Tumor Response Predicts Survival Time of Nivolumab Monotherapy for Advanced Gastric Cancer: A Subgroup Analysis of the DELIVER Trial (JACCRO GC-08).

BACKGROUND: This prospective observational study evaluated the real-world effectiveness of nivolumab monotherapy in previously treated advanced gastric cancer (GC). A preplanned 2-year final analysis was performed to confirm survival and tumor behavior with nivolumab monotherapy. PATIENTS AND METHODS: The primary endpoint was overall survival (OS). The data regarding tumor size were prospectively collected and evaluated using the RECIST criteria. Exploratory analyses were performed for survival according to the tumor response and depth of response (DpR) in patients with measurable lesions who were receiving nivolumab monotherapy as third- or later-line therapy. RESULTS: In 487 patients, the median OS and progression-free survival (PFS) were 5.8 (95% CI 5.3-6.9) months and 1.8 (95% CI 1.7-2.0) months, respectively. The response rate (RR) was 14.5% in 282 patients with measurable lesions. In 234 patients treated with third- or later-line, the DpR was found to be associated with PFS and OS in the Spearman analysis (r = 0.55 and 0.44, respectively) as well as using a discrete variable. When the DpR was divided into 5 groups (-20%≥DpR; -20%

Risk of flare and damage accrual after tapering glucocorticoids in modified serologically active clinically quiescent patients with systemic lupus erythematosus: a multinational observational cohort study.

OBJECTIVES: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE). METHODS: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred. RESULTS: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day. CONCLUSIONS: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients.

Impact of interstitial lung disease on clinical remission and unfavourable events of rheumatoid arthritis: results from the IORRA cohort.

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.

Long-term safety and efficacy of mogamulizumab (anti-CCR4) for treating virus-associated myelopathy.

Some carriers of human T-cell leukaemia virus type 1 (HTLV-1), a retrovirus that primarily infects CD4+ T cells and causes lifelong infection, develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Current treatments for HAM/TSP are insufficient with problematic long-term side effects. This study evaluated the long-term safety and efficacy of the anti-CCR4 antibody mogamulizumab in patients with HAM/TSP over a 4-year period. We conducted an open-label, extended long-term study (UMIN trial number: UMIN000019942) of a phase 1-2a trial with mogamulizumab for HAM/TSP (UMIN000012655). The study participants were patients with corticosteroid-resistant HAM/TSP who could walk 10 m with or without assistive tools. Mogamulizumab was administered at 0.01, 0.03, 0.1 or 0.3 mg/kg at intervals of ≥8 weeks (0.01 and 0.03 mg/kg) or ≥12 weeks (0.1 and 0.3 mg/kg). HTLV-1 proviral load, CSF inflammatory markers and clinical symptoms were summarized by descriptive statistics. Missing observations were imputed using the last-observation-carried-forward method. As a post hoc analysis, we evaluated the therapeutic effect of mogamulizumab on gait function by comparing it with contemporary control data from a HAM/TSP patient registry. Of the 21 participants in the phase 1-2a, 18 (86%) enrolled in the long-term study and 15 (71%) continued repeated doses of mogamulizumab for 4 years. The median dose was 0.1 mg/kg after 4 years. Seventeen of 21 participants (81%) experienced grade 1-2 skin-related adverse events. Observed grade 3 drug-related adverse effects included three cases of lymphopenia and one case each of microscopic polyangiitis, elevated levels of aspartate aminotransferase, and neutropenia. Four of 21 participants (19%) developed neutralizing antibodies. After 4 years, the peripheral blood proviral load and the number of infected cells in CSF decreased by 60.7% and 66.3%, respectively. Neopterin and CXCL10 CSF concentrations decreased by 37.0% and 31.0%, respectively. Among the 18 participants, spasticity and Osame Motor Disability Score (OMDS) improved in 17 (94%) and four (22%), respectively. However, 10 m walking time worsened by 7.3% on average. Comparison with the contemporary control group demonstrated that mogamulizumab inhibited OMDS progression (P = 0.02). The results of the study suggest that mogamulizumab has long-term safety and inhibitory effects on lower limb motor disability progression in corticosteroid-treated patients with HAM/TSP. This will provide a basis for the application of mogamulizumab in HAM/TSP treatment.

