Objective. To determine whether the efficacy of diacerein persists at 2 months after the end of a 3-month treatment period, compared with placebo, in patients with painful knee osteoarthritis (OA).Methods. After a 1-week nonsteroidal antiinflammatory drug washout period, patients received either diacerein or placebo for 3 months, followed by an off-treatment period of 3 months to determine the carryover effects of the drug. Although patients were followed up through month 6, the primary efficacy end point was the percent change from baseline in pain (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] A) at month 5 (i.e., 2 months after the end of treatment) compared with placebo. The co-primary efficacy end point was the percent change from baseline in the total WOMAC score, also at month 5 versus placebo.Results. Two hundred three patients were screened, and 168 patients with painful knee OA were randomized. One hundred sixty-five patients were analyzed in an intent-to-treat analysis. At month 5, diacerein showed statistically significant superiority versus placebo as assessed with both the WOMAC A (P < 0.0001) and the total WOMAC (P < 0.0001), demonstrating the carryover effect of the drug. This superiority was already evident from month 2 for pain (P ‫؍‬ 0.001) and month 1 for total WOMAC (P ‫؍‬ 0.0021). Diacerein was safe and well tolerated. No serious or previously undocumented adverse events were observed during the study.Conclusion. This is the first published study of a symptomatic slow-acting OA drug in which the time of assessment of the primary outcome end points was 2 months after the end of a 3-month treatment period. The results show that diacerein is safe and effective for the treatment of knee OA and has a long carryover effect.Osteoarthritis (OA) is a disease affecting synovial joints and is characterized by degradation and loss of articular cartilage with subchondral bone remodeling, osteophyte formation, and synovial membrane inflammation (1,2). Clinical signs include fluctuating joint pain, swelling, stiffness, and loss of mobility, which increase in severity as the disease progresses. In the absence of a curative agent, the main objectives of OA management are to reduce symptoms, minimize functional disability, and limit the progression of structural changes, with the ultimate goal of delaying or avoiding arthroplasty.

Intravenous cyclophosphamide is considered to be the standard of care for the treatment of proliferative lupus nephritis. However, its use is limited by potentially severe toxic effects. Cyclosporine A has been suggested to be an efficient and safe treatment alternative to cyclophosphamide. Forty patients with clinically active proliferative lupus nephritis were randomly assigned to one of two sequential induction and maintenance treatment regimens based either on cyclophosphamide or Cyclosporine A. The primary outcomes were remission (defined as normal urinary sediment, proteinuria <0.3 g/24 h, and stable s-creatinine) and response to therapy (defined as stable s-creatinine, 50% reduction in proteinuria, and either normalization of urinary sediment or significant improvement in C3) at the end of induction and maintenance phase. Secondary outcomes were incidence of adverse events, and relapse-free survival. At the end of the induction phase, 24% of the 21 patients treated by cyclophosphamide achieved remission, and 52% achieved response, as compared with 26% and 43%, respectively of the 19 patients treated by the Cyclosporine A. At the end of the maintenance phase, 14% of patients in cyclophosphamide group, and 37% in Cyclosporine A group had remission, and 38% and 58% respectively response. Treatment with Cyclosporine A was associated with transient increase in blood pressure and reversible decrease in glomerular filtration rate. There was no significant difference in median relapse-free survival. In conclusion, Cyclosporine A was as effective as cyclophosphamide in the trial of sequential induction and maintenance treatment in patients with proliferative lupus nephritis and preserved renal function.(ClinicalTrials.gov identifier: NCT00976300)

