Takahito Suto

Efficacy at 52 weeks of daily clinical use of iguratimod in patients with rheumatoid arthritis

Abstract Objective. In recent years, the use of one or more conventional synthetic disease-modifying antirheumatic drugs has been recommended for the treatment of rheumatoid arthritis (RA). We performed a 52-week study on the efficacy and safety of iguratimod (IGU) against patients with RA in daily clinical use. Methods. Forty-one patients were enrolled in this study, and the clinical course of RA was regularly evaluated during the 52 weeks of treatment. Results. The survival rate at week 52 was 53.7%. The disease activity score (DAS) 28-erythrocyte sedimentation rate, DAS28-C-reactive protein, simplified disease activity index, and clinical disease activity index were all significantly decreased at week 52. The matrix metalloproteinase-3 level was significantly decreased at week 52 by combination therapy of IGU and methotrexate. There were one case of the onset of interstitial pneumonia (IP), one exacerbation of IP, and one case of the onset of Pneumocystis jiroveci pneumonia. Conclusions. IGU is effective for RA patients when used for daily clinical treatment for 52 weeks.

Prediction of Large Joint Destruction in Patients With Rheumatoid Arthritis Using 18F-FDG PET/CT and Disease Activity Score.

AbstractThe assessments of joint damage in patients with rheumatoid arthritis (RA) are mainly restricted to small joints in the hands and feet. However, the development of arthritis in RA patients often involves the large joints, such as the shoulder, elbow, hip, knee, and ankle. Few studies have been reported regarding the degree of large joint destruction in RA patients. 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) visualizes the disease activity in large joints affected by RA. In this study, the associations between destruction of the large joints and the findings of FDG-PET/CT as well as laboratory parameters were investigated, and factors associated with large joint destruction after the administration of biological therapy were identified in RA patients.A total of 264 large joints in 23 RA patients (6 men and 17 women; mean age of 66.9 ± 7.9 years) were assessed in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The extent of FDG uptake in large joints (shoulder, elbow, wrist, hip, knee, and ankle) was analyzed using the maximum standardized uptake value (SUVmax). Radiographs of the 12 large joints per patient obtained at baseline and after 2 years were assessed according to Larsens method. A logistic regression analysis was performed to determine the factors most significantly contributing to the progression of joint destruction within 2 years.Radiographic progression of joint destruction was detected in 33 joints. The SUVmax at baseline and 6 months, and the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) at 6, 12, and 24 months were significantly higher in the group with progressive joint destruction. The SUVmax at baseline and DAS28-ESR at 6 months were found to be factors associated with joint destruction at 2 years (P < 0.05).The FDG uptake in the joints with destruction was higher than that observed in the joints without destruction. The SUVmax at baseline and the DAS28-ESR at 6 months after the biological treatment were identified to be significant factors predicting destruction of the large joints at 2 years.

Effect of total knee arthroplasty on other joints in patients with rheumatoid arthritis evaluated by 18-FDG-PET

The objective of this study was to assess arthritis of the whole body before and after total knee arthroplasty (TKA) in patients with rheumatoid arthritis (RA) using positron emission tomography (PET).

Predictive factors related to shoulder joint destruction in rheumatoid arthritis patients treated with biologics: A prospective study

Abstract Objective: The aim of this study was to assess the risk factors for shoulder joint destruction in rheumatoid arthritis (RA) patients treated with biologics. Methods: Thirty shoulders of 29 patients with RA were assessed using 18F-fluorodeoxyglucose positron emission tomography (PET) and magnetic resonance imaging (MRI) before starting biologics and 6 months later. The mean age (range) was 54 (18–72) years, and the mean disease duration was 7 (0.8–30) years. The radiographic findings were assessed at baseline and 3 years later. The inflammation markers and RA disease activity were also assessed. These parameters were compared between the progression of joint destruction group and the no progression group. Results: The SUVmax on PET, the rate of synovitis, and the rate of rotator cuff tear on MRI before biologic treatment were significantly higher in the progression of joint destruction group. SUVmax and synovitis on MRI after 6 months were also significantly higher in the progression of joint destruction group. On logistic regression analysis, the SUV at baseline of the shoulder joint was the main risk factor for joint destruction. Conclusion: The detection of synovitis by imaging was more important than disease activity and inflammation markers for assessing the progression of shoulder joint destruction.

Short-term daily teriparatide in patients with rheumatoid arthritis

Abstract Objective: The aim of this study was to compare the efficacy of six-month teriparatide treatment followed by six-month bisphosphonate therapy with 12-month bisphosphonate monotherapy in Japanese rheumatoid arthritis (RA) patients who had not been previously treated for osteoporosis. Methods: A total of 34 RA patients with osteoporosis were enrolled. Thirteen patients received six-month teriparatide prior to six-month minodronate therapy (PTH group), and 21 patients received 12-month minodronate therapy (BP group). Bone mineral density (BMD), and bone turnover markers were measured prior to and 6 and 12 months after the initiation of treatment. Results: Bone mineral density of the spine was significantly increased after 12 months of treatment in both groups. In the PTH group, the mean percent change of BMD of the spine was significantly higher at 12 months after the initiation of treatment, as compared to the BP group (PTH group: 9.9 ± 1.5%, BP group: 5.5 ± 0.7%). Femoral neck BMD was significantly increased only in the PTH group after 12 months. Conclusion: Therapy involving six-month teriparatide followed by six-month minodronate therapy increased spine BMD to a greater degree than 12-month minodronate monotherapy. The strategy of short-term administration of teriparatide for RA patients with osteoporosis might be useful when additional bisphosphonate therapy is considered.

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

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

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

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

FRI0101 Assessment of Large Joint Destruction in Patients with Rheumatoid Arthritis: A Prospective Study Using FDG-PET/CT and Arashi Scoring Method

Background Larsen method has been widely used to assess large joint destruction in patients with rheumatoid arthritis (RA). In that method, various changes might be included within one grade. 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) can visualize the disease activity in large joints affected by RA. Objectives The associations between destruction of the large joint and FDG-PET/CT findings were investigated using a new radiographic evaluation method “ARASHI Scoring system”1. Methods A total of 260 large joints (shoulder, elbow, hip, knee and ankle) in 26 RA patients (six males and 20 females; mean age of 66.9 years) were assessed in this study. FDG-PET/CT was performed at baseline and six months after the initiation of biological therapy. The extent of FDG uptake in large joints was analyzed using the maximum standardized uptake value (SUVmax). Radiographs of the 10 large joints per patient obtained at baseline and after three years were evaluated according to the ARASHI change score. A multiple regression analysis was performed to determine the factors most significantly contributing to the progression of large joint destruction within three years. Results Eighteen joints had previously been treated with joint replacement surgery at baseline and nine joints were treated with joint replacement surgery in three years. They were excluded from this study, so we evaluated 233 large joints. The ARASHI status score (score at baseline), SUVmax at baseline, DAS28-ESR and ΔSUV (SUVmax at baseline – SUVmax at six months) were significantly associated with high level changes of ARASHI change score. A multiple regression analysis revealed ΔSUV was found to be the most associated factor with joint destruction at three years (p<0.05). Conclusions We investigated large joint destruction in RA patients using FDG-PET/CT and ARASHI scoring method. This study suggested the importance to decrease SUV value in RA patients with high level of SUVmax at baseline for the prevention of large joint destruction. References Kaneko A, Matsushita I, Kanbe K, Arai K, Kuga Y, Abe A, Matsumoto T, Nakagawa N, Nishida K. Development and validation of a new radiographic scoring system to evaluate bone and cartilage destruction and healing of large joints with rheumatoid arthritis: ARASHI (Assessment of rheumatoid arthritis by scoring of large joint destruction and healing in radiographic imaging) study. Mod Rheumatol. 2013 Nov;23(6):1053–62. Disclosure of Interest None declared

THU0092 The Long-Lasting Benefits of Upper Extremity Surgery for Disabled Patients with Rheumatoid Arthritis

Background The treatment of rheumatoid arthritis (RA) has made significant advances in the last decade, because of the introduction of biologics and the development of “Treat to Target (T2T)” treatment modalities. However, while the ADL of such patients have improved and the level at which patients can use their upper limb functions has increased, there have been few reports of postoperative long-term results of upper extremity surgery in RA patients. Objectives To investigate a long-lasting effect of upper extremity surgery on patients with RA, a questionnaire survey was conducted. Methods A questionnaire was sent to 89 RA patients who underwent upper-extremity surgery between January 2002 and December 2003. It inquired about the present condition of the surgically treated site, the satisfaction level, and reasons why the patient was satisfied or not. Acceptable replies were obtained from 68 patients (76.4%, mean age at surgery 57.5), regarding 98 sites (shoulder: 1, elbow: 20, wrist: 46, thumb: 16, fingers: 15). The surgical procedures included total elbow arthroplasty in 13 patients, wrist synovectomy and a Darrach procedure in 35 patients, Radiolunate arthrodesis in 17 patients, Swanson implant arthroplasty at the metacarpophalangeal joint in 26 patients, and so on. Results The mean DAS28-ESR(4) at the time of surgery was 4.51, and it significantly decreased to 2.89 at present (P<0.01). Grip power increased from 158mmHg to 180mmHg in the patients who received wrist surgeries (P=0.049). The modified health assessment questionnaire (mHAQ) showed an improvement trend compared with the time of surgery, but no significant reduction was observed. However, when we compared only the items that evaluated the upper extremity function (items 1, 3, 5, 7) among the items of mHAQ, then a significant decrease was observed in the postoperative level 0.64 in comparison to the preoperative level 0.86 (P=0.02). Regarding usefulness, 85.6% of the patients answered “better” than the preoperative condition. Regarding the satisfaction level, 85.5% answered “highly satisfied” or “satisfied”. The level was relatively high regarding the wrist (88.9%) and the fingers (93.8%) compared to the elbow (77.8%) and the thumb (81.3%). The most frequent reason for being satisfied was “pain relief” at all sites. The reason for not being satisfied was a “decrease in power” in the elbow and the thumb, and a “decrease in motion” in the wrist. In the thumb and the fingers, an “improved appearance” was a frequent reason for being satisfied. Conclusions A long-lasting favorable effect was thus found in RA patients that underwent upper extremity surgery. Disclosure of Interest None declared

AB0318 Prediction of Large Joint Destruction in Patients with Rheumatoid Arthritis Using FDG-PET/CT

Background The assessments of joint damage in patients with rheumatoid arthritis (RA) are mainly restricted to small joints in the hands and feet. However, the development of arthritis in RA patients often involves the large joints, such as the shoulder, elbow, hip, knee and ankle. Few previous reports have studied the predictive value of radiographic findings for destruction of the large joints in RA patients. 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) precisely visualizes the disease activity in large joints affected by RA. Furthermore, the response on FDG-PET correlates with the clinical response to biologic treatment. However, it is not thoroughly understood whether FDG-PET/CT findings correlate with the severity of destruction in the large joints of the RA patients. Objectives To investigate the associations between destruction of the large joints and FDG-PET/CT findings, the disease activity and laboratory parameters after the administration of biological therapy in patients with RA. Methods 23 RA patients (six males and 17 females; mean age of 66.9±7.9 years) were assessed in this study. FDG-PET/CT was performed before the initiation of biological therapy and six months after the therapy. The extent of FDG uptake in large joints (shoulder, elbow, hand, hip, knee and ankle) was analyzed using the maximum standardized uptake value (SUVmax). Radiographs of the 12 large joints per patient, for a total of 276 joints, were obtained at baseline and after two years. Twelve joints had previously been treated with joint replacement surgery at baseline and were excluded from this analysis. A total of 264 large joints were assessed according to Larsens method. The disease activity and laboratory parameters were evaluated at baseline and six, 12 and 24 months after the therapy. A logistic regression analysis was performed to determine the factors most significantly contributing to the progression of joint destruction within two years. Results Among the 264 joints, radiographic progression of joint destruction was detected in 33 joints. The SUVmax at baseline and six months and the disease activity score (DAS) 28 – erythrocyte sedimentation rate (ESR) at six, 12 and 24 months were significantly higher in the group with progressive joint destruction. The multivariate logistic regression analysis revealed the SUVmax at baseline and DAS28-ESR at six months were found to be factors associated with joint destruction at two years (p<0.05). Conclusions The FDG uptake was significantly higher in the large joints demonstrating radiographic progression of destruction at two years after the initiation of biological therapy. The SUV max at baseline and the DAS28–ESR at six months after the biological treatment were identified to be significant factors predicting destruction of the large joints at two years. Disclosure of Interest None declared