In 2011, the maximum dose for methotrexate (MTX) was also increased in Japan, enabling more strategic treatment. Increased doses of MTX and its combined use with biological disease-modifying antirheumatic drugs (bDMARDs) may be expected to improve long-term prognosis even in patients with high disease activity, for whom treatment had heretofore been difficult. On the other hand, the use of high-dose MTX and bDMARDs has been associated with increased medical costs.　
    Under the fiscal year 2014 revisions to medical treatment fees, four major changes were made in regard to rheumatoid arthritis (RA) treatment as follows: revisions to the index at the time of medical certificate creation according to the Act on Welfare of Physically Disabled Persons, the guidance and management fees for self-injection at home of bDMARDs, and addition of health insurance points for rehabilitation, and an increase to the target rate of generic drugs. Physicians in charge of RA treatment should have a sufficient knowledge of social insurance systems as well as a detailed understanding of revision contents. Moreover, in order to maintain social security systems, it is essential for individual clinicians to minimize medical costs as much as possible and protect finite healthcare resources.

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Objectives: This study investigated the effects of aging on the estimation of disease activity and physical function in patients with rheumatoid arthritis (RA).
Methods: 777 patients with RA participated in this study. We compared the composite measures, i.e., disease activity score 28 (DAS28), DAS28-CRP, simplified disease activity index, clinical disease activity index, and Japanese Health Assessment Questionnaire (JHAQ) score among groups of patients aged <60 years (A), in their 60s (B), and >70 years (C).
Results: Groups A, B, and C consisted of 225, 259, and 293 patients, respectively. The average age and age of onset were 64.18 and 55.08 years, respectively. All composite measures were significantly higher in group C than in the other groups. There were significant differences in the erythrocyte sedimentation rate (ESR) among the three groups. The JHAQ score was significantly higher in group C than in the other two groups. According to multiple regression analysis using the JHAQ score as a dependent variable, patient age was a significant independent variable, and the parameter estimate was 0.0118.
Conclusions: (1) Elderly and elderly onset patients with RA have increased markedly in Japan. (2) Disease activity can be overestimated in elderly RA patients using composite measures. When evaluating elderly RA patients, elevations of ESR and patient’s global assessment not due to disease activity should be considered. (3) Patient age is an independent factor linked to a higher JHAQ score in elderly patients with RA, and the JHAQ score increases by approximately 0.12 points for every 10 years.

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Objective: Sometimes there is some discordance in patient’s response and patient’s global assessment (PGA). We investigated the relationship of 5 kinds of patient’s response and PGA with actual patient’ rheumatoid activity in 104 patients with rheumatoid arthritis (RA).
Methods: 5 kinds of patient’s response (very good, good, tolerable, bad and very bad) to doctor’s question about the state of their rheumatism and other indices (PGA, doctor’s global assessment: DGA, serum CRP levels, DAS28CRP levels, modified HAQ levels) were compared. Furthermore, sex differences of two groups (very good, tolerable) were compared.
Results: 17 male and 87 female patients were enrolled. Average age was 63 years and average duration was 13 years. There were 10 very good cases, 30 good cases, 49 tolerable cases, 14 bad cases, and 1 very bad case. The clinical data (PGA, DGA, DAS28CRP, mHAQ) deteriorated in parallel with deterioration of response. On the other hand, age, duration, stage, class and serum CRP levels did not show consistent trends. In PGA, the mean value deteriorated according to the deterioration of response although each patient’s PGA showed a large variation. PGA showed highest correlation with patient response and the second highest correlation was mHAQ. As a result of considering gender differences, the very good group showed that the rheumatoid activity was relatively worse in males, and in the tolerable group, the rheumatoid activity was relatively worse in females.
Conclusion: Sometimes there is a large dissociation with patient’s response and PGA, It is necessary to consider the backgrounds and gender differences in individual patients.

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[Purpose] To determine the changes that have occurred over a 10-year period in the medical care of rheumatoid arthritis (RA) performed by orthopedic surgeons at outpatient clinic in the Osaka Prefecture.
[Methods] An anonymous questionnaire on the medical care of RA, mainly regarding drug therapy, was administered three times (in 2003, 2008, and 2013) among members of the Osaka Clinical Orthopedic Association. The responses received from the mail-back survey were tallied and recorded.
[Results] The collection rates for each survey were 34.7% (139/401) in 2003, 31.7% (145/459) in 2008, and 24.5% (115/469) in 2013. With regard to therapeutic drugs for treating RA, the use of methotrexate (MTX) increased as a first-line agent, salazosulfapyridine (SASP) tended to increase as a second-line agent, and steroid use decreased.
In addition, the induction rate of biopharmaceutical agents and the use of combination therapy with disease-modifying antirheumatic drugs (DMARDs) increased.
[Conclusion] From 2003–2013, bio agents have been launched one after another, and some clinics aggressively prescribe them. The rate of using subcutaneous injections was particularly high, and as a result of these changes in RA treatment, the relationship between hospitals/clinics and foundation hospitals and/or collagen disease specialists has been promoted. DMARDs include MTX, SASP, bucillamine, and tacrolimus, and the treatment cost has dramatically increased, resulting in an increased rate of concomitant use of each DMARD.

