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

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

Univariate linear regression analysis on putative risk factors for radiographic progression: non-genetic and genetic factors.

*<p>Alleles shown as major allele/minor allele.</p>†<p>P<0.05.</p><p>ACPA, anti-citrullinated peptide antibody; RF, rheumatoid factor. MAF; Minor allele frequency in the tested population, SE, shared epitope; <i>PADI4</i>, peptidyl arginine deiminase type IV; <i>TNFAIP3</i>, tumor necrosis factor, alpha-induced protein 3; <i>CCR6</i>, C-C chemokine receptor type 6; <i>B3GNT2</i>, UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 2; <i>ANXA3</i>, annexin A3; <i>CSF2</i>, colony stimulating factor 2; <i>CD83</i>, CD83 molecule; <i>NFKBIE</i>, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon; <i>ARID5B</i>, AT rich interactive domain 5B [MRF1-like]; <i>PDE2A</i>, phosphodiesterase 2A, cGMP-stimulated; <i>ARAP1</i>, ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1; <i>PLD4</i>, phospholipase D family, member 4; <i>PTPN2</i>, protein tyrosine phosphatase, non-receptor type 2.</p

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

Demographic and clinical characteristics of patients at 5 years from onset.

<p>Data are presented as median (interquartile range) or n (%).</p>*<p>Cut-off = 4.5 IU/ml.</p>†<p>Maximum value in the first 5-year period of the disease was used, cut-off = 15.0 IU/ml.</p><p>SHS, Sharp/van der Heijde score; ACPA, anti-citrullinated peptide antibody; RF, rheumatoid factor; DMARDs, disease-modifying anti-rheumatic drugs.</p

Probability plot of Sharp/van der Heijde score of the hands at the 5-year disease duration.

<p>Each point on the plot represents the Sharp/van der Heijde score (SHS) of the hands at the 5-year disease duration, which representing approximate value of the radiographic progression in the first 5 years after onset of RA, in an individual patient. A zero value represents a patient without any radiographic progression, and the right-side tail represents patients with the most progression.</p

Safety and effectiveness of iguratimod in patients with rheumatoid arthritis: Final report of a 52-week, multicenter postmarketing surveillance study

<p><b>Objectives:</b> We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA).</p> <p><b>Methods:</b> This multicenter, prospective, observational study included all evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52.</p> <p><b>Results:</b> Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52.</p> <p><b>Conclusion:</b> Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.</p