysiology of the disorder being treated.

Patients with rheumatoid arthritis in clinical remission and ultrasound-defined active synovitis exhibit higher disease activity and increased serum levels of angiogenic biomarkers.

INTRODUCTION: The aim of this study was to identify and characterize subclinical synovitis in patients with rheumatoid arthritis (RA) in clinical remission using power Doppler ultrasound (PDUS) and serum levels of biomarkers of inflammation and/or angiogenesis. METHODS: We selected patients with RA in clinical remission defined as a Disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for more than six months tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands was performed by a sonographer. Synovial hypertrophy (SH) and PDUS signal were scored (grades 0 to 3). SH ≥2 and a PDUS signal was classified as active synovitis. Serum levels of biomarkers of inflammation/angiogenesis were determined by Quantibody Human Array. RESULTS: This study included 55 patients, of whom 25 (45.4%) met criteria for ultrasound-defined active synovitis. Patients with active synovitis had higher DAS28-C reactive protein (P = 0.023), DAS28-ESR (P = 0.06), simplified disease activity score, SDAI (P = 0.064), and only 12% were taking oral glucocorticoids (≤5 mg/day) compared with 40% of patients without active synovitis (P = 0.044). Patients with synovitis also had significantly higher serum levels of the angiogenic biomarkers angiopoietin-2 (P = 0.038), vascular endothelial growth factor-D (P = 0.018), placental growth factor (P = 0.043), stromal cell-derived factor-1 (P = 0.035), matrix metallopeptidase-2 (P = 0.027) and basic fibroblast growth factor (bFGF) (P = 0.007), but not of pro-inflammatory cytokines. CONCLUSIONS: Nearly half of the patients with RA in clinical remission had ultrasound-defined active synovitis, higher disease activity and less frequent oral glucocorticoid consumption than patients without active synovitis. This clinical situation was associated with a specific biological profile characterized by an excess of angiogenic mediators rather than persistent proinflammatory cytokine responses.

Effects of intravenous pamidronate on renal function, bone mineral metabolism and bone mass in patients with severe osteoporosis.

INTRODUCTION: To analyze the effects of intravenous pamidronate (APD) on bone remodelling, bone mineral density (BMD), fractures and bone mineral metabolism parameters, and the rate of adverse events, with special attention to renal function, in patients with osteoporosis with intolerance and/or any contraindication to oral bisphosphonates. METHODS: We analyzed prospectively 17 osteoporotic patients (age, 66.8 +/- 9.4 years): 65% women, 82% with prevalent vertebral fractures. All patients received APD therapy (30 mg intravenously every 3 months) and were followed up for 1 year. We analyzed serum amino-terminal propeptide of type I procollagen and urinary N-terminal cross-linked telopeptide of type I collagen (as markers of bone turnover), serum calcium, phosphate, parathormone, 25OH-vitamin D, creatinine, and the creatinine clearance: at baseline, 1 week after starting APD treatment, and thereafter for every 3 months (before infusion) during 1 year. We also analyzed lumbar and femoral BMD at baseline and after 1 year, the incidence of new fractures, and the treatment-related adverse events. RESULTS: One week after starting APD treatment, a significant decrease of N-terminal cross-linked telopeptide of type I collagen (32%) (P < 0.05) and an increase of parathormone values (72%) (P < 0.01) were observed, without significant differences found thereafter. No significant differences were observed in BMD evolution and in the other parameters analyzed throughout the study, nor in impairment of renal function. Sixty-four percent of patients suffered new skeletal fractures, 41% of patients showed flu-like syndrome after APD infusion, and 1 patient was withdrawn from treatment because of adverse events. CONCLUSION: Patients with severe osteoporosis receiving APD infusions had a high rate of fractures without significant changes in bone mass or in bone markers; nevertheless, such a therapeutic regimen showed a good renal safety profile, suggesting that APD at this dosage is safe but ineffective for treating severe osteoporosis.

Health-related quality of life in rheumatoid arthritis: therapeutic education plus pharmacological treatment versus pharmacological treatment only.

OBJECTIVE: To determine whether therapeutic education added to conventional drug therapy reduced disability and pain in patients with early rheumatoid arthritis (RA). METHODS: Fourty-three patients with RA, 29F/14 M, were included in a randomized, controlled trial and assigned to a control group receiving conventional pharmacological treatment only (n=21), or an intervention group receiving therapeutic education added to conventional pharmacological treatment (n=22). The main outcome variable was self-reported disability on the Stanford health assessment questionnaire (HAQ). RESULTS: At 18 months, patients in the intervention group had less disability (HAQ), pain intensity, number of tender and swollen joints, and patient's and physician's global assessments (p=0.003, 0.031, 0.003, 0.001, 0.014, and 0.004, respectively) compared with baseline, and improvements in disability and number of tender and swollen joints (p=0.024, 0.040, and 0.003, respectively), compared with controls. CONCLUSIONS: Patients receiving pharmacological treatment and therapeutic education had a better evolution than those receiving only pharmacological treatment.