The therapeutic effect of denosumab (DMAb) was assessed in female osteoporosis patients using radial dual-energy X-ray absorptiometry (radial DXA): those with postmenopausal osteoporosis (PO group), PO with rheumatoid arthritis (RA group), and PO with RA receiving glucocorticoids (RA + GC group).　In all, PO patients 60 years of age or older with a % young adult mean value of <70%, as determined by radial DXA were treated with DMAb. The DMAb treatment group comprised PO group, RA group, and RA+GC group. The control group comprised PO group and RA group who received oral bisphosphonate (BP). The bone mineral density (BMD) was determined by using radial DXA. The bone turnover marker, type I collagen cross-linked N-telopeptide, (NTx) were also measured.　Radial DXA revealed a significant increase in the DMAb treatment, but not in the BP treatment. The onset of an increase in BMD with DMAb was slower in RA group than in those without. The effect of DMAb in preventing increased NTx levels was smaller in the RA and RA + GC groups than in the PO group. The adherence to DMAb treatment was statistically significantly greater than for BP treatment.　RA is commonly associated with osteoporosis but there is no established treatment approach. DMAb may be first-line osteoporosis drug in rheumatoid arthritis patients.

　In the development of the world's first anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody, denosumab, studies conducted by Japanese researchers have made a great contribution. The first achievement is the establishment of a system for co-culture system of osteoblasts and bone marrow macrophages, which contributed to the verification of the hypothesis that osteoblasts determine the fate of osteoclasts; the second is the discovery of osteoclastogenesis inhibitory factor (OCIF/OPG); and the third is the identification of osteoclast differentiation factor or RANKL, which is a target protein of OCIF. This identification of RANKL prompted drug discovery, leading to the development of denosumab by Amgen USA Inc. In 2010, denosumab was approved as a therapeutic agent for osteoporosis in the EU and the USA, and in 2017, a new indication "Inhibition of progression of bone erosion associated with rheumatoid arthritis" was approved in Japan, ahead of other countries in the world. In the realization of the new indication, Japanese clinicians on rheumatoid arthritis have also made a remarkable contribution. In this article, we present the developmental history of denosumab following the identification of RANKL, from its basic research to clinical application.

Background: C-OPERA demonstrated the efficacy and safety of certolizumab pegol (CZP) plus methotrexate (MTX) compared to placebo (PBO)+MTX in Japanese MTX-naïve early rheumatoid arthritis (ERA) patients with poor prognostic factors.Objectives: To identify baseline disease prognostic factors associated with 52 weeks DAS28-ESR remission rate and radiographic outcomes with CZP+MTX and PBO+MTX treatment in Japanese MTX-naïve early rheumatoid arthritis patients.Methods: Patients were randomized 1:1 to CZP+MTX (n=159) or PBO+MTX (n=157). CZP 400mg was administered at Weeks 0, 2 and 4, followed by CZP 200mg Q2W to Week 52. Disease Activity Score 28-joint assessment (DAS28)-erythrocyte sedimentation rate (ESR) and change from baseline in modified Total Sharp Score (ΔmTSS) were evaluated at Week 52. DAS28-ESR < 2.6 was defined as remission, and yearly increase of mTSS > 3 was defined as rapid radiographic progression (RRP).Results: Lower remission rate was observed in patients with higher baseline DAS28-ESR, Simplified Disease Activity Index (SDAI), Health Assessment Questionnaire Disability Index (HAQ-DI), and C reactive protein (CRP), and greater progression of bone destruction (higher change in mTSS or higher RRP rate) was observed in patients with higher baseline DAS28-ESR, SDAI, HAQ-DI, CRP, mTSS, matrix metalloproteinase (MMP)-3, rheumatoid factor (RF), tumor necrosis factor (TNF)α, and interleukin (IL)-6 in the PBO+MTX group. Better clinical and radiographic outcomes were observed in CZP+MTX patients compared to PBO+MTX patients.Conclusions: Higher baseline DAS28-ESR, SDAI, HAQ-DI, CRP, mTSS, MMP-3, RF, TNFα, and IL-6 may be associated with poor outcomes in PBO+MTX-treated patients. CZP+MTX patients showed better outcomes vs PBO+MTX, even in patients with higher risk of progression identified by baseline factors.

