Plain radiographic examination is a basic tool used to assess joint damage in RA. Radiograph shows pocket erosion in bare areas, joint space narrowing and roughness of subchondral bone in RA. Modified total Sharp score is a useful method for the evaluation of small changes of joints in early stage of RA. However, only small joints in hands and feet are assessed by this scoring system. We developed the ARASHI scoring system for the evaluation of large joint damage in RA. This scoring system is well related to Larsen grade and further detail of large joint changes can be evaluated.
Ultrasonographic（US）examination in RA is a very useful tool to make early diagnosis and to evaluate efficacy of treatment. Thickness of synovium and effusion are detected using gray scale method of US, and abnormal vascular signal can be detected by power Doppler method. Sensitivity and specificity for detecting synovitis using us is as high as MRI. Power Doppler signal is strongly related to subsequent joint damage.
MRI is more sensitive than conventional radiography in detecting bone erosions in early RA. MRI erosion is detected as a well-defined area of abnormal signal. MRI can identify bone edema in patients with RA which cannot be visualized by radiographic technique. Bone marrow edema has been described as an ill-defined area of abnormal signal intensity. The presence of bone marrow edema can be a marker of inflammatory activity of RA and be defined as a pre-erosive lesion which enables us to predict joint damage.
Objective: To investigate the change of bone mineral density（BMD）in patients with rheumatoid arthritis（RA）over 10 years. Methods: In a longitudinal study of 36 patients with RA, we collected clinical data and measured lumber spine and hip BMD by dual-energy X-ray absorptiometry at baseline and at the time 10 years or more. BMD was measured as the percentage of young adult mean（YAM）. We compared clinical characteristics between patients with an increase in lumber spine YAM of < 5% and those with YAM of < 5% at final follow-up. Results: The median age was 60.5 years old, the median disease duration of RA was 9.5 years, and the mean follow-up period was 10.4 years. Lumbar spine BMD increased from 81.2% of YAM at baseline to 91.0% of YAM at follow-up, while total hip BMD decreased from 80.6% of YAM at baseline to 77.0% of YAM at follow-up. The patients with an increase in lumber spine YAM of ≥ 5% were higher age and lower prednisolone dose at baseline, and showed a high rate of antiresorptive drug intervention during the follow up period. Conclusion: We investigated long-term change of BMD in patients with RA. Our findings suggest that osteoporosis treatment for RA is important for an increase in spine BMD over 10 years.
Purpose: An interview-based study was conducted to clarify aging-associated attitude changes in elderly patients with rheumatoid arthritis（RA）and determine divergence between patients and rheumatologists in private practice（RP）in Japan.
Methods: Overall, 20 Japanese rheumatologists and their randomly chosen 1,066 patients completed a 10-item questionnaire, which configured generation, dwelling area, job status/style of RPs and patients, coping with extra-articular comorbidities, activities of daily living decline, cognitive decline, needing admission, bedridden status, end-of-life care, and identical medical alliance image. All questions were matched between patients and rheumatologists, and mismatches were statistically evaluated with chi square test.
Results: Overall, >64% of patients with RA desired that their rheumatologist, similar to general physicians, should not only treat RA but also its associated comorbidities and >90% of RPs did cope with it. Most patients relied on their attending RPs and desired to receive care during admissions. Answers that demonstrated partial mismatch between patients with RA and their attending RPs were concerning end-of-life care. In elderly patients, the image at the end-of-life is concretely configured（p < 0.05）. In >90% of elderly patients with RA who have a detailed image for death and desired end-of-life care, only ５ of 20 rheumatologists were prepared for providing the care（p < 0.05）.
Conclusions: Continued care up to and including death is needed in Japanese RPs such as general physicians. Japanese rheumatologists need to cope with aging problems of patients honestly.
Objective: Agalactosyl（galactose-deficient in the Fc-linked N-glycans, G0）anti-citrullinated peptide antibodies（ACPAs）were recently reported. This study investigated the changes in anti-agalactosyl immunoglobulin G antibodies（carbohydrate in rheumatoid factors [CARFs]）in patients with rheumatoid arthritis（RA）receiving infliximab（IFX）or etanercept（ETN）.
Methods: Data from 80 patients were collected retrospectively. ETN（n=40）or IFX（n=40）with or without methotrexate（ MTX）were injected according to the approved method and the clinical response was evaluated 6 months after administration. CARF measurements were obtained by electrochemiluminescence immunoassay（ECLIA）. ACPA determinations were performed at one timepoint by chemiluminescent immunoassay（CLIA）using anti-cyclic citrullinated peptide antibodies（anti-CCP）.
Results: CARF levels at baseline were positively correlated with ACPA（Spearman’s rank correlation coefficient, rs=0.621, n=37, p=4.1 × 10-5）. Baseline CARFs and ACPA levels were positively correlated with C-reactive protein（CRP）（rs=0.337, n=80, p=0.002, and rs=0.467, n=37, p=0.004, respectively）. The percent changes of CARFs from baseline were decreased significantly（median= −42.3%, p=0.0002）. The percent change from baseline CARFs was positively correlated with the percent change from baseline of the Disease Activity Score in 28 joints based on CRP levels（DAS28-CRP）（rs=0.438, p=4.8×10-5）after 6 months of treatment.
Conclusions: We show the first evidence in humans that the percent change of CARFs from baseline is positively correlated with the percent change of Disease Activity Score from baseline after 6 months of infliximab or etanercept treatment in RA patients.
［Objective］Vasculitis syndrome includes several symptoms, and delays in diagnosis adversely influence the prognosis of affected organs and overall survival. We investigated the treatment of vasculitis syndrome in rural Japan. ［Methods］We distributed a questionnaire on vasculitis syndrome intended for doctors of internal medicine, orthopedic surgery, and dermatology from November 2017 to December 2017. ［Results］Of the 206 practitioners and 40 hospital physicians, 98 and 25 responded to the questionnaire（response rate of 47.6% and 62.5%, respectively）. Although the clinical practice guideline for the management of antineutrophil cytoplasmic antibody（ANCA）-associated vasculitis was the most recognized, recognition of the guideline by practitioners was low. Renal dysfunction, proteinuria, and hematuria were considered signs of renal vasculitis, but the most common time of referral to a specialist was when renal dysfunction had already progressed. ［Conclusions］The recognition of vasculitis guidelines by rural Japanese physicians is inadequate, and patients with vasculitis are referred to a specialist after organ involvement.
Background: Patients with rheumatoid arthritis（RA）need to take lifelong oral or injectable medication to alleviate their symptoms and prevent disease progression. However, some patients may not adhere or poorly adhere to treatment and have poor understanding of medication. This study is aimed at determining the effect of educating visiting pharmacists regarding administration of medication for patients with RA who poorly adhere to treatment regimens.
Methods: A prospective analysis was performed by enrolling 19 patients with RA who were treated with different types of medication. SDAI markers of RA disease activity were evaluated just before and after the pharmacist visit.
Results: The results（Mean ± SD）were as follows: age（years）, 74.4 ± 6.1; disease duration（months）, 144.2 ± 114.5; use of biological agents, 42.1%; use of MTX and its dosage（mg/week）, 84.2% and 6.6 ± 2.7; presence of dementia, 2; living alone, 8; Period from the effective date of visiting pharmacists to the examination date（day）, 66.9±20.5. The mean values of SDAI just before and after the pharmacist visit showed improvements; from 7.99 ± 6.88 to 4.39 ± 3.47（p = 0.0352）. All patients reported satisfaction with the overall effectiveness of the care.
Conclusion: Pharmacists visiting patients with poor adherence to RA treatment is useful for improving RA disease activity.
Background: Iguratimod（IGU）is a conventional synthetic disease-modifying antirheumatic drug（csDMARD）developed in Japan, and its influence on the renal function is poorly understood. Aim: To evaluate the influence of IGU on renal function. Methods: We evaluated 201 patients in whom the administration of IGU for rheumatoid arthritis（RA）had been newly started in Niigata Rheumatic Center from 2015 to 2016. In December 2017, we retrospectively investigated the clinical data of patients at the time of IGU initiation and after three and six months of IGU treatment. We also assessed the changes in the RA disease activity and renal function. Regarding the patients who discontinued IGU during the observational period, the data at the time of withdrawal and three months after discontinuation were compared. Results: The RA disease activity decreased significantly after 3 months of IGU treatment（DAS28-ESR 4.1（3.2-4.8）vs. 3.2（2.3-4.1）, p<0.001）. The estimated glomerular filtration rate（eGFR）also decreased significantly after 3 months（77.3（63.9-91.2）vs. 68.3（54.8-81.4）, p<0.001）. During the first 6 months, 51 patients discontinued IGU, with a decline in the renal function mentioned as the cause in 7 cases. Among the patients who discontinued IGU, the eGFR significantly recovered at 3 months after discontinuation（70.7（57.6-79.7）vs. 75.7（63.4-88.7）, p=0.002）. In multiple regression analysis, significant risk factors for over 10ml/min decline of eGFR included coadministration of non-steroidal anti-inflammatory drugs（NSAIDs）（odds ratio [OR], 3.89; 95% credible interval [CrI], 8.3 to 180.0）. Conclusion: Severe renal dysfunction was rare, but the eGFR significantly decreased after starting IGU. When administering IGU, we must be alert for not only hepatic but also renal dysfunction. However, recovery was observed after discontinuation, suggesting that such dysfunction is reversible.
Life expectancy in Japan is increasing. Better treatment options have also improved the prognosis for patients with rheumatoid arthritis（RA）. Therefore, it is important to understand the direction of treatment for elderly-onset RA.
According to data from the Japan Society of Kidney Disease Guidelines 2012 for chronic kidney disease（CKD）, renal function declines with age in 1 out of 3 people aged 70-79 years and in 1 in 2 aged ≥ 80 years. Drugs that deteriorate renal function are difficult to use.
Japanese Society of Nephrology Association guidelines（2012）for CKD patients classify drug use by creatinine clearance（Ccr/min）＞b50, 10-50, and ＜ 10 on dialysis. Adalimumab, infliximab, etanercept, tocilizumab, salazosulfapyridine can be used to treat RA when Ccr/min is 10-50 or ＜ 10; methotrexate is prescribed for Ccr/min ＞b50. Because these are guidelines from 2012, they do not include new biological products that are currently used（e.g., JAK inhibitors）.
In the annual report of the Japanese Rheumatology Association from the NinJa database（2012-2014）, the group with eGFR ＜ 30 mL/min/1.73 m2 showed a significant decrease in the RA activity indices of DAS 28-ESR, DAS 28-CRP, CDAI, SDAI when compared with the groups of eGFR ＜ 30 to 60 mL/min/1.73 m2 and eGFR ＜ 60 to 100 mL/min/1.73 m2. In other words, patients with RA and CKD at stage G4（eGFR ＜ 15-29 mL/min/ 1.73 m2）and G5（eGFR ＜ 15 mL/min/ 1.73 m2）had poor control of disease activity. Based on these existing reports, it is important to discuss kidney function in elderly-onset RA and the selection of treatment for this population considering data from current studies in our department.
The treatment of rheumatoid arthritis（RA）has improved dramatically following the advent of biological disease-modifying antirheumatic drugs（bDMARDs）. However, these bDMARDs require intravenous or subcutaneous injection and some patients fail to respond to them. Janus kinase （JAK）, which constitutively binds to cytokine receptors, plays an important role in the pathological processes of RA. Several JAK inhibitors that belong to a class of targeted synthetic DMARDs have been developed as new therapies for patients with RA. Two JAK inhibitors, tofacitinib and baricitinib, have already been approved in Japan. Results of phase III clinical trials using those JAK inhibitors have shown feasible efficacy and tolerable safety. Both drugs are effective in patients who showed inadequate response to bDMARDs as well as conventional synthetic DMARDs such as methotrexate. Since serious infections occur at a rate similar to other bDMARDs, the patients should be monitored carefully and regularly for adverse effects. Although JAK inhibitors are potent therapies for RA, more cautious consideration and measurement for their risk-benefit ratio are needed, after considering the safety results of ongoing post marketing surveillance.
Rheumatoid arthritis（RA）is an inflammatory and autoimmune disease characterized by synovitis and bone erosion. In the affected joints, synovial fibroblasts proliferation and massive infiltration of leukocytes are observed. The leukocyte infiltration into the tissues is tightly and spatiotemporally regulated by the interaction between chemokines and their receptors. Increased expression of fractalkine（FKN）and abundant infiltration of CX3CR1-expressed cells in RA joints have been reported. Therefore intervention of FKN-CX3CR1 axis could be a candidate target for RA treatment. In the collagen-induced mice arthritis model, anti-mouse fractalkine monoclonal antibody（anti-FKN mAb）showed therapeutic efficacy on synovial inflammation with the suppression of leukocytes infiltration. Furthermore, anti-FKN mAb improved the bone destruction by the direct inhibition of CX3CR1-expressed osteoclast precursors migration into the affected joints. In a Phase I clinical trial in RA patients, the humanized anti-human fractalkine monoclonal antibody（E6011）appeared to be safe and well tolerated in RA patients, and also showed effectiveness. Phase II clinical trials are in progress. In this review, we outline the contribution of FKN and CX3CR1 in RA pathogenesis and discuss the possibility for the treatment of RA by the blockade of FKN-CX3CR1 interaction.