Demographic, clinical and therapeutic data at the time of an enrollment in IORRA.

<p>*Maximum value of RF measured in the cohort project during 2000–2010 for each individual was used.</p>†<p>Cut-off  = 4.5 IU/ml.</p><p>IORRA, Institute of Rheumatology Rheumatoid Arthritis cohort study; BMI, body mass index; DAS28, disease activity score in 28 joints; J-HAQ, the Japanese version of Health Assessment Questionnaire; RF, rheumatoid factor; ACPA, anti-citrullinated peptide antibody; TKR, total knee replacement; DMARDs, disease modifying antirheumatic drugs.</p

Multivariate Cox proportional hazards model of each SNP associated with the occurrence of hip fracture.

<p>All analyses were adjusted for independent non-genetic factors: age, body mass index, Japanese version of Health Assessment Questionnaire disability score, and history of total knee replacement. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104587#pone.0104587-Furuya1" target="_blank">[7]</a>.</p><p>*Alleles are listed as major allele/minor allele.</p><p>SNP, single nucleotide polymorphism; MAF, minor allele frequency; HR, hazard ratio; CI, confidence interval; <i>OPG</i>, osteoprotegerin; <i>ZBTB40</i>, zinc finger and BTB domain containing 40; <i>MHC</i>, major histocompatibility complex; <i>RANK</i>, receptor activator of the nuclear factor-κB; <i>SPTBN1</i>, spectrin β nonerythrocytic 1; <i>LRP4</i>, low-density lipoprotein receptor-related protein 4.</p

Efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis who were refractory or intolerant to anti-tumor necrosis factor therapy: Subgroup analysis of a randomized, double-blind, multicenter, phase 3 study (SIRROUND-T)

<p><b>Objective:</b> To evaluate the efficacy and safety of sirukumab, a human anti-interleukin six monoclonal antibody, in Japanese patients with rheumatoid arthritis who were refractory to anti-tumor necrosis factor therapy.</p> <p><b>Methods:</b> This subgroup analysis, based on a double-blind, placebo-controlled, 52-week phase 3, global study (SIRROUND-T) assessed the American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint). Secondary endpoints: ACR 50, Disease Activity Score in 28 joints-C reactive protein, Health Assessment Questionnaire-Disability Index and safety were assessed.</p> <p><b>Results</b> 116/878 patients received sirukumab 50 mg/4 weeks (q4w, <i>n</i> = 35), 100 mg/2 weeks (q2w, <i>n</i> = 44) or placebo (<i>n</i> = 37) subcutaneously. Significantly more patients achieved ACR 20 response at week 16 with sirukumab (50 mg q4w:20 [57.1%]; <i>p</i> < .001, 100 mg q2w:24 [54.5%]; <i>p</i> = .001) versus placebo (7 [18.9%]); consistent significant improvement in secondary endpoints at week 24 and 52 was observed. At week 24, incidence of treatment-emergent adverse events (TEAEs) was numerically higher with sirukumab groups (50 mg q4w:29 [82.9%]; 100 mg q2w:38 [86.4%] versus placebo (28 [75.7%]); however, at week 52, sirukumab combined groups had comparable incidence of TEAEs.</p> <p><b>Conclusion:</b> Efficacy findings through 52 weeks were comparable between sirukumab doses in Japanese patients and consistent with primary SIRROUND-T study results. No new safety signals were observed.</p

Efficacy and safety of sirukumab in Japanese patients with moderate to severe rheumatoid arthritis inadequately controlled by disease modifying anti-rheumatic drugs: Subgroup analysis of a phase 3 study

<p><b>Objective:</b> To evaluate the efficacy and safety of sirukumab in Japanese patients with active rheumatoid arthritis (RA) uncontrolled by disease-modifying antirheumatic drugs.</p> <p><b>Methods:</b> This subgroup analysis based on a double-blind, placebo-controlled, 52-week phase 3 study (SIRROUND-D) assessed American College of Rheumatology (ACR) 20 response at week 16 and van der Heijde-modified Sharp score (vdH-S) at week 52 (coprimary endpoints).</p> <p><b>Results:</b> A total of 168 (Japanese)/1670 patients received sirukumab 50 mg/4 weeks (q4w, <i>n</i> = 58), 100 mg/every 2 weeks (q2w, <i>n</i> = 54), or placebo (<i>n</i> = 56) subcutaneously. Significantly more patients achieved ACR20 response at week 16 with sirukumab (50 mg q4w: 69.0%; 100mg q2w: 66.7%) vs. placebo (21.4%; <i>p</i> < .001). Median change from baseline in total vdH-S score at week 52 was significantly lower with sirukumab (50 mg q4w: 0.3, <i>p</i> = .024; 100 mg q2w: 0.0, <i>p</i> = .002) vs. placebo (1.3). Sirukumab consistently showed greater improvements in secondary endpoints at weeks 24 and 52. Nasopharyngitis, elevated liver enzymes, injection site erythema and upper respiratory tract infections were the common treatment-emergent adverse events (TEAEs). Incidences of TEAEs and serious AEs were consistent between sirukumab groups through week 52.</p> <p><b>Conclusion:</b> Sirukumab showed clinically meaningful improvements consistent with significant improvements in the global study. No new safety signals were observed.</p

Boxplots representing the distribution of Sharp/van der Heijde score (SHS) of the hands according to the number of the risk factors.

