In Japan, 16 years and 12 years elapsed from the approval of MTX and biologic agents for the treatment of RA. These drugs, which has been initially used as a final tool, become to be used from early disease period according to the concept of early diagnosis, early treatment, and T2T, is one of the standard treatment. The powerful anti-inflammatory effect of these drugs would be able to calm down the synovitis more efficiently, then severe limb deformity and large bone defect, which were well common in the past, have been less. In the West, the number of orthopedic surgery in RA patients, particularly joint replacement surgery, is decreasing. And the disease duration of whom have undertaken the surgery has been extended. However, in refractory cases which are resistant to any drugs or have many complication, joint destruction would progress and in cases that joint destruction had already progressed until the inflammation was well controlled, osteoarthritic change would progress, then those cases will need joint replacement surgery. On the other hand, hand and foot surgery tend to increase according to decreasing large joint destruction and to improving quality of life. Joint preserving surgery of forefoot tend to be widely accepted instead of resection arthroplasty. And synovectomy, which declined because of unpromising long term effect, trend to be reconsidered because longer effect could be promising thanks to improved medical treatment.

OBJECTIVES: To evaluate disease activity, function, radiographic progression for efficacy and adverse events (AEs) for safety of methotrexate (MTX) at doses of over 8mg/week for rheumatoid arthritis (RA), for which the dose was restricted by the Japanese government until 2011.
METHODS: A retrospective observational study for one year was performed using medical records from 108 RA patients using Disease Activity Score 28-joint assessment using erythrocyte sedimentation rate (DAS28-ESR) to assess disease activity, modified Health Assessment Questionnaire (mHAQ) for functional assessment, modified total Sharp score (mTSS) for image assessment. Safety was evaluated by the relationship between AEs and their prognosis.
RESULTS: DAS28-ESR decreased significantly (P < 0.0001) from 4.3 ± 1.4 to 3.4 ± 1.5 over the one-year observation period. The cases of patients with low disease activity plus remission were significantly increased from 24 (22.2%) at 0 months to 40 cases (47.6%) at 12 months (P < 0.001), with mHAQ changing from 0.69 to 0.55 (P < 0.01), and annual progression of mTSS from 8.2 to 1.02 (P < 0.01). The AEs, such as liver dysfunction, fever, vomiting, pneumonia and shingles were observed by 48 cases (44.4%) and MTX was discontinued in 2 cases. Body weight was one of predictors of AE (P = 0.001). Frequency of severe AEs was significantly related to age （P = 0.02）and combination with DMARDs (P < 0.001).
CONCLUSIONS: Increasing the dose of MTX over 8mg/week showed clinical improvement and effected suppression of joint destruction. However, we need to consider AEs, especially focusing on body weight, age and combination with DMARDs.

[Objective] We have retrospectively compared a triple therapy consisting of a combination of disease-modifying anti-rheumatic drugs with biologic agents for patients with established rheumatoid arthritis (RA) who had not improved despite treatment with methotrexate (MTX).
[Materials and Methods] We classified patients in 2 groups, one group added Tacrolimus (TAC) and Mizoribine (MZR) (S group) and the other added TNF inhibitor (B group). DAS28CRP, modified total sharp score and ARASHI change score which is scoring system of large joint destruction were evaluated and compared between both groups. We also estimated and compared the survival rate and the reasons of discontinuation of each group.
[Results] There was no significant difference in baseline characteristics between two groups. Both groups showed significant improvement of disease activity. The improvement rate of DAS28CRP in the B group was higher than that in the S group at 1 month after the treatment. However, no significant difference was observed between　two groups at 3 months after treatment and it continued during 2 years. There was no significant difference in radiographic progression of large joints. However the progression of small joint damage was more severe than that in S group. Sixteen percent in S group and 4.3% in B group had discontinued because of adverse events.
[Conclusion] Triple therapy using TAC, MZR and MTX had advantage in medical exponses compared with biologics for established RA patients. However the triple therapy might be inferior to biologics in inhibiting small joint destruction and safety, we should be careful about them.

Objectives: The aim of this study is to investigate an efficacy of low-dose tacrolimus for patients with rheumatoid arthritis (RA) who showed an inadequate response to disease-modifying antirheumatic drugs (DMARDs) including methotrexate (MTX).
Methods: Forty-seven patients with RA who showed an inadequate response to DMARDs were introduced low-dose tacrolimus between August 2006 and November 2013. Forty patients (34 women and 6 men; mean age, 68 years) continued the tacrolimus administration more than two years and were investigated retrospectively. Starting dosage was 1 to 1.5 mg/day and the dose was increased or reduced depending on their clinical response. Disease activity and clinical response were evaluated by Disease Activity Score including C-reactive protein (DAS28-CRP) and European League Against Rheumatism (EULAR) response criteria. Serum MMP-3 and modified Total Sharp Score (mTSS) by yearly change were evaluated to estimate progression of joint destruction.
Results: The mean tacrolimus dosage was 1.2 mg/day at the baseline and maintained in low-dose. DAS28-CRP was significantly improved at 6 months after administration. At 24 months, 21 (52.5%) showed low disease activity and remission, while 11 cases (27.5%) showed no response by EULAR improvement criteria. The serum MMP-3 was significantly improved at 6 months. Structural remission achievement rate in ΔmTSS≦0.5 was 37.5% and 52.5% in the first and second year, respectively.
Conclusions: Low-dose tacrolimus caused significant improvement in both clinical and structural remission. Tacrolimus is easy to use because of its safety and the effect of even a low-dose can be expected for patients with RA who had an inadequate response to DMARDs including MTX.

