Yukio Yonemoto

The assessment of biologic treatment in patients with rheumatoid arthritis using FDG-PET/CT

OBJECTIVES To evaluate whether there is a correlation between the differences in joint uptake of 2-[18F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) and the improvement of clinical findings in RA patients undergoing anti-TNF therapies. METHODS Twenty-two patients who received anti-TNF therapies, including infliximab for 16 patients and etanercept for 6 patients, were assessed. PET with (18)F-FDG studies and clinical assessments were performed at baseline and 6 months after the initiation of therapy. The maximal standardized uptake value (SUV(max)) was used as a representative value for the assessment of the FDG uptake in the bilateral shoulder, elbow, wrist, hip, knee and ankle joints. Spearmans rank correlation test was applied to assess the correlation between the SUV and the clinical parameters. RESULTS The ΔSUV (12 joints), the difference in the SUV(max) of the affected 12 joints before and after treatment, was positively correlated with the ΔDAS28 (r = 0.609, P = 0.003), ΔDAS28-CRP (r = 0.656, P = 0.001) and Δtender joint count (TJC) (r = 0.609, P = 0.003). There were also significantly positive correlations between ΔSUV (8 joints); the difference in the SUV(max) of the bilateral shoulder, elbow, wrist and knee joints before and after treatment and the ΔDAS28 (r = 0.642, P = 0.001), ΔDAS28-CRP (r = 0.712, P < 0.001) and ΔTJC (r = 0.608, P = 0.003), respectively. CONCLUSION The FDG uptake observed in the inflamed RA joints may reflect disease activity. The FDG-PET response was correlated with the clinical response to the biologic treatment of RA.

Efficacy of the clinical use of iguratimod therapy in patients with rheumatoid arthritis

Abstract Objective. Iguratimod (IGU) is a new synthetic disease-modifying antirheumatic drug intended to treat patients with rheumatoid arthritis (RA). We conducted a 24-week study on the efficacy of IGU in RA patients with daily clinical use. Methods. Forty-one patients were enrolled in this study, and the improvement in RA was evaluated every 4 weeks during the 24 weeks. Results. The patients global assessment of the disease activity with a scale (Pt VAS) was significantly decreased beginning at week 4. The disease activity score (DAS) 28-erythrocyte sedimentation rate, DAS28-C-reactive protein (CRP), simplified disease activity index and clinical disease activity index all significantly decreased at week 24. The matrix metalloproteinase-3 level was significantly decreased by the combination treatment with methotrexate at week 24. According to a logistic regression analysis, the factor which was most associated with the achievement of low disease activity (DAS28-CRP < 2.7) at week 24 was the DAS28-CRP at week 0. Conclusions. IGU had significant clinical effects on the RA patients within 24 weeks. IGU might therefore represent a new practical choice to treat RA patients.

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.

Evaluation of tocilizumab therapy in patients with rheumatoid arthritis based on FDG-PET/CT

BackgroundPositron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) can detect the presence of synovitis in rheumatoid arthritis (RA) patients. The aim of this study was to investigate whether the findings of FDG-PET matched the conventional assessments of the disease activity score (DAS) 28, DAS28-CRP, simplified disease activity index (SDAI) and clinical disease activity index (CDAI) in RA patients receiving tocilizumab (TCZ) therapy.MethodsSeventeen RA patients treated with TCZ were assessed. FDG-PET was performed at baseline and three and six months after the initiation of TCZ therapy. The maximum SUV (SUVmax) of the bilateral shoulder, elbow, wrist, hip, knee and ankle joints were added together (total SUV) and were used to assess the degree of FDG uptake as a representative parameter. The correlations between the ΔSUV and the difference in the clinical parameters at baseline and at each observation period, and the differences in each clinical parameters, were assessed.ResultsThe ΔSUV, the differences in the total SUV at baseline and at three/six months after starting treatment positively correlated with the ΔDAS28 (r = 0.615 p = 0.009/ r = 0.775 p < 0.001), ΔDAS28-CRP (r = 0.696, p = 0.002/ r = 0.828, p < 0.001), ΔSDAI (r = 0.652, p = 0.005/ r = 0.686, p = 0.002) and ΔCDAI (r = 0.662, p = 0.004/ r = 0.711, p = 0.001) for each period. The total SUV was significantly decreased at three and six months after the initiation of TCZ (p < 0.05).ConclusionsA reduction in the FDG uptake was observed at three and six months after the initiation of TCZ therapy. The disease activity estimated on FDG-PET/CT matched the conventional parameters following the TCZ therapy in RA patients.

A Clinical and Ultrasonographic Study of Risk Factors for Elbow Injury in Young Baseball Players

Purpose. To determine the risk factors for elbow injury and its association with glenohumeral internal rotation deficit among young baseball players. Methods. 229 baseball players aged 9 to 14 (mean, 11) years completed a self-administered questionnaire with items related to years of playing baseball, hours of training per weekday, days of training per week, and past and present experience of elbow pain. Two orthopaedic surgeons measured the range of motion of both shoulders and elbows. Another 2 orthopaedic surgeons performed ultrasonography to detect any elbow abnormality such as fragmentation of the medial epicondylar apophysis and osteochondritis dissecans of the capitellum. Using univariate and multivariable analyses, participants with or without elbow abnormality were compared to determine the risk factors for elbow abnormality. Results. Elbow abnormality was detected in 100 of the participants and comprised osteochondritis dissecans of the capitellum (n=18) and fragmentation of the medial epicondylar apophysis (n=82). Elbow abnormality was associated with being a pitcher, past and present experience of elbow pain, loss of elbow extension, and the side-to-side internal rotation difference. The 100 participants with elbow abnormality were stratified into symptomatic (n=57) or asymptomatic (n=43) of elbow pain. Those with elbow abnormality and elbow pain was associated with being a pitcher. Conclusion. Being a pitcher was a risk factor for both elbow abnormality and elbow pain. Nonetheless, 43% of baseball players with elbow abnormality were asymptomatic. The use of ultrasonography was effective in detecting elbow abnormality and enabling early treatment.

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).

Comparison of golimumab 100-mg monotherapy to golimumab 50 mg plus methotrexate in patients with rheumatoid arthritis: Results from a multicenter, cohort study

Objective. The aim of this study was to compare the efficacy and safety of golimumab (GLM) 50 mg + methotrexate (MTX) combination therapy and GLM 100 mg monotherapy in patients with rheumatoid arthritis (RA). Methods. The subjects were 115 RA patients (92 females and 23 males; median (range) age, 64 (17–87) years; median (range) disease duration, 8 (0.6–48) years) started on GLM. Eighty-three patients received GLM 50 mg/4 weeks + MTX (C group; median (range) MTX dosage 8 (2–16) mg/week), and 32 patients received GLM 100 mg/4 weeks (M group). Serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), matrix metalloproteinase-3, disease activity score (DAS) 28-ESR, DAS28-CRP, simplified disease activity index, and clinical disease activity index were evaluated 4, 12, and 24 weeks after starting GLM. Results. There were no significant differences in disease activity, adverse events, and drug continuation rates at 24 weeks between the groups. The DAS28-ESR remission rate was 34% in the C group and 26% in the M group. Conclusions. GLM 100 mg monotherapy improved disease activity as well as GLM 50 mg + MTX combination therapy. GLM 100 mg monotherapy appears to have a sufficient therapeutic effect in RA patients who cannot take MTX.

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.