Yasumori Sobue’s research while affiliated with Nagoya Memorial Hospital and other places

Aim To compare the clinical effectiveness of baricitinib and filgotinib in the treatment of rheumatoid arthritis (RA). Methods This retrospective study included 101 and 103 consecutive patients treated with baricitinib and filgotinib, respectively, between 2020 and 2023. Drug retention was analyzed using Kaplan–Meier curves, with the log‐rank test for between‐group comparisons. Differences in Clinical Disease Activity Index (CDAI) score from baseline were assessed using paired t ‐tests, and generalized estimating equations were used to compare the treatment groups. Results Baseline characteristics were similar between the baricitinib and filgotinib groups. Drug retention rates due to ineffectiveness or adverse events did not differ significantly between the two groups. In the baricitinib group, the estimated mean CDAI score significantly decreased from 17.8 at baseline to 9.1 at 4 weeks, 6.6 at 12 weeks, and 6.3 at 24 weeks ( p < 0.001 for all comparisons). In the filgotinib group, the estimated mean CDAI score significantly decreased from 16.5 at baseline to 7.8 at 4 weeks, 6.2 at 12 weeks, and 6.1 at 24 weeks ( p < 0.001 for all comparisons). No significant differences were observed between the two groups in CDAI score at any time point evaluated, or in the proportion of patients who achieved CDAI remission (CDAI ≤ 2.8) at baseline (7% vs. 5%) and after 4 (23% vs. 21%), 12 (33% vs. 33%), and 24 weeks (33% vs. 37%). Conclusion Baricitinib and filgotinib demonstrated comparable drug retention rates and effectiveness in reducing disease activity among patients with RA over a 24‐week follow‐up period.

Objectives To examine risk factors for non‐frailty rheumatoid arthritis (RA) patients progressing to frailty. Methods A total of 304 RA patients with records for frailty assessment based on the Japanese Cardiovascular Health Study (J‐CHS) criteria from 2020 to 2024 were included. Patients classified as non‐frail (J‐CHS scores 0–3) in 2020 were followed annually, and those who did and did not progress to frailty were categorized into the frailty progression (n = 100) and non‐frailty progression (n = 204) groups, respectively. Risk factors for frailty progression were analyzed using the Cox proportional hazards model. Changes in DAS28‐ESR and HAQ‐DI between baseline and frailty progression were compared using a paired t‐test. Results Compared to the non‐frailty progression group, the frailty progression group was older (62.9 vs. 68.5 years) and had a longer duration of disease (9.1 vs. 14.2 years), lower methotrexate (MTX) use (74.4% vs. 56.1%), higher mean DAS28‐ESR (2.40 vs. 2.77), and higher HAQ‐DI (0.17 vs. 0.45). Both groups had high biological/targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs) use rates (34.3% vs. 42.0%). Risk factors for frailty events included age ≥ 65 years (HR 1.86), duration of disease ≥ 10 years (HR 1.64), DAS28‐ESR < 2.6 (HR 0.64), HAQ‐DI ≤ 0.5 (HR 0.45), and MTX use (HR 0.63). DAS28‐ESR remained at a low disease activity level (baseline vs. frailty progression: 2.77 vs. 2.90), whereas HAQ‐DI worsened at frailty progression compared to baseline (0.45 vs. 0.66). Conclusions Optimizing MTX use and achieving DAS/HAQ remission are crucial for preventing frailty. Non‐medication‐based approaches are also essential.

Objective The present non-inferiority study was designed to compare the effect of discontinuing versus continuing methotrexate (MTX) alongside certolizumab pegol (CZP) on maintaining low disease activity (LDA) in rheumatoid arthritis (RA) patients already stable on combination therapy. Methods This multicentre, open-label, randomised, controlled trial included RA patients with sustained LDA (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with CZP + MTX. Patients were randomised 1:1 by computer to either continue MTX (CZP + MTX group) or discontinue MTX after a 12-week reduction period (CZP group) using a dynamic allocation strategy with the minimisation method. The primary endpoint was the proportion of patients maintaining LDA without a flare (i.e., a CDAI score > 10 or intervention with rescue treatments for any reason) at week 36 (24 weeks after MTX discontinuation). Non-inferiority is verified if the lower limit of the 90% confidence interval (CI) using normal approximation for the difference in the proportion of cases that maintained LDA at week 36 between the intervention group and control group exceeds the non-inferiority margin. Results All 84 screened patients were randomised to the CZP + MTX group (n = 41) and CZP group (n = 43), and were included in the efficacy analysis. Proportions (90% CI) of patients who maintained LDA at week 36 were 85.4% (76.3 to 94.4%) in the CZP + MTX group and 83.7% (74.5 to 93.0%) in the CZP group. The difference (90% CI) between the two groups was − 1.6% (-14.6 to 11.3%), with the lower limit of the 90% CI exceeding the non-inferiority margin of -18%. Reported adverse events were broadly similar between the two groups. The proportion of patients with gastrointestinal symptoms, as assessed by a self-administered questionnaire, was significantly lower in the CZP group than in the CZP + MTX group at week 36 (2.4% vs. 15.8%, P = 0.034). Conclusion Discontinuing concomitant MTX in RA patients on CZP is clinically feasible for maintaining LDA. Trial registration Japan Registry of Clinical Trials (jRCTs041200048).