Objective: To investigate the efficacy of certolizumab pegol (CZP), a newly-introduced tumor necrosis factor-α (TNF-α) inhibitor (TNFi) with pharmacological characteristics distinct from other TNFis, which is approved for rheumatoid arthritis (RA) by the Japanese Ministry of Health, Labor, and Welfare.Patients and Methods: The clinical course of patients with RA who received CZP treatment at a Rheumatology Department of a referral hospital in Japan were retrospectively evaluated to assess the clinical efficacy and adverse events (AEs) of CZP.Results: Eight of the ten patients completed 24 weeks of CZP treatment, and six patients with sufficient information on clinical course were evaluated to assess RA disease activity. All six patients, including those with a history of treatment with other TNFis and two patients who received concurrent treatment with three subcutaneous TNFis, achieved improvement in RA disease activity. Conversely, two patients had to terminate CZP treatment in less than three months after CZP treatment initiation due to AEs. Importantly, both of the patients received glucocorticoids concurrently with CZP.Conclusion: CZP might have utility even in RA patients that are refractory to other TNFis. However, careful observation for early AEs, particularly in patients with concomitant glucocorticoid use, is indispensable.

　We encountered a 35 year-old patient with rheumatoid arthritis (RA) who achieved delivery by caesarean section with the use of certolizumab pegol (CZP).　Caesarean section was performed because the patient had a history of enucleation of myoma uteri.　It has been reported that there is minimal placental transfer of CZP because of its Fc-free structure since the Fc part of CZP is replaced by polyethylene glycol. Like etanercept (ETN), CZP might be a desirable biological disease-modifying antirheumatic drug for RA patients who wish to give birth.

Objective: By assessing dropout of rheumatoid arthritis (RA) cases due to inadequate effect of Tocilizumab (TCZ) therapy in the Akita Orthopedic Group on Rheumatoid Arthritis registry, this study aimed to investigate more effective ways to use this drug.Subjects and methods: This study included 177 patients who were treated with TCZ, consisting of 95 treatment-naive patients (group N) and 82 patients switching to TCZ therapy (group S). We retrospectively collected data on patient characteristics, duration of treatment before discontinuation, treatment details after discontinuation, disease activity.Results: TCZ therapy was discontinued due to inadequate effect in 12 patients. Patient mean age was 58 years (range, 44-82 years). Mean disease duration was 120 months (range, 6-366 months). Group N included 4 patients, and group S included 8, all of whom switched from tumor necrosis factor (TNF) inhibitors. The mean duration of TCZ therapy before discontinuation was 30 months (range, 6-67 months). After discontinuation, TCZ was switched to other biopharmaceuticals in 10 patients, consisting of 2 patients who switched to TNF inhibitors and 8 who switched to abatacept (ABT). At the final evaluation, 3 patients switched to TNF inhibitors again. Clinical disease activity index (CDAI) was 20.3 ± 13.4 (mean ± standard deviation) at the start of therapy and 12.4 ± 8.1 at the time of discontinuation. Six patients achieved low disease activity (LDA). CDAI at the final evaluation was 9.5 ± 8.4. LDA was achieved in 8 patients.Conclusion: Dropout cases due to inadequate effect of TCZ for RA included many patients who switched from TNF inhibitors. TNF inhibitors and ABT can equally replace TCZ for dropout cases. TCZ can be more effectively and continuously used, based on comprehensive assessment of its effect.

　Attention needs to be paid to the masking of the symptoms of bacterial infections during the use of tocilizumab (TCZ). We experienced the case of a 60-year-old female patient, who was diagnosed with rheumatoid arthritis (RA) at the age of 49 and whose treatment of TCZ was started at the age of 56. In three years and eight months after TCZ was started, she presented a gradually worsening pain and swelling at the distal end of the right lower leg. The body temperature was 36.4℃, and the value of C-reactive protein (CRP) was 0.92 mg/dl on admission. Abscess formation was seen at the same site as the local inflammation in magnetic resonance imaging. Thus, drainage treatment was performed and Methicillin-resistant Staphylococcus aureus (MRSA) was detected from the abscess. TCZ was discontinued and the intravenous administration of antibiotics lasted three weeks. The body temperature did not exceed 37℃ during the course of treatment. Our case highlighted the need for judgment through clinical features and bodily symptoms rather than the value of the laboratory tests when the MRSA abscess appeared in RA patients treated with TCZ.

　Objective: There is no rheumatoid arthritis (RA) network in Saitama Prefecture. Therefore, our clinic is cooperating with a local hospital in testing both methotrexate (MTX) and biological disease-modifying anti-rheumatic drugs (bDMARDs) therapy in RA. The purpose is to investigate the treatment outcomes of RA and to establish what role the nurses can play in this process.　Methods: A total of 78 RA patients were included in this study: 26 patients who underwent MTX therapy were categorized as M group, 14 patients who underwent bDMARDs were categorized as b group, and 38 patients who underwent conventional synthetic DMARDs (csDMARDs) therