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Objectives: The impact of osteoarthritis (OA) on the initial treatment response of rheumatoid arthritis (RA) by treat-to-target practice was compared between the patients with an onset age of ≥65 years old [late-onset RA (LORA)] and those with an onset age of <65 years old [young-onset RA (YORA)]., Methods: A retrospective study was conducted on the patients with RA, who were referred to Department of Rheumatology, Niigata Rheumatic Center without treatment between January 2021 and July 2022. Patients with grade ≥3 OA according to the Kellgren-Lawrence (K-L) classification in either the knee or hand were classified in the OA (+) group and others were in the OA (-) group. The clinical data were compared at diagnosis and 1 year after the initial treatment between the groups for 74 LORA and 59 YORA patients, respectively., Results: One year after starting treatment in the LORA patients, the OA (+) group had poorer disease activity control and greater disability in several activities of daily living than the OA (-) group. In the YORA patients, there were no differences in activities of daily living disability between the groups., Conclusions: In the initial treatment of the LORA patients, the prevalence of OA was high, and the impact of OA on LORA was larger than on YORA., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Objectives: The aim is to evaluate the relevance of serum immunoglobulin G (IgG) titres against periodontopathic bacteria to predict the clinical response to 1-year treatment with biological disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA) patients., Methods: Data were collected from 50 RA patients who had received conventional synthetic DMARDs, corticosteroids, or non-steroidal anti-inflammatory drugs before (baseline) and after 1-year treatment with bDMARDs in a retrospective cohort study. Changes in rheumatologic conditions were compared between the two groups for low and high baseline IgG titres against Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans according to their median measurements., Results: Twenty-five patients with low anti-P. gingivalis IgG titres showed significantly greater decreases in changes in the Clinical Disease Activity Index and swollen joint count than 25 patients with high anti-P. gingivalis IgG titres (p = .04 for both). Bivariate and multivariate analyses revealed a significantly positive association of baseline anti-P. gingivalis IgG titres with Clinical Disease Activity Index changes (p = .02 and p = .002). However, post-treatment rheumatologic conditions were comparable between 25 patients each in the low and high baseline anti-A. actinomycetemcomitans IgG titre groups., Conclusions: Baseline serum anti-P. gingivalis IgG titres are predictive of the clinical response to 1-year treatment with bDMARDs in RA patients., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Infliximab is a human-murine chimeric monoclonal IgG antibody against tumor necrosis factor that is used in combination with methotrexate for the treatment of moderate to severe rheumatoid arthritis (RA). The trough concentration of serum infliximab required to control disease activity in RA is ≥1 μg/mL, and we investigated whether this trough concentration can predict the effectiveness of RA treatment., Methods: We retrospectively analyzed the cases of 76 patients with RA. The REMICHECK Q® (REMIQ) is a kit that can check for serum infliximab concentrations. Infliximab concentrations >1 μg/mL at 14 weeks after an initial infliximab induction is considered REMIQ-positive, otherwise considered REMIQ-negative. Here, we determined the retention rates and investigated the clinical and serologic features of REMIQ-positive and REMIQ-negative patients., Results: At 14 weeks, significantly more of the REMIQ-positive patients (n = 46) were responders compared to the non-responders (n = 30). The retention rate at 54 weeks was also significantly higher in the REMIQ-positive group versus the negative group. After 14 weeks, more patients in the REMIQ-negative group were considered inadequate responders, and their infliximab doses were escalated. At baseline, the REMIQ-positive group had significantly lower C-reactive protein (CRP) levels compared to the negative group. Cox regression analysis with multiple variables showed that the positivity of REMIQ (hazard ratio [HR] 2.10 and 95% confidence interval [CI]: 1.55-5.71) at baseline was associated with the achievement of low disease activity. The positivities of rheumatoid factor and anti-CCP antibody at baseline were associated with the achievement of remission with infliximab treatment (HR 0.44, 95% CI: 0.09-0.82 and HR 0.35, 95% CI: 0.04-0.48, respectively)., Conclusions: The results of this study suggest that the control of RA disease activity may be facilitated by using the REMIQ kit at 14 weeks to check whether it is necessary to increase a patient's infliximab dose to ensure a therapeutic blood concentration that will help the patient achieve low disease activity., Competing Interests: YN has received research grants from AbbVie Japan GK, Eisai Co., and Mitsubishi Tanabe Pharma Corp. and speaker fees from AbbVie Japan GK, Astellas Pharma, Asahi Kasei, Chugai Pharmaceutical Co., Eisai Co., Eli Lilly Japan K.K., Daiichi-Sankyo, GlaxoSmithKline K.K., Mitsubishi Tanabe Pharma Corp., Novartis Japan, Takeda, Ono, Otsuka Co., Pfizer, Janssen, and UCB Japan. The author declares no conflict of interest. YN is serving as one of the Guest editors of this journal. We declare that YN had no involvement in the peer review of this article and have no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Josef Jampílek., (© 2023 The Author(s). Published by IMR Press.)