Objectives: This study aims to investigate the association between frailty and oral function in rheumatoid arthritis (RA) patients and to identify practical markers for early frailty detection and potential intervention strategies. Patients and methods: A multi-center observational cohort study (T-FLAG) included a total of 661 RA patients (475 males, 186 females; mean age: 68.5±13.5 years; range, 18 to 100 years) between June 2023 and August 2023. Frailty was assessed using the Kihon Checklist (KCL) (frailty: score ≥8). Oral function scores were based on Question 13 (“difficulty eating hard foods”), Question 14 (“choking”), and Question 15 (“dry mouth”) of the KCL. Receiver operating characteristic (ROC) curves were generated to assess the association between frailty and oral function scores. Multivariate logistic regression was used to analyze factors associated with oral function. Results: Among the 661 participants, 39.5% were frail. Frailty rates tended to increase with increasing oral function scores. The optimal cut-off score for oral function corresponding to frailty was 2 points, with a specificity of 89.2% and a sensitivity of 54.8%. Multivariate analysis identified age and Health Assessment Questionnaire-Disability Index (HAQ-DI) as significant factors associated with oral function decline (i.e., a total score of ≥2 for Questions 13-15 of the KCL). Conclusion: Frailty is strongly associated with oral function decline in RA patients. This finding highlights the importance of monitoring the oral function of RA patients, since it not only reflects physical function, but also serves as a potential marker of frailty. Targeted interventions to improve oral function may play a vital role in reducing frailty risk and enhancing the overall well-being of RA patients.

We compared the efficacy of romosozumab and denosumab in elderly women with primary osteoporosis and knee osteoarthritis in a randomized controlled trial. A total of 112 participants aged 75–90 years were randomized equally into the romosozumab and denosumab groups. Among these, 49 and 52 participants, respectively, who received their initial dose were included in the analysis. The primary outcome was change in lumbar spine (LS)-bone mineral density (BMD) at 12 months in the romosozumab group versus the denosumab group. Secondary outcomes were changes in knee osteophyte development, patient-reported outcomes (PROs), and the incidence of serious adverse events. Mean age of participants was 80.9 years. There was no difference in baseline LS-BMD between the two groups, with a T-score of -2.6. The mean percentage change in LS-BMD at 12 months was significantly higher in the romosozumab group (13.7%) than in the denosumab group (8.5%; p = 0.0035). No significant differences were observed in knee osteophyte development and PROs between the two groups. Serious adverse events included a case of mitral regurgitation in the romosozumab group. These findings emphasize the need for refined treatment strategies in high-risk populations, highlighting romosozumab’s benefits and the need to monitor cardiovascular risks.

Objectives: To identify factors associated with probable sarcopenia in patients with rheumatoid arthritis (RA). Methods: Probable sarcopenia was diagnosed using the SARC-F questionnaire. Patients with difficult-to-treat RA (D2T-RA) were defined as those with a history of using ≥2 biological/targeted synthetic (b/ts) disease-modifying antirheumatic drugs (b/tsDMARDs) who had moderate or high disease activity. Among 486 patients, 101 were classified into the probable sarcopenia group (SARC-F ≥4), and 385 were classified into the non-probable sarcopenia group (SARC-F <4). Factors associated with probable sarcopenia were examined using multiple logistic regression analysis. Additionally, patients were divided into the D2T-RA (n=38) and non-D2T-RA (n=448) groups, and the proportion of probable sarcopenia and RA treatment status were compared. Results: Factors associated with probable sarcopenia included age (adjusted OR: 1.03), BMI (OR:1.16), D2T-RA (OR:3.39), and HAQ-DI (OR:1.38), and diabetes mellitus (OR:2.77). The proportion of probable sarcopenia was significantly higher (60.5% vs. 17.4%), and the rate of MTX use was significantly lower (34.2% vs. 64.1%), in the D2T-RA group than in the non-D2T-RA group. Moreover, in the D2T-RA group, most patients used two or three b/tsDMARDs (two: 68.4%, three: 21.1%). Conclusions: D2T-RA was associated with probable sarcopenia. Tight control by treatment enhancement may help overcome sarcopenia.

