Additional file 1: of The underrated prevalence of depression in Japanese patients with rheumatoid arthritis - evidence from a Nationwide survey in Japan

Reviewer reports and AU response to reviewers. (DOCX 18 kb

Correction: Baseline Serum Osteopontin Levels Predict the Clinical Effectiveness of Tocilizumab but Not Infliximab in Biologic-Naïve Patients with Rheumatoid Arthritis: A Single-Center Prospective Study at 1 Year (the Keio First-Bio Cohort Study)

<p>Correction: Baseline Serum Osteopontin Levels Predict the Clinical Effectiveness of Tocilizumab but Not Infliximab in Biologic-Naïve Patients with Rheumatoid Arthritis: A Single-Center Prospective Study at 1 Year (the Keio First-Bio Cohort Study)</p

Predictive ability of osteopontin for clinical remission in patients with RA who received tocilizumab (TCZ) or infliximab (IFX).

<p>(A) Logistic regression analysis showing significant association of increasing baseline osteopontin (OPN) levels with decreasing predicted probability of achieving Clinical Disease Activity Index (CDAI) remission at 1 year in the TCZ (tocilizumab) group. (B) ROC curve showing a cut-off baseline OPN level of 17.3 ng/mL, discriminating between CDAI remission and non-remission at 1 year in the TCZ group, with a sensitivity of 66% and a specificity of 80%. (C) Logistic regression analysis showing no significant association of baseline OPN levels with predicted probability of achieving CDAI remission at 1 year in the IFX (infliximab) group. Categorical changes in clinical indices such as (D) CDAI, (E) Simplified Disease Activity Index (SDAI), and (F) disease activity score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR) over 1-year treatment of TCZ or IFX, stratified by low or high baseline OPN levels (cut-off: 17.3 ng/mL). H, high disease activity; M, moderate disease activity; L, low disease activity; R, remission.</p

Categorical changes in clinical indices.

<p>(A) Clinical Disease Activity Index (CDAI), (B) Simplified Disease Activity Index (SDAI), and (C) disease activity score with 28 joint counts, erythrocyte sedimentation rate (DAS28-ESR), over 1-year treatment of infliximab (IFX) or tocilizumab (TCZ). H, high disease activity; M, moderate disease activity; L, low disease activity; R, remission.</p

Residual symptoms and disease burden among patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review

<p><b>Objectives:</b> To identify, describe and summarize evidence on residual symptoms and disease burdens in rheumatoid arthritis (RA) patients qualified as being in remission or low disease activity (LDA).</p> <p><b>Methods:</b> A systematic literature review (SLR) was conducted according to Cochrane collaboration guidelines. The population of interest was adult patients with RA in remission or LDA. The reported outcomes of interest were any symptoms or burdens.</p> <p><b>Results:</b> Fifty-one publications were identified through an eDatabase search. Together with 17 articles found through other sources, 68 were included for full text review. The most commonly reported residual symptoms were pain (number of studies = 25), fatigue (<i>n</i> = 21) and morning stiffness (<i>n</i> = 5). Reported disease burdens included mental health (<i>n</i> = 15), sleep disturbances (<i>n</i> = 7) and work productivity (<i>n</i> = 5), impairment in quality of life (<i>n</i> = 21), and functional disability (<i>n</i> = 34). Substantial residual symptoms and disease burdens were found to be present in patients in remission or LDA.</p> <p><b>Conclusion:</b> This is the first SLR to investigate residual symptoms and disease burdens in RA patients in remission or LDA. The results indicate that despite achieving conventional clinical targets, the disease continues to affect patients, suggesting the existence of unmet need under the current treatment paradigm.</p

Additional file 1: Figure S1. of A new bioassay for measuring the strength of IL-6/STAT3 signal inhibition by tocilizumab in patients with rheumatoid arthritis

Transition in CDAI for each group of patients administered TCZ at different intervals. Transition in CDAI for the 3-week group (A), 4-week group (B) and 5-week group (C). TCZ tocilizumab, CDAI clinical disease activity index. (TIF 1404 kb

Determinants of Patient’s Global Assessment of Disease Activity and Physician’s Global Assessment of Disease Activity in patients with rheumatoid arthritis: A <i>post hoc</i> analysis of overall and Japanese results from phase 3 clinical trials

<p><b>Objectives:</b> To assess the determinants of Patient’s Global Assessment of Disease Activity (PtGA) and Physician’s Global Assessment of Disease Activity (PhGA) in overall and Japanese patients with rheumatoid arthritis (RA) from two large randomized controlled trials.</p> <p><b>Methods:</b><i>Post hoc</i> analysis of overall and Japanese RA patients who had previous inadequate responses to methotrexate or who had no/minimal previous disease-modifying antirheumatic drug treatment. We examined correlations between PtGA/PhGA and tender joint count in 28 joints (TJC28), swollen joint count in 28 joints (SJC28), inflammatory markers, pain visual analog scale (VAS), and other patient-reported outcomes at baseline, Week 12, and Week 24. Determinants of PtGA/PhGA were identified.</p> <p><b>Results:</b> In overall populations, pain VAS was the main determinant of PtGA, whereas TJC28 was the main determinant of PhGA in both studies. In Japanese populations, consistent with overall populations, pain VAS was the main determinant of PtGA in both studies; in contrast to overall populations, pain VAS and SJC28/TJC28 played an important role in PhGA.</p> <p><b>Conclusion:</b> Pain was the most important determinant of PtGA, whereas determinants of PhGA varied between populations/studies and were mostly explained by pain/joint counts. Physicians should be aware of patients’ perceptions of disease activity when performing assessments/prescribing treatments.</p

Obstacles to the implementation of the treat-to-target strategy for rheumatoid arthritis in clinical practice in Japan

<p><i>Objective.</i> To clarify the obstacles preventing the implementation of the treat-to-target (T2T) strategy for rheumatoid arthritis (RA) in clinical practice.</p> <p><i>Methods.</i> A total of 301 rheumatologists in Japan completed a questionnaire. In the first section, participants were indirectly questioned on the implementation of basic components of T2T, and in the second section, participants were directly questioned on their level of agreement and application.</p> <p><i>Results.</i> Although nearly all participants set treatment targets for the majority of RA patients with moderate to high disease activity, the proportion who set clinical remission as their target was 59%, with only 45% of these using composite measures. The proportion of participants who monitored X-rays and Health Assessment Questionnaires for all their patients was 44% and 14%, respectively. The proportion of participants who did not discuss treatment strategies was 44%, with approximately half of these reasoning that this was due to a proportion of patients having a lack of understanding of the treatment strategy or inability to make decisions. When participants were directly questioned, there was a high level of agreement with the T2T recommendations.</p> <p><i>Conclusion</i>. Although there was a high level of agreement with the T2T recommendations, major obstacles preventing its full implementation still remain.</p

Risk of disease flares after SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus

This study aims to elucidate the effectiveness and safety of SARS-CoV-2 mRNA vaccination in patients with systemic lupus erythematosus (SLE). We enrolled uninfected SLE patients who received two vaccine doses (BNT162b2 or mRNA-1273) and historical unvaccinated patients. Neutralizing antibodies, adverse reactions, and disease flares were evaluated 4 weeks after the second vaccination. Ninety patients were enrolled in each group. Among the vaccinated patients, SLE Disease Activity Index (SLEDAI), and prednisolone doses before vaccination were 2, and 5 mg/d, respectively. After the second vaccination, 19 (21.1%) had no neutralizing antibodies. Adverse reactions occurred in 88.9% within 3 d. Negative antibodies were associated with anemia and mycophenolate mofetil administration. SLEDAI increased modestly but significantly after vaccination, with 13 (14.4%) experiencing flares and 4 (4.4%) severe flares (nephritis in three and vasculitis in one). The flare rate was higher in vaccinated patients than unvaccinated controls. The mean duration between the second vaccination and flares was 35 d, and flares occurred at least 8 days after vaccination. Multivariable analysis showed that high SLEDAI and anti-dsDNA antibodies were associated with flares. The vaccine type, neutralizing antibody titer, and adverse reaction frequency did not affect flares. Therefore, residual disease activity before vaccination increases flare risk.</p

Additional file 1: Figure S1. of Enhanced IgG4 production by follicular helper 2 T cells and the involvement of follicular helper 1 T cells in the pathogenesis of IgG4-related disease

Flow cytometric analysis of the percentage of circulating follicular helper T (Tfh) cells and activated Tfh cells. The percentage of Tfh cells (A) and activated Tfh cells (B) from patients with IgG4-related disease (IgG4-RD) (n = 17), primary Sjögren’s syndrome (pSS) (n = 20), multicentric Castleman’s disease (MCD) (n = 5), and healthy controls (HC) (n = 12). *P < 0.05; **P < 0.0001 for analysis using the Kruskal-Wallis test, followed by group-wise comparisons using the Mann-Whitney U test. (TIF 42 kb