Objectives: To assess whether periodontitis severity affects the clinical response to biological disease-modifying antirheumatic drugs (bDMARDs) for 1 year in rheumatoid arthritis (RA) patients., Methods: Data were collected from 50 RA patients who had received corticosteroids, conventional synthetic DMARDs, or non-steroidal anti-inflammatory drugs before (baseline) and after 1 year of bDMARD therapy in a retrospective study. Rheumatologic conditions were compared between the two periodontitis severity groups according to the periodontal inflamed surface area (PISA) or Centers for Disease Control and Prevention (CDC)/American Academy of Periodontology (AAP) case definitions., Results: Twenty-eight patients with no or mild periodontitis showed significantly greater decreases in changes in Clinical Disease Activity Index (CDAI) and tender and swollen joint count in comparison to 22 patients with moderate and severe periodontitis (p = .02, p = .01, and p = .03). Both bivariate and multivariate analyses revealed a significantly positive association between the baseline CDC/AAP definitions and CDAI changes (p = .005 and p = .0038). However, rheumatologic conditions were comparable between 25 patients each in the low and high PISA groups., Conclusions: Baseline periodontitis severity according to the CDC/AAP definitions is associated with the clinical response to bDMARDs for 1 year in RA patients., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective Sarcopenia is characterized by a loss of muscle mass and strength, which leads to frailty and mortality. Rheumatoid arthritis (RA) is considered to be a cause of sarcopenia. The present study assessed the effectiveness of biological disease-modifying antirheumatic drugs (bDMARDs) on sarcopenia. Methods This was a prospective cohort study including 48 patients [11 men, 37 women; 67.5 (57.0-74.8) years old] with RA who started bDMARDs in Niigata Rheumatic Center. We monitored the physical ability, nutritional status and body composition at the baseline, 6 months and 12 months. The physical activity was measured by the Health Assessment Questionnaire (HAQ) and 10-m walking test (10MWT). The nutritional status was assessed by the controlling nutrition status (CONUT) score. Results Among the 48 patients who started bDMARDs, 21 were classified as having sarcopenia. The physical activity and nutritional status were significantly ameliorated after 12 months of bDMARDs. The body composition analysis showed a significant increase in the body weight but no significant increase in the skeletal muscle mass index. The proportion of patients diagnosed with sarcopenia decreased significantly after 12 months of bDMARDs (43.8% vs. 27.1%, p=0.039). Among the 21 patients who were diagnosed with sarcopenia when starting bDMARDs, the skeletal muscle index was significantly increased after 12 months of bDMARDs. [5.22 (4.76-5.43) kg/m 2 vs. 5.44 (4.84-5.77), p=0.039]. Conclusion Biologics may be useful in the treatment of sarcopenia through mechanisms such as improving the disease activity, physical activity and nutritional status.

We experienced a patient in her 30s with rheumatoid arthritis (RA) who achieved delivery with the use of certolizumab pegol (CZP) and tacrolimus (TAC) during pregnancy. She developed RA in X - 3 year and was treated with salazosulfapyridine (SASP). In X - 2 year, she became pregnant and discontinued SASP and had a normal delivery despite joint pain during pregnancy. She restarted SASP in X - 1 year and became pregnant again in X year. She experienced a flare-up of RA and was referred to our rheumatic centre. We introduced CZP and TAC, and she discontinued these agents and started prednisolone just before delivery. There is reportedly minimal placental transfer of CZP because of its Fc-free structure, since the Fc part of CZP is replaced by polyethylene glycol. TAC was contraindicated during pregnancy until 2018, but its usage in such patients is now approved. Despite the flare-up of RA during pregnancy, we were able to reduce the disease activity by introducing CZP and TAC during pregnancy. We believe that the present findings support the efficacy of this approach for treating RA flare during pregnancy., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective Treatment of elderly patients with rheumatoid arthritis (RA) has been controversial because they often have serious comorbidities and cannot use methotrexate (MTX). In Japan, golimumab (GLM) 100 mg without MTX is approved. We investigated the effectiveness and safety of GLM in elderly patients with RA. Methods The GLM survival rate was evaluated using the Kaplan-Meier method. Disease activities, laboratory findings, and treatments were evaluated. Patients We enrolled 168 patients with RA in our hospital. Using age ≥75 years old to identify elderly patients, younger (n=111) and elderly (n=57) groups were established. Elderly patients were divided into 2 groups according to the MTX treatment status (with, n=27; without, n=25). Results The GLM survival rates were 80.8% and 82.3% in elderly and younger patients, respectively (p=0.762). At 52 weeks, the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) was improved in elderly patients (4.26 vs. 3.31, p<0.001); the Health Assessment Questionnaire Disability Index (HAQ-DI) was unchanged (1.12 vs. 0.88, p=0.694). When elderly patients were compared according to the MTX treatment status, the DAS28-ESR had improved in both groups (with MTX: 3.82 vs. 2.68, p<0.001; without MTX: 4.76 vs. 4.25, p=0.026); however, the HAQ-DI had not. The GLM survival rates at 52 weeks were 85% and 76% in patients with and without MTX, respectively. Conclusion In elderly patients with RA, GLM was effective, regardless of MTX treatment status, but it did not affect the HAQ-DI. GLM survival rates were comparable between elderly and younger patients. GLM may be a suitable option for elderly patients with RA who cannot use MTX.

With the introduction of methotrexate, biological disease-modifying antirheumatic drugs (bDMARDs), and targeted synthetic DMARDs (tsDMARDs), the disease activity of patients with rheumatoid arthritis has been dramatically ameliorated. However, these drugs have strong immunosuppressive effects and can cause reactivation of hepatitis B virus (HBV) in patients with resolved HBV infection. Corticosteroids or immunosuppressants used for other connective tissue diseases or vasculitis also carry a risk of inducing reactivation of HBV. Therefore, every rheumatologist should know how to detect the resolved infection of HBV in patients with rheumatic diseases receiving immunosuppressive therapy and how to monitor it when resolved infection is revealed. Of note, the cut-off index was changed from 2.1 log copies/ml to 20 IU/ml (1.3 Log IU/ml) in 2017. Rheumatologists should start nucleic acid analog administration at reactivation of HBV while performing ongoing immunosuppressive therapy in order to prevent severe or fulminant hepatitis. A low titer of HBs antibody (Ab) or lack of HBs Ab is a risk factor of reactivation of HBV. However, the reactivation of HBV cannot be prevented by HBs Ab titers at baseline or changes overtime. Rheumatologists should recognize that every immunosuppressive therapy, regardless of the mode of action, has a potential risk of reactivation. To facilitate proper management of patients with HBV infection, collaboration between rheumatologists and hepatologists is strongly encouraged. Patients' education, systems for checking electronic medical charts, and multidisciplinary efforts are considered important for detecting HBV reactivation.

Objective To evaluate the effectiveness and drug retention rate of golimumab (GLM) for long-term use in daily practice for patients with rheumatoid arthritis (RA). Methods Patients with RA who started GLM therapy with a minimum follow-up period of 52 weeks were included. The patients were divided into a biologic-naïve group and switch group. The disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (DAS28-ESR), grip power, and Japanese version of the health assessment questionnaire (J-HAQ) score were assessed. In addition, the treatment continuation rate was evaluated at the final follow-up. Patients Sixty-five patients [58 women and 7 men; median (range) age, 69 (61-74) years; median (range) disease duration, 9 (5-16) years] were included. Twenty-eight patients were biologic-naïve (naïve group), and 37 were switched to biologics (switch group). Results The median (range) follow-up period was 134 (58-162) weeks. The DAS28-ESR improved from a median (range) of 4.31 (3.52-5.25) to 2.65 (2.28-3.77) in the naïve group and from 4.27 (3.19-4.89) to 2.89 (2.49-3.88) in the switch group. The grip power improved in both groups (p<0.01); however, the J-HAQ score showed no marked improvement in either group. The continuation rates were 22/28 (78.6%) in the naïve group, and 26/37 (70.3%) in the switch group at the final follow-up. Conclusion We herein report for the first time that the long-term use of GLM improves the grip power. Improving the grip power may help prevent sarcopenia and frailty in the future. Given the efficacy and high continuation rate, we suggest that GLM would be a well-tolerated treatment option for RA.

Objectives: This retrospective study aimed to investigate the risk factors associated with delayed wound healing (DWH) after orthopedic surgery in rheumatoid arthritis (RA) patients treated with biological disease-modifying antirheumatic drugs (bDMARDs)., Methods: We reviewed medical records of 276 orthopedic procedures for 187 RA patients treated with bDMARDs. As a preoperative nutritional status assessment, we evaluated body mass index, prognostic nutritional index (PNI), and controlling nutritional status (CONUT). We evaluated DAS28-CRP, DAS28-ESR, face scale, global health, and HAQ-DI to assess the disease activity. Univariate and multivariate logistic regression analyses were performed to evaluate the risk factors for DWH., Results: In 276 procedures, DWH was identified in 24 patients (8.7%). Disease duration, foot and ankle surgery, and preoperative use of tocilizumab were significant in the univariate analyses. These variables were entered into a multivariate model, and it was revealed that preoperative use of tocilizumab and procedures in the foot and ankle were associated with an increased risk of DWH., Conclusion: The current retrospective study suggested that preoperative use of tocilizumab and procedures in the foot and ankle were risk factors for DWH.

Objectives: We evaluated whether the periodontal inflamed surface area (PISA), a measure of the inflammatory burden posed by periodontitis, is associated with the clinical response to biological disease-modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA). Methods: We conducted a retrospective study that collected rheumatologic and periodontal data from 54 patients with RA who had received corticosteroid, conventional synthetic DMARDs, or non-steroidal anti-inflammatory drugs before (baseline) and after 6 months of bDMARD therapy. After the patients were divided into two groups based on high or low PISA according to the median measurements at baseline, the rheumatologic condition was compared between the groups. Results: The patients with a low PISA showed significantly lower values for the Clinical Disease Activity Index (CDAI) ( p  = .008), swollen joint count ( p  = .02), and patient's and evaluator's global assessment ( p  = .01 and p  = .03) and significantly greater decreases in changes in the CDAI from baseline to 6 months than the patients with a high PISA ( p  = .01), although these values were comparable at baseline. Both univariate and multivariate analyses revealed a significantly positive correlation between the baseline PISA and changes in the CDAI ( p  = .04 and p  < .001). Conclusion: The PISA is associated with the clinical response to bDMARDs in patients with RA.

Objective To investigate the clinical outcomes of rheumatoid arthritis (RA) patients who discontinued infliximab (IFX) treatment at our hospital. Methods Among 249 patients receiving IFX from 2007 to 2015, we retrospectively investigated the clinical courses of 18 who discontinued IFX after achieving the 28-joint disease activity score based on the erythrocyte sedimentation (DAS28-ESR) clinical remission (CR) and whose clinical courses were available continuously for 96 weeks after discontinuation. Results At IFX introduction, the median age was 56.9 (range 36.1-72.4) years, and the disease duration was 5.2 (0.4-25.6) years. The median duration of maintaining either CR or a low disease activity (LDA) with IFX was 37.2 (4.0-91.4) months, and the total duration of IFX therapy was 45.8 (17.1-96.9) months. After discontinuation, 8 patients (44.4%) maintained CR/LDA for 96 weeks (no-flare group), and 10 (55.6%) experienced flares (DAS28-ESR≥3.2) within 96 weeks (flare group). In the no-flare group, six patients receiving intensified conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy to prevent flare ups simultaneously either with or immediately after discontinuing IFX. In the flare group, four patients received intensified csDMARD therapy. Six patients restarted biological DMARDs (bDMARDs), and all achieved CR again. Ultimately, 12 patients (66.7%) maintained a Bio-free disease control for 96 weeks. A comparison of the clinical backgrounds between the flare and no-flare groups showed no marked difference in their disease duration, IFX dosage, duration of maintaining CR with IFX, or concomitant csDMARDs use. Conclusion Irrespective of the RA disease duration, more than half of all patients maintained a Bio-free condition for 96 weeks. Continuing LDA with IFX for a sufficiently long period of time before discontinuation and preventive intensification of csDMARD therapy may help maintain a Bio-free condition.

Objectives The present study was performed with the aim of analyzing the biological disease-modifying antirheumatic drug (bDMARD)-free (Bio-free) condition of adalimumab (ADA)-treated rheumatoid arthritis (RA) patients in a real-world setting. Methods ADA was used in the treatment of 130 (male, n=21; female, n=109 females) RA patients. Among them, 26 patients (20.0%) discontinued ADA due to a good response. We analyzed 20 patients who were followed up for more than 6 months after the discontinuation of ADA. The Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) and modified health assessment questionnaires (mHAQs) were evaluated. Results The mean age of the patients was 53.4±11.1 years. The mean disease duration was 4.5±4.3 years. Sixteen patients were bDMARD-naïve, while 4 switched from bDMARDs to ADA. At 6 months after the discontinuation ADA, 19 patients had achieved a clinical remission, and 1 had achieved a low disease activity. The Bio-free period was 26.4±15.5 months. The dose of prednisolone was significantly reduced from baseline (3.45±3.17 mg/day) at 6 months after the discontinuation of ADA (2.63±2.78 mg/day). The dose of methotrexate was unchanged. The number of conventional synthetic DMARDs (csDMARDs) was significantly increased (0.8±0.6 to 1.4±1.06). The mHAQ values were significantly ameliorated by ADA and remained good in patients with a Bio-free condition. A multivariate analysis showed that the dose of methotrexate (MTX) was an important factor for achieving a Bio-free condition. Conclusion A sustainable Bio-free condition in a real clinical setting can be achieved and may be a suitable way of reducing medical costs. The dose of MTX and the additional administration of csDMARDs is therefore thought to be important for ensuring a good outcome in these patients.

Objectives: The intensification of infliximab (IFX) treatment, involving escalation of the dose and shortening of interval, was approved in Japan in July 2009. We consider IFX intensification therapy to be preferable for patients with treatment-resistant active rheumatoid arthritis (RA). We retrospectively compared the efficacy of IFX with that of other bDMARDs in methotrexate (MTX)-resistant patients., Methods: Patients who satisfied the following criteria were enrolled: (i) those who started bDMARDs between February 2011 and December 2016, and (ii) those who required bDMARDs after 180 d of MTX treatment. We compared 33 patients who had been treated with IFX (IFX group) and 146 who had received other bDMARDs treatment (non-IFX group)., Results: IFX was administered at a dose of 6.98 mg/kg/8-week equivalent at 52 weeks. Clinical disease activity index clinical remission (CDAI-CR) was achieved in 49 of the 179 patients at 52 weeks and 13 of these 49 patients received IFX. Logistic regression analysis showed that treatment with IFX was an important variable for the achievement of CDAI-CR at 52 weeks (odds ratio 2.69, 95% confidence interval 1.13-6.42). The severity and frequency of adverse events did not differ., Conclusion: Intensification of IFX was effective and well tolerated for MTX resistant patients.

Methotrexate (MTX) is the first choice disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA) and is referred to as an "anchor drug"; its use has been steadily increasing annually. However, MTX-related lymphoproliferative diseases (MTX-LPDs) have emerged as important complications in the patients with RA. There have been no reports of intra-articular MTX-LPDs of the patients with RA. Atypical cells were found in the patient's joint fluid by cytological examinations, and MTX-LPDs were suspected. The patient discontinued MTX and open synovectomy was performed. The histological findings and immunohistochemical staining of the specimens confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) of MTX-LPDs. After the operation of the patient's left knee joint, pains and swollen joint disappeared with no relapse. The cytological examinations of the synovial fluid followed by knee operation were effective for early diagnosis of MTX-LPD. MTX discontinuation with no chemotherapy followed up with a knee operation improved the recovery of the MTX-LPD.

Objective: To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T)., Methods: In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS) -7 ], and baseline vdH-mTSS [0.986 (0.976-0.996), p = 0.009]. A factor associated with ΔvdH-mTSS < SDC was SDAI remission at week 24 [3.53 (1.62-7.71), p = 0.002]., Conclusion: Predictive validity of SDAI remission for good outcomes was verified in a T2T-implementing cohort in the current clinical settings.

Conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) other than methotrexate (MTX: anchor csDMARDs) are effective for single use, reinforcement of MTX, biologics and induction and maintenance of biologics-free condition. Newly developed iguratimod (IGU) does not suppress immunological reaction, therefore, it is useful for single use or combination with other csDMARDs in patients with complications. IGU can be used as a first csDMARDs before MTX use during the screening for MTX. IGU might be effective for reinforcement of MTX, biologics and induction and maintenance of biologics-free condition just like other csDMARDs. IGU can be used in wide variety of situation of the treatment of rheumatoid arthritis and it is desired that after the all-case surveillance condition for approval, IGU become a standard csDMARDs all over the world which was made in Japan.

Objective: The aim of this study was to analyze the efficacy of adalimumab (ADA) in patients with rheumatoid arthritis treated with or without methotrexate (MTX) and determine impact of the MTX dose., Methods: Pearson's product-moment correlation coefficient was used to assess the correlations between the improvement in the Disease Activity Score (DAS) 28- erythrocyte sedimentation rate (ESR) score and the MTX dose in patients receiving treatment with MTX at a dose of <8 mg/week, 8 mg/week and >8 mg/week., Patients: ADA therapy was initiated in 68 rheumatoid arthritis patients between July 2008 and June 2013. The mean MTX dose was 9.6 ± 2.6 mg/week, and the patients were followed for 24 weeks., Results: The mean DAS28-ESR scores at baseline and week 24 were 4.6 ± 1.3 and 2.7 ± 1.2 in the 60 patients treated with MTX and 4.5 ± 1.0 and 4.2 ± 1.5 in the eight patients treated without MTX, respectively. Clinical remission was achieved in 48% and 25% of the patients, respectively, by week 24. Moreover, 90.0% of the patients taking MTX continued to receive ADA until week 24, while 50.0% of the patients not taking MTX continued to receive ADA until week 24. Among the 35 patients receiving MTX at a dose of >8 mg/week, the DAS28-ESR scores decreased rapidly from 4.4 ± 1.2 at baseline to 3.2 ± 1.1 at week 4 and further decreased to 2.4 ± 1.0 at week 24. Meanwhile, clinical remission was achieved in 57% of the patients receiving MTX at a dose of >8 mg/week and 36% of those receiving MTX at a dose of ≤8 mg/week. A significant correlation was noted between the improvement in the DAS-ESR score and the MTX dose., Conclusion: In this study population, enhanced clinical efficacy of ADA was achieved in combination with the administration of a sufficient dose of MTX, determined to be >8 mg/week.

Background: Tumor necrosis factor (TNF)-α inhibitor has been shown to affect the periodontal condition of patients with rheumatoid arthritis (RA). The aim of the present study is to assess the effect of a fully humanized anti-TNF-α monoclonal antibody, adalimumab (ADA), on the periodontal condition of patients with RA and to compare serum protein profiles before and after ADA therapy., Methods: The study participants consisted of 20 patients with RA treated with ADA. Clinical periodontal and rheumatologic parameters and serum cytokine levels were evaluated at baseline and 3 months later. Serum protein spot volume was examined with two-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis. Proteins with significant difference in abundance before and after ADA therapy were found and identified using mass spectrometry and protein databases., Results: The patients showed a significant decrease in gingival index (P = 0.002), bleeding on probing (P = 0.003), probing depth (P = 0.002), disease activity score including 28 joints using C-reactive protein (P <0.001), and serum levels of TNF-α (P <0.001) and interleukin-6 (P <0.001) after ADA medication, although plaque levels were comparable. Among a total of 495 protein spots obtained, nine spots were significantly decreased in abundance at reassessment, corresponding to complement factor H, phospholipase D, serum amyloid A, complement component 4, and α-1-acid glycoprotein (P <0.01)., Conclusion: These results suggest a beneficial effect of ADA therapy on the periodontal condition of patients with RA, which might be related to differences in serum protein profiles before and after ADA therapy.

Purpose: To reveal how often patients with rheumatoid arthritis (RA) or any of other connective tissue diseases (CTDs) who take prednisolone (PSL) manifest postprandial hyperglycemia, and to evaluate the effects of divided daily dose administration of PSL, and of acarbose and nateglinide, on RA patients., Method: The blood sugar (BS) levels of the patients were measured after meals. For in-patients who showed postprandial hyperglycemia, the daily dose of PSL was divided and nateglinide and/or acarbose were/was added if their BS levels did not improve sufficiently. The patients with BS levels that were well controlled for three months were compared with the patients with poorly controlled BS levels., Results: The BS levels of 78 patients, including 16 patients with diabetes mellitus (DM), were measured after meals, and 27 of them were newly diagnosed with DM. Five of 14 patients who took a steady dose of PSL showed high BS levels after lunch (over 200 mg/dl) without elevated HbA1c. The combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia significantly. The period from the start of PSL administration to intervention was significantly longer in patients with good control at three months than the corresponding period in those with poor control., Conclusion: The prevalence of postprandial hyperglycemia was high in patients with RA/CTD taking PSL; accordingly, measurement of the BS level after each meal was valuable. Combination therapy of divided-dose PSL and nateglinide and/or acarbose improved postprandial hyperglycemia.

Objective: To compare reasons for discontinuation and drug retention rates per reason among anticytokine therapies, infliximab, etanercept and tocilizumab, and the risk of discontinuation of biological agents due to adverse events (AE) in patients with rheumatoid arthritis (RA)., Method: This prospective cohort study included Japanese RA patients who started infliximab (n=412, 636.0 patient-years (PY)), etanercept (n=442, 765.3 PY), or tocilizumab (n=168, 206.5 PY) as the first biological therapy after their enrolment in the Registry of Japanese Rheumatoid Arthritis Patients for Long-term Safety (REAL) database. Drug retention rates were calculated using the Kaplan-Meier method. To compare risks of drug discontinuation due to AE for patients treated with these biological agents, the Cox proportional hazard model was applied., Results: The authors found significant differences among the three therapeutic groups in demography, clinical status, comorbidities and usage of concomitant drugs. Development of AE was the most frequent reason for discontinuation of biological agents in the etanercept and tocilizumab groups, and the second most frequent reason in the infliximab group. Discontinuation due to good control was observed most frequently in the infliximab group. Compared with etanercept, the use of infliximab (HR 1.69; 95% CI 1.14 to 2.51) and tocilizumab (HR 1.98; 95% CI 1.04 to 3.76) was significantly associated with a higher risk of discontinuation of biological agents due to AE., Conclusions: Reasons for discontinuation are significantly different among biological agents. The use of infliximab and tocilizumab was significantly associated with treatment discontinuation due to AE compared with etanercept.

Methotrexate (MTX) is indispensable for the treatment of rheumatoid arthritis (RA). However, a small number of patients treated with MTX occasionally encounter some life-threatening events, including myelosuppression. Renal insufficiency, one of risk factors for these events, is difficult to assess because the serum creatinine concentration level and estimated glomerular filtration rate are sometimes inaccurately determined in aged RA patients. As a better indicator to evaluate this pathology, we measured the serum cystatin-C (Cys-C) level in 78 RA patients ≥ 50 years who were treated with MTX and observed for a year. The measurement achieved successful screening of two patients with leukocytopenia, one with interstitial lung disease (ILD), and two with liver dysfunction. An additional four referral inpatients with MTX-induced adverse events (three with pancytopenia, one with ILD) were enrolled for analysis, amounting to 82 patients. The logistic regression analysis showed that a correlation was observed between myelotoxicity and serum Cys-C level (elevation per 0.1 mg/dl; odds ratio 2.34, 95% confidence interval 1.08-5.09, p = 0.03). In conclusion, elderly RA patients potentially have subclinical renal insufficiency detected by the serum Cys-C concentration level. The elevated level of serum Cys-C is a more sensitive indicator to predict MTX-induced myelotoxicity than that of serum creatinine.

Magnetic resonance imaging (MRI) is a useful tool for evaluating disease activity and therapeutic efficacy in rheumatoid arthritis (RA). However, conventional whole-body MRI is inconvenient on several levels. We have therefore developed a new low-field extremity MRI (compact MRI, cMRI) and examined its clinical utility. Thirteen RA patients treated with anti-tumor necrosis factor (TNF) biologics were included in the study. The MRI was performed twice using a 0.21-T extremity MRI system. The MRI images were scored using our proposed cMRI scoring system, which we devised with reference to the Outcome Measures in Rheumatology Clinical Trials RA MRI score (OMERACT RAMRIS). In our cMRI scoring system, synovitis, bone edema, and bone erosion are separately graded on a scale from 0 to 3 by imaging over the whole hand, including the proximal interphalangeal joint. The total cMRI score (cMRIS) is then obtained by calculating the total bone erosion score x 1.5 + total bone edema score x 1.25 + total synovitis score. In this study, one patient showed a progression of bone destruction even under low clinical activity, as assessed by the disease activity score on 28 joints (DAS28); however, another patient's cMRIS decreased concurrently with the decrease in DAS28, with the positive correlation observed between DeltaDAS28 and DeltacMRIS (R = 0.055, P < 0.05). We conclude that cMRI and cMRIS are useful for assessing total disease activity and as a method linking MRI image evaluation to clinical evaluation.

The efficacy of infliximab, a chimeric antibody against tumor necrosis factor-alpha used to treat patients with rheumatoid arthritis (RA), tends to decrease as patients develop human antichimeric antibody against infliximab (HACA). The clinical study reported here was designed to evaluate the efficacy of mizoribine (MZR) pulse therapy in patients who show a reduced or insufficient response to infliximab. Ten RA patients who had active arthritis despite infliximab therapy were treated with MZR pulse therapy at a dose of 100 mg MZR and methotrexate (MTX) and the disease activity assessed at baseline and at weeks 4-8, 12-16, and 20-24. The dose was increased to 150 mg in those patients who showed an insufficient response to MZR. The mean 28-joint disease activity score (DAS28) at weeks 12-16 and 20-24 of therapy was significantly lower than that at baseline. A moderate or good European League against Rheumatism (EULAR) response was achieved in seven patients (70%) at weeks 12-16 and in five patients (50%) at weeks 20-24. The dose of 150 mg MZR was effective in one of the three patients who showed an insufficient response to pulse therapy with 100 mg MZR. Based on these results, we propose that MZR pulse therapy should be attempted before the patient is switched to other biologics.

We treated a case of adult-onset severe-form anaphylactoid purpura. This case had been diagnosed as anaphylactoid purpura pathologically by skin biopsy. However, his clinical manifestations were atypical in view of complicated massive gastrointestinal hemorrhage. Intensive therapy including corticosteroid and cyclophosphamide transiently improved his condition. Nevertheless, the beta-D-glucan value in peripheral blood was gradually elevated. Prophylactic use of fluconazole failed to prevent contraction of invasive mycosis. Finally, he suddenly suffered from diffuse cerebral hemorrhage. Postmortem examination revealed systemic invasive aspergillosis as the cause of death.

Objectives: The aim is to evaluate the treatment and prognosis of coronavirus disease 2019 (COVID-19) according to the time of onset and dominant strain in patients with rheumatic diseases. Methods: This study analysed a nationwide COVID-19 registry of Japanese patients with rheumatic diseases compiled between June 2020 and December 2022. The primary endpoints of the study were hypoxaemia incidence and mortality. Multivariate logistic regression analysis was performed to assess differences according to the period of onset. Results: A total of 760 patients were compared across four periods. Hypoxaemia rates were 34.9, 27.2, 13.8, and 6.1% and mortality rates were 5.6, 3.5, 1.8, and 0% until June 2021, between July and December 2021, January and June 2022, and July and December 2022, respectively. History of vaccination (odds ratio, 0.39; 95% confidence interval, 0.18–0.84) and onset during the July to December 2022 Omicron BA.5–dominant period (odds ratio, 0.17; 95% confidence interval, 0.07–0.41) were negatively associated with hypoxaemia in the multivariate model, adjusting for age, sex, obesity, glucocorticoid dose, and comorbidities. Over the Omicron-dominant period, antiviral treatment was administered in 30.5% of patients with a low probability of hypoxaemia. Conclusions: COVID-19 prognosis improved over time in patients with rheumatic diseases, especially in the Omicron BA.5–dominant period. In the future, treatment of mild cases should be optimised. [ABSTRACT FROM AUTHOR]

Objectives: To determine whether serum immunity to Porphyromonas gingivalis peptidylarginine deiminase (PPAD) affects the clinical response to biological disease-modifying antirheumatic drug (bDMARD) in patients with rheumatoid arthritis (RA). Methods: In a retrospective study, rheumatologic and periodontal conditions of 60 patients with RA who had been treated with conventional synthetic DMARD were evaluated before (baseline) and after 3 and 6 months of bDMARD therapy. After serum levels of anti-PPAD immunoglobulin G (IgG) were determined at baseline, the patients were respectively divided into two groups for high and low anti-PPAD IgG titers according to the median measurements. Genotypes at 8 functional single nucleotide polymorphisms (SNPs) related to RA were also determined. Results: After 3 and 6 months of therapy, patients with low anti-PPAD IgG titers showed a significantly greater decrease in changes in the Disease Activity Score including 28 joints using C-reactive protein (DAS28-CRP) (P = 0.04 for both) and anti-cyclic citrullinated peptide (CCP) IgG levels (P = 0.03 and P = 0.04) than patients with high anti-PPAD IgG titers, although these parameter values were comparable at baseline. The anti-PPAD IgG titers were significantly positively correlated with changes in the DAS28-CRP (P = 0.01 for both) and the anti-CCP IgG levels (P = 0.02 for both) from baseline to 3 and 6 months later. A multiple regression analysis revealed a significantly positive association between the anti-PPAD IgG titers and changes in the DAS28-CRP after 6 months of bDMARD therapy (P = 0.006), after adjusting for age, gender, smoking, periodontal condition, and RA-related SNPs. Conclusion: The serum IgG levels to PPAD affect the clinical response to bDMARD in patients with RA. [ABSTRACT FROM AUTHOR]