This was a 13-week, multicentre, randomised, parallel, double-blind study. One hundred men and women volunteers aged ≥ 40 years with knee osteoarthritis (KOA) were randomised to once daily enzymatic hydrolysed collagen (EHC) 10 g or glucosamine sulphate (GS) 1.5 g for 90 consecutive days. Follow-up took place after two weeks and after one, two and three months. Primary [visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC Index)] and secondary outcomes variables, assessed at weeks two, four, eight and 12, were KOA pain intensity measured by quadruple visual analogue scales in the target knee, the WOMAC total score index, patient's and investigator's global assessments of disease activity, joint assessment, use of rescue medication (ibuprofen 400 mg tablets) and assessment of Quality of Life index (SF-36 Questionnaire). Safety and tolerability were also evaluated. Clear improvement was observed in both joint pain and symptoms in patients with KOA treated with EHC (Colatech®) and significant differences were observed. Mean reductions from baseline for EHC 10 g daily and GS 1.5 g, respectively, were KOA pain intensity reduction in the target knee for Colatech® (p < 0.05): WOMAC index decrease ≤ 15 points at the last visit (day 90) for Colatech® in 16 patients (34.04%) (p < 0.05) and for glucosamine in six patients (13.04%); total score index for painful joints: Colatech® 1.6 (p < 0.05) and glucosamine 1.8; total score index for swollen joints: Colatech® 0.5 (p < 0.05) and glucosamine 0.7; patient's global assessment of efficacy as the sum of improvement good + ideal: 80.8% for Colatech® and 46.6% for glucosamine (p < 0.05). EHC (Colatech®) showed superior improvement over GS in the SF-36 Questionnaire in the Physical Health Index (42.0 for Colatech and 40.0 for glucosamine). The incidence of adverse events was similar in both groups. Both EHC and GS were well tolerated.

Objective To evaluate the extended follow-up of the CYCLOFA-LUNE trial, a randomized prospective trial comparing two sequential induction and maintenance treatment regimens for proliferative lupus nephritis based either on cyclophosphamide (CPH) or cyclosporine A (CyA). Patients and methods Data for kidney function and adverse events were collected by a cross-sectional survey for 38 of 40 patients initially randomized in the CYCLOFA-LUNE trial. Results The median follow-up time was 7.7 years (range 5.0-10.3). Rates of renal impairment and end-stage renal disease, adverse events (death, cardiovascular event, tumor, premature menopause) did not differ between the CPH and CyA group, nor did mean serum creatinine, 24 h proteinuria and SLICC damage score at last follow-up. Most patients in both groups were still treated with glucocorticoids, other immunosuppressant agents and blood pressure lowering drugs. Conclusion An immunosuppressive regimen based on CyA achieved similar clinical results to that based on CPH in the very long term.

aBackground. ADAM33 and STAT6 belong to the candidate genes that have been commonly associated with asthma, bronchial hyperresponsiveness or IgE levels. Our objective was to assess the association of 11 SNPs of the ADAM33 and 6 of the STAT6 and their haplotypes with IgE levels and asthma. We also evaluated the possible role of parental origin of haplotypes on IgE levels. Methods. We enrolled 109 children with asthma and 45 healthy controls. Genotyping was performed by TaqMan probes and confirmed by sequencing. Haplotype construction was based on the knowledge of parental genotypes and also inferred by using the EM algorithm and Bayes' theorem. Results. None of the SNPs were associated with elevated IgE level or asthma. We found that the most frequent STAT6 haplotype ATTCAA (built from rs324012, rs324011, rs841718, rs3024974, rs3024974, rs4559 SNPs, respectively) was associated with elevated total IgE levels (P=0.01) and this haplotype was predominantly transmitted paternally (P<0.001). We compared our results with those of studies performed on German and Australian Caucasian populations and found that rs324011, rs3024974 and rs4559 SNPs in STAT6 should have a major effect on IgE levels. Therefore, we suggest the TCA haplotype alone (built from rs324011, rs3024974 and rs4559 SNPs, respectively) in STAT6 is associated with total IgE elevation. Conclusions. The influence of paternal origin of the STAT6 haplotype on IgE levels is surprising but the exact role of possible paternal imprinting in STAT6 regulation should be investigated and confirmed in future studies.