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    Post-marketing surveillance was performed to clarify the condition of actual use of mizoribine in treating patients with rheumatoid arthritis, collect information about its safety and efficacy under the condition of actual use and promote its proper use. The safety analysis population included 3,325 patients who started to receive mizoribine between October 2008 and October 2010. Their mean age was 66.2±12.5 years and those over 65 years and those over 75 years accounted for 61.1% and 28.4%, respectively. Complications were detected in 59.3% of the subjects. A total of 330 subjects experienced 392 episodes of adverse drug reactions. The incidence of adverse drug reactions was 9.92% and that of serious adverse drug reactions was 1.32%. Based on the European League Against Rheumatism (EULAR) response criteria, the efficacy of mizoribine was rated and the treatment responses observed 24 weeks later were classified as follows: good response (13.4%), moderate response (32.6%), and no response (54.0%). Although there was no difference between the subjects over 65 years and those under 65 years in terms of the incidence of adverse drug reactions and efficacy of mizoribine, the incidence of serious adverse drug reactions in the subjects over 65 years was significantly higher than that in the subjects under 65 years. Mizoribine was administered to high-risk patients including the elderly and those with complications in the post-marketing surveillance. As mizoribine could be administered in a relatively effective and safe manner, this drug could be a treatment option in these patients.

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Objective: To assess the significance of power doppler ultrasonography (PDUS) in the evaluation of synovial lesion of the knee joint by comparing the PDUS findings with site-matched histopathological findings.
Methods: We studied 23 patients who were undergoing arthroplasty of the knee joint because of rheumatoid arthritis (RA) or osteoarthritis (OA). Predetermined sites of the knee joint were examined with US before arthroplasty. Synovitis was classified semiquantitatively with grey scale (GS) and PDUS findings. Synovial tissues were obtained during arthroplasty from the corresponding sites evaluated by the US. Histopathology of the synovial tissue was evaluated by haematoxylin and eosin staining and immunohistochemical staining with factor VIII.
Results:. We compared imaging findings of preoperative PDUS with histopathological findings of the synovial specimens. We found that the PDUS findings were mostly correlated with each histopathological grade of synovitis and the vascularity showed the highest correlation with the PDUS findings as expected. However, the site-matched comparison indicated that the blood vessels were not apparently detected by the PDUS. Thus, the sensitivity and specificity of PDUS findings for histopathological vascularity were 91% and 58%, respectively.
Conclusion: We found that the PDUS findings were mostly correlated with each histopathological score of synovitis with highest correlation to vascularity. However, the site-matched comparison indicated that the blood vessels without inflammatory cell infiltrates were not apparently detected by the PDUS.

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Purpose: The therapeutic effect of hyaluronic acid (HA) on osteoarthritis (OA) was assessed in Kb1 rabbits by histopathological examination.
Materials: An OA model was prepared in rabbits according to Ishiguro’s method. Then an HA preparation (SUVENYL^Ⓡ HA [ MW 2.7 million Da] or Synvisc^Ⓡ HA [mixture of cross-linked HA prepared from rooster’ combs]) or saline was repeatedly injected into the left knee joint of the each rabbit. Knee joint tissues were fixed in 10% formalin and paraffin embedded specimens were routinely processed for histological examination.
Methods: The therapeutic effect of HA on joint cartilage was assessed from the following three sets of parameters: (1) maintenance of proteoglycan, HA, or type II collagen; (2) degeneration of the extra cellular matrix and cartilage, assessed by observing aggrecan degradation products or apoptotic cells; and (3) remodeling evaluated by staining with Ki67 or detection of hyaluronan synthase (HAS) 2 or 3 mRNA.
Results: The histological grade of OA for the tibial compartment was 4.81 ± 0.25 in the saline group, and 4.69 ± 0.25 in the SVENYL^Ⓡ HA-treated group, and 4.77 ± 0.26 in the Synvisc^Ⓡ HA-treated group, while the grade for femoral compartment were 4.69 ± 0.25, 4.35 ± 0.43 and 4.38 ± 0.30, respectively. The residual levels of proteoglycan, type II collagen, and HA were increased in the femurs of the two HA- treated groups compared with the saline group. In addition, the positive ratio of apoptosis and aggrecan degradation products were significantly decreased in the HA-treaed groups compared with the saline group. Moreover, the number of Ki67 positive cells and the expression of HAS2 and HAS3 mRNAs were significantly greater in HA-treated groups than in the saline group. In the tibia, the trends of these parameters were similar to those for femur, but differences among the three groups were smaller.
Conclusions: Efficacy of HA was demonstrated by a reduction of parameters indicating cartilage damage, and an increase of parameters indicating a remodeling effect on cartilage.

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    Methotrexate (MTX) is one of the disease-modifying antirheumatic drugs (DMARDs), and is administered to patients with active rheumatoid arthritis (RA). Tacrolimus (TAC) is administered to RA patients as monotherapy or part of combination therapy, and excellent therapeutic effects have been reported. On the other hand, an increased risk of infectious diseases is a possible adverse effect of both drugs. We herein report the case of a patient who developed Pneumocystis pneumonia (PCP) during combination therapy with MTX and TAC. A 64-year-old female developed RA in 2009. In July 2010, she was given MTX at 4 mg/week, then TAC was added in December 2010. She was admitted to our hospital because of general malaise, cough and sputum in August 2012. On the chest X-ray and computed tomography (CT) scans, ground-glass opacities were observed throughout the lung. A bronchoalveolar lavage fluid (BALF) examination was performed, and the detection of cysts of Pneumocystis Jirovecii by a speculum and its DNA by polymerase chain reaction (PCR) in the washings were confirmed. Sulfamethoxazole/trimethoprim and high-dose prednisolone were administered to the patient, however the sulfamethoxazole/trimethoprim treatment was discontinued on the tenth day because of the appearance of a drug-associated rash, and the patient was subsequently treated with pentamidine. The pneumonia successfully resolved after these treatments. While interstitial pneumonia and drug-induced lung injuries are common respiratory complications that occur during the treatment of RA, PCP was observed in the present case. Therefore, when respiratory symptoms appear in the patients with RA during these treatments, the possibility of PCP has to be considered.

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