Rheumatoid arthritis(RA)is a debilitating disease involving progressive joint destruction and resulting in significant social and economic burden. The therapeutic effect of RA treatments has dramatically improved with the introduction of biologics;however, in order to optimize benefits commensurate with the escalating cost of healthcare, it is essential to conduct health economics evaluations of these biologics. Cost-effectiveness is analyzed using simulation models based on accumulated clinical data; however, such analyses are unfamiliar to most clinicians. In the present article, we analyzed the cost-effectiveness of sequences of treatment with biologics (with or without tocilizumab) administered to RA patients in the prospective cohort database of the Institute of Rheumatology, Rheumatoid Arthritis (IORRA). Our analyses demonstrated that improved cost-effectiveness depended on ⑴ the inexpensiveness of the biologics if the biologics have similar safety and effectiveness, ⑵ a higher rate of persistence with therapy resulting from low-frequency of secondary failure or adverse events, and ⑶ the optimal selection of patients expected to have a low risk of developing adverse events and a high probability of response to the target biologics. These data suggest the possibility that health economics evaluation of biologics might be strongly affected by the balance between effectiveness and safety in daily clinical practice. It is highly recommended that for all biologics(not only tocilizumab discussed in this article), the validity of their appropriate use be confirmed by collating health economics evaluations and effectiveness and safety data from daily clinical practice.

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    The involvement of the cervical spine is a common complication of rheumatoid arthritis(RA). The inflammatory process can lead to progressive joint destruction and ligamentous laxity, which can result in cervical spine subluxation and instability. These anatomic deformities may cause the spinal cord or brain stem compression, with resultant neurological deficits, such as cervical myelopathy, paresis, and even death. Treatment paradigms for RA have recently undergone a major shift. Standard of care now entails initiating immediate treatment using aggressive therapy with disease-modifying antirheumatic drugs or a combination of disease-modifying antirheumatid drugs plus biological agents. Biological agents have been reported to reduce disease activity and retard or even halt structural damage to peripheral joints. However whether the strong disease-controlling activity of biological agents can also stave off or delay progression of cervical spine lesions in RA is not fully elucidated. In this manuscript the pathology, radiographic diagnosis and treatment strategy for cervical lesions are reviewed.

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    It is estimated that there are about 100 hundred children with Juvenile-onset fibromyalgia (JFM), that accounts for 2. 5-5.0% of all patients having fibromyalgia including adults in Japan. The condition is characterized by widespread musculoskeletal pain and other associated symptoms, including fatigue, nonrestorative sleep,headaches, irritable bowel symptoms, dysautonomia and mood disorders such as anxiety and/or depression. JFM is diagnosed on the combination of disease history, physical examination to determine the 18 tender points and allodynia, pain from gently touching their hair, and negative results of blood tests. Recent studies have reveled that genetic influences, biologic factors,and environment are associated with the“Central Sensitization”.
    This Review focuses on our current knowledge of the condition, provides an update of the latest research advances, and highlights areas for further study.

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    The objective of this study is to compare the efficacy of tacrolimus (TAC) among different prescribing patterns in patients with rheumatoid arthritis (RA). 107RA patients treated with TAC as monotherapy or with other DMARDs were included in this study. Patients treated with TAC monotherapy were called MG (40cases). Patients treated with TAC which was added onto non-biological DMARDs were called CG (48cases). Patients treated with TAC which was added onto biological DMARDs were called BG (19cases). Disease activity score 28 using erythrocyte sedimentation rate (DAS28), C-reactive protein level (CRP) and modified health assessment questionnaire(mHAQ) were used to evaluate the efficacy of TAC and compare the three groups. Mean improvement values (MIV) for one year in DAS28 were 0.67, 0.73 and 1.21 in MG, CG and BG, respectively (not significant). MIV for one year in CRP (mg/dl) were 1.46, 1.55 and 3.65 in MG, CG and BG, respectively (significant between MG and BG). MIV for one year in mHAQ were 0.159, 0.052 and 0.148 in MG, CG and BG, respectively (not significant). Although the efficacy of TAC in BG was the best among three groups, there were the differences in the patientsʼcharacteristics among three groups. It was suggested that TAC could be used in variety of situation in the treatment of RA.

