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Objectives: To update an evidence base informing the 2024 Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA) in older adults. Methods: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs, CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results: Observational studies confirmed a pivotal role of methotrexate in the treatment of older RA patients. The meta-analysis showed that tumour necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that biological disease-modifying antirheumatic drugs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs. Conclusions: This systematic review provides the necessary evidence for developing 2024 Japan College of Rheumatology clinical practice guidelines for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired. [ABSTRACT FROM AUTHOR]

The article "Prevalence of high and low serum alkaline phosphatase levels and the associated factors in patients with rheumatoid arthritis: Results from the IORRA cohort study" published in Modern Rheumatology in 2024 discusses the prevalence of high and low serum alkaline phosphatase (ALP) levels in Japanese patients with rheumatoid arthritis (RA). The study found that 7.9% of patients had high ALP levels and 1.3% had low ALP levels. Factors associated with ALP levels included age, disease activity, serum AST levels, active vitamin D3 use, and antiresorptive agent use. The study highlights the importance of monitoring ALP levels in RA patients and the potential impact of medications on ALP levels. [Extracted from the article]

Objectives: Late-onset rheumatoid arthritis (LORA), which has been increasing in recent years, lacks evidence for initial treatment. Japanese rheumatology experts recognized this gap and addressed it by developing consensus statements on the first clinical application of LORA. Methods: These statements were created following an introductory discussion about treatment fundamentals, which included a review of existing literature and cohort data. The steering committee created a draft, which was refined using a modified Delphi method that involved panel members reaching a consensus. The panel made decisions based on input from geriatric experts, clinical epidemiologists, guideline developers, patient groups, and the LORA Research Subcommittee of the Japan College of Rheumatology. Results: The consensus identified four established facts, three basic approaches, and six expert opinions for managing LORA. Methotrexate was recommended as the primary treatment, with molecular-targeted agents being considered if treatment goals cannot be achieved. An emphasis was placed on assessing the lives of older patients due to challenges in risk management and methotrexate accessibility caused by comorbidities or cognitive decline. Conclusions: The experts substantiated and refined 13 statements for the initial treatment of LORA. To validate these claims, the next is to conduct a registry study focusing on new LORA cases. [ABSTRACT FROM AUTHOR]

Objectives We aimed to examine the impact of concomitant interstitial lung disease (ILD) on achieving clinical remission and the occurrence of unfavourable clinical events in patients with RA. Methods Among the participants in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort from 2011 to 2012, patients not achieving remission of 28-joint disease activity score (DAS28) at baseline and those with chest CT images were enrolled. Based on the chest CT images, the patients were divided into two groups: the ILD group and non-ILD group. The associations among the presence of ILD with time to achieving DAS28 remission and development of death, hospitalized infection, major adverse cardiac events (MACE), or malignancy within 5 years were evaluated using time-dependent Cox regression models. Results We enrolled 287 patients in the ILD group and 1235 in the non-ILD group. DAS28 remission was achieved at least once in 55.7% and 75.0% of the ILD and non-ILD groups within 5 years, respectively. Presence of ILD was significantly associated with failure to achieve DAS28 remission (adjusted hazard ratio [aHR]: 0.71; 95% CI: 0.58, 0.89). ILD was also a significant factor associated with death (aHR: 3.24; 95% CI: 2.08, 5.03), hospitalized infection (aHR 2.60; 95% CI: 1.77, 3.83), MACE (aHR: 3.40; 95% CI: 1.76, 6.58), and lung cancer (aHR: 16.0; 95% CI: 3.22, 79.2), but not with malignant lymphoma (aHR: 2.27; 95% CI: 0.59, 8.81). Conclusion Concomitant ILD was a significant factor associated with failure to achieve clinical remission and the occurrence of the unfavourable clinical events in patients with RA. [ABSTRACT FROM AUTHOR]

Objectives: To explore the patient-reported outcomes (PROs) associated with work productivity and activity impairment (WPAI) in patients with rheumatoid arthritis (RA) in clinical remission. Methods: We enrolled patients with RA ≥18years and with a simplified disease activity index ≤3.3 from the Institute of Rheumatology, Rheumatoid Arthritis data set collected in October 2017. The pain-visual analogue scale, patients' global assessment visual analogue scale (VAS), Japanese version of the Healthcare Assessment Questionnaire (J-HAQ) Disability Index, and duration of morning joint stiffness were selected as the PROs. To evaluate work productivity and activity, the WPAI for RA instrument (WPAI-RA) was used. To assess the contribution of each PRO to the WPAI-RA score, an analysis of variance model was constructed. Results: The mean age of the 2614 patients was 62.4years; 85.1 % were female. Median values of the WPAI-RA score were 1.1 % for absenteeism, 6.5% for presenteeism, 7.4% for work impairment, and 10.2% for activity impairment. Morning joint stiffness contributed the most to absenteeism (18.0%), while pain-VAS contributed the most to presenteeism (57.4%), work productivity loss (51.1 %), and daily activity impairment (53.7%). J-HAQ was the second most contributing factor to presenteeism (17.4%), work productivity loss (16.3%), and daily activity impairment (26.0%). Conclusions: The pain-VAS and J-HAQ highly contributed to WPAI in patients with RA in clinical remission. [ABSTRACT FROM AUTHOR]