<p>Risk factors; SE allele carrier, PADI4 risk allele carrier, ACPA positive, female and age at onset under 50. Each box represents the interquartile range of values, with the bold line showing the median value. The vertical lines show maximum and minimum value that fall within 1.5 box lengths, the open circles show extreme values >1.5 box plot lengths. PADI4, peptidyl arginine deiminase type IV ACPA, anti-citrullinated peptide antibody.</p

Stepwise multiple regression analysis on risk factors for radiographic progression (n = 830).

<p>Multiple R squared value = 0.055.</p><p>95% CI, 95% confidence interval; ACPA, anti-citrullinated peptide antibody; SE, shared epitope; <i>PADI4</i>, peptidyl arginine deiminase type IV.</p

Safety and efficacy of CT-P13 in Japanese patients with rheumatoid arthritis in an extension phase or after switching from infliximab

<p><i>Objectives</i>: This study aimed to evaluate the safety of CT-P13 in patients with rheumatoid arthritis (RA) during long-term treatment or after switching from innovator infliximab (IFX).</p> <p><i>Methods</i>: Patients who completed 54 weeks of treatment in a phase I/II study (PI/II) received CT-P13 at an initial dose of 3 mg/kg at Week 62, with dose increases permitted up to 10 mg/kg. The primary endpoint was adverse event (AE) incidence.</p> <p><i>Results</i>: Thirty-four of 38 patients in the maintenance group and 29 of 33 in the switch group reported at least one AE. Safety profiles in both groups were similar to those in PI/II. Eleven of 28 patients who were positive for anti-drug antibodies (ADA) at Week 62 discontinued the study before Week 110. Forty-one of 43 ADA-negative patients remained negative, and 10 of 28 ADA-positive patients became negative during the study. The mean DAS28 (ESR) at Week 134 was 3.166 in the maintenance group and 3.955 in the switch group.</p> <p><i>Conclusions</i>: CT-P13 was well tolerated in patients who maintained the treatment after 54 weeks and in patients who switched to CT-P13 after 54 weeks of IFX treatment. The study also demonstrated a stable clinical efficacy of CT-P13 in RA patients.</p

Utilization of functional electrical stimulation-assisted cycle ergometry in the critically ill

This work is about muscle weakness of critically ill patients, about its history, etiology, pathophysiology, incidence at departments of intensive care, diagnostics and therapy. The intensive physical therapy showed to be one of the preventive factors. The rehabilitation of critically ill patients has its specific procedures, especially for unconscious patients. It is possible to start the therapy only in concordance with safety criteria. The work includes data from a research, done on 27 patients from the Department of Anaesthesia and Intensive Care of Královské Vinohrady University Hospital in Prague. In a half year period, the effects of assisted electrical ergometry on cross section of rectus femoris muscle and on muscle strength of limbs were observed. The aim of this work is to find out, if this intensive rehabilitation will have any effect on given parameters. Keywords: ICUAW, rehabilitation, safety criteria, manual muscle strength testing, measuring the cross sectional diameter of the rectus femoris muscl

Boxplots representing the distribution of Sharp/van der Heijde score (SHS) of the hands in each category of independent risk factors for joint destruction.

<p>Risk factors; the number of HLA-DRB1 shared epitope, the number of PADI4 risk alleles, ACPA status (negative [<4.5 IU/ml] and positive), gender (female and male) and age at onset (categorized as “age under 30”, “30 s”, “40 s”, “50 s”, “60 s” and “age over 70”). Each box represents the interquartile range of values, with the bold line showing the median value. The vertical lines show maximum and minimum value that fall within 1.5 box lengths, the open circles show extreme values >1.5 box plot lengths. The P values were given by the univariate linear regression analyses (a log-transformed SHS was used as the dependent variable). PADI4, peptidyl arginine deiminase type IV ACPA, anti-citrullinated peptide antibody.</p

Histogram of distribution of the log-transformed SHS (hands).

<p>Histogram of distribution of the log-transformed SHS (hands).</p