Aim The objective of this study was to compare the clinical effectiveness of baricitinib and abatacept in patients with rheumatoid arthritis (RA). Methods This study included 274 patients treated with abatacept and 241 treated with baricitinib who were followed for >52 weeks. Potential treatment selection bias was addressed by using inverse probability of treatment weighting. The paired t‐test was used to assess differences in Clinical Disease Activity Index (CDAI) score relative to baseline. A generalized estimating equation was used to compare the two treatment groups. Results The estimated mean CDAI score was 18.2 at baseline and significantly decreased to 12.6 at 4 weeks, 8.9 at 12 weeks, 7.4 at 24 weeks, and 6.1 at 52 weeks in the abatacept group. The estimated mean CDAI score was 18.6 at baseline and significantly decreased to 9.5 at 4 weeks, 6.5 at 12 weeks, 5.7 at 24 weeks, and 5.5 at 52 weeks in the baricitinib group. The baricitinib group had significantly lower CDAI scores at 4, 12, and 24 weeks compared to the abatacept group. Subgroup analyses revealed that this difference was evident among patients with high disease activity and without concomitant use of methotrexate but was less pronounced among those with remission to moderate disease activity status with methotrexate use. Conclusion Both baricitinib and abatacept were effective in reducing disease activity in patients with RA. Baricitinib demonstrated potential advantages over abatacept in terms of early disease control, particularly in patients with high disease activity and without methotrexate use.

Background This study aimed to investigate the prevalence of social frailty and associated factors. Methods A total of 655 consecutive patients who were able to complete the Kihon Checklist (KCL) and the Questionnaire on Social Frailty between June and August 2022 were enrolled. Social frailty was assessed using the Makizako Social Frailty Index. Patient characteristics were analyzed by analysis of variance. Factors associated with social frailty were analyzed using multivariate logistic analysis. Spearman’s rank correlation coefficients were used to examine correlations between each KCL domain and social frailty. Results Mean age was 68 years, and disease duration was 12 years; 73% of patients were female. Social frailty was present in 30.8% of patients, with 36.5% classified as social pre-frailty. Multivariate analysis revealed age and HAQ-DI to be independent factors associated with social frailty. The proportion of social frailty increased with increasing age and worsening HAQ-DI scores. The KCL domain “Isolation” was the most strongly associated with social frailty (r = 0.601, P < 0.001), with higher scores associated with a higher proportion of social frailty. Conclusions Social frailty in RA patients is associated with age and physical impairment (HAQ-DI). Moreover, the KCL domain “Isolation” was strongly associated with social frailty.

Objectives Locomotive syndrome (LS) leads to reduced physical function and a high risk of becoming bedridden. Grip strength serves as an indicator of upper limb and overall physical function. Rheumatoid arthritis (RA) patients with reduced grip strength frequently show finger and wrist joint inflammation. The purpose of this study was to verify grip strength as an evaluation tool for physical function and LS in RA patients. Methods As part of an ongoing multicenter observational study, 591 consecutive RA patients whose background information was available, including data for the 25-question Geriatric Locomotive Function Scale (GLFS-25) and grip strength, were examined. LS was defined as a GLFS-25 score ≥ 16 points. Finger and wrist joint inflammation were defined as tender or swollen joints. Results Among the 591 patients, 244 (41.3%) patients had LS, and 167 (28.3%) were male. Receiver operating characteristic curve analysis yielded cut-off values of grip strength for LS of 24 kg (specificity 72.2%; sensitivity 62.7%) for males and 17 kg (specificity 65.7%; sensitivity 67.6%) for females. Multivariable logistic regression analysis revealed a significant association of grip strength with LS, even after adjusting for finger and wrist joint inflammation. Conclusions LS was significantly associated with grip strength, even after adjusting for the presence of finger and wrist joint inflammation. We recommend adopting grip strength measurement as a screening tool for evaluating LS and guiding interventions.