Clinically relevant advances in rheumatoid arthritis therapy

Owing to the success of biologics in the treatment of rheumatoid arthritis (RA), several novel drugs have been introduced in the therapeutic armamentarium, although not all of them have been approved in all countries worldwide. Among the drugs are tumour necrosis factor (TNF) inhibitors such as certolizumab pegol and golimumab (the latter of which was the first TNF blocker shown to be effective in patients who had been unsuccessfully treated with other TNF blockers and which can be applied only once a month), and the interleukin-6 receptor antagonist tocilizumab, which not only opens up a completely new field of anti-inflammatory modulation of RA pathophysiology, but also highlights the challenge of novel potential side effects. Moreover, aside from clinical studies showing efficacy in the inhibition of osteoclast activation by the anti-RANKL (receptor activator of nuclear factor-kappa B ligand) antibody denosumab, an improved form of steroid application known as slow-release ‘tempus tablet’ for treatment of RA and several developments in the small-molecule area have been addressed by clinical trials

Cardiovascular risk management in patients with inflammatory arthritis: what is good for the joint is good for the heart and vice versa!

Owing to the prominent long-term systemic inflammatory reaction in patients with arthritides and a growing body of data illustrating that this inflammatory reaction imposes a considerable risk for the development or aggravation of cardiovascular (CV) disease or overall CV risk, numerous researchers and clinicians have put enormous effort into the analysis of the effects of risk factors on the course of CV disease in these patients and the therapeutic options to antagonize progressive atherosclerosis. To achieve this challenging goal, investigators have shown that all treatment strategies must include the ‘non-rheumatic’ approaches, such as lowering blood pressure, stopping smoking, and improving metabolic status, in tight association with lowering the overall disease activity of the underlying rheumatic entity using antiphlogistic drugs and conventional as well as biologic disease-modifying drugs

Dysbalance of angiogenic and angiostatic mediators in patients with mixed connective tissue disease

Objective: Vascular disease is common in mixed connective tissue disease (MCTD). The aim of the present study was to investigate, whether dysbalance of angiogenic and angiostatic factors occurs in MCTD. Methods: In all, 38 patients with MCTD, and 40 patients with systemic sclerosis (SSc) for comparison, were included. Four centres contributed to this cross-sectional analysis. A total of 66 healthy volunteers were used as controls. The serum levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin were determined by ELISA. For comparisons between controls and patients with MCTD and detection of associations of serum levels with dichotomous clinical parameters in patients with MCTD the Mann–Whitney test was used. Results: Serum levels of the angiogenic factor VEGF were significantly elevated in patients with MCTD and SSc. Significantly increased levels of the angiostatic factor endostatin were also detected in MCTD, but not in SSc. No differences were observed for bFGF. Levels of VEGF were higher in patients with MCTD with pulmonary arterial hypertension (PAH), acrosclerosis and myositis. In multivariate linear regression analysis, an additive model of PAH, myositis and lymphadenopathy accounted for 79% of the variability of the VEGF levels (r=0.889). Conclusions: Molecular factors modulating angiogenic responses are dysregulated in patients with MCTD and SSc with increases of VEGF in MCTD and SSc and selective upregulation of endostatin in MCTD. Furthermore, high serum levels of VEGF might characterise patients with MCTD with a more severe course of the disease with increased prevalence of PAH and myositis

Treatment of active lupus nephritis with the novel immunosuppressant 15-deoxyspergualin: an open-label dose escalation study

Introduction: As the immunosuppressive potency of 15-deoxyspergualin (DSG) has been shown in the therapy of renal transplant rejection and Wegener's granulomatosis, the intention of this study was to evaluate the safety of DSG in the therapy of lupus nephritis (LN). Methods: Patients with histologically proven active LN after prior treatment with at least one immunosuppressant were treated with 0.5 mg/kg normal body weight/day DSG, injected subcutaneously for 14 days, followed by a break of one week. These cycles were repeated to a maximum of 9 times. Doses of oral corticosteroids were gradually reduced to 7.5 mg/day or lower by cycle 4. Response was measured according to a predefined decision pattern. The dose of DSG was adjusted depending on the efficacy and side effects. Results: 21 patients were included in this phase-I/II study. After the first DSG injection, one patient was excluded from the study due to renal failure. 5 patients dropped out due to adverse events or serious adverse events including fever, leukopenia, oral candidiasis, herpes zoster or pneumonia. 11/20 patients achieved partial (4) or complete responses (7), 8 were judged as treatment failures and one patient was not assessable. 12 patients completed all 9 cycles; in those patients, proteinuria decreased from 5.88g/day to 3.37g/day (P = 0.028), Selena-SLEDAI decreased from 17.6 to 11.7. In 13/20 patients, proteinuria decreased by at least 50%; in 7 patients to less than 1g/day. Conclusions: Although the number of patients was small, we could demonstrate that DSG provides a tolerably safe treatment for LN. The improvement in proteinuria encourages larger controlled trials

EUSTAR biobanking: recommendations for the collection, storage and distribution of biospecimens in scleroderma research

The European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) has established an online database with clinical data of currently more than 8200 patients with systemic sclerosis (SSc). In addition to clinical research, EUSTAR fosters biomolecular studies to develop novel biomarkers and therapies for SSc. High-quality biospecimens are the basis for successful biomolecular studies. The EUSTAR biobanking group has therefore developed recommendations to standardise the collection, storage and distribution of SSc biospecimens at EUSTAR centres. These recommendations consider the scientific challenges associated with biomolecular research in SSc and the organisational requirements of EUSTAR. They were approved by the EUSTAR executive committee as well as the EUSTAR board. Once they become effective, these recommendations will be the basis for international EUSTAR studies with large numbers of SSc biospecimens. These recommendations might also be followed by other SSc consortia to enable exchange of biosamples between different SSc initiatives and might serve as a template for biobanking initiatives in other rheumatic diseases