Object: We examined the effect of kidney insufficiency upon serum metalloproteinase-3 (MMP-3) levels, as an index of the disease activity in rheumatoid arthritis (RA) patients.
Methods: 332 patients with RA (within 66 kidney insufficiency i.e. estimated glomerular filtration rate (eGFR) <60 ml/min/1.73㎡) and 307 patients without RA (non-RA) (within 63 kidney insufficiency) were registered for cross-sectional examination. We examined the relations between CRP or DAS-28-CRP and serum MMP-3 level or the MMP-3 / Creatinine (Cr) ratio (the value that divided serum MMP-3 levels by serum Cr level) in RA patients.
Results: Serum MMP-3 levels had negatively correlated with eGFR in RA and non-RA patients. Serum MMP-3 levels and MMP-3 / Cr ratio had positively correlated with serum CRP levels and DAS28-CRP in RA patients with and without kidney insufficiency. Variances of serum MMP-3 levels to serum CRP levels and DAS28-CRP were elevated in RA patients with kidney insufficiency compared with those without kidney insufficiency. On the other hand, variances of MMP-3 / Cr ratio to serum CRP levels and DAS28-CRP were equivalent in spite of kidney insufficiency in RA patients. Logistic analysis indicated that the MMP-3 / Cr ratio was not independently associated with eGFR in RA patients.
Discussion: Serum MMP-3 levels increase with independence on inflammation and disease activity in RA patients with kidney insufficiency. The MMP-3 / Cr ratio may be a useful index for evaluation of inflammation and disease activity of RA patients with kidney insufficiency.

Objectives: To examine the relationship between clinical features and disease activity in patients with primary Sjögren’s syndrome (pSS) evaluated by ESSPRI (EULAR Sjögren’s Syndrome Patient Reported Index) and ESSDAI (EULAR Sjögren’s Syndrome Disease Activity Index).
Patients and Methods: Clinical data of 74 patients with pSS (60.7±12.6 years old) who visited our hospital between Aug. 2010 and Dec. 2014 were collected from medical charts.
Results: All patients were women. Average age ±SD at visit and at onset were 60.7±12.6 and 48.0±13.7 years old, respectively. ESSPRI and ESSDAI were assessed in 72 and 70 patients, and the median score of them were 4.3 and 3.0, respectively. Corticosteroids users were 60.8% and average dose (prednisolone equivalent) was 3.1±2.1 mg/day. Number of patients with low (ESSDAI < 5), moderate (5 ~ 13), and high disease activity (≧14) were 45, 19, and 6, receptivity. Corticosteroids were used in all patients with high disease activity and its dose (6.3 mg/day) was significantly higher than that in patients with moderate or low disease activity (2.7 mg/day each). Patients with onset age at less than 40 (younger onset) had significantly high ESSDAI score (median 7.0) compared with 40 or over (median 2.0), and there was a marked difference in its domain of lymphadenopathy. There was no difference of ESSPRI between the two groups; however, its item of fatigue score was significantly higher in younger onset patients.
Conclusions: Younger onset pSS patients had higher disease activity, and severity of fatigue and lymphadenopathy were the clinical characteristics.

    A 68-year-old female was diagnosed with malignant lymphoma while undergoing treatment for rheumatoid arthritis (RA). She was started on chemotherapy including rituximab (RTX). Consequently, malignant lymphoma remitted, and RA improved. However, when RA recurred approximately 1 year after the chemotherapy, RTX treatment was repeated following which the symptoms disappeared, and this effect was maintained for about 1 year. RA recurred at an interval of approximately 1 year, and it improved each time with RTX treatment. Increase in rheumatoid factor was detected just before RA recurrences. Therefore, rheumatoid factor was considered to be a useful predictor of RA recurrence.

(Introduction) It has been reported that biologic agents suppress the progression of the joint destruction in rheumatoid arthritis (RA). For this reason, joint replacement surgery for large joints has been reported to decrease, but small joint surgeries have been reported to increase on the other hand. The purpose of this article is to review the new trend of RA hand surgery.
(Wrist joint surgery) In this new era, synovectomy (including of arthroscopic synovectomy) is important especially for patients of early stage RA wrist joint when the involved joint does not favourably respond to conservative treatment. For the joint destructive case, arthroplasty (with Sauvé-Kapandji procedure, for example) or joint fusion might be selected. Recovery of Function and range of motion will be essential for new trend of RA wrist surgery.
(Finger joint surgery) Finger joint synovectomy have been recommended to perform for early stage which is before any deformities are observed. In this stage, joint conserving surgery will be essential. Operation for RA hand deformities have to be indicated according as needs of patients. Pursuing both functional recovery and cosmetic improvement is the new trend. We have to announce that severe RA hand deformity can be improved. There are expectaions for improvement of artificial finger joints in the future. Meticulous rehabilitation and bracing will be required than ever as postoperative care.
(Conclusion) New trend of RA hand surgery has been reviewed. More progress will be observed in this field, and so RA hand surgery is important and will be expected to become advanced in future.