Self-controlled Case Series Study for Acute Kidney Injury after Starting Proton Pump Inhibitors or Potassium-Competitive Acid Blocker in Patients with Cancer Using a Large Claims Database.

To investigate the risk of acute kidney injury (AKI) in patients with cancer following the initiation of proton pump inhibitors (PPIs) and potassium-competitive acid blocker (PCAB), considering sex and anti-cancer drug use. We conducted a self-controlled case-series study using the Japan Medical Data Center claims data from 12422 patients with cancer who were prescribed PPIs or PCAB between January 2017 and December 2019. Considering the timing of PPI or PCAB, control period (days -120 to -1), risk period 1 (days 0 to +30), and risk period 2 (days +31 to +365) were defined. To assess the incidence rate ratio (IRR) and 95% confidence interval (CI) as the risk ratio, we adjusted for anti-cancer drugs to assess the risk of AKI. Additionally, we also examined sex differences to identify the risk of AKI. AKI was observed in risk period 1 [2.05 (1.12-3.72), p = 0.0192], but a slight reduction was noted in risk period 2 [0.60 (0.36-1.00), p = 0.0481]. A sex-specific increase in the risk of AKI was observed only in males during risk period 1 [2.18 (1.10-4.32), p = 0.0260], with a reduction in risk period 2 [0.48 (0.26-0.89), p = 0.0200]. We identified an increased risk of AKI in patients with cancer starting PPIs or PCAB particularly in males within 30 d after PPI or PCAB initiation, emphasizing the need for vigilant monitoring and management of AKI in this patient population.

Delayed global standardization and prefectural disparities in systematic lupus erythematosus treatment in Japan: a nationwide study using the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

OBJECTIVES: To evaluate the status of the global standardization of, and prefectural differences in, systematic lupus erythematosus (SLE) treatments in Japan. METHODS: The Japanese National Database of Health Insurance Claims and Specific Health Checkups (NDB Japan) was used. A patient with SLE was defined as having a disease with ICD10 code M321 or M329 between April 2019 and March 2020, for which oral corticosteroids (OCS), immunosuppressive agents or biologic agents were prescribed at least once during a given month. SLE treatments were evaluated by treatment center type and prefecture. RESULTS: In total, 74,277 patients met the definition of SLE. The SLE prevalence was 60 per 100,000 (range: 47 - 102 per 100,000 by prefecture). Nationwide, 79.4% of the patients (range: 52.1% - 93.3% by prefecture) visited a specialized treatment center (STC); 37.4% (range: 26.4% - 51.3% by prefecture) received only OCS, with fewer of these patients visiting a STC than a non-STC (34.8% and 49.7%, p<0.001); and 21.4% (range: 10.7% - 35.0%) received HCQ, with more of these patients visiting a STC than a non-STC (23.0% and 13.5%; p<0.001). CONCLUSIONS: NDB Japan demonstrated delayed global standardization of, and prefectural disparity in, SLE treatments in Japan.

Intravenous immunoglobulin treatment for obstetric antiphospholipid syndrome refractory to conventional therapy: A single-arm, open-labelled multicentre clinical trial.

OBJECTIVES: The objective of the study was to compare the efficacy of intravenous immunoglobulin (IVIG) therapy for obstetric antiphospholipid syndrome (APS) refractory to conventional treatment. METHODS: We conducted a single-arm, open-label multicentre clinical intervention trial. The enrolled criteria were patients with refractory APS who had a history of still or premature birth before 30 weeks of gestational age, even though they had been treated with conventional treatment, i.e. heparin and low-dose aspirin. After confirming the foetal heartbeats, a single course of IVIG (0.4 g/kg body weight daily for 5 days) was added to conventional treatment. The primary outcome was a live birth ratio of >30 weeks of gestational period, and the secondary outcome included improving pregnancy outcomes compared to previous pregnancy. RESULTS: Twenty-five per cent of patients (2 of 8 cases) achieved a live birth after the 30th week of pregnancy by IVIG-only add-on treatment, which is the same prevalence as the historical control. However, by adding other second-line therapy to IVIG and conventional treatment, further three patients (37.5%) achieved improvements in pregnancy outcome compared to previous treatments. In total, five patients (62.5%) were able to achieve preferable pregnancy outcomes through combination treatment including IVIG. CONCLUSIONS: This clinical trial could not demonstrate the efficacy of IVIG-only add-on therapy at improving the pregnancy outcomes of patients with obstetric APS refractory to conventional treatment. However, the combination of IVIG with rituximab or statins adding to conventional treatment improved pregnancy outcomes and resulted in more live births. Further studies are needed to investigate the efficacy of multi-targeted therapy to treat obstetric refractory APS.

