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Objective Perspectives of women aged 18–45 years with chronic rheumatic diseases (CRD), and clinicians, in the Asia-Pacific (APAC) region are reported. Methods Online surveys were completed by women, pregnant in the past 2–5 years, with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and rheumatologists, obstetricians, orthopaedic surgeons who medically manage CRDs. Results Among 210 (RA 122, PsA 48, axSpA 40) patients, 52% (n = 109/210) delayed their decision to have children, most commonly due to concerns of passing on disease to offspring. 33% (n = 70/210) discussed family planning with a healthcare professional at diagnosis. Patients most often initiated discussions. 94% (n = 193/205) stopped treatment around pregnancy due to fear of fetal harm. 66% (n = 139/210) of patients felt they did not receive all relevant information on the impact of CRDs and treatment on pregnancy. Among 335 clinicians who participated, 82% (n = 143/174) of rheumatologists, 86% (n = 72/84) of obstetricians and 43% (n = 33/77) of orthopaedic surgeons agreed good disease control during pregnancy was their primary goal. 69% (n = 120/174) of rheumatologists were ‘very comfortable’ with prescribing tumour necrosis factor inhibitors (TNFi) for women aged 18–45 years. Comfort levels generally decreased with the onset of family planning. More obstetricians and orthopaedic surgeons supported avoiding TNFi during pregnancy than rheumatologists (40% [n = 34/84]/38% [n = 29/77] versus 16% [n = 28/174]). Access to more TNFi safety data during pregnancy was considered paramount for increasing clinician comfort. Conclusions Patients and physicians need current information and multidisciplinary discussions for improved management of CRD in women in APAC.

Objectives Romosozumab is a newly released and widely known molecular-targeted drug for severe osteoporosis treatment with comparable effectiveness to denosumab. However, there have been no reports discussing the efficacy of those treatments for rheumatoid arthritis (RA) patients, especially those receiving glucocorticoids. This retrospective observational registry study compared the efficacy of 12-month treatment of denosumab and romosozumab in RA patients under the influence of glucocorticoid intake. Methods Following propensity score matching, 36 patients each in the denosumab and romosozumab groups were analysed in this study. Drug effectiveness was evaluated by measuring bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck at baseline, 6 and 12 months as well as alterations in P1NP, TRACP-5b, and simplified disease activity index (SDAI). The occurrence of adverse events and new fractures was also assessed. Results At 12 months of treatment, BMD at the lumbar spine was increased by 7.5% in the denosumab group and 8.7% in the romosozumab group, which were both significantly and comparably elevated over baseline. At the total hip and femoral neck, romosozumab tended to exhibit favourable efficacy to increase BMD versus denosumab. Both P1NP and TRACP-5b were significantly lower in the denosumab group as compared with the baseline. Conversely in the romosozumab group, P1NP was increased over baseline, while TRACP-5b was decreased. Regarding SDAI alterations, both the romosozumab and denosumab groups exhibited comparable improvements in RA disease activity over time during treatment. Recorded adverse events and new fractures during treatment were few and minor in both groups. Conclusions Romosozumab exhibited comparable efficacy to denosumab for increasing BMD even under the influence of glucocorticoids for treating RA. Both drugs may be therefore suitable for managing osteoporosis in patients with RA and glucocorticoid intake.

Resume Objectif Etudier les facteurs predictifs de poussee de polyarthrite rhumatoide (PR) apres arret du methotrexate chez des patients japonais presentant une faible activite stable de la maladie sous traitement combine de tocilizumab (TCZ) et methotrexate (MTX). Methodes Cette etude prospective multicentrique en ouvert non controlee porte sur des patients japonais atteints de PR presentant une faible activite de la maladie (indice CDAI [Clinical Disease Activity Index] ≤ 10) depuis ≥ 12 semaines sous traitement combine de TCZ et MTX. Le MTX a ete arrete apres 12 semaines d’administration toutes les deux semaines tandis que le TCZ etait maintenu. Une poussee de la maladie a ete definie comme soit un score CDAI > 10, soit l’administration d’un traitement de secours pour quelque cause que ce soit, meme avec un CDAI ≤ 10. L’influence des caracteristiques a l’inclusion sur les poussees de la maladie a la semaine 64 (52 semaines apres l’arret du MTX) a ete evaluee par des modeles de regression logistique. Resultats Des analyses d’efficacite ont ete effectuees chez 49 patients, dont 15 avaient presente une poussee de la maladie a la semaine 64. La proportion (intervalle de confiance [IC] a 95 %) de patients ayant une faible activite de la maladie sans poussee a la semaine 64 etait de 69,4 % (54,6–81,8 %). L’intervalle d’administration du TCZ etait plus long que celui indique sur l’etiquette au Japon (c.-a-d. administration par intraveineuse toutes les quatre semaines ou sous-cutanee toutes les deux semaines) chez 27 % des patients presentant une poussee et 6 % des patients sans poussee. Selon l’analyse multivariee, le sexe masculin (odds ratio [OR] 18,00, IC 95 % 2,80–115,56) et l’intervalle d’administration etendu du TCZ (OR 12,00, IC 95 % 1,72–83,80) etaient des facteurs predictifs independants de poussee de la maladie. Conclusion Les patients de sexe masculin et ceux recevant du TCZ selon un intervalle etendu presentent un risque eleve de poussee de la maladie apres l’arret du MTX concomitant. Numero d’enregistrement de l’essai jRCTs041180071, UMIN000021247.

Objectives Patients with rheumatoid arthritis (RA) usually switch to a second biological disease-modifying antirheumatic drugs (bDMARDs) when the first has proven to be ineffective, although some may discontinue bDMARDs treatment altogether. We investigated the total rate of bDMARDs retention and the risk of bDMARDs discontinuation in patients with RA. Methods The study included 564 patients with RA who started bDMARDs treatment before 2008 ( Results Among 564 patients, 74 had discontinued bDMARDs treatment due to AEs. Male sex and Steinbrocker class 3–4 were more frequent, while rheumatoid factor and concomitant methotrexate treatment were less frequent, in those aged ≥65 years than in those aged Conclusions Older patients are at higher risk of discontinuing bDMARDs treatment due to AEs than younger patients.

Glucocorticoids are important drugs used to treat rheumatoid arthritis. We recommend glucocorticoid discontinuation as soon as possible given the associated side-effects, but many patients continue to take oral glucocorticoids long-term. The present study aimed to explore factors associated with glucocorticoid discontinuation at 52 weeks after initiating biological disease-modifying antirheumatic drugs (bDMARDs). Subjects were 564 patients from a Japanese multicenter registry who were administered glucocorticoids and methotrexate (MTX) followed by initiation of the first bDMARD. We examined the status of oral glucocorticoid use at 52 weeks after initiating the first bDMARD. By 52 weeks after bDMARD initiation, 164 patients (29.1%) discontinued glucocorticoids. Multivariable analysis identified age, MTX dose, and glucocorticoid dose as factors independently associated with glucocorticoid discontinuation. After adjusting for baseline characteristics using propensity score matching, among patient groups administered MTX ≤ 8 mg/week and MTX > 8 mg/week, 105 pairs remained. A significantly higher rate of glucocorticoid discontinuation (41.0%) was noted for patients administered MTX > 8 mg/week. Our findings suggest that glucocorticoids may be discontinued after initiating bDMARDs. Moreover, higher MTX doses (>8 mg/week) at the time of bDMARD initiation were associated with glucocorticoid discontinuation among patients treated with bDMARDs.

This study aimed to evaluate the short-term effectiveness and safety profiles of baricitinib and explore factors associated with improved short-term effectiveness in patients with rheumatoid arthritis (RA) in clinical settings. A total of 113 consecutive RA patients who had been treated with baricitinib were registered in a Japanese multicenter registry and followed for at least 24 weeks. Mean age was 66.1 years, mean RA disease duration was 14.0 years, 71.1% had a history of use of biologics or JAK inhibitors (targeted DMARDs), and 48.3% and 40.0% were receiving concomitant methotrexate and oral prednisone, respectively. Mean DAS28-CRP significantly decreased from 3.55 at baseline to 2.32 at 24 weeks. At 24 weeks, 68.2% and 64.1% of patients achieved low disease activity (LDA) and moderate or good response, respectively. Multivariate logistic regression analysis revealed that no previous targeted DMARD use and lower DAS28-CRP score at baseline were independently associated with achievement of LDA at 24 weeks. While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan–Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.

This cross-sectional study aimed to determine the predictors of a walking speed1 m/s. Factors associated with the health of muscle cells, including the phase angle analyzed using bioimpedance analysis, answers to the mini-nutritional assessment-short form, albumin levels, leg muscle quality and vitamin D levels, were assessed.The study participants were outpatients from the Locomotor Frailty Outpatient Clinic which was established at our center in 2016 (231 women, 76.5 ± 7.6 years; 137 men, 78.0 ± 6.3 years). Participants were classified into two groups, with 1 m/s walking speed as the cutoff value. Binominal logistic regression analysis was performed with walking speed as the dependent variable, and age, leg muscle quality, mini-nutritional assessment-short form answers, albumin levels, vitamin D levels and the phase angle as explanatory variables. Leg muscle quality was defined as the mean value of both lower limbs' isometric knee extensor strength, divided by the mean value of both lower limbs' muscle mass through bioimpedance analysis.The explanatory variables associated with decreased walking speed among women were leg muscle quality (P = 0.004, odds ratio: 0.57) and phase angle (P = 0.017, odds ratio: 0.42). Men were also more likely to have leg muscle quality (P = 0.004, odds ratio: 0.43).Leg muscle quality and the phase angle of lower extremities were independently associated with low walking speeds (1 m/s) among older outpatients. Geriatr Gerontol Int 2022; 22: 603-609.

This study aimed to evaluate the efficacy of add-on iguratimod (IGU) in patients with rheumatoid arthritis (RA patients) who inadequately respond to either tocilizumab (TCZ) or tumor necrosis factor alpha inhibitors (TNFi).Twenty-three RA patients treated with TCZ (the TCZ group) and 23 RA patients treated with TNFi (the TNFi group) were enrolled in this 24-week retrospective study from our multicenter registry. All inadequate responders to either TCZ or TNFi received add-on IGU. Baseline demographics and disease activity at 24 weeks after initiating add-on IGU were compared between the two groups.Baseline clinical disease activity index (CDAI) values in the TCZ group and TNFi group were 14.1 and 11.8 (Add-on IGU was more effective in inadequate responders to TCZ than in inadequate responders to TNFi.

Objectives The study aimed to investigate the effectiveness and tolerance of biological disease-modifying antirheumatic drugs (bDMARDs) therapy administered concomitantly with tacrolimus (TAC) treatment in patients with rheumatoid arthritis. Methods 2792 patients who underwent therapy with five bDMARDs (etanercept: ETN, adalimumab, golimumab, tocilizumab, and abatacept: ABT) were enrolled. Among the study subjects, 1582 were concomitant methotrexate (MTX group), 147 were concomitant TAC (TAC group), and 1063 were non-concomitant MTX and TAC (non-MTX/TAC group). The primary outcome was the incident rate of discontinuation of bDMARDs by adverse events (AEs) or loss of efficacy. Results Concerning the analysis for each reasons of discontinuation, including AEs and loss of efficacy, the hazards ratio (HR) was significantly lower in the TAC group than in non-MTX/TAC groups (AEs: HR = 0.39, 95% confidence interval, 0.23–0.68, loss of efficacy: HR = 0.49, 95% confidence interval, 0.30–0.78). The loss of efficacy with the use of ETN and ABT was lower in the TAC group than in non-MTX/TAC groups. Concomitant TAC did not induce elevated risk for discontinuation of AEs in all bDMARD analyses. Conclusions Concomitant TAC with ABT or ETN showed higher retention rates than bDMARDs therapy without TAC or MTX. AEs did not increase over long-term observation.

Surgical resection is the standard treatment for the management of localized penile cancer and a neo-urethral meatus is generally created on the penile stump or perineum. Neo-urethral meatus is often stenosed and requires repeated transurethral manipulations such as dilation and urethrotomy. These procedures are generally futile and are associated with poor quality of life. Here, we report a case of penile cancer that developed a neo-meatal stenosis after total penectomy, which was subsequently salvaged by perineal urethrostomy using Blandy technique. A 72-year-old male who was diagnosed with localized penile cancer, underwent total penectomy and creation of neo-meatus on the perineum. Neo-meatus stenosis had developed in the patient and he received repeated urethral dilations without any success. Finally, when the patient was unable to void, he was referred to us for the amelioration of meatal stenosis through the placement of a suprapubic catheter. Because the condition of the residual bulbar urethra was adequate and its length was enough, we planned to create a non-transecting perineal urethrostomy by Blandy technique. An inverted U-shaped perineal incision was made, and a skin flap was created. The scarred neo-meatus and spongiofibrosis at the distal bulbar urethra were completely excised. The residual bulbar urethra was exposed, and a longitudinal ventral incision of 4 cm was made. The edge of the bare urethral mucosa and tunica albuginea of the corpus spongiosum were sutured by 4-0 PDS for hemostasis. The apex of the U-shaped skin flap was brought to the proximal margin of the urethrotomy and a tension-free anastomosis was created between the skin flap and the urethral plate. Thereafter, the skin of the perineum was sutured to the open longitudinal urethrotomy. The patient started to void on the 5th day post-surgery. The subject could void without the help of any intervention and did not require any instrument, sixteen weeks after the surgery.

As older people become frail, they tend to fall more easily. Moreover, women have a higher rate of falls than men. However, effective strategies to avoid elderly women falling are lacking. The Timed Up and Go test is a well-known indicator of falling tendency. This study clarifies the motor elements related to the Timed Up and Go test according to the degree of weakness in older outpatients to specify exercise intervention to improve weakness and prevent falls. Participants were 145 female outpatients who visited the Locomo-Frail outpatient clinic, classified into three groups (robust, prefrail, and frail, according to the definition of the Japanese Cardiovascular Health Study. Vertical ground reaction force parameters were measured for all participants when they stood up from a chair, walking speed, and the Timed Up and Go test. Results showed that walking speed is related to the Timed Up and Go test in the robust group; balance ability is related to the Timed Up and Go test in the prefrail group; and instantaneous force is related to the Timed Up and Go test in the frail group. These results suggest that weakness can be improved by performing exercise interventions of balance and instantaneous force elements in the prefrail and frail groups, respectively.

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.

Discontinuation of biologic therapy in rheumatoid arthritis is attributable to various reasons, with the most important cause being insufficient response. In this study, we investigated the association between rheumatoid factor (RF) and anti-citrullinated protein autoantibody (ACPA) status and the discontinuation of tumor necrosis factor inhibitors (TNFi) therapy due to insufficient response in bio-naïve rheumatoid arthritis (RA) patients.This study included patients enrolled in the Tsurumai Biologic Communication Registry in Japan. The crude comparison of TNFi discontinuation due to ineffectiveness between seropositive and seronegative patients was analyzed using the cumulative incidence function of competing events and Gray test. We assessed the associations between baseline patient characteristics and discontinuation of TNFi therapy due to insufficient response using Fine-Gray proportional hazard regression. Fine-Gray proportional hazard analysis considered competing events of interest, including insufficient response, adverse event, palliation, and personal reasons.Of 1237 patients evaluated, 79.3% were positive for RF and 85.4% for ACPA; 72.6% were double positive and 11.1% were double negative. TNFi therapy had been discontinued because of insufficient response at 200 weeks in 19.8% RF-positive, 16.7% RF-negative, 23.0% ACPA-positive, and 13.8% ACPA-negative patients. There was a significantly higher discontinuation rate due to insufficient response in ACPA-positive patients than in ACPA-negative patients using Gray test, with a similar trend as that for RF status. RF positivity was significantly predictive of the discontinuation of TNFi therapy due to ineffectiveness using Fine-Gray proportional hazard regression analysis after adjusting for baseline characteristics, including age, sex, stage, class, disease activity at baseline, methotrexate use, and prednisolone use [hazard ratio 1.73 (95% confidence interval 1.07-2.80)].Using Fine-Gray proportional hazard regression, we demonstrated that RF positivity was related to a higher discontinuation rate of TNFi therapy due to ineffectiveness in bio-naïve RA patients. Key Points • RF positivity is related to a higher discontinuation rate of TNFi therapy due to ineffectiveness. • ACPA is not predictive of a discontinuation of TNFi therapy due to ineffectiveness.

To compare the clinical outcomes of abatacept between rheumatoid arthritis patients with and without concomitant methotrexate (MTX) treatment in daily clinical practice. 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. 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. 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. • 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.

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.

Objective To investigate predictors of disease flare after methotrexate discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing tocilizumab plus methotrexate combination therapy. Methods Participants of this multicenter, open-label, uncontrolled, prospective study were RA patients maintaining low disease activity (Clinical Disease Activity Index [CDAI] ≤ 10) for ≥ 12 weeks with tocilizumab plus methotrexate. Methotrexate was discontinued after 12 weeks of biweekly administration while continuing tocilizumab therapy. Disease flare was defined as either a CDAI score > 10 or intervention with rescue treatments for any reason even if the CDAI score was ≤ 10. The impact of baseline characteristics on disease flare at week 64 (52 weeks after methotrexate discontinuation) was assessed with logistic regression models. Results Efficacy analyses were performed in 49 patients, of whom 15 had a disease flare by week 64. The proportion (95% confidence interval [CI]) of patients who maintained low disease activity without a flare at week 64 was 69.4% (54.6–81.8%). The dosing interval of tocilizumab was longer than that described on the drug label in Japan (i.e., intravenously every 4 weeks, or subcutaneously every 2 weeks) in 27% and 6% of patients with and without a flare, respectively. Multivariate analysis revealed that male sex (odds ratio [OR]: 18.00, 95% CI: 2.80–115.56) and extended dosing interval of tocilizumab (OR: 12.00, 95% CI: 1.72–83.80) were independent predictors of disease flare. Conclusion Male patients and those receiving tocilizumab at an extended dosing interval are at high risk of disease flare after discontinuation of concomitant methotrexate. Trial registration number jRCTs041180071, UMIN000021247.

We developed an electrostatic energy of transfer (EET) analysis applicable to periodic boundary condition, including a nonrectangular unit cell. It was applied to monoclinic ribonuclease A crystallized with ethanol as a precipitant. Macrobond analysis was also carried out. Owing to the low ionic strength of the solvent region, atomic EET values were non-negligible even at long-distance points. Most of the molecular EET values—defined as the individual contribution of each surrounding molecule—were positive. The inclusion of the molecular EET values of hydration water molecules reduced the repulsive force, and the evaluation of hydration effects in protein crystals was found to be imperative.

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).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.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.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.

Objectives: To evaluate the efficacy and safety of methotrexate (MTX) discontinuation in Japanese rheumatoid arthritis (RA) patients with sustained low disease activity undergoing combinati...

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.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.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).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.

Background It has been demonstrated that biological DMARDs (bDMARDs) treatment rapidly improved sign and symptom in patients with rheumatoid arthritis (RA). Those were evaluated using composite measures or biomarkers in daily clinical practice or clinical studies. Although rapid improvement of composite measures or biomarkers is important in the treatment of RA, primary important goal of treatment is improvement of long term health-related quality of life (HR-QOL) [1]. HR-QOL is based on physical function such as muscle power and agility. Objectives This study investigated the efficacy of bDMARDs on physical function and fall risk in patients with RA. Methods Periodic evaluation of physical function by the staffs in rehabilitation center in our institute has been performed in addition to routine rheumatology evaluation (SDAI, biomarkers, mHAQ) in RA patient initiated their first bDMARDs treatment from Oct. 2015 to Feb. 2018. 47 cases was registered in total. Evaluation of physical function included evaluation of muscle power (grasping power [GP] and knee extension power [KEP]), agility (Time up and go test [TUG] and 10m walking time [10mW]) and questionnaire using mHAQ, portable fall risk index [2] and the 25-question geriatric locomotive function scale (locomo25) [3] at baseline (initiation of bDMARDs), 1month, 3months, 6months and 12months. Disease activity of RA (SDAI, CRPMMP-3) was evaluated at same time point. Although 26 cases have passed one year from initiation of bDMARDs treatment, 9 cases dropped out from evaluation of physical function due to stopping of bDMARDs treatment or patient’s hope not to e evaluated on physical function or major joint surgery performed in patient which was influence physical function. Results of early 17 cases who completed evaluation at 12 months were investigated in this study. Results Baseline patients characteristics was as follow (n=17): mean age 59.1 years old, RA duration 13.7 years, Mean SDAI 19.6, mean CRP 1.9mg/dl. Used bDMARDs were tocilizumab in 5 cases, golimumab in 4 cases, etanercept in 3 cases, abatacept in 3 case, certolizumab in one case and infliximab-biosimilar in one case. Date is presents as mean values at baseline-1-3-6-12 months below. SDAI and CRP were significantly improved on and after one month (SDAI: 19.6-9.6-5.8-5.7-5.5, CRP [mg/dl]: 1.9-0.3-0.3-0.3-0.8). GP and knee extension power significantly improved on and after one months except KEP at 3 months (GP [kg]: 12.3-14.1-15.9-16.9-17.4, KEP [N/kg] 2.6-3.1-3.1-3.4-3.5). TUG at 10mW significantly improved on and after one months except TUC at 3months and 10mW at 3 months (TUG [s]: 9.3-8.0-8.2-7.3-7.4, 10mW[s]: 8.3-7.7-7.5-6.9-6.8). MHAQ significantly improved on and from 6 months (0.46-0.33-0.19-0.20-0.12). Locomo25 significantly improved on and from 1 month (31.7-20.6-18.5-16.7-15.0). Portable fall risk index significantly improved at only 12 months (8.8-8.6-7.8-7.8-6.8). Conclusion Signs and symptoms of RA were rapidly improved after the initiation of bDMARDs treatment and improvement of physical function was also rapidly improved. The changes from baseline and one month were more drastic in composite measure or biomarker of inflammation than that in muscle power and agility in respect with p-values. Inhibition of fall were achieved 12 months after bDMARDs initiation. These results suggested that physiotherapy might play an important role in RA patients treated with bDMARDs to gain more rapid improvement of physical function. References [1] Smolen JS, et al. Ann Rheum Dis2016. [2] Toba K, et al. Jpn J Geriat2005. [3] Seichi A at al. J Orthop Sci2012. Disclosure of Interests None declared

Background Iguratimod (IGU) is csDMARDs developed in Japan and used in Japanese daily practice since 2012. Although IGU was developed as an anti-inflammatory drug at first, anti-rheumatic effect was found in experiments using type II collagen-induced arthritis model mice 1). Main mode of action of IGU was thought to be inhibition of NF-kB resulted in decreased production of IL-6, IL-8 and TNF-alpha 2). Clinical trials performed in Japan showed that efficacy of IGU was equal to sulfasalazine when used as monotherapy in patients with RA 3). Additive efficacy to MTX was also shown in double-blind randomised trial in RA patients 4). We reported efficacy of IGU in daily clinical practice in EULAR2017 5). IGU is prescribed as monotherapy or concomitantly with other DMARDs such as MTX, csDMARDs other than MTX or biological DMARDs. Objectives Influences of different concomitant drugs were compared in RA patients treated with IGU in this retrospective study. Methods 178 RA patients treated with IGU in our institute from April 2013 to June 2017 were included. Patients were divided into four groups. (1) Group in which IGU was started as monotherapy (MONO-G: n=59). (2) Group in which IGU was added on to MTX treatment without bDMARDs (MTX-G: n=81). (3) Group in which IGU was added on to csDMARDs treatment other than MTX (sulfasalazine, tacrolimus, bucillamin) (CSD-G: n=26). (4) Group in which IGU was added onto bDMARDs treatment. (BIO-G: n=12). Patients’ characteristics, time course of disease activity (LOCF analysis), continuation rates of IGU (Kaplan-Meier) and reasons of stopping IGU were investigated and compared between groups. Results Baseline characteristics was as below. Mean age was 71.4 years old (yo) in MONO-G, 58.3 yo in MTX-G, 70.1 yo in CSD-G, and 58.7 yo in BIO-G. RA duration was 10.2 years in MONO-G, 8.9 years in MTX-G, 11.2 years in CSD-G, and 15.1 years in BIO-G. SDAI at initiation of IGU was 14.2 in MONO-G, 12.8 in MTX-G, 21.3 in CSD-G, and 18.4 in BIO-G. SDAI was significantly improved over time in all four groups (Fig. 1). There were no significant differences in ΔSDAI from baseline to 1 year between groups by one-way ANOVA (Bonferroni). Continuation rates of IGU at one year and three years were 66.6% and 21.2% in MONO-G, 77.8% and 57.1% in MTX-G, 69.2% and 39.7% in CSD-G and 75.0% and 75.0% in BIO-G. Continuation rate in MTX-G was significantly favorable compared with that in MONO-G and CSD-G by Log-rank test (Fig. 2). Most frequent reason for stopping IGU was liver damage (10 cases). Second frequent reason was intermittent pneumonia in 4 cases and infectious pneumonia in 4 cases. Conclusion IGU seemed to be the most tolerant in MTX-G and the second most tolerant in BIO-G. Although higher aged population who might have several comorbidities was included in MONO-G and CSD-G, moderate efficacy of IGU was seen in those groups. Although biological DMARDs is effective in RA patients, the cost is very expensive. IGU is comparative cheap (¥9,200/month) and suitable for RA patients with economic difficulties. As IGU decreased TNF-alpha production via inhibition of NF-kB, MTX+IGU may have similar mode of action with MTX+TNF inhibitor. Although small cases were included in BIO-G, Continuation rate of IGU in BIO-G was good. References [1] Aikawa, et al. Inflamm res. 51; 188-194 2002. [2] Kohno, et al. J Rheumatol. 28; 2591-2596 2001. [3] Hara, et al. Mod Rheumatol. 17; 1-9 2007. [4] Ishiguro, et al. Mod Rheumatol. 23; 430-439 2013. [5] Hirano, et al. Ann Rheum Dis. suppl2; 285 2017. Disclosure of Interests None declared

Background The joint destruction inhibitory effect of biological disease-modifying anti-rheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) has been reported in a lot of studies. Most of them are evaluated in small joints such as hands and feet, there are few reports on the joint destruction inhibitory effect in large joints such as knees which are frequently affected in disease course of RA1). Although bDMARDs is very effective drugs, we experience RA patients in whom total knee arthroplasties (TKA) are performed after the initiation of bDMARDs treatment2). Objectives To investigate the rate of TKA during bDMARDs treatment and to explore associated factors of subsequent TKA after the initiation of bDMARDs treatment in RA patients. Methods 356 knee joints of 184 RA patients who initiated bDMARDs treatment in our institute from March 2004 to November 2013 were included in this retrospective study. They were retrospectively studied over the course of a minimum of 5 years of follow up. Knees in which TKA were already performed before the initiation of bDMARDs treatment were excluded in this study. Patients’ characteristics and rates of subsequent TKA over time were investigated. Next, factors associated with subsequent TKA were explored using univariate and multivariate analysis. The X-ray change (Larsen grade3), ARASHI score4)) at the last observation after 5 years or more was also examined. ARASHI score was developed in Japan to assess destruction of large joints such as knees or hips. Results Baseline patients’ characteristics were below. Mean age was 57.1 years old. 152 female and 32 male. MTX was concomitant in 85.7% of patients. Prednisolone was concomitant in 53.7% of patients, First bDMARDs were infliximab in 67 cases, etanercept in 67 cases, adalimumab in 35 cases, tocilizumab in 6 cases, abatacept in 9 cases, golimumab in 0 cases and certolizumab in 0 cases. Agents were changed according to clinical necessity. The median follow-up period was 7.8 years. TKA were performed in 20 knees (5.95%) in total. Baseline extent of joint destruction of knees which was evaluated using Larsen grade and ARASHI score, joint destruction, age, disease duration, steinbrocker class, concomitant corticosteroids, concomitant methotrexate, DAS28-CRP, SDAI, MMP-3, mHAQ, swelling of the knees,and tenderness of the knees were associated with subsequent TKA in univariates analysis. Multivariate analysis revealed that the extent of baseline joint Destruction and mHAQ were associated with subsequent TKA (Larsen grade: Odds ratio; 6.17, 95%, confidence interval; 2.93-12.98, ARASHI score: Odds ratio; 3.50, 95% confidence interval; 2.18-5.62, mHAQ : Odds ratio; 3.56, 95% confidence interval; 1.06-11.93). Cut-off value was calculated as 2 in Larsen grade, 3 in ARASHI score and 1.5 in mHAQ using receiver operating characteristic analysis. There were significant differences in the rates of subsequent TKA if knees were divided according to baseline Larsen grade, ARASHI score and mHAQ (Fig1). Baseline ARASHI status score in progressed knees which was worsened after over 5 years were increased compared with that in knees which was stable. There was no significant difference in baseline Larsen grade between progressed knees and non-progressed knees. Conclusion It was suggested that baseline joint destruction and mHAQ at the initiation of bDMARDs in RA patients was predictive factors of subsequent TKA and progression of joint destruction of knees during long-term bDMARDs treatment. Early intervention with effective bDMARDs is necessary to prevent destruction of knee joints and subsequent TKA in RA patients whose knee joints are affected. References [1] Drossaers-Bakker, et al. Rheumatology. 2000 [2] Seki, et al. Clin Rheumatol. 2009 [3] Larsen, et al. Scand J Rheumatol. 1979 [4] Kaneko, et al. Mod Rheumatol. 2013 Disclosure of Interests None declared

Background The onset and diagnosis of chronic rheumatic disease (CRD) in women often overlap with their peak reproductive years. A previous survey1 reported fears and misconceptions amongst women with CRD in Germany, France, UK, Italy and Spain (EU5) on their journey to motherhood. Objectives To explore the perspectives of women with CRD in Asia-Pacific (APAC) regarding disease management and pregnancy, and the support they receive compared with patients in Europe. Methods Women of childbearing age (18−45 years) with self-reported moderate to severe CRD (rheumatoid arthritis [RA], psoriatic arthritis [PsA], axial spondyloarthritis [axSpA]/ankylosing spondylitis [AS]) from Australia (AUS), Japan (JPN) and Hong Kong/Taiwan (HK/TW) completed a 20-min online survey (Sep−Nov 2018), similar to the previous EU5 survey.1 Participants had been pregnant in the past 2–5 years. Results 210 APAC participants had CRD (RA: n=122, PsA: n=48, axSpA/AS: n=40); 306 EU5 participants had CRD. Most APAC patients had moderate CRD (77%; severe: 23%). In their most recent pregnancy, 40% of the women were actively trying to get pregnant, 40% were neutral and 20% were either not thinking about a pregnancy or were actively trying to avoid it. Prior to pregnancy, more women consulted rheumatologists (62%) vs primary care physicians (26%) or OB/GYNs (20%; multiple responses were possible). Pregnancy planning was first discussed with a healthcare professional (HCP) at diagnosis (33%), at treatment initiation (32%) or during a regular visit (30%). Similar to EU5, discussions on family planning with HCPs in APAC were most often initiated by patients (Figure A). APAC and EU5 patients delayed pregnancy for similar reasons including: fear of passing on health issues to their child, not feeling physically healthy enough to carry a child to term, not being emotionally ready to become a parent (Figure B). Antepartum, 55% of women reported disease improvement, 27% stable disease and 18% worsening disease activity. Compared with EU5, APAC women were less likely to have a treatment plan aligned between HCPs (APAC: 50%; EU5: 65%). The most frequently reported reasons for cessation of medications in pregnancy were ‘worried about the treatment harming the foetus’ (HK/TW: 68%; JPN: 59%; EU5: 54%) and ‘switched to a safer treatment’ (AUS: 52%). Similar to EU5, most women in APAC discussed breastfeeding with an HCP (>85%). However, whether women felt they had to decide between treatment and breastfeeding postpartum varied (HK/TW: 79%; EU5: 69%; JPN: 66%; AUS: 43%). Compared with EU5, fewer women in APAC felt they had all the information they needed on the impact of rheumatic disease and treatment on pregnancy and health (APAC: 34%; EU5: 56%). Conclusion Fears and misconceptions about family planning, pregnancy and breastfeeding are common amongst women with CRD in APAC and Europe. In APAC, there may be a greater need for patient access to consistent and accurate information. Pregnancy planning with input from both physicians and obstetricians could alleviate patient concerns and minimise delays to pregnancy or treatment interruption. Reference [1] Tincani A. ARD2018;77(Suppl):A866. Acknowledgement We thank the patients who participated. This study was funded by UCB Pharma, conducted by Hummingbird, medical writing by Rohini Bose, Costello Medical, Singapore. Disclosure of Interests Yoshiya Tanaka Grant/research support from: Abbvie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, MSD, Ono, Taisho-Toyama, Takeda, Speakers bureau: Abbvie, Asahi-kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Eisai, Glaxo-Smithkline, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer Japan Inc, Sanofi, Takeda, UCB, YL Biologics, Claire Barrett Grant/research support from: Nil, Consultant for: Nil, Speakers bureau: Nil, Yuji Hirano: None declared, Kei Ikeda: None declared, Kathy Paizis Speakers bureau: Alexion- SOMANZ breakfast session Cairns 2018 Thrombotic microangiopathy and pregnancy - $ 1300 Alexion – Meeting presentation aHUS and pregnancy June 2018 Autoimmune disease in pregnancy Nov 2018 UCB $550 pending, Azusa Sameshima: None declared, Yu-Jih Su: None declared, Carine Saadoun Employee of: UCB Pharma, Priscilla C Wong: None declared

Background:There are four kinds of drugs for rheumatoid arthritis (RA) patients who are refractory or intolerant to methotrexate (MTX) or other conventional synthetic disease-modifying anti-rheumatic drugs, namely, tumor necrosis factor inhibitors (TNFi), inteleukin-6 inhibitors (IL-6i), abatacept (ABT) and Janus kinase inhibitors (JAKi). Although these drugs have distinct mechanism of action (MOA) to reduce disease activity of RA, the effects of these drugs of reducing disease activity or inhibiting joint damage are similar according past clinical trials. However, their different MOA may induce different change in body of RA patients. If there are some differences in body of RA patients treated different drugs which have different MOA, some differences may appear in clinical parameters and laboratory data we clinician are able to know in daily clinical practice.Objectives:This retrospective cross-sectional study assessed differences in clinical parameters and laboratory data in RA patients who met the treatment goal with biologic agents (BIO) or JAKi.Methods:Data from the Toyohashi RA database (TRAD) was used. The TRAD is a collection of single-center retrospective data. Participants were BIO- or JAK-treated RA patients with clinical disease activity remission (REM) or low disease activity (LDA) [clinical disease activity index (CDAI) ≤ 10]categorized by BIO treatment with TNFi (reference), IL-6i, or ABT, and JAKi treatment. Clinical parameters [tender joint counts (TJ), swollen joint counts (SJ), patient’s global assessment (PtGA), patient’s pain assessment (PainVAS), physician’s global assessment (PhGA) and modified health assessment questionnaire (mHAQ)] and laboratory data [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloprotease-3 (MMP-3), white blood cell counts (WBC), hemoglobin (Hb), platelet cell counts (PLT), neutrophils counts (Neut), lymphocyte counts (Lymph) and estimated glomerular filtration rate (eGFR)] were investigated in cross-sectional manner. They are statistically compared using the Dunnett test.Results:171 TNFi, 71 IL-6i, 50 ABT, and 18 JAKi cases are categorized in REM or LDA. Patients’ characteristics (means) are as follows (TNFi/IL-6i/ABT/JAKi). Age (63.1/63.7/72.4/60.6; years old), RA duration (17.0/12.7/18.2/11.3; years), %female (83.0/71.8/88.0/83.3), %rheumatoid factor positive (81.9/80.3/90.0/88.9), %anti-cyclic citrullinated peptide antibody (84.6/74.6/97.9/73.3), %prednisolone (PSL) concomitant (3.5/4.2/18.0/11.1) and %MTX concomitant (77.2/15.5/26.0/83.3). Parameters with statistical significance (means) were: TNFi/IL-6i-ESR 34.5/14.0 mm/hr, MMP-3 47.5/71.9 ng/mL, WBC 6124/5404 /µL, Lymph 2112/1646 µL; TNFi/ABT-TJ 0.4/1.0, PtGA 13.3/20.0 mm, PainVAS 15.7/21.6 mm, PhGA 7.4/11.1 mm, CRP 0.1/0.4 mg/dL, ESR 34.5/44.2 mm/hr, MMP-3: 47.5/72.9 ng/mL, Lymph 2112/1816 µL, Neut 3364/4233 µL, eGFR 75.4/65.3 mL/min/1.73m2; and TNFi/JAKi-PLT 21.7/29.3 104/µL, Lymph 2112/1326 µL.Conclusion:Although differences of rates of administering concomitant PSL or MTX should be considered, clinical parameter and laboratory data differences result from differences in the targeted cytokine between TNFi and IL-6i, differences in patient characteristics between TNFi and ABT, and differences in the MOA between TNFi and JAKi.Disclosure of Interests:None declared

Background:A definition of difficult-to-treat rheumatoid arthritis (D2T RA) was recently proposed by the European League Against Rheumatism (EULAR) [1]. However, information on the incidence rates of D2T RA in real-world clinical practice is lacking.Objectives:The aim of this retrospective cross-sectional study was to evaluate the incidence rates of D2T RA in clinical practice in Japan.Methods:Data from the Toyohashi RA database (TRAD) was used. The TRAD is a collection of single-center retrospective data. Patients with RA who fulfilled the following three requirements were included in this study: (1) had been treated with >1 biological or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD); (2) >1 year had passed since b/tsDMARD treatment was initiated; and (3) regularly visited our institute at the time of investigation. The number of targeted patients was 363. The criteria of D2T RA used in this study were modified from the EULAR definition for simplification of the investigation as follows: (a) ≥2 b/t DMARDs with different mechanisms of action had been administered; (b) at least moderate disease activity (DAS28-ESR > 3.2 or clinical disease activity index [CDAI] > 10) at the time of investigation; and (c) 7.5-mg/day of prednisolone (PSL) or more was administered at the time of investigation. In this study, D2T RA was defined as criteria (a) + (b) or (a) + (c) or (a) + (b) + (c). The 363 patients were categorized into four groups as follows: group A, DT2 RA; group B, patients with RA who had been treated with ≥2 b/tsDMARDs and did not fulfill the D2T RA definition; group C, RA patients who had been treated with one kind of b/tsDMARD with the same mechanism of action (e.g., two kinds of tumor necrosis factor inhibitors) and fulfilled either or both criteria (b) and (c); and group D, patients with RA who had been treated with one kind of b/tsDMARD with the same mechanism of action (e.g., a tumor necrosis factor inhibitors or two interleukin 6 inhibitors) and did not fulfill either or both criteria (b) and (c). The incidence rates of D2T RA were calculated, and the patients’ characteristics at the time of initiation of the b/tsDMARD treatment were compared between the groups.Results:The number of patients in groups A, B, C, and D were 34, 53, 94, and 182, respectively. Of all the patients included in this study, 9.4% were categorized into group A, those with D2T RA, and 39.1% were treated with ≥2 b/tsDMARDs and categorized into group A (Fig 1). The patients’ characteristics were as follows (group A/B/C/D): mean age (57.1/54.3/61.4/56.2 years), RA duration (10.0/6.7/13.8/8.2 years), %Steinbrocker stage III+IV (%; 84.0/60.0/77.3/54.3), %Steinbrocker class 3 + 4 (%; 68.0/33.3/43.4/23.0), methotrexate (MTX) concomitant rate (%; 79.4/92.5/74.5/91.8), PSL concomitant rate (%; 91.2/52.8/55.3/43.4), DAS28-ESR score (5.5/5.0/5.5/4.7), and CDAI score (12.3/13.7/22.7/16.9). There were statistically significant differences in RA duration, %stage III+IV, %class 3 + 4 and PSL concomitant rate between group A and B.Conclusion:D2T RA occurred in 9.4% of patients treated with b/tsDMARDs. Incidence rate was increased to 39.1% after the treatment with ≥2 b/tsDMARDs. The patients with D2T RA tended to be older, have a long RA duration, be treated without concomitant MTX, be treated with concomitant PSL, and have higher disease activity at the time of starting the b/tsDMARD treatment. The baseline patient characteristics in group C were similar to those in group A. In the future, we suggest that patients with D2T RA be included in group C.References:[1]Nagy et al. Ann Rheum Dis 2021; 80: 31-35.Disclosure of Interests:None declared

Background:Rheumatoid arthritis (RA) patients who failed a first biologic agent due to any reasons have the option of switching to a second one along with the strategy of biologic agent treatment. Patients go over switching to the next one at failing their biologic agent. On the other hand, there are some patients who discontinue any biologic agent treatment due to various reasons such as tolerability concern, complications, economic issue, remission and so on1 2. The impact of this concern has been less studied.Objectives:The objective of this study was to investigate the reasons and the risk factors for discontinuation any biologic agent in RA patients.Methods:To Include patients who are observed long-term, patients who underwent biologic agent treatment between 2003 and 2007 at Nagoya University Hospital and 12 other institutes (Tsurumai Biologics Communication Study Group) were enrolled. 570 patients who were confirmed continuation or discontinuation of biologic agent treatment were enrolled. The last observation was September 2017. We analyzed the retention rate of biologic agent treatment and the reasons for discontinuation. To identify the risks for discontinuation, baseline demographics were compared between the continuing group and the disc continuing group using cox hazard regression analysis.Results:In total 570 patients, the average duration of treatment with biologics was 6.6±3.3 (years) and total patient-year was 3739 in this study. 458 patients were administered biologics continuously, 112 patients were withdrawn. Table 1 showed the demographic data in total patients. The retention rate was 96.0% (discontinuation n=23) at least 1 year from starting biologics treatment, 92.6% (n=42) at 3 years, 88.2% (n=67) at 5 years, 84.4% (n=89) at 7 years, 81.1% (n=108) at 10 years. In 112 patients who discontinued, the reasons were adverse events in 74 patients, lack of effectiveness in 11 patients, others in 27 patients. Comparison of incidence for discontinuation using cumulative hazard function, the reason of adverse events was significantly higher than others reasons (Figure 1). To identify the risks of discontinuation, we analyzed by multivariable Cox proportional hazard modeling in patients who discontinued treatment due to adverse events, the risk factors (hazard ratio: HR, confidence interval: CI) were over 3 of Steinblocker class (HR 1.85 [1.02-2.04]), age (HR:1.07 [1.04-1.10]) and Non-concomitant with methotrexate (HR 1.90 [1.08-3.33]) (Figure 2).Table 1.Age (years)56.1 ± 13.4Gender n (% male)110 (19%) n (% female)460 (81%)Disease duration (years)11.1 ± 9.8stage 1,2104 (19%) 3,4455 (81%)class 1,2336 (60%) 3,4225 (40%)Methotrexate use, no (%)400 (70%)Glucocorticoid use, no (%)262 (47%)Rheumatoid Factor, no (%)287 (65%)anti CCP antibody, no (%)137 (87%)Conclusion:The most common reason for discontinuation was adverse events in long term observation. The risk factors for discontinuation were class, age, and non-concomitant MTX. These results suggested that comorbidity has a significant impact on continuation rates because there are some reasons of non-concomitant MTX in addition to relate with age and the activities of daily living.References:[1]Marussa B, et al. j.clin thera. 2011; 33(7): 901-913[2]Alejandro S, et al. Rheumatol. 2016; 55(3): 523-34Disclosure of Interests:KENYA TERABE: None declared, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Shuji Asai Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Janssen, Takeda, and UCB Japan, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Yasuhide Kanayama: None declared, Toshihisa Kojima Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Consultant of: AbbVie, Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis

BACKGROUND Our purpose in this study was to clarify whether differences in subject group attributes could affect data acquisition in proton magnetic resonance spectroscopy ((1)H-MRS). METHODS Subjects without diabetes mellitus (DM) were divided into two groups (group A, in their 20s; group B, 30-60 years old). Subjects with DM formed group C (30-60 years old). The numbers of subjects were 19, 27, and 22 for group A, B, and C respectively. For all subjects, (1)H-MRS measurements were taken of the soleus muscle (SOL) and the anterior tibial muscle (AT). We defined the success of the measurements by the detection of intramyocellular lipids. Moreover, we also measured the full width at half maximum of the water peaks for all subjects. RESULTS The success rate was significantly higher for the AT (100%) than for the SOL (81.6%) (P

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.

Background:Daily teriparatide (dTP) strongly affects bone metabolism in patients with rheumatoid arthritis (RA), resulting in increased bone mineral density (BMD). We reported the 2-year results of dTP treatment for osteoporosis (OP) in patients with RA in EULAR2014 [1]. Drugs affecting bone metabolism, such as biological agents (BIOs) and glucocorticoids (GCs), are frequently administered to patients with RA in addition to dTP in daily clinical practice. Although dTP increases bone turnover, BIOs reduce osteoclast activity and GCs decrease bone turnover. We reported the effects of GCs or BIOs on the efficacy of dTP in EULAR2015 [2]. The present retrospective study investigated the effects of GCs or BIOs on the efficacy of dTP in patients with RA using a larger patient cohort.Objectives:To evaluate the effects of BIOs, GCs, or both on the efficacy of dTP treatment for OP in patients with RA.Methods:The study included 56 female patients who had completed 2 years of dTP treatment. We separated these patients into four groups according to their treatment regimen at dTP initiation: B(−)G(−),included patients who did not receive BIOs or GCs (n = 14); B(+)G(−), included patients treated only with BIOs (n = 8); B(−)G(+), included patients treated only with GCs (n = 24); and B(+)G(+),included patients treated with both BIOs and GCs (n = 10). We determined baseline (BL) characteristics, % changes in BMD in the lumbar spine (LS) and total hip (TH) from BL to 24 months, and % changes in serum bone turnover markers (BTMs), such as BAP, P1NP, NTX, and TRACP-5b, from BL to 6 months after dTP initiation. Dunnett’s test was used for comparisons between B(−)G(−) and other groups.Results:The mean ages of the B(−)G(−), B(+)G(−), B(−)G(+), and B(+)G(+) groups at BL were 70.0, 65.5, 69.6, and 71.5 years, whereas the mean duration of RA in these groups were 15.4, 20.8, 69.9, and 71.5 years, respectively. Furthermore, the mean baseline DAS28-CRP levels in these groups were 2.8, 2.2, 2.8, and 2.3. The mean LS-BMD (g/cm2) at BL were 0.795, 0.819, 0.826, and 0.853, whereas the mean TH-BMD at BL were 0.619, 0.570, 0.601, and 0.629, respectively. The mean % changes in LS-BMD at 24 months were 15.5%, 12.7%, 11.9%, and 8.1%, respectively (Fig 1A). There were no significant differences between B(−)G(−) and other groups. The mean % changes in TH-BMD at 24 months in the B(−)G(−), B(+)G(−), B(−)G(+), and B(+)G(+) groups were 6.4%, 5.3%, 4.4%, and 1.5%, respectively (Fig 1B) A significant difference was observed between the B(−)G(−) and B(+)G(+) groups (p = 0.03). The % changes in BTMs in the B(−)G(−), B(+)G(−), B(−)G(+), and B(+)G(+) groups were as follows: BAP, 90.5%, 44.0%, 29.5%, and 87.7%; P1NP, 374.1%, 338.2%, 225.9%, and 640.0%; NTX, 75.2%, 106.6%, 42.5%, and 80.5%; and TRACP-5b, 75.8%, 43.85, 20.4%, and 122.3%, respectively. No significant differences were observed in the changes in BTMs among the groups.Conclusion:This study suggested that concomitant use of BIOs and GCs inhibited the increase in BMD induced by dTP treatment in patients with RA, particularly TH-BMD. Although BTM analysis revealed no statistical significance, GCs tended to decrease the % change in BTMs.References:[1]Hirano et al. Ann Rheum Dis 2014: 73 (Suppl 2): 166[2]Hirano et al. Ann Rheum Dis 2015: 74 (Suppl 2): 528Disclosure of Interests:Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Hironobu Kosugiyama: None declared, Kyosuke Hattori: None declared, Daisuke Kihira: None declared

Background:Osteoporosis (OP) is frequent complication identified in patients with rheumatoid arthritis (RA). Effective treatment must be provided to treat OP in RA (RAOP). Denosumab (DMB) is one of the promising drugs that are currently being used for the treatment of RAOP. We reported the results of 12-month DMB treatment for RAOP as part of Japanese multicenter registry study (TBCR-BONE) in EULAR2016 [1]. Recently, a treatment goal of OP was reported by the American Society for Bone and Mineral Research and the National Osteoporosis Foundation (ASBMR-NOF) working group [2]. This report advocated that the goal of treatment is a T-score of >-2.5 at the femoral neck, total hip (TH) or lumbar spine (LS) on DXA if the primary reason for starting treatment was a T-score of ≤-2.5 at the abovementioned skeletal sites. The working group noted that it was reasonable to expect that initial treatment should offer at least a 50% chance of achieving the treatment goal within 3 to 5 years of initiating therapy. We have reported the achievement rates of treatment goal in RAOP with 3-year DMB treatment on RAOP in EULAR2019 [3].Objectives:The aim of this retrospective study was to evaluate whether 5-year DMB treatment can achieve treatment goal of OP using data from TBCR-BONE.Methods:The study included 46 female patients who had completed 5-year DMB treatment. The LS-BMD analysis included 22 patients with a baseline (BL) LS-BMD T-score of ≤ -2.5. The TH-BMD analysis included 29 patients with a BL TH-BMD T-score of ≤ -2.5. Similar to clinical setting in Japan, 60mg of DMB was administered once every 6 months with a vitamin D3 supplement. BL characteristics, change in T-score over time, and achievement of the treatment goal (T-score>-2.5) were evaluated.Results:BL characteristics of the 46 female patients included: mean age of 69.1 years and RA duration of 16 years. Prednisolone was administered to 37% of the patients. In the LS-BMD analysis, T-scores improved significantly; the mean value at BL was −3.4, which increased to −3.0 at 1 year, −2.6 at 3 years, and ultimately to −2.5 at 5 years. The fraction of patients who achieved the treatment goal was as follows: 36.4% at 1 year, 40.9% at 2 years, 45.5% at 3 years, 50.0% at 4 years, and 54.5% at 5 years (Fig. 1A). The patients who achieved this treatment goal were those who had a significantly lower risk of fracture at BL as determined by FRAX (17.9% vs. 32.2%, p = 0.044), who had significantly higher BL serum TRACP-5b level (572.8 vs. 401.0: p = 0.03), and who had significantly better BL LS-BMD T-scores (−3.0 vs. −3.9, p < 0.01) than the nonachievers. In the TH-BMD analysis, T-scores improved significantly; the mean value at BL was −3.0, and it increased to −3.0 at 1 year, −2.7 at 3 years, and reached −2.7 at 5 years. The fraction of patients who achieved the treatment goal was as follows: 20.7% at 1 year, 31.0% at 2 years, 34.5% at 3 years, 31.0% at 4 years, and 37.9% at 5 years (Fig. 1B). The patients who achieved this treatment goal were those who had significantly better BL TH-BMD T-scores (−2.7 vs. −3.2: p < 0.01) than the nonachievers. Cut-off values at BL for achievement of the treatment goal determined using ROC analysis were −3.1 for the LS-BMD (sensitivity 83.3%, specificity 90.0%) and −2.85 for the TH-BMD (sensitivity 100.0%, specificity 81.0%).Conclusion:The results of this study suggested that achievement of the treatment goal was comparatively easy for those with LS-BMD loss; however, it was comparatively difficult for those with TH-BMD loss. Early initiation or longer duration of DMB therapy may be necessary to improve achievement rates. Likewise, other agents, such as romosozumab, may be considered for those with significant TH-BMD loss.References:[1]Hiranoet al.Ann Rheum Dis 2016; 75 (Suppl 2): 94[2]Cummingset al.J Bone Miner Res 2017; 32: 3-10[3]Hiranoet al.Ann Rheum Dis 2019; 78 (Suppl 2): A940Disclosure of Interests:Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Yasuhide Kanayama: None declared, Hironobu Kosugiyama: None declared, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda

Background:Cervical lesions are known to occur at high frequency as a complication of rheumatoid arthritis (RA). Treatment with biological agents are more clinically effective than the DMARDs that were in use previously, in particular, with their efficacy in suppressing joint destruction having been emphasized. We reported the efficacy of infliximab, anti-tumor necrosis factor antibodies for suppressing the radiographic progression of RA cervical lesions at ACR2009, EULAR2010, 11, 12, 13, 14,16 and 18. However there is still few studies of efficacy of against RA cervical lesions of Abatacept (ABT) that inhibits T cell activation by binding to CD80/86.Objectives:To evaluate the efficacy of ABT for suppressing the radiographic progression of RA cervical lesions comparison with MTX for 2 years.Methods:We used ABT or MTX for treating Japanese patients with active RA who fulfilled the ACR criteria in 1987. The final study cohort of each 60 and 75 patients received continuous ABT and MTX treatment for at least 2 years. For evaluation of cervical lesions, the atlanto-dental interval (ADI), the space available for the spinal cord (SAC), and the Ranawat value were measured by plain lateral radiographs in the flexion position, at initiation and Year 1,2.Results:In the patients receiving ABT (n=60) and MTX (n =75), the number of female were each 48(80%) and 52(69%) cases(p=0.160). The mean age was 67.7 ± 12.9 and 63.6 ± 11.0 years old (p=0.004); disease duration was 16.7 ± 14.2 and 8.0 ± 9.5 years (pConclusion:This study suggested that ABT treatment can be used to suppress the progression of RA cervical lesions more than MTX treatment.Disclosure of Interests:Yasuhide Kanayama: None declared, Toshihisa Kojima Grant/research support from: Chugai, Eli Lilly, Astellas, Abbvie, and Novartis, Consultant of: AbbVie, Speakers bureau: AbbVie, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Janssen, Mitsubishi Tanabe, Pfizer, and Takeda, Yuji Hirano Speakers bureau: Tanabe-Mitsubishi, Pfizer, Eisai, Abbie, Chugai, Bristol-Meyers, Jansen, Astellas, UCB, Eli-Lilly, Asahikasei, Daiichi-Sankyo, Amgen, Nobunori Takahashi Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Janssen, Mitsubishi Tanabe, Ono, Pfizer, Takeda, and UCB Japan, Yukiyoshi Oishi: None declared, Naoki Ishiguro Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi-Sankyo, Eisai, Kaken, Mitsubishi Tanabe, Otsuka, Pfizer, Takeda, and Zimmer Biomet, Consultant of: Ono, Speakers bureau: Astellas, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, and Taisho Toyama

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.

Background: Biological (BIO) therapy has become a standard therapy in the treatment of rheumatoid arthritis (RA) and long-term outcomes has increasingly evaluated. Elderly people has increased in Japan and 27.3% of whole people in Japan was 65 years of age or older in 2016. We reported treatment retention rate of BIO therapy in RA patients in EULAR2015 annual meeting as mixed data of elderly RA patients (ERA) and younger RA patients (YRA) 1). Objectives: This observational cohort study investigated the treatment retention rate in ERA compared with YRA. Methods: Toyohashi RA Database (TRAD) was used. 330 RA patients who initiated any of BIO agents (infliximab, etanercept, adalimumab, tocilizumab, abatacept, golimumab, infliximab-BS) as first Bio in our institute from 2003 to 2016 were included in this study. Switching from one Bio agent to another was defined as continuation of Bio therapy in this study. Stopping of BIO therapy was defined as non-administration for longer than 3 months for any reasons other than remission and pregnancy related. We divided whole patients into two categories using age at initiation of BIO therapy such as YRA (64 years of age or younger) and ERA (65 years of age or older). ERA was further subdivided into two categories such as yERA (65–74 years of age) and oERA (75 years of age or older). We investigated patients’ characteristics, treatment retention rate by Kaplan-Meier method and reasons of stopping BIO therapy and compared them between categories. Results: Baseline characteristics at the initiation of BIO treatment: %female was 82.4%. Mean age was 58.1 years old (210 YRA, 98 yERA and 22 oERA). Mean RA duration was 10.9 years. % methotrexate (MTX) concomitant was 82.1% and mean used dose was 8.9 mg/weeks (MTX dose was restricted up to 8 mg/weeks until 2011 in Japan and 16 mg/w after 2011). % prednisolone (PSL) concomitant was 50.9%. % Bio monotherapy was 9.1%. Mean baseline DAS28-CRP and SDAI was 4.6 and 24.4, respectively. % high disease activity measured using DAS28 and SDAI at baseline was 44.4% and 42.2%, respectively (Fig1). Baseline disease activity were getting lower year by year. Continuation rate of BIO treatment in whole patients is 88.4% at 1 year, 82.0% at 3 years, 72.2% at 5 year and 57.1% at 10 years. There were significant differences in continuation rate of BIO treatment between YRA and ERA (Fig2), between YRA and yERA and between YRA and oERA, but not between yERA and oERA. Major reasons (over 10%) of stopping BIO therapy in YRA were infection other than respiratory system (15.7%), infection of respiratory systems (11.8%), ineffectiveness (11.8%) and malignancy (11.8%). Major reasons in ERA were infection of respiratory systems (21.3%) and infection other than respiratory systems (10.6%). YRA: younger RA patients, ERA: elderly RA patients Conclusions: Although continuation rate of BIO treatment in ERA was inferior to that in YRA, that in yERA was not significantly different from that in oERA. Serious infection, especially in respiratory systems, was most frequent reason for stopping BIO therapy in ERA. These results suggested that BIO therapy in ERA demands close attention to infection and special strategies might need in the treatment of ERA people. Reference [1] Hirano Y, et al. Ann Rheum Dis2015;74:700. Disclosure of Interest: None declared

Background Cervical lesions are known to occur at high frequency as a complication of rheumatoid arthritis (RA). Treatment with biological agents are more clinically effective than the DMARDs that were in use previously, in particular, with their efficacy in suppressing joint destruction having been emphasized. We reported the efficacy of infliximab (IFX), anti-tumor necrosis factor antibodies for suppressing the radiographic progression of RA cervical lesions at ACR2009, EULAR2010, 11, 12, 13 and 14. However there is still few studies of efficacy of against RA cervical lesions of IFX comparison with methotrexate (MTX). Objectives To evaluate the efficacy of IFX for suppressing the radiographic progression of RA cervical lesions comparison with MTX for 2 years. Methods We used MTX or MTX+IFX for treating Japanese patients with active RA who fulfilled the ACR criteria in 1987. The final study cohort of each 40 and 88 patients received continuous MTX and IFX treatment for at least 2 years. MTX was used in all patients receiving IFX. For evaluation of cervical lesions, the atlanto-dental interval (ADI), the space available for the spinal cord (SAC), and the Ranawat value were measured by plain lateral radiographs in the flexion position, at initiation and Year 1,2. Results In the patients receiving MTX (n=40) and IFX (n=88), the number of female were each 33 (83%) and 75 (85%) cases (p=0.794). The mean age was 62.5 ± 10.7 and 53.9 ± 12.9 years old (p Conclusions This study suggested that IFX treatment can be used to suppress the progression of RA cervical lesions more than MTX treatment. Disclosure of Interest Y. Kanayama: None declared, T. Kojima Speakers bureau: Mitsubishi Tanabe Pharma, Takeda Pharma, Eisai Pharma, AbbVie,Bristol-Myers Squibb, and Pfizer, Janssenn Pharmaceutical Companies, Astellas Pharma and Chugai Pharma., Y. Hirano Speakers bureau: Abbvie Japan, Eisai, Mitsubishi Tanabe Pharma, Pfizer, Chugai Pharmaceutical, and Bristol-Myers Squibb., N. Takahashi Speakers bureau: Abbvie Japan Co. Ltd, Eisai Co. Ltd, UCB Japan Co. Ltd, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Pfizer Co. Ltd, Chugai Pharmaceutical Co. Ltd,Janssen Pharmaceutical K.K., and Bristol-Myers Squibb Co. Ltd., Y. Yabe: None declared, N. Ishiguro Grant/research support from: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, TaishoToyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, AbbVie, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan, Speakers bureau: Daiichi Sankyo, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Taisho Toyama Pharmaceutical, Kaken Pharmaceutical, Eisai, Janssen Pharmaceutical, Bristol-Myers Squibb, AbbVie, Chugai Pharmaceutical, Mitsubishi Tanabe Pharmaceutical, Astellas Pharma, and Pfizer Japan.

Objective To determine the effects of concomitant methotrexate (MTX) on the incidence of large joint replacement resulting from the progression of large joint destruction in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors. Methods A retrospective cohort study was performed using a multicenter registry. In total, 803 patients with RA who received etanercept or adalimumab were included. The first large joint replacement during treatment with etanercept or adalimumab was used as the outcome variable in predictive analyses. The cumulative incidence of large joint replacement was estimated using Kaplan-Meier curves, and the impact of concomitant MTX on the incidence of large joint replacement was assessed with Cox proportional hazards models. Propensity score matching was used to reduce selection bias. Results Of all patients, 601 (75%) received concomitant MTX at a median dosage of 8 mg/week (interquartile range 6–8). A total of 49 patients (62 joints) underwent large joint replacement during treatment with etanercept or adalimumab. The incidence of large joint replacement for patients with concomitant MTX was significantly lower than that for patients without MTX (P < 0.001). Multivariate analysis revealed that concomitant MTX independently predicted large joint replacement (hazard ratio 0.36, 95% confidence interval 0.20–0.65). Additionally, propensity score–matched analysis demonstrated that patients with concomitant MTX had a significantly lower incidence of large joint replacement than those without concomitant MTX (P = 0.032). Conclusion Concomitant MTX reduces the incidence of large joint replacement in patients with RA treated with TNF inhibitors.

This retrospective observational study aimed to examine the efficacy of iguratimod with and without concomitant methotrexate (MTX) and to estimate the adequate observational period for predicting low disease activity (LDA) achievement at 24 weeks in patients with rheumatoid arthritis (RA).All patients treated with iguratimod were registered in a Japanese multicenter registry. Multivariate analyses were performed to identify predictive factors for LDA achievement at 24 weeks. Receiver operating characteristic (ROC) curve analyses were performed to estimate the association of 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) at each time point with achievement of LDA at 24 weeks and determine a cut-off for DAS28-ESR.A total of 123 patients were treated with iguratimod with (n = 65) or without (n = 58) MTX. Iguratimod therapy resulted in significant clinical improvement in both groups. Multivariate analysis revealed that DAS28-ESR at each time point was an independent significant predictor of LDA achievement at 24 weeks. Cut-off values of DAS28-ESR at 12 weeks based on ROC curves were 3.2 and 3.6 in patients with and without MTX, respectively.Iguratimod was effective in RA patients in clinical practice. Our results suggest that 12 weeks may be a sufficient period to judge the medium-term efficacy of iguratimod in patients treated with and without MTX.