Objectives: The aim is to investigate the trends in risks of overall and site-specific malignancies in patients with rheumatoid arthritis (RA). Methods: Among Japanese patients with RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort, all malignancies that occurred from 2000 to 2013 were extracted. The standardized incidence ratios and 95% confidence intervals for overall and site-specific malignancies were calculated during three periods: pre-biologics, 2000-04; early biologics, 2005-09; and recent biologics, 2010-13. Risk factors for overall and specific malignancies were analysed using time-dependent Cox regression models. Results: Among 11,299 patients with RA (68,483 person-years), 507 malignancies were confirmed. Similar risks were observed versus the general Japanese population for overall malignancies throughout the three periods, with standardized incidence ratios (95% confidence intervals) of 0.96 (0.80-1.14) in the pre-biologics period, 0.95 (0.82-1.09) in the early biologics period, and 0.87 (0.75-1.01) in the recent biologics period. A significantly increased risk for malignant lymphoma was observed throughout the observation period (standardized incidence ratio 4.61, 95% confidence interval 3.58-5.85). The disease activity was a significant risk factor for overall malignancies and lung cancer. Conclusions: Despite the expanding use of methotrexate and biologics, there were no increases in malignancy risk in Japanese patients with RA. [ABSTRACT FROM AUTHOR]

Objectives To construct a predictive model for the Sharp/van der Heijde score (SHS) and assess its applicability in clinical research settings. Material and methods A prediction model for SHS was constructed in three steps using convolutional neural networks (CNN) and an in-house RA image database: orientation, detection and damage prediction. A predictive model for radiographic progression (ΔSHS >3/year) was developed using a graph convolutional network (GCN). A multiple regression model was used to assess the association between predicted SHS using the CNN model and clinical features. Results In the orientation and detection phases, 100% accuracy was achieved in the image orientation correction, and all predicted joint coordinates were within 10 pixels of the correct coordinates. In the damage prediction phase, the κ values between the model and expert 1 were 0.879 and 0.865 for erosion and joint space narrowing, respectively. Using a dataset scored by experts 1 and 2, a minimal overfitting was determined to the scoring by expert 1. High-titre RF was an independent risk factor of Δ SHS per year, as predicted by the CNN model in biologics users. The AUCs of the GCN model for predicting ΔSHS >3/year in patients with and without biologics at baseline were 0.753 and 0.734, respectively, superior to those of the other models. The RF titre was the most important feature in predicting ΔSHS >3/year in biologics users in the GCN model. Conclusion A high-performance scoring model for SHS that is applicable to clinical research was constructed. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the cost-effectiveness of abatacept (ABA) as first-line (1L) therapy in Japanese rheumatoid arthritis (RA) patients using data from the Institute of Rheumatology, Rheumatoid Arthritis database. Methods: A decision-analytic model was used to estimate the cost per American College of Rheumatology response of at least 50% improvement (ACR50) responder and per patient in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) remission from a Japanese healthcare payers' perspective over a 2-year time horizon. Clinical characteristics of patients on ABA-1L were matched with those of patients on ABA second or later line (2L+) or tumour necrosis factor inhibitor (TNFi)-1L directly or using propensity scores. Resource utilisation and medical costs were calculated from the Japan Medical Data Center claims database. Parameter uncertainty was addressed by sensitivity and subgroup analyses (age, treatment duration, Japanese version of Health Assessment Questionnaire [J-HAQ] score). Results: Incremental costs per member per month (ΔPMPM) for ABA-1L versus TNFi-1L and ABA-2L+ were -1,571 Japanese Yen (JPY) and 81 JPY, respectively. For ABA-1L versus TNFi-1L, ΔPMPM by ACR50 response was -11,715 JPY and by CDAI and SDAI remission 11,602 JPY and 47,003 JPY, respectively. Corresponding costs for ABA-1L were lower for all outcome parameters versus those for ABA-2L+. Scenario analyses showed that ABA-1L was cost-effective over TNFi-1L in patients <65 years for any outcome. Furthermore, ABA-1L was cost-effective over ABA-2L+ for all outcomes in patients with age <65 years, disease duration <5 years and J-HAQ ≥1.5. Conclusions: ABA-1L demonstrated a favourable cost-effectiveness profile in RA patients, accruing savings for the Japanese healthcare payers. [ABSTRACT FROM AUTHOR]