Nationwide epidemiological survey of juvenile idiopathic arthritis during transition to young adulthood in Japan using the National Database of Designated Incurable Diseases of Japan.

Objectives We aimed to assess the unmet medical needs of young adult patients with juvenile idiopathic arthritis by evaluating real-world treatment data. Methods We analyzed data on juvenile idiopathic arthritis in the 20-29 age group from the National Database of Designated Incurable Diseases of Japan, which records severe cases or those requiring high-cost medical care registered between April 2018 and March 2020. Results Overall, 322 patients with juvenile idiopathic arthritis transitioning to adulthood were included. A high frequency of methotrexate use was observed among all juvenile idiopathic arthritis subtypes. The frequency of methotrexate use at registration was significantly higher in patients with rheumatoid factor-positive polyarthritis and those with oligoarthritis or polyarthritis than in those with systemic arthritis. The historical use percentage of any biological disease-modifying antirheumatic drug was ≥85% for all juvenile idiopathic arthritis subtypes. The proportion of patients with ≥2 biological disease-modifying antirheumatic drug prescriptions was significantly higher in patients with rheumatoid factor-positive polyarthritis than in those with systemic arthritis. Conclusions High-cost drugs were necessary for many patients with juvenile idiopathic arthritis transitioning to young adulthood and registered in the database. Further studies on the medical interventions and support for these patients are needed.

Unincreased mortality of patients with early rheumatoid arthritis compared to the general population in the past 17 years: Analyses from the IORRA cohort.

OBJECTIVES: The aim of this article is to investigate the mortality rate of patients with early rheumatoid arthritis (RA) over the past 17 years. METHODS: Japanese patients with early RA enrolled in the Institute of Rheumatology, Rheumatoid Arthritis cohort from 2001 to 2012 were classified into Groups A (2001-06) and B (2007-12). The standardized mortality ratio (SMR) and 5-year survival rate were calculated. RESULTS: Groups A and B had 1609 and 1608 patients, of which 167 and 178 patients were lost during follow-up and 47 and 45 deaths were confirmed, respectively. The SMR (95% confidence intervals) for Groups A and B were 0.81 (0.59-1.08) and 0.78 (0.57-1.04), respectively, with the condition that all untraceable patients were alive. Assuming that the mortality rate of untraceable patients was twice as high as that of the general population, the SMR was 0.90 (0.68-1.19) for Group A and 0.92 (0.68-1.23) for Group B. The 5-year survival rates were 96.9% and 97.0% for Groups A and B, respectively. CONCLUSIONS: The 5-year mortality of patients with early RA has been comparable to that of the general Japanese population. The 5-year survival rate has been stable over the past 17 years.

Factors contributing to the improvement in J-HAQ after 3 years of treatment with abatacept in biologic-naïve rheumatoid arthritis patients: Interim results of a long-term, observational, multicentre study in Japan (ORIGAMI).

OBJECTIVES: We investigated the long-term effectiveness, safety, and factors affecting Japanese Health Assessment Questionnaire (J-HAQ) improvement during abatacept treatment in Japanese rheumatoid arthritis (RA) patients. METHODS: The ORIGAMI study is an ongoing observational study of biologic-naïve RA patients with moderate disease activity treated with subcutaneous abatacept (125 mg, once-weekly). Patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) were extracted from the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry as an historical, weighted control group. The primary endpoint for this interim analysis was the proportion of patients with J-HAQ remission (score ≤0.5) at 3 years. RESULTS: Among 279 abatacept-treated and 220 csDMARD-treated patients, J-HAQ remission was achieved at 3 years in 40.5% (95% confidence interval [CI] 34.7%-46.2%) and 28.9% (95% CI 9.9%-47.8%), respectively. Age, RA duration <1 year, baseline J-HAQ score, and Simplified Disease Activity Index remission at 6 months were associated with 3-year J-HAQ remission in the abatacept group. Overall, 24/298 patients (8.1%; safety analysis set) experienced serious adverse drug reactions with an incidence of 5.3 per 100 person-years. CONCLUSIONS: This study confirmed the 3-year effectiveness and safety, and revealed potential factors associated with J-HAQ remission in biologic-naïve RA patients treated with abatacept in real-world clinical practice.

