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Background: The study aimed to compare the effectiveness of photodynamic therapy (PDT) and topical clobetasol therapy in treating oral lichen planus (OLP). To address the absence of commercially available drug carriers, innovative proprietary solutions were developed. These carriers were designed to enhance the therapies: one for the photosensitizer to reduce its contact time with the mucosa, and another for the steroid to prolong its contact duration. Methods: A randomized, single-blind clinical trial lasting three months was conducted on 29 patients with bilateral oral lichen planus using a full contralateral split-mouth design. The authors utilized proprietary carriers containing 5% methylene blue and 0.025%. Lesion size, as well as scores on the Thongprasom, Abisis, and VASs, were assessed during the study. Results: Relatively low rates of complete remission of lichen were demonstrated immediately after treatment, 10.3% after PDT and 3.4% after clobetasol, but after 3 months, 79% after PDT, and 62% after CLO. After 3 months of treatment, a reduction of 79.88% for PDT and 56.3% for CLO in the area of the evaluated lesions was achieved. Conclusions: PDT emerges as an equally effective method for treating OLP in terms of clinical outcomes, with the added advantage of avoiding many complications associated with conventional therapy.

The development of polymer matrices as dental drug carriers takes into account the following technological aspects of the developed formulations: the composition and the technology used to manufacture them, which affect the properties of the carriers, as well as the testing methods for assessing their behavior at application sites. The first part of this paper characterizes the methods for fabricating dental drug carriers, i.e., the solvent-casting method (SCM), lyophilization method (LM), electrospinning (ES) and 3D printing (3DP), describing the selection of technological parameters and pointing out both the advantages of using the mentioned methods and their limitations. The second part of this paper describes testing methods to study the formulation properties, including their physical and chemical, pharmaceutical, biological and in vivo evaluation. Comprehensive in vitro evaluation of carrier properties permits optimization of formulation parameters to achieve prolonged retention time in the dynamic oral environment and is essential for explaining carrier behavior during clinical evaluation, consequently enabling the selection of the optimal formulation for oral application.

Currently, there is no surgical assistance system that can perform a three-dimensional (3D) planned total hip arthroplasty (THA) by methods other than surgical assistance navigation or robots. However, they are expensive, cumbersome, and subject to additional invasiveness, so there is a need for a simpler and less expensive 3D surgical support system. In this study, THA was performed using the anterolateral approach (Watson-Jones) in the supine position in 23 subjects to examine the efficacy and safety of a patient-specific femoral guide linked to 3D surgery support software. In 48% of the subjects, the difference in anterior torsion angle from the preoperative plan was within ±5 degrees, while in 83% of the subjects, the difference was within ±10 degrees. The 95% confidence interval (4.61-8.70) of the absolute difference did not fall below the pre-defined threshold of 7.2 degrees (p = 0.293). No adverse events were observed other than 2 cases (8.7%) of hemorrhage that required a blood transfusion. We confirmed the efficacy and safety of the patient-specific femoral guide in anterolateral supine approach THA.

A hippocampal mossy fiber synapse implicated in learning and memory is a complex structure in which a presynaptic bouton attaches to the dendritic trunk by puncta adherentia junctions (PAJs) and wraps multiply branched spines. The postsynaptic densities (PSDs) are localized at the heads of each of these spines and faces to the presynaptic active zones. We previously showed that the scaffolding protein afadin regulates the formation of the PAJs, PSDs, and active zones in the mossy fiber synapse. Afadin has two splice variants: l-afadin and s-afadin. l-Afadin, but not s-afadin, regulates the formation of the PAJs but the roles of s-afadin in synaptogenesis remain unknown. We found here that s-afadin more preferentially bound to MAGUIN (a product of the Cnksr2 gene) than l-afadin in vivo and in vitro. MAGUIN/CNKSR2 is one of the causative genes for nonsyndromic X-linked intellectual disability accompanied by epilepsy and aphasia. Genetic ablation of MAGUIN impaired PSD-95 localization and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptor surface accumulation in cultured hippocampal neurons. Our electrophysiological analysis revealed that the postsynaptic response to glutamate, but not its release from the presynapse, was impaired in the MAGUIN-deficient cultured hippocampal neurons. Furthermore, disruption of MAGUIN did not increase the seizure susceptibility to flurothyl, a GABA A receptor antagonist. These results indicate that s-afadin binds to MAGUIN and regulates the PSD-95-dependent cell surface localization of the AMPA receptor and glutamatergic synaptic responses in the hippocampal neurons and that MAGUIN is not involved in the induction of epileptic seizure by flurothyl in our mouse model., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

To improve component-placement accuracy in total knee arthroplasty, we developed two devices: an original extramedullary patient-specific guide for the femur and an original extramedullary universal guide for the tibia (EM-TIBIA). We also developed a new function in ZedView, a three-dimensional surgical assistive software, that provides the parameters necessary to install the EM-TIBIA. Compared with conventional manual methods based on X-ray two-dimensional images or ZedView, these newly developed devices function as an extramedullary intraoperative support guide in conjunction with ZedView, simplifying surgical procedures. We conducted a study to evaluate the efficacy and safety of the surgery using the new guides and software function. Nineteen patients underwent surgery. On the femoral side, the mean absolute difference of the installation alignment was within 3° for all parameters. On the other hand, on the tibial side, the mean absolute difference from the preoperative plan for the rotation was 5.26±5.30°. The proportion of patients whose difference fell within ±3° was 52.6% (95% confi dence interval: 28.9 to 75.6%), and did not meet the pre-specified criteria for efficacy (P=0.261). No serious adverse events were reported, and no excessive bleeding, thrombosis, infections, or intraoperative or postoperative fractures were noted. The two new guides can easily reproduce the preoperative plan as 3D intraoperative support jigs, but errors can occur on the tibia side due to soft tissue that is not recognized by CT, creating problems in installation accuracy.

Background: Oral Lichen planus (OLP) is a chronic inflammatory disease. Topical steroids are used as the treatment of choice. The alternative is photodynamic therapy (PDT). The study aimed to fabricate optimal biodegradable matrices for methylene blue or triamcinolone acetonide because of a lack of currently commercially available carriers that could adhere to the mucous., Methods: The study was designed as a 12-week single-blind prospective randomized clinical trial with 30 patients, full contralateral split-mouth design. Matrices for steroid and photosensitizer and laser device were fabricated. Fractal and texture analysis of photographs, taken in 405, 450, 405 + 450 nm wavelength, of lesions was performed to increase the objectivity of the assessment of treatment., Results: We achieved two total responses for treatment in case of steroid therapy and one in the case of PDT. Partial response was noted in 17 lesions treated using local steroid therapy and 21 in the case of PDT. No statistically significant differences were found between the effectiveness of both used methods. Statistically significant differences in fractal dimension before and after treatment were observed only in the analysis of photographs taken in 405 + 450 nm wavelength., Conclusions: Photodynamic therapy and topical steroid therapy are effective methods for treating OLP. Using a carrier offers the possibility of a more predictable and effective method of drug delivery into the mucous membrane. Autofluorescence enables the detection of lesions especially at the early stage of their development.

Background: The aim of the study was to compare the effectiveness of photodynamic therapy (PDT) to steroid therapy in the treatment of oral lichen planus (OLP). Due to the lack of commercially available drug carriers, innovative proprietary solutions were used for both the photosensitiser and the steroid carrier-in the first case to shorten and in the second to extend the contact of the active substance with the mucosa., Methods: A prospective, randomised, single-blind, 12-week full contralateral split-mouth clinical trial of 30 patients with bilateral oral lichen planus was conducted. The prepared matrices were incorporated with active substances methylene blue 5% and 0,05% triamcinolone. The size of lesions, Thongprasom, ABISIS, and VAS scale were evaluated., Results: Relatively high rates of complete remission of lichen were demonstrated: immediately after treatment, 33.3% with PDT and 22.2% with triamcinolone (TA), and after 3 months, 54.2% with PDT and 62.9% with TA. After 3 months of treatment, a reduction in the area of evaluated lesions of 52.7% for PDT and 41.7% for TA was achieved., Conclusion: In situations of topical or general contraindications to oral corticosteroids, resistance to them, or the need for repeated treatment in a short period of time, PDT appears to be a very promising treatment option.

Polymers in drug formulation technology and the engineering of biomaterials for the treatment of oral diseases constitute a group of excipients that often possess additional properties in addition to their primary function, i.e., biological activity, sensitivity to stimuli, mucoadhesive properties, improved penetration of the active pharmaceutical ingredient (API) across biological barriers, and effects on wound healing or gingival and bone tissue regeneration. Through the use of multifunctional polymers, it has become possible to design carriers and materials tailored to the specific conditions and site of application, to deliver the active substance directly to the affected tissue, including intra-periodontal pocket delivery, and to release the active substance in a timed manner, allowing for the improvement of the form of application and further development of therapeutic strategies. The scope of this review is polymeric drug carriers and materials developed from selected multifunctional groups of natural, semi-synthetic, and synthetic polymers for topical therapeutic applications. Moreover, the characteristics of the topical application and the needs for the properties of carriers for topical administration of an active substance in the treatment of oral diseases are presented to more understand the difficulties associated with the design of optimal active substance carriers and materials for the treatment of lesions located in the oral cavity.

This study aimed to evaluate the effectiveness of abatacept (ABA) by anti-cyclic citrullinated peptide (ACPA) status on disease activity as well as radiographic progression in patients with rheumatoid arthritis (RA) in clinical settings. A retrospective cohort study was conducted using data from a multicenter registry. Data from a total of 553 consecutive RA patients treated with intravenous ABA were included. We primarily compared the status of disease activity (SDAI) and radiographic progression (van der Heijde modified total Sharp score: mTSS) between the ACPA-negative (N = 107) and ACPA-positive (N = 446) groups. 'ACPA positive' was defined as ≥ 13.5 U/mL of anti-CCP antibody. Baseline characteristics between groups were similar. The proportion of patients who achieved low disease activity (LDA; SDAI ≤ 11) at 52 weeks was significantly higher in the ACPA-positive group. Multivariate logistic regression analysis identified ACPA positivity as an independent predictor for achievement of LDA at 52 weeks. Drug retention rate at 52 weeks estimated by the Kaplan-Meier curve was significantly higher in the ACPA-positive group. Achievement rate of structural remission (ΔmTSS ≤ 0.5) at 52 weeks was similar between groups. ABA treatment demonstrated a significantly higher clinical response and higher drug retention rate in ACPA-positive patients. Progression of joint destruction was similar between the ACPA-negative and ACPA-positive groups. Close attention should be paid to joint destruction even in patients showing a favorable response to ABA, especially when the ACPA status is positive.

Objectives: To explore predictive factors including MMP-3 for achievement of low disease activity (LDA) at 52 weeks in bio-switch rheumatoid arthritis (RA) patients treated with abatacept, for whom obtaining a good clinical response can be difficult., Methods: Participants were 423 consecutive patients with RA treated with abatacept who were observed for longer than 52 weeks and registered in the TBCR, a Japanese multicentre registry system. Multivariate logistic regression analysis was used to study factors that predict the achievement of LDA at 52 weeks in bio-naïve (n=234) and bio-switch (n=189) groups., Results: ROC analysis revealed that MMP-3 improvement rates at 12 weeks in bio-switch patients had the highest AUC with a cut-off value of 20.0% for predicting LDA achievement at 52 weeks. Multivariate logistic regression analysis revealed that, in addition to DAS28-CRP at baseline, achieving 20% improvement in MMP-3 levels at 12 weeks was an independent predictive factor (adjusted OR: 4.277, p=0.003) in the bio-switch group, whereas DAS28 was the only predictor in the bio-naïve group. Patients who achieved 20% improvement in MMP-3 levels at 12 weeks had significantly higher achievement rates of LDA at 52 weeks compared to those who did not achieve 20% improvement in the bio-switch group (60.0 vs. 33.3%, p=0.001)., Conclusions: Our findings suggest that improvement in MMP-3 levels is key to predicting the clinical efficacy of abatacept. Closer attention paid not only to major clinical indices, but also changes in MMP-3 levels, could improve our ability to optimise clinical results when treating bio-switch patients.

The aim of this study was to develop and assess a polyvinyl alcohol-cellulose derivatives-based film with incorporated povidone-iodine (PVP-I) predicted for applications in the treatment of periodontitis. Films were fabricated by solvent-casting, and their physical characteristics, such as their surface and structure morphology, mechanical properties, and disintegrating time, were evaluated. For in vitro iodine release studies and evaluation, the antimicrobial activity was tested using a modified disc diffusion method against five microbial strains. For further use, we selected the film with polyvinyl alcohol-hydroxypropyl methylcellulose (PVA/HPMC_B) based on acceptable physicochemical properties. To assess the subacute toxicity of the film composition, the tissue regeneration process was tested in rats and compared to a conventional dressing commonly used in wound healing (Spongostan). Seven days after implantation, dorsal skin sections and blood samples (n = 10, in total n = 30) were examined. The wound area, epithelium, and dermis were evaluated microscopically, while the blood collected from the rats underwent biochemical analysis. The blood biochemistry results were comparable in all three groups. No significant histological differences between the Spongostan and the placebo film developed after subcutaneous implantation were observed. In contrast, the inflammation stage was reduced and the "scar" in the dermis was smaller when PVP-I and PVA/HPMC_B films were used. A smaller local inflammatory response inflicted less tissue damage, leading to the activation of subsequent regeneration phases and restoration of the area to its original state. The results obtained confirmed that PVP-I incorporated into PVA-hydroxypropyl methylcellulose film is a promising drug carrier, working faster and more effectively than the other two dressing materials evaluated. These developments provide a promising alternative in tissue regeneration and the wound healing process.

Objective: Abatacept (ABT) demonstrates good clinical efficacy and retention in rheumatoid arthritis (RA) patients. However, no rescue treatment option against inadequate response to ABT exists. Since tacrolimus (TAC) and ABT suppress T lymphocytes via different mechanisms and a combination of these agents could potentially be effective, this study aimed to examine the efficacy and safety of add-on TAC therapy in RA patients with inadequate response to ABT., Methods: Of 550 patients treated with ABT and registered in a Japanese multicenter registry, 25 consecutive patients who underwent add-on TAC therapy and were followed for longer than 24 weeks were included in this study., Results: Mean patient age was 67.0 years, disease duration was 16.2 years, and duration of ABT treatment was 1.2 years at the initiation of add-on TAC therapy. Mean TAC dose was 1.2 mg/d at baseline and 1.6 mg/d at week 24. Mean Disease Activity Score of 28 joints - erythrocyte sedimentation rate was significantly improved at week 24 (3.35) relative to baseline (4.97). The proportion of patients who achieved low disease activity or remission was 40.0%, and the European League Against Rheumatism moderate or good response was 72.0%. ABT retention rate was 92.0% at week 24, as calculated by Kaplan-Meier analysis. Only one patient discontinued add-on TAC therapy due to an adverse event (itching sensation)., Conclusion: This is the first report describing the efficacy and safety profile of add-on TAC therapy with a focus on RA patients with inadequate response to ABT. Our findings suggest that add-on TAC therapy is a worthwhile complementary treatment option in daily clinical practice., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objective: To study the clinical effectiveness and long-term retention rate of abatacept (ABA) in elderly rheumatoid arthritis (RA) patients in daily clinical practice. Methods: A retrospective cohort study was performed using data from a multicenter registry. Our study population comprised 500 consecutive RA patients treated with ABA. We compared clinical effectiveness and ABA retention rates between the Young (≤62 years), Middle (62 to 72 years), and Elderly (≥72 years) groups. We also performed separate examinations to identify predictive factors for ABA discontinuation in those with versus those without concomitant methotrexate (MTX) treatment. Results: Mean age was 52.7 years in the Young group, 67.7 years in the Middle group, and 78.1 years in the Elderly group. No significant group-dependent differences were found in mean DAS28 score, categorical distribution of DAS28, and EULAR response rate across the 52 weeks. The ABA retention rates at three years as determined by the Kaplan-Meier method were similar in all three groups. Patient age was not a significant predictor of ABA discontinuation due to adverse events in patients with concomitant MTX; however, it was found to be a significant predictor for those who did not use MTX (Cox hazard model). Conclusion: ABA would be a reasonable treatment option for elderly RA patients from the viewpoints of both clinical effectiveness and long-term retention. However, physicians should watch carefully for any serious adverse reactions in elderly RA patients with intolerance to MTX.

Objective: To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice., Methods: A retrospective cohort study was performed using data from a multicentre registry. A total of 176 consecutive rheumatoid arthritis patients treated with abatacept were included. The propensity score based on multiple baseline characteristic variables was calculated, and 41 of 86 patients treated without MTX (MTX(-)) and 41 of 90 patients treated with concomitant MTX (MTX(+)) were statistically extracted and analysed. Clinical outcomes were evaluated and compared between the two groups over a 52-week period., Results: Baseline characteristics were statistically comparable. No significant differences were observed in the following clinical outcomes from baseline throughout the 52-week period: drug retention rate (MTX(-)/MTX(+) 79.1%/80.5%), mean change in disease activity score based on 28 joints (DAS28-CRP) from baseline (- 1.35/- 1.54), low disease activity rate (48.8%/43.9%), clinical remission rate (31.7%/36.6%), moderate European League Against Rheumatism (EULAR) response rate (68.3%/68.3%), and good EULAR response rate (36.6%/41.1%) at 52 weeks., Conclusion: In rheumatoid arthritis patients with similar background characteristics undergoing abatacept treatment, concomitant MTX does not seem to affect clinical outcomes. Abatacept would be a suitable treatment option in daily clinical practice in patients with contraindications to MTX., Key Points: • This is the first study to directly compare the clinical efficacy and safety of abatacept between patients with and without concomitant methotrexate (MTX) treatment in 'real-world' settings using the propensity score matching method. • There were no significant differences in clinical outcomes of abatacept between patients with and without concomitant MTX treatment. • We used data from a large Japanese multicentre registry for biologics in rheumatoid arthritis, thereby decreasing selection bias based on the personal preferences of physicians.

In total hip arthroplasty (THA), it is generally accepted that the bones of the acetabular cup and femur of hip joint must be accurately cut and components (artificial joint parts) be implanted in exact positions at exact angles to achieve improvement of daily living (ADL) and quality of life (QOL). However, with the conventional surgical method, it is difficult to grasp and measure the acetabular cup and femoral stem precisely during surgery, making some kind of reliable guide necessary. Although it was reported that an accurate angle was achieved in acetabular cup implantation by support instruments for surgical planning, an effective support instrument is now being developed for stem implantation on the out-of-reach femur side. This is the first clinical study to assess the efficacy and safety of anterolateral approach THA using an extracorporeal patient-specific femoral guide (PSG) for stem implantation with three-dimensional (3D) surgical support software in patients with hip joint disease.

This study aimed to evaluate whether normal serum matrix metalloproteinase-3 (MMP-3) levels can be used to predict clinical remission and normal physical function at a single time point when treating patients with rheumatoid arthritis (RA) in daily practice settings. Subjects were all 1321 RA patients who were treated at our hospital. The accuracy of serum MMP-3 levels was larger than those of C-reactive protein (CRP) levels for predicting clinical remission [Simplified Disease Activity Index (SDAI) ≤ 3.3], normal function [Disability Index of the Health Assessment Questionnaire (HAQ-DI) ≤ 0.5], and both in clinical remission and with normal function (clinical remission + normal function) using receiver operating characteristic curve analysis. Serum MMP-3 levels were significantly correlated with CRP levels [r 0.229 (men), r 0.476 (women)] using Pearson's correlation coefficients. Among patients with normal CRP levels (n = 807), the percentage of patients in clinical remission, with normal function, and with clinical remission + normal function having normal serum MMP-3 levels was significantly higher than those with abnormal serum MMP-3 levels. In addition, among patients with the 28-point count Disease Activity Score-CRP (DAS28-CRP) remission (DAS28-CRP < 2.3), the percentage of patients in clinical remission, with normal function, and with clinical remission + normal function having normal serum MMP-3 levels was significantly higher than those with abnormal serum MMP-3 levels. Our findings suggest that normal serum MMP-3 levels, in combination with CRP levels or disease activity, are useful for predicting clinical remission and normal physical function in patients with RA.

Objective: This study aimed to examine anxiety and depression experienced by patients with rheumatoid arthritis (RA) using EuroQoL 5-Dimensional Descriptive System (EQ-5D) and Hospital Anxiety and Depression Scale (HADS) scores., Methods: We analyzed 1005 Japanese patients with RA. Stepwise multiple linear regression analysis was performed to evaluate the independent influence of variables on EQ-5D and HADS scores. Pearson correlation coefficients were also calculated to explore relationships between variables., Results: The mean EQ-5D score was 0.74 for all patients (mean age, 63.2 years; mean disease duration, 13.6 years; mean Health Assessment Questionnaire Disability Index [HAQ-DI], 0.78; mean HADS total [HADS-T] score, 10.3; mean disease activity score assessed by 28 joints based on CRP [DAS28-CRP], 2.8). The EQ-5D score was strongly correlated with HAQ-DI and was moderately correlated with age, Steinbrocker functional class, HADS-T score, tender joint count assessed by 28 joints, pain on a visual analog scale (pain-VAS), patient's global assessment of disease activity (general-VAS), and DAS28-CRP. The HADS-T score was moderately correlated with HAQ-DI, pain-VAS, general-VAS, and DAS28-CRP. Factors that influenced the EQ-5D score included HAQ-DI (β = -0.533), pain-VAS (β = -0.128), HADS-T score (β = -0.142), DAS28-CRP (β = -0.187), and prednisolone use (β = -0.056). Factors that influenced the HADS score included HAQ-DI (β = 0.348), general-VAS (β = 0.145), disease duration (β = 0.094), and worklessness (β = 0.083)., Conclusions: The HADS score is an independent factor associated with EQ-5D in patients with RA. Our findings suggest that the assessment of anxiety and depression is essential in achieving better quality of life for patients with RA.

Objective: This study aimed to evaluate whether the level of serum matrix metalloproteinase-3 (MMP-3), a marker of synovium inflammation, is affected by clinical characteristics of patients in rheumatoid arthritis (RA) patients., Methods: We analyzed data from 1087 female patients with RA. Pearson's correlation coefficients were calculated to explore associations between variables. Stepwise multiple linear regression analysis was performed to evaluate patient background variables that could potentially affect serum MMP-3 levels., Results: Serum MMP-3 was moderately correlated with C-reactive protein (CRP) (r: 0.478). Factors that independently influenced serum MMP-3 levels were CRP (β: 0.450), prednisolone (PSL) use (β: 0.100), estimated glomerular filtration rate (eGFR) (β: -0.085), swollen joint count assessed on 28 joints (β: 0.072), and body mass index (β: -0.061) in female patients with RA. In RA patients with PSL use, factors that independently influenced serum MMP-3 levels were CRP (β: 0.480), eGFR (β: -0.175), and PSL dose (β: 0.171)., Conclusions: Our findings suggest that steroid therapy and renal dysfunction affect serum MMP-3 levels in patients with RA.

Objective: This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA)., Methods: Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis., Results: DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively., Conclusion: Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

This study aimed to evaluate whether targeting clinical remission is appropriate for suppressing physical dysfunction in patients with early rheumatoid arthritis (RA). Subjects were all 75 early RA patients (within 2 years of onset) who were continuously treated with biologics for 12 months at our hospital. We evaluated the Simplified Disease Activity Index (SDAI) and Disability Index of the Health Assessment Questionnaire (HAQ-DI) at 3, 6, and 12 months from the initiation of biologics therapy. Rates of functional remission (HAQ-DI ≤ 0.5) at 12 months in the clinical remission (SDAI ≤ 3.3) group and the low disease activity [LDA (3.3 < SDAI ≤11)] group were 97 and 86%, respectively. Multivariate logistic regression analysis revealed that duration of disease and SDAI at 6 months were significantly associated with the achievement of functional remission at 12 months. The best cut-off value of SDAI at 6 months for predicting functional remission at 12 months was 15.7 by receiver operating characteristic curve analysis. HAQ-DI scores in the LDA group were significantly higher than those in the clinical remission group at 6 and 12 months. The mean HAQ-DI score at 12 months in the clinical remission group improved significantly relative to the mean HAQ-DI score at 6 months in the LDA group. Our findings highlight the importance of achieving LDA at least by 6 months after initiating biologics therapy, and achieving clinical remission as soon as possible, in order to minimize physical dysfunction in patients with early RA.

Objective: To evaluate the rates of retention and discontinuation of adalimumab (ADA) due to efficacy and safety in Japanese patients with rheumatoid arthritis (RA)., Methods: All patients with RA (n = 476) who were treated with ADA in the Tsurumai Biologics Communication Registry were enrolled., Results: The retention rate of ADA was 46% at 5 years. When focusing on insufficient efficacy, previous biologics use and high baseline disease activity were significant risk factors for up to 1 year. Methotrexate (MTX) use was a significantly low risk factor after 1 year of treatment., Conclusion: Concomitant MTX contributes to the longterm efficacy of ADA therapy.

This study aimed to identify predictive factors for achieving low disease activity (LDA) in rheumatoid arthritis (RA) patients switching from tumor necrosis factor inhibitors (TNFis) to abatacept (ABT). Patients who were registered in the multicenter observational Tsurumai Biologics Communication Registry (TBCR) were enrolled in this study. Predictive factors for LDA achievement at each time point were determined by univariate and multivariate logistic regression analyses. The cutoffs of 28-point count Disease Activity Score (DAS28)-C-reactive protein (CRP) and ΔDAS28-CRP from baseline up to 24 weeks for LDA achievement at 52 weeks were explored using receiver operating characteristic (ROC) curves. Of 2771 RA patients registered until 2013, 76 with moderate or high disease activity were selected. Twenty-six percent of the patients achieved LDA. Multivariate analysis confirmed that DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks were independent factors for LDA achievement at 52 weeks [odds ratio (OR) 0.26, 95% confident interval (CI) (0.12-0.56), OR 0.25, 95% CI (0.11-0.57), respectively]. The best cutoff values of DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks for LDA at 52 weeks were 3.9 (sensitivity 0.85, specificity 0.78) and -0.97 (sensitivity 0.70, specificity 0.70), respectively. Seventy-one percent of patients who achieved both of these cutoff values at 12 weeks achieved LDA at 52 weeks. Our findings suggest that the clinical course up to 12 weeks is important for predicting long-term outcomes when switching from TNFis to ABT.