Efficacy of switching from originator etanercept to biosimilar YLB113 in real-world patients with rheumatoid arthritis: A retrospective 12 months follow-up study.

Purpose: To investigate the disease activity in real-world patients with rheumatoid arthritis (RA) who switched from originator etanercept (ETN) to biosimilar YLB113. Methods: Forty one RA patients who switched from ETN to YLB113 were divided into 2 groups based on the Disease Activity Score based on the 28-joint count (DAS28) 12 months after switching (R group: DAS28 < 2.6, N group: DAS28 ≥ 2.6), and the baseline characteristics were statistically examined. A receiver operating characteristics (ROC) analysis was performed to estimate the cut-off value of DAS28 at baseline to achieve remission 12 months after switching. Results: There was no significant difference in the DAS28 at baseline and 12 months after switching (p = .83). Sixteen out of the 20 patients in remission at baseline achieved remission after switching. A univariate analysis revealed the rheumatoid factor (p = .04) and DAS28 (p < .001) at baseline were significantly lower in the R group than in the N group. Furthermore, logistic regression analysis revealed DAS28 was an independent factor (p = .004) for achieving remission 12 months after switching. An ROC curve analysis showed the optimal cut-off value for DAS28 at baseline to achieve remission at 12 months after switching was 2.5. Conclusions: RA patients who achieved remission using originator ETN, were able to maintain remission even if they switched to YLB113.

Total elbow arthroplasty for hemophilic osteoproliferative elbow arthritis with severe flexion contracture: A case report.

Total elbow arthroplasty is effective for pain relief and the functional improvement of severe symptomatic hemophilic osteoproliferative arthropathy. Nevertheless, high complication rates have been reported. This report describes clinical results obtained at 30-month follow-up of total elbow arthroplasty in a hemophilic patient with severe flexion contracture. A 50-year-old patient with advanced left elbow hemophilic arthropathy underwent unlinked total elbow arthroplasty. He had sustained an intraoperative fracture of the medial part of a supracondylar humerus complication. To control perioperative bleeding, strict factor VIII replacement therapy was performed under the guidance of hematologists. The total elbow range of motion was 35° preoperatively, but it had improved to 110° postoperatively. The Patient-Rated Elbow Evaluation Japanese version score, which was 53.7 preoperatively, improved to 10.7 postoperatively. During the 30 months after operation, no complication occurred. Good clinical results have been obtained under close collaboration with hematologists and close patient adherence following treatment.

The impact of bDMARDs on postoperative complications in patients with rheumatoid arthritis: A systematic review and meta-analysis.

BACKGROUND: The influence of biological disease-modifying antirheumatic drugs (bDMARDs) on postoperative surgical site infection (SSI) and venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA) has not yet been clarified. METHODS: A systematic literature search was performed using PubMed, Web of ScienceTM, Scopus, and The Cochrane Library databases to identify eligible studies published up to August 2023. All studies comparing postoperative SSI or VTE rates in RA patients with or without bDMARD treatment were included. The protocol for this study was registered in PROSPERO (CRD42021246264) and is available on the University of York website. RESULTS: Overall, 20 studies with 71,885 RA patients and 6 studies with 7918 RA patients were included for postoperative SSI and VTE comparisons, respectively. Patients treated with bDMARDs had significantly higher rates of postoperative SSI than those without treatment (odds ratio 1.50, 95% confidence interval 1.23-1.83, P < .0001). However, these significant differences disappeared in the analysis restricted to 9 studies involving non-tumor necrosis factor α inhibitors. The use of bDMARDs seemed to increase the rate of postoperative VTE (odds ratio 2.20, 95% confidence interval 1.30-3.72, P = .003). A subgroup analysis showed that postoperative osseous complications were significantly less frequent in RA patients with bDMARD treatment than in those without treatment. CONCLUSION: RA patients treated with bDMARDs had an increased risk of not only postoperative SSI but also VTE. While bDMARD usage merits appropriate attention, there might be positive aspects as well. Further data will be needed to confirm the postoperative risks of bDMARD usage in RA patients.

Choice of and response to treatment in patients with early-diagnosed rheumatoid arthritis: Real-world data from an inception cohort in Japan (NICER-J).

OBJECTIVE: Various guidelines recommend that patients with early rheumatoid arthritis (RA) try to achieve clinical remission within 6 months, and early therapeutic intervention is important to this end. This study aimed to investigate short-term treatment outcomes of patients with early-diagnosed RA in clinical practice and to examine predictive factors for achieving remission. METHODS: Of the 210 patients enrolled in the multicenter RA inception cohort, 172 patients who were followed up to 6 months after treatment initiation (baseline) were included. Logistic regression analysis was used to examine the impact of baseline characteristics on achievement of Boolean remission at 6 months. RESULTS: Participants (mean age, 62 years) initiated treatment after a mean of 19 days from RA diagnosis. At baseline and 3 and 6 months after treatment initiation, proportions of patients using methotrexate (MTX) were 87.8%, 89.0%, and 88.3%, respectively, and rates of Boolean remission were 1.8%, 27.8%, and 34.5%, respectively. Multivariate analysis revealed that physician global assessment (PhGA) (Odds ratio (OR): 0.84, 95% confidence interval (CI): 0.71-0.99) and glucocorticoid use (OR: 0.26, 95% CI: 0.10-0.65) at baseline were independent factors that predicted Boolean remission at 6 months. CONCLUSION: After a diagnosis of RA, satisfactory therapeutic effects were achieved at 6 months after the initiation of treatment centered on MTX according to the treat to target strategy. PhGA and glucocorticoid use at treatment initiation are useful for predicting the achievement of treatment goals.

Anti-drug antibodies and rheumatoid factor level in patients with rheumatoid arthritis using the infliximab biosimilar CT-P13.

BACKGROUND: This study evaluated the existence of anti-drug antibodies (ADAs) before and 52 weeks after switching from intravenous infliximab (IFX) to intravenous CT-P13 in patients with rheumatoid arthritis (RA). METHODS: We performed a prospective observational study. Twenty-eight patients (7 males and 21 females) received intravenous CT-P13 after intravenous IFX, and the clinical data were collected from medical records. Rheumatoid factor (RF) and anti-CCP antibody were examined at baseline. At baseline and 52 weeks after the start of CT-P13 treatment, the Disease Activity Score based on the 28-joint count and the levels of C-reactive protein, matrix metalloproteinase-3, and ADA, as well as the erythrocyte sedimentation rate were evaluated. ADAs were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Seven (25%) and 6 (21.4%) cases were positive for ADAs at baseline and 52 weeks after, respectively. One case became newly positive for ADAs at week 52. Two of the ADA-positive cases became ADA-negative 52 weeks after. The ADA-positive group showed significantly higher RF values at baseline than the ADA-negative group (p = 0.03). No difference was observed between the ADA-positive group and the ADA-negative group regarding other clinical parameters. CONCLUSIONS: The positive rate of ADAs did not increase after switching from intravenous IFX to intravenous CT-P13. Among the patients with ADAs, a high level of RF was observed at baseline.

Do biologic therapies reduce aortic inflammation in rheumatoid arthritis patients?

OBJECTIVES: Rheumatoid arthritis (RA) patients have an increased risk of cardiovascular disease (CVD). In the present study, we evaluated the inflammatory activity of the ascending aorta in RA patients who received biological treatment. METHODS: We assessed the aortic wall inflammation of RA patients using 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography before and after 6 months of biologic therapies. We also compared the inflammatory activity at the aortic wall in RA patients with remission or low disease activity (RLDA) and those with moderate or high disease activity (MHDA). The aortic uptake was measured by the standardized uptake value (SUV) and the target-to-background ratio (TBR). RESULTS: A total of 64 patients were included in the analysis (mean age, 58.4 ± 13.8 years old; female, 77%). The Disease Activity Score for 28 joints (DAS28) erythrocyte sedimentation rate (ESR) had significantly decreased after 6 months: from 5.0 ± 1.2 to 3.3 ± 1.2 (p < 0.001). The FDG uptake in the ascending aorta changed from baseline to 6 months, showing a maximum SUV (SUVmax) of 1.83 ± 0.34 to 1.90 ± 0.34 (p = 0.059) and TBR of 1.71 ± 0.23 to 1.75 ± 0.24 (p = 0.222). The SUVmax and TBR after 6 months were significantly higher in the RLDA group than in the MHDA group (2.05 ± 0.32 vs. 1.79 ± 0.33 (p = 0.002) and 1.89 ± 0.33 vs. 1.65 ± 0.20 (p = 0.001), respectively). The percentage of monocytes also significantly increased from baseline to 6 months: from 5.9 ± 1.6 to 6.9 ± 2.6 (p = 0.032). CONCLUSION: The inflammation activity at the ascending aorta in RA patients did not change significantly after 6 months of biological treatment. RA patients with a low disease activity or in clinical remission after 6 months of biological treatment still had an increased inflammatory activity at the aortic wall.

Does periodontitis affect the treatment response of biologics in the treatment of rheumatoid arthritis?

BACKGROUND: Rheumatoid arthritis (RA) and periodontitis (PD) have been suggested to share many clinical and pathological features. However, few reports have investigated the relationship between the degree of PD and the treatment response to RA. This study aimed to examine the relationship between the extent of PD and the treatment response to biologics in RA patients using FDG-PET/CT. METHODS: Sixty RA patients (male, n = 14; female, n = 46; average age, 58.3 years) treated with biologic agents were included in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The maximum standardized uptake value (SUVmax) was used as a representative value for the assessment of the FDG uptake in periodontal tissue and joints including the bilateral shoulders, elbows, wrists, hip, knees, and ankle joints. The Disease Activity Score (DAS) 28-CRP and the following clinical parameters were assessed: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and matrix metalloproteinase 3 (MMP-3). The relationship between the treatment response of RA and the baseline SUVmax of the periodontal tissue was evaluated. RESULTS: The baseline periodontal SUVmax was related to patient age (r = 0.302, p = 0.009) and the ACPA level (r = 0.265, p = 0.025). The DAS28-CRP, CRP, ESR, MMP-3, and joint SUVmax values were significantly decreased after 6 months of biological therapy. However, the mean periodontal SUVmax, ACPA, and RF showed no significant changes after treatment. There was a significantly negative correlation between the baseline periodontal SUVmax and the treatment response of DAS28-CRP (r = - 0.369, p = 0.004). CONCLUSION: There was a negative correlation between the extent of PD at baseline and the treatment response of RA patients who received biological therapy. The evaluation of the periodontal condition is considered to be an essential part for the management of RA.

Association between upper extremity dysfunction and sleep disturbance in an elderly general population.

OBJECTIVE: Several upper extremity disorders are associated with sleep disturbance in patient populations. This study evaluated the relation between self-assessment of upper extremity function and sleep disturbance in an elderly general population. METHODS: A total of 159 participants (56 men, 103 women, 38-88 years old, mean age of 66.4 years) completed a self-administered questionnaire including items for sex, weight, height, and dominant hand. Upper extremity dysfunction was investigated using Quick Disabilities of the Arm, Shoulder, and Hand of the Japanese Society for Surgery of the Hand. The sleep disturbance severity was evaluated using a Japanese version of the Athens Insomnia Scale. Quality of life was assessed using the EuroQol-5-dimension-3-level, Japanese version. We measured the bilateral hand grip as an indicator of hand muscle function. Statistical tests were applied to clarify the association between upper extremity dysfunction and screening results for sleep disturbance. RESULTS: Of 159 participants, 45 (28.3%) had sleep disturbance as assessed using Japanese version of the Athens Insomnia Scale (11 men and 34 women; mean age of 68.1 years). Japanese version of the Athens Insomnia Scale scores correlated with the EuroQol index; EuroQol visual analog scale; and Quick Disabilities of the Arm, Shoulder, and Hand scores. The Quick Disabilities of the Arm, Shoulder, and Hand score and dominant grip strength of the participants with sleep disturbance were significantly higher than those of the no sleep disturbance group. The EuroQol index score and visual analog scale of those reporting a sleep disturbance were significantly lower than those of the no sleep disturbance group. CONCLUSION: Self-administered upper extremity health condition as assessed using Quick Disabilities of the Arm, Shoulder, and Hand correlated with sleep disturbance. Our results suggest a link between upper extremity conditions and sleep disturbance.

Shoulder tenderness was associated with the inflammatory changes on magnetic resonance imaging in patients with rheumatoid arthritis.

The aim of this study was to assess the association between the shoulder tenderness and the inflammatory changes on magnetic resonance imaging (MRI) in the rheumatoid shoulder. Forty-one shoulders of 41 patients with rheumatoid arthritis (RA) were examined. We evaluated synovitis, erosion and bone marrow edema, by counting the numbers of each positive site, and rotator cuff tears on shoulder MRI. The association between the shoulder tenderness and the MRI findings were statistically analyzed. Twenty-three of 41 patients had tenderness in the shoulder joints. There were 20 shoulders (48.8%) with rotator cuff tear, and no significant difference was observed in the prevalence of rotator cuff tear between the tenderness group and non-tenderness group (p = 0.080). There were no significant differences in the demographic data between these two groups. In MRI findings, we found significant difference for the synovitis (p = 0.001) and bone marrow edema (p = 0.021). Synovitis was strongly associated with the shoulder tenderness (OR: 3.996, 95% CI: 1.651-9.671). Synovitis was the factor most associated with shoulder tenderness.

Effects of denosumab on bone mineral density and bone turnover markers in rheumatoid arthritis patients switching from bisphosphonates.

BACKGROUND: To compare the efficacy of 12-month denosumab treatment on bone mineral density (BMD) and bone turnover markers (BTMs) between treatment-naïve osteoporosis patients with rheumatoid arthritis (RA) and those with previous bisphosphonate (BP) therapy. METHODS: A total of 36 RA patients with osteoporosis completed 12-month follow-up. Twenty-five patients were osteoporotic treatment-naïve (naïve group), and 11 patients were previously treated with BPs (switch group) (average 7.9 years). BMD and BTMs were measured before and 6 and 12 months after treatment. RESULTS: BTM levels were higher in the naïve group at baseline. However, the same level of suppression was achieved at 6 months in both groups. Spine BMD increased significantly in both groups. There was no significant difference in the mean percent changes of BMD of the spine (naïve group: 6.8 ± 0.8, switch group: 5.1 ± 1.5), femoral neck (2.9 ± 1.4, 2.9 ± 1.3), and total hip (1.7 ± 0.9, 1.4 ± 1.1) between these two groups at 12 months. CONCLUSIONS: The effects of denosumab on BMD and BTMs of the switch group after long-term BP treatment are comparable to those of the naïve group in RA patients. Thus, switching BPs to denosumab is one of the useful options to treat osteoporosis with RA.

The three-year efficacy of iguratimod in clinical daily practice in patients with rheumatoid arthritis.

Objectives: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid arthritis (RA) patients. Methods: Sixty-nine RA patients (14 males and 55 females, mean age of 64.0 years) receiving IGU-containing therapies were enrolled. We divided these patients into three groups based on the treatment at the baseline: an IGU group, a methotrexate (MTX) plus IGU group, and a biologics plus IGU group. The baseline characteristics and clinical course were evaluated over three years. Predictive factors associated with the achievement of low disease activity (LDA) were statistically analyzed. Results: The survival rate of IGU therapy at 3 years was 40.6%. The disease activity was significantly decreased in the IGU group and MTX plus IGU group compared with the baseline. Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the factors associated with the achievement of remission or LDA at three years. Conclusion: IGU was effective without MTX or bDMARDs as well as in combination with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of IGU were associated with clinical remission or LDA achievement at three years.

Shoulder Stretching Intervention Reduces the Incidence of Shoulder and Elbow Injuries in High School Baseball Players: a Time-to-Event Analysis.

We prospectively evaluated the effects of a prevention program on the incidence of shoulder and elbow injuries in high school baseball pitchers. Ninety-two pitchers participated in this study and were taught to perform stretching and strength exercises aimed at improving shoulder external rotation strength in the preseason. The pitchers freely chose to participate in one of four groups [SM-group: performed both exercises, S-group: performed stretching exercise only, M-group: performed strength training only, and N-group: performed neither intervention]. Injury was defined as inability to play for ≥8 days because of shoulder/elbow symptoms. Kaplan-Meier survival curves were generated and hazard ratios (HRs) for injury occurrence were calculated using multivariate Cox regression. Log-rank test was used for between-group comparisons of survival distributions. The injuries occurred in 25, 35, and 57% of participants and median times to injury were 89, 92, and 29.5 days in the S- (n = 32), SM- (n = 46), and N- (n = 14) group, respectively. Nobody chose M-group. HRs were 0.36 and 0.47 for the S- and SM-group, respectively, based on the N-group. The incidence of injury was significantly lower in the S-group than in the N-group (p = 0.04). Daily posterior shoulder stretching may reduce the incidence of the injuries in high school baseball pitchers.

Bone turnover markers and the factors associated with atypical femur fractures among Japanese patients.

Many previous reports have indicated that atypical femur fractures (AFFs) are associated with the administration of bisphosphonates (BPs). A number of risk factors and hypotheses regarding the pathogenesis of AFFs have been reported to date. The purpose of the present study was to identify the factors associated with AFFs in Japanese individuals and to elucidate the association between bone metabolism and AFFs by evaluating bone turnover markers (BTMs). We prospectively reviewed all patients with femur fractures and identified the patients with AFFs and typical femur fractures (TFFs). We collected the demographic and clinical data that were relevant to the present study, namely age, gender, affected side, affected site, concomitant medical history, and comorbid conditions, and measured the levels of BTMs within 24h after trauma. Welch's test and Fisher's exact probability test were used for the statistical analyses. A total of 338 patients, including 10 patients with AFFs and 328 patients with TFFs, were analyzed under the inclusion criteria. The use of BPs (p<0.001) and collagen disease and chronic granulomatous disease (CD/CGD) (p=0.025) were more frequently observed in patients with AFFs than in patients with TFFs, while the levels of BTMs, including N-terminal propeptides of type 1 procollagen (P1NP), isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) and undercarboxylated osteocalcin (ucOC) were significantly lower in patients with AFFs than in patients with TFFs. Furthermore, the level of TRACP-5b was found to be significantly lower in patients with atypical subtrochanteric fractures than in atypical diaphyseal fractures (p=0.025). Moreover, the levels of P1NP (p=0.016) and TRACP-5b (p=0.015) were found to be significantly lower in patients with AFFs than in patients with TFFs in a subgroup analysis of BPs users. The use of BPs was considered to be a factor associated with AFFs. Our comparison of the BTMs in patients with AFFs and TFFs indicated that the severe suppression of bone turnover was associated with the pathogenesis of AFFs. The extent of the influence of suppressed turnover on the pathogenesis of AFFs may differ depending on the fracture site.