Associations of disease duration and anti-citrullinated peptide antibody status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis: Post hoc analysis of a multicentre, real-world observational study in Japan (ORIGAMI).

OBJECTIVES: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA). METHODS: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both. RESULTS: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models. CONCLUSIONS: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity.

The BEETS (JACCRO CC-18) trial: an observational and translational study of BRAF-mutated metastatic colorectal cancer.

For BRAF V600E-mutated metastatic colorectal cancer (mCRC), the BEACON phase 3 trial showed survival benefit of triplet therapy with cetuximab (anti-EGFR antibody), encorafenib (BRAF inhibitor) and binimetinib (MEK inhibitor) as well as doublet therapy with cetuximab and encorafenib over irinotecan-based chemotherapy plus anti-EGFR antibody. Both regimens are standards of care in Japan, but definite biomarkers for predicting efficacy and selecting treatment remain lacking. The mechanisms underlying resistance to these regimens also warrant urgent exploration to further evolve treatment. This prospective observational/translational study evaluated real-word clinical outcomes with cetuximab and encorafenib with or without binimetinib for BRAF-mutated mCRC patients and investigated biomarkers for response and resistance by collecting blood samples before and after treatment. Clinical Trial Registration: UMIN000045530 (https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000051983).

The BEETS trial is a study that looks at how well two combinations of targeted therapies (cetuximab + encorafenib with or without binimetinib) work and how safe they are for patients with advanced colorectal cancer that has a mutation (change) in the BRAF gene. In this trial, patients participate voluntarily instead of being assigned to one of the two therapy groups. When a patient has BRAF-mutated advanced colorectal cancer, it means that the cancer cells in their body have changes in a gene called BRAF. This gene normally produces a protein called BRAF, which is involved in the growth of cells. However, when there is a mutation in this gene, it can cause the production of an overactive BRAF protein, leading to fast and excessive cell growth and division. For patients with BRAF-mutated advanced colorectal cancer, combinations of targeted therapies have been found to be effective as a second- or third-line treatment, based on the results of a phase 3 clinical trial. The main goal of the BEETS trial is to evaluate how well these treatments work and how safe they are when used in real-world clinical practice. Additionally, the study will use laboratory tests (liquid biopsy) to explore new biomarkers that can help predict how well a treatment will work and assist in selecting the most suitable treatment plans. We hope that the findings of this study will contribute to improving the overall management of this specific type of cancer.

Survival analysis among pediatric patients receiving kidney replacement therapy: a Japanese nationwide cohort study.

BACKGROUND: Limited data are available on the survival and causes of death in pediatric patients with chronic kidney disease (CKD) stage 5 receiving kidney replacement therapy (KRT) in Asia. METHODS: Data were obtained from the Japanese nationwide cross-sectional CKD stage 5 survey on pediatric patients (<20 years of age) who started KRT from 2006 to 2013. The cohort was divided into three groups according to age at the start of KRT: <1, 1-5, and 6-19 years. RESULTS: Among the 701 children who were included, 59.3% were boys. Peritoneal dialysis was the most common initial modality of KRT (60.3%). Median age at KRT initiation was 10.2 years. Infants (<1 year old) accounted for 16.0% of the total cohort. Overall survival at 1 and 5 years was 97.2% and 92.5%, respectively. Infants had significantly lower survival rates than the other groups (hazard ratio, 5.35; 95% CI, 2.60-11.03; P < 0.001). In contrast, after the age of 1 year, the survival rate improved and did not differ from that of other age groups. The most common causes of death were infection (35.9%) and sudden death (15.4%). CONCLUSIONS: The overall survival rate of pediatric patients with CKD stage 5 in Japan is like that in other high-income countries. Age at initiation of KRT is an important factor affecting survival since the poorest survival rate was observed in infants. Further improvement in infant dialysis therapy is still needed to improve survival of the youngest children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Depression and health-related quality of life in adolescents and young adults with childhood-onset end-stage kidney disease: a multicenter study in Japan.

BACKGROUND: Patient survival and physical outcomes among children with end-stage kidney disease (ESKD) have significantly improved, and recent research has focused on long-term depression symptoms and health-related quality of life (HRQOL). However, no studies have been conducted among adolescents and young adults with childhood-onset ESKD in Japan. METHODS: This multicenter study included 45 adolescents and young adults aged 16-39 years who developed ESKD at age < 20 years. Depression symptoms were measured using the Beck Depression Inventory (BDI)-II. The Short Form-36 Health Survey (SF-36) was used to assess HRQOL. Factors associated with depression and HRQOL were analyzed. RESULTS: Depression (BDI-II score ≥ 14) was observed in 13 (29%) patients. Patient's SF-36 physical component summary (PCS) and mental component summary (MCS) scores were comparable with those for the general population. Lower estimated glomerular filtration rate, higher BDI-II scores, and lower body mass index were associated with lower PCS scores. BDI-II scores were negatively correlated with MCS scores. We observed a trend that unemployment was associated with lower MCS scores. CONCLUSIONS: Depression is frequently observed among adolescents and young adults with childhood-onset ESKD. Regular screening for psychosocial concerns, maintaining stable graft functions, and achieving optimal nutritional status may contribute to improved well-being among these patients.

Mortality and risk of progression to adult T cell leukemia/lymphoma in HTLV-1-associated myelopathy/tropical spastic paraparesis.

Human T cell leukemia virus 1 (HTLV-1) causes the functionally debilitating disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) as well as adult T cell leukemia lymphoma (ATLL). Although there were concerns that the mortality of HAM/TSP could be affected by the development of ATLL, prospective evidence was lacking in this area. In this 5-y prospective cohort study, we determined the mortality, prevalence, and incidence of ATLL in 527 HAM/TSP patients. The standard mortality ratio of HAM/TSP patients was 2.25, and ATLL was one of the major causes of death (5/33 deaths). ATLL prevalence and incidence in these patients were 3.0% and 3.81 per 1,000 person-y, respectively. To identify patients at a high risk of developing ATLL, flow cytometry, Southern blotting, and targeted sequencing data were analyzed in a separate cohort of 218 HAM/TSP patients. In 17% of the HAM/TSP patients, we identified an increase in T cells positive for cell adhesion molecule 1 (CADM1), a marker for ATLL and HTLV-1-infected cells. Genomic analysis revealed that somatic mutations of HTLV-1-infected cells were seen in 90% of these cases and 11% of them had dominant clone and developed ATLL in the longitudinal observation. In this study, we were able to demonstrate the increased mortality in patients with HAM/TSP and a significant effect of ATLL on their prognosis. Having dominant clonal expansion of HTLV-1-infected cells with ATLL-associated somatic mutations may be important characteristics of patients with HAM/TSP who are at an increased risk of developing ATLL.

Randomized trial of advice from healthcare professionals to eliminate constriction by maternal clothing on the trunk to prevent preterm birth and improve health status.

AIM: Women's clothing during pregnancy may influence perinatal outcomes. A preliminary study suggested that midwives' advice to avoid wearing tight clothing during pregnancy may reduce the risk of preterm delivery. We examined the effects of such advice to pregnant women on the risk of preterm birth and health status during pregnancy. METHODS: An open-label evaluator-blinded randomized controlled trial was conducted at the National Centre for Child Health and Development in Tokyo, Japan. Normal pregnant women were randomly assigned to receive constrictive clothing elimination care or standard care at 20 weeks gestation. The control group was issued leaflets concerning anemia prevention at entry and skin care at 30 weeks' gestation, along with a brief explanation and answers to questions by midwives as standard care. The intervention group received advice from midwives concerning avoiding constrictive clothing in addition to standard care. The primary outcome was the incidence of preterm birth (<37 weeks). The secondary outcomes were 12 indicators related to preterm delivery or health status. RESULTS: Among 624 randomly assigned women, 599 (intervention group, n = 306; control group, n = 293) completed the study between February 2015 and August 2016. The incidence of preterm birth in the intervention and control groups was 4.2% (13/306) and 5.1% (15/293), respectively (p = 0.614). There were no significant differences regarding any secondary outcomes, including obstetric outcomes and physical/mental indicators, during pregnancy. CONCLUSIONS: Advice from midwives to avoid constrictive clothing during pregnancy did not influence the incidence of preterm birth or maternal health status. TRIAL REGISTRATION: UMIN000016853 (March 30, 2015).

Association of disease activity using SDAI and DAS28, but not JADAS-27, with subsequent changes in physical function in adult patients with juvenile idiopathic arthritis.

OBJECTIVES: To investigate an optimal composite score for disease activity in adult JIA from the viewpoint of the subsequent changes in physical function. METHODS: Patients with JIA under the following conditions were enrolled: 1) disease onset < 18 years; 2) registered in the database by Tokyo Women's Medical University for the first time between 2000 and 2020; and 3) ≥18 years old at the time of registration. Patients were stratified according to mean disease activity scores in SDAI, DAS28, and JADAS-27 during the first year from baseline. Trends of estimated mean change in Japanese-HAQ score (ΔJ-HAQ) from baseline to 2 years later was examined across the stratified groups of each index. RESULTS: We included 294 eligible individuals (median age at onset, 14.0 years; RF positive in 64.7%). A significant increasing trend of the estimated mean ΔJ-HAQ at 2 years after baseline was observed along with an increase in the mean disease activity during the first year measured using DAS28 (p = 0.01) and SDAI (p = 0.018), but not using JADAS-27. CONCLUSIONS: Disease activity measured using SDAI and DAS28, but not using JADAS27, was significantly associated with subsequent changes in physical function in adult patients with JIA.

Surgical intervention for patients with rheumatoid arthritis is declining except for foot and ankle surgery: A single-centre, 20-year observational cohort study.

OBJECTIVES: A global downward trend in the number of rheumatoid arthritis (RA)-related surgeries has been reported. The purpose of our study was to investigate the latest trends in RA-related surgeries in a single-centre Japanese RA cohort. METHODS: This study was a retrospective analysis of RA-related surgeries between 2001 and 2020 in the Institute of Rheumatology Rheumatoid Arthritis cohort. An average of 4944 patients per semi-annual survey was included in the study. The primary goal was to analyse the half-year period prevalence proportion (HPP) of RA-related surgeries in a 20-year period, and the secondary goal was to analyse the HPP of surgeries by site or by categories of disease activity. RESULTS: There has been a downward trend in the HPP of RA-related surgeries in the 20-year study period. The total HPP of RA-related surgeries decreased by 50.3% during the 20-year study period. There was a significant decrease in knee, hip, shoulder/elbow, and hand procedures. Only foot/ankle joint surgeries significantly increased in volume during this period (p = .001). The HPP of RA-related surgeries remained unchanged in patients with remission or low disease activity. CONCLUSIONS: The number of RA-related surgeries decreased over a 20-year period, but foot/ankle joint surgeries increased in the site-specific evaluation.

Subjective symptoms contributing to the quality of life of rheumatoid arthritis patients with clinical remission from the IORRA database.

OBJECTIVES: To explore patient-reported outcomes (PROs) related to quality of life (QOL) in patients with rheumatoid arthritis (RA) who achieved clinical remission. METHODS: In the Institute of Rheumatology, Rheumatoid Arthritis dataset, RA patients >18 years old who met the simplified disease activity index (SDAI) remission criteria in April 2017 were enrolled in this analysis. Pain-visual analogue scale (pain-VAS) (0-100 mm), patient's global assessment of disease activity (Pt-GA; 0-100 mm), Japanese version of the Health Assessment Questionnaire, duration of morning joint stiffness, and fatigue [Checklist Individual Strength 8R (CIS)] were the tools used to evaluate PROs. To assess the contribution of each PRO to the European QOL-5 Dimensions-5 Level (EQ-5D-5L) score, an analysis of variance was conducted. RESULTS: Among the 2443 patients with remission, the mean EQ-5D-5L was 0.9. The mean pain-VAS and Pt-GA were 7.2 and 7.4, respectively. Factors that significantly contributed to the EQ-5D-5L were pain-VAS (48.8%), CIS score (18.1%), and Pt-GA (15.6%). Around 82.5% of the variance in EQ-5D-5L was explained by the three PROs. CONCLUSIONS: This study demonstrated that pain-VAS, CIS, and Pt-GA were significant contributors to the EQ-5D-5L score in patients with RA who achieved the simplified disease activity index remission criteria.

Association between patient-reported outcomes and impairments in work and activity in patients with rheumatoid arthritis in clinical remission: A retrospective analysis using the IORRA database.

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 ≥18 years 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 62.4 years; 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.