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    Objective:To determine the efficacy and safety of step-up therapy with disease-modifying antirheumatic drugs (DMARDs), including mizoribine, in the treatment of patients with rheumatoid arthritis (RA). In addition,we aimed to identify the characteristics of patients who would benefit from step-up therapy with mizoribine.
    Methods:Step-up therapy with DMARDs including mizoribine was administered to patients with RA who visited our hospital between October 2009 and end of September 2013. Patients who received mizoribine for at least 6months were enrolled as subjects.
    Results: The mean age of the subjects was72. 3years; of these, 11patients (55％) were aged 70-79 years and 4 patients (20％) were aged ＞80years. Prior to the initiation of mizoribine treatment, most patients were treated with an average of 3.5 agents. The mean number of agents used for treating these patients was 4.6, among which mizoribine was added last during treatment in 6patients. The change in Disease Activity Score-28-C-reactive protein (DAS 28-CRP) scores after initiation of step-up therapy with mizoribine were as follows:initial medical examination, 2.97; initiation of mizoribine treatment, 2.82; and final evaluation, 2.21. A significant decrease in the DAS 28-CRP score was observed, as compared to the baseline score (p＝0.043). Adverse events were noted in 5 patients (25％), which included herpes zoster in 4patients, skin infection in 2 patients (toe paronychia and dermatitis, one in each patient), and acute exacerbation of chronic bronchitis in 1patient. All symptoms were resolved by drug withdrawal, or treatment with appropriate medication, and the step-up therapy could be resumed.
    Conclusion: We observed that step-up therapy with mizoribine has been shown to be a potentially useful treatment option for the treatment of RA patients having a complication and elderly patients who should be treated carefully.

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    This study compared early clinical efficacy among three anti-TNF agents (IFX, ETN, ADA) in RA patients. Bio-naive RA patients treated with concomitant MTX were included. Clinical data at initiation and at 6 weeks in IFX-G (n＝64) and clinical data at initiation and at 4weeks in ETN-G (n＝43) and ADA-G (n＝24) were used. Improvement rate (%) and improvement value (Delta) of 6 indices (DAS28-ESR, DAS28-C RP, VAS, CRP, ESR, MMP-3, mHAQ) were compared between groups. Comparison between ETN 25mg/w-G and ETN 50mg/w-G was also performed. d-DAS28-ESR was 1.20 in IFX-G, 1.20 in ETN-G and 1.11 in ADA-G.%DAS28-ESR was 22.3% in IFX-G, 22.0% in ETN-G and 18.3% in ADA-G. No significant difference was observed between groups. d-DAS28-ESR in ETN 25mg/w-G was 1.32 and 1.01 in ETN 50mg/w-G. There was no significant difference in early clinical efficacy between ETN 25mg/w-G and ETN 50mg/w-G. This study showed that all three anti-TNF agents had the same extent of early clinical efficacy and that early efficacy in ETN 25mg/w-G was comparable to that in ETN 50mg/w-G.

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Objective: We evaluated the usefulness of tramadol/acetaminophen combination tablets (TRAM/APAP) for chronic pain in patients with rheumatoid arthritis (RA) who withdrew from treatment with biologics due to infection.
Subjects and methods:6 female RA patients with an average age of 67 years were received TRAM/APAP at our department. The disease durations ranged from 2 to 30 years (mean: 11years). The biologics used were infliximab, abatacept, and tocilizumab in 2 patients each. The infections were herpes zoster in 2 patients, and cellulitis, pyelonephritis, pneumonia,and conjun ctivitis in 1 patient each. All patients had also been receiving NSAIDs. The doses of TRAM/APAP were two tablets in 1 patient, three tablets in 4, and four tablets in 1. Efficacy was assessed by visual analog scale (VAS) at 4 and 8 weeks after administration.
Results: VAS scores were decreased at 4 weeks after administration in all patients. The mean VAS score decreased from 67.3mm before administration to 44.0mm at 4 weeks and 39.5mm at 8 weeks after administration, showing significant improvement. Adverse reactions occurred in 4 of the 6 patients, including drowsiness in 3 and nausea in 1. None of the patients discontinued treatment due to adverse reactions.
Conclusion: TRAM/APAP was considered to be among the potent treatment options for chronic pain difficult to control in RA patients withdrawing from treatment with biologics.

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    There have been several reports that systemic lupus erythematosus (SLE) may develop after administration of anti-tumor necrosis factor (TNF)-α agents though lupus nephritis is rarely occurs in such case. Here a case of 35-year old woman with rheumatoid arthritis is presented. She had been treated with etanercept for 3 months because of resistance to salazosulfapyridine, when fever, skin rash, stomatitis and proteinuria occurred and she was diagnosed as having SLE with lupus nephritis. These findings suggest that we should pay attention to the possibility of manifestation of SLE including various clinical findings of SLE or presence of serum anti-nuclear antibodies during the treatment with TNF-α.

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    We observed an anti-U3RNP antibody-positive case of systemic sclerosis (SSc) who developed thrombotic microangiopathy (TMA) with renal crisis and various other critical organ involvements. A 59-year-old woman consulted our outpatient department with cold-induced discoloration of the fingers, and the follow-up was started for Raynaudʼs phenomenon and antinuclear antibody positivity in2011. In the following year, she was diagnosed as SSc, based on progressive dermal sclerosis and fingertip pitting scars. In April 2013, she developed TMA with renal crisis,and acute heart failure at the same time, and was admitted to our hospital with an emergency. Administration of the ACE inhibitor, hemodialysis, and plasma exchange were started and high blood pressure and cytopenia due to TMA were controlled well. Methylpredonisolone pulse therapy to address progressive severe myocardial dysfunction was accompanied by a marked response,however, this resulted in diffuse alveolar hemorrhage shortly after. The respiratory damage subsided through continuation of the above treatment and strict management of cardiorespiratory condition. With the intensive therapy, each state of the disease was improved and stabilized successfully. In contrast to what our patient showed, some studies have suggested Japanese SSc patients with anti-U3RNP antibody positivity tend to have less frequent and less severe internal organ dysfunction. Multiple life-threatening complications, which our case presented with, are considered quite rare especially in a Japanese case with this antibody positivity and are thus worth reporting.

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    Since the beginning of the 21st century, because of both the advancement of high-quality medical care and the development of aging society with rapidly growing elderly population,the amount of work has enormously increased in the hospital. Because payment system of medical fee has been changed from the system based upon fee-for-service to the comprehensive payment system by DPC, we have started providing an added valve that is“early treatment and early discharge”for patients. This time, the several elements of team medical care which is difficult to manage will be discussed.
    According how to share the medical information, a team medical care can be classified info two types;“integrated type”which is based upon information sharing by conference and“Lego block type”which is based upon information shared by the personal information exchange. On the other hand, from the standpoint of daily clinical practice such as the diagnosis and treatment of rheumatoid arthritis, a team medical care be classified again info two types;“leverage”type and“task shift”type.
    “Leverage”type of team medical care means a team medical work managed by using the“lever”; i.e., the medical staff works in accordance with the diagnosis and the instructions made by doctors. In this case,expertise of the medical staff, quality of medical care and productivity of the work are not so high. “Leverage”type of team medical care has a major role in reducing the burden of doctors and nurses.
    “Task shift”type of team medical care means the transference of medical care to other specialized medical profession. In this case, the medical profession will assess patients independently with their own skill and may intervene according to their own judgement. With high expertise of the medical staff, this“task shift”type of team medical care enhances the quality of medical care. By increasing the number of medical personnels, it may be possible to increase productivity of the work.

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    With the introduction of biologics, the treatment options and outcomes for patients with rheumatoid arthritis (RA) have improved. As the medical condition differs among cases, management requires caring for individual patientʼs needs. The various medical staff, including doctors, nurses, physical therapists, occupational therapists, social workers, and other professionals, should work cooperatively to treat patients. The multidisciplinary team approach is necessary for management of RA patients in a center for rheumatic disease.
    The most important issues for the multidisciplinary team approach are goal setting of the team and division of roles. Meetings and conferences among the medical staff are useful. The assessment and management of disease require high levels of communication and cooperation. The leader and coordinator play critical roles in the team. In most cases, doctors play the lead role, while nurses and social workers act as coordinators. As treatments for RA improve,cooperation is needed among clinics and hospitals. The medical staff in the rheumatic center should become role models in the area, and continuously obtain new knowledge regarding rheumatology to improve their medical skill. Many of the staff in our institute have been attending congresses and lectures to become professional staff.

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