This study aimed to compare the efficacy and safety of baricitinib in patients with rheumatoid arthritis (RA) receiving different doses based on renal function. We conducted a retrospective study within the JAK Study Group, involving 23 facilities in Fukuoka Prefecture, examining patients treated with baricitinib for RA. Patients were categorized into two dose groups: 4 mg with normal/mild renal dysfunction and 2 mg with moderate renal dysfunction. Baricitinib’s efficacy, retention rate, and safety were compared between the groups after propensity score matching. After propensity score matching, disease duration, methotrexate dosage, and anti-cyclic citrullinated peptide antibody positivity rate were balanced across 33 patients in both groups. No significant differences were observed between the groups in tender/swollen joint counts, changes in evaluator/patient global assessments, achievement rate of low disease activity, remission rate on clinical/simplified disease activity indices, or retention rate. Additionally, the incidence of adverse events aligned with previous reports, indicating similar drug safety profiles. Baricitinib 2 mg in RA patients with moderate renal dysfunction showed comparable efficacy and retention rate to 4 mg in patients with normal/mild renal dysfunction. The incidence and types of adverse events were consistent with previous studies, indicating the safety of the drug at these dosages.

The efficacy and safety of sarilumab (SARI) were investigated in real-world clinical practice in Japan. Subjects were 121 rheumatoid arthritis (RA) patients in 23 medical institutions in Fukuoka Prefecture, Japan, who started treatment with SARI between May 2018 and November 2021. Data on the SARI starting dose, patients’ baseline characteristics, disease activity, and blood test data at the start of treatment, as well as follow-up data on the SARI dose, disease activity, and adverse events until Week 52. Safety and the continuation rate calculated by the Kaplan–Meier method were evaluated, and the effectiveness of treatment at 1 year was assessed using the clinical disease activity index (CDAI). Patients’ baseline characteristics for which significant differences were evident were adjusted with a propensity score by using the inverse probability of treatment-weighting (IPTW) method. The continuation rate at Week 52 was 66.1

Objectives We performed post-hoc analyses of the ORIGAMI study to investigate whether concomitant methotrexate (MTX) influences the clinical outcomes of abatacept in biologic-naive patients with rheumatoid arthritis. Methods Enrolled patients (n = 325) were divided into two groups according to whether abatacept was prescribed without (MTX-) or with (MTX+) concomitant MTX. We compared the changes in Simplified Disease Activity Index (SDAI), Disease Activity Score-28 with C-reactive protein (DAS28-CRP), and Japanese Health Assessment Questionnaire (J-HAQ) through to 52 weeks of treatment, the abatacept retention rate, and safety. Results At Week 52, the mean SDAI (8.9 vs. 8.8), DAS28-CRP (2.6 vs. 2.6), and J-HAQ (0.92 vs. 0.91) scores were comparable in the MTX- (n = 129) and MTX+ (n = 150) groups. Multivariable logistic regression revealed no significant association between MTX use and SDAI (low disease activity) or J-HAQ (minimum clinically important difference). The abatacept retention rates, estimated using the Kaplan-Meier method, were 73.2% and 66.7% in the MTX- and MTX+ groups, respectively. Adverse events occurred in 47.5% (of 139) and 52.2% (of 159) of patients in the MTX- and MTX+ groups, respectively. Conclusion The effectiveness and safety of abatacept appeared comparable with or without concomitant MTX in this real-world clinical setting.

Purpose: Two anti-TNF biologics, infliximab and etanercept, are extremely useful for inflammatory diseases such as rheumatoid arthritis (RA). However, approximately 20 to 30% of RA have been described as non-responders. Here, we analyzed the statistical relationships of whole genome single nucleotide polymorphisms (SNPs) with remission or low disease activity (LDA) among RA and developed algorithms using SNPs to predict effectiveness of these biologics. Methods: The total study subjects (first, second and validation population for each infliximab and etanercept) were 260 RA patients for infliximab and another 251 RA patients for etanercept. Effectiveness of infliximab and etanercept was assessed using DAS28-CRP. In first, second and the combined population, relationships of 277,339 SNPs with remission and LDA were analyzed using case-control analyses by Fisher’s exact tests for each infliximab and etanercept. We picked up SNPs (P < 0.05) from each first, second and combined population. Then, 10 SNPs with lower P value in the combined population were selected from common SNPs among the first, second and combined populations. We developed algorithms using the 10 SNPs to predict effectiveness of infliximab and etanercept. In the validation population, availability of the algorithms was evaluated. Results: Using combined infliximab-remission and LDA algorithms in the validation population, the accuracy was 90.4%. Using combined etanercept-remission and LDA algorithms in validation population, the accuracy was 76.8%. Conclusions: The combined use of our two algorithms using SNPs may be very useful in the prediction of remission or LDA before treatment with infliximab or etanercept.

Abatacept may exert its clinical effect on rheumatoid arthritis (RA) by suppressing anti-cyclic citrullinated peptide (CCP) antibody production. This study was undertaken to test this hypothesis by examining the changes of disease activity of RA and anti-CCP antibody levels over time after starting abatacept. Sixty Japanese RA patients who started abatacept were included in this multicenter, prospective observational study. Simple Disease Activity Index (SDAI) and anti-CCP antibody levels were evaluated at 12, 24, and 52 weeks. The mean SDAI score significantly decreased within 12 weeks after starting abatacept and was maintained thereafter. On the contrary, the mean anti-CCP antibody levels did not change until 52 weeks. At the individual level, there were substantial changes of anti-CCP antibody levels, but these were not correlated with the changes of disease activity at any time points. Thus, abatacept reduces the disease activity of RA independently of modulating anti-CCP antibody production.

Objectives: To investigate the efficacy of suppressing joint destruction with subcutaneous tocilizumab (TCZ-SC) for Japanese rheumatoid arthritis (RA) patients in the real-world clinical setting. Methods: This 1-year prospective, multicenter study included 110 RA patients in whom TCZ-SC was newly initiated. Primary endpoint was the change from baseline in vdH-modified total Sharp score (mTSS) at week 52. Structural remission was defined as yearly mTSS of 0.5 or less. Disease activity was evaluated using the disease activity score (DAS28-ESR) and clinical disease activity index (CDAI). Results: At baseline, the patients? mean age was 58.6 years, and the mean disease duration was 10.6 years. The proportion of patients who were na?ve for biologics was 44.5%, and 64.5% concomitantly received methotrexate. The yearly mTSS showed significant improvement from 9.41 before TCZ-SC initiation to ?0.15 after 52 weeks. The structural remission rate was 76.1%. After 52 weeks, the DAS28-ESR and CDAI remission rates were 52% and 21%, respectively. Although the previous usage of biologics and baseline disease activity significantly affected the clinical remission, no factors with significant effects on structural remission were identified. Conclusion: These findings support the efficacy of TCZ-SC in suppressing disease activity as well as joint destruction over a 1-year period.

Objective: Upper limit of methotrexate (MTX) for patients with rheumatoid arthritis (RA) was recently increased from 8 to 16mg/week in Japan. We therefore examined the effect of concomitant MTX dose on the efficacy of adalimumab (ADA) in clinical practice.Method: Sixty-one consecutive RA patients treated with ADA were followed for minimum 52 weeks and retrospectively compared by MTX dose; patients receiving concomitant MTX of 10mg/week or more (MTX >= 10mg group) and <10mg/week (MTX <10mg group). Disease activity and remission were evaluated by the disease activity score 28 (DAS28) criteria.Results: The MTX >= 10mg group consistently showed better improvement in DAS28 and resulted in more patients (52.8%) with DAS28-remission compared with the MTX <10mg group (26.1%). Multivariate analysis showed that MTX >= 10mg had a significant effect on DAS28 remission with odds ratio of 5.12. ADA retention rate was 72.2% in MTX 10mg group compared with 52.0% in MTX <10mg group. Discontinuation of ADA due to adverse events were comparable in the MTX 10mg and MTX <10mg groups (11.1% vs. 12.0%).Conclusions: These findings support the critical role of concomitant MTX in the efficacy of ADA, and recommend use of MTX >= 10mg in Japanese RA patients.

Objective. To evaluate the longterm safety and efficacy of subcutaneous tocilizumab (TCZ-SC) as monotherapy in patients with rheumatoid arthritis (RA). Methods. Of 346 patients who received 24 weeks of double-blind treatment with either TCZ-SC monotherapy, 162 mg every 2 weeks (q2w); or intravenous TCZ (TCZ-IV) monotherapy, 8 mg/kg every 4 weeks; 319 patients continued to receive TCZ-SC q2w in the 84-week open-label extension (OLE) of the MUSASHI study (JAPICCTI-101117). Efficacy, safety, and immunogenicity were evaluated for all patients treated with TCZ during 108 weeks. Results. The proportions of patients who achieved American College of Rheumatology 20/50/70 responses, low disease activity [28-joint Disease Activity Score (DAS28) ≤ 3.2], or remission (DAS28 < 2.6) at Week 24 were maintained until Week 108. The incidences of adverse events and serious adverse events were 498.3 and 16.9 per 100 patient-years (PY), respectively. The overall safety of TCZ-SC monotherapy was similar to that of TCZ-IV monotherapy. Rates of injection site reactions (ISR) through 108 weeks remained similar to rates through 24 weeks. ISR were mild and did not cause any patient withdrawals. No serious hypersensitivity events (including anaphylactic reactions) occurred. Anti-TCZ antibodies were present in 2.1% of patients treated with TCZ-SC monotherapy. Conclusion. TCZ-SC monotherapy maintained a favorable safety profile and consistent efficacy throughout the 108-week study. Like TCZ-IV, TCZ-SC could provide an additional treatment option for patients with RA.

BACKGROUND:Tumor necrosis factor (TNF)-α inhibitors are widely used for rheumatoid arthritis (RA). However, there are several risks to use TNFα inhibitors. Given the properties of TNF-α inhibitors, prevention and early detection of tuberculosis (TB) are especially important. Even among TNF-α inhibitors, the risk of TB infection differs according to each drug. The incidence of TB is lowest with etanercept (ETN). We present a case of urinary tract TB during treatment with ETN.CASE REPORT:A 58-year-old woman was receiving ETN for RA. Before starting ETN, isoniazid (INH) prophylaxis was started. RA was well controlled by ETN. However, 32 months after starting ETN, she noticed urinary frequency and a sensation of residual urine. The diagnosis was elusive, and it took 3 months until urinary tract TB was finally diagnosed. The TB resolved with antituberculosis medication, but RA disease activity flared up after ETN was discontinued. ETN was resumed with careful monitoring for TB recurrence. After resuming ETN, the RA was again well controlled, with no recurrence of TB.CONCLUSIONS:Patients should be monitored for development of TB during ETN treatment, but ETN can be used safely with careful management.

A multicenter, open‐label, dose‐escalation phase 1/2 study was undertaken to evaluate the optimal subcutaneous tocilizumab dose that would result in exposure comparable to the intravenous tocilizumab 8‐mg/kg approved dose in patients with rheumatoid arthritis. A pharmacokinetic and biomarker approach was used to estimate the clinical optimal dose regimen of subcutaneous tocilizumab. Safety and efficacy of subcutaneous tocilizumab were assessed as secondary end points. Patients received subcutaneous tocilizumab at 81 mg every 2 weeks (q2w) (n = 8), 162 mg q2w (n = 12), or 162 mg weekly (qw) (n = 12) for 24 weeks. 88% of 162‐mg q2w patients and 100% of 162‐mg qw patients maintained mean serum trough tocilizumab concentrations of ≥1 µg/mL, and had exposure comparable with the approved intravenous tocilizumab dose of 8 mg/kg; this resulted in normalized C‐reactive protein levels and improvement in ACR20/50/70 responses. The most common adverse events were abnormal laboratory results, which were mild in severity. Anti‐tocilizumab antibodies were detected in a few patients in the 81‐mg q2w and 162‐mg qw groups. In conclusion, coupled with efficacy and tolerability results, the appropriate dose of subcutaneous tocilizumab was determined to be 162 mg q2w for Japanese patients.

Objectives. This study aimed to evaluate the remission in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ), based on prospectively registered data in clinical practice. Methods. We studied 114 consecutive RA patients treated with TCZ for an average of 3.5 years. Remission was evaluated by using the EULAR criteria and the new ACR/EULAR Boolean-based criteria. Results. Among 114 patients (average age 52.2 years; average disease duration 10.6 years), 76 (67 %) had previously received anti-TNF biologics. Mean baseline DAS28-ESR of 5.4 and improved to 2.4 at 36 months. Overall, DAS28-ESR <2.6 was attained by 66.7 %, while ACR/EULAR remission was attained by 35.1 %. ACR/EULAR remission rate was significantly higher in the patients who were biologics-naïve and had good response at the first month. Among 23 patients who completed the treatment for 3 years and had ACR/EULAR remission at 1 year, 15 (65 %) remained in the remission and 16 (70 %) had a DAS28-ESR <2.6 at the final follow-up. The retention rate at 36 months was 68.2 %. Conclusions. In patients with RA, TCZ is highly effective for both biologics-naïve patients and patients previously exposed to biologics, achieving a high remission rate and drug continuation rate (68.2 %) in clinical practice.

Objectives This study aimed to evaluate the remission in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ), based on prospectively registered data in clinical practice. Methods We studied 114 consecutive RA patients treated with TCZ for an average of 3.5 years. Remission was evaluated by using the EULAR criteria and the new ACR/ EULAR Boolean-based criteria. Results Among 114 patients (average age 52.2 years; average disease duration 10.6 years), 76 (67 %) had previously received anti-TNF biologics. Mean baseline DAS28-ESR of 5.4 and improved to 2.4 at 36 months. Overall, DAS28-ESR \2.6 was attained by 66.7 %, while ACR/EULAR remission was attained by 35.1 %. ACR/ EULAR remission rate was significantly higher in the

Background and Objectives Limited data are available regarding the use of golimumab (100 mg) every 4 weeks, with or without methotrexate (MTX). The aim of this retrospective analysis was to evaluate the effectiveness and safety of golimumab following usual clinical practice in Japanese patients with rheumatoid arthritis (RA) according to the recommendations given in the Japanese package insert.Patients and Methods Japanese RA patients with moderate-to-high disease activity, according to the 28-joint disease activity score based on C-reactive protein (DAS28-CRP) criteria, despite treatment with MTX or another biological agent, were enrolled. Patients were assigned to 50 mg golimumab plus MTX or 100 mg golimumab monotherapy every 4 weeks for 24 weeks. All patients were given MTX if it was not contraindicated. The primary endpoint was the proportion of patients achieving clinical remission (defined as a DAS28-CRP <2.3 or a simplified disease activity index [SDAI] score <3.3) at 24 weeks.Results Most patients received combined 50 mg golimumab plus MTX (41/43). In these patients, the primary endpoint, clinical remission, was attained in 83 % of patients according to DAS28-CRP criteria (p < 0.001) and 69 % according to SDAI criteria (p < 0.001) by week 24. Adverse events were reported in 11.6 % of patients receiving golimumab.Conclusions Golimumab (50 mg) plus MTX effectively reduced the signs and symptoms of RA and was generally well tolerated in patients with an inadequate response to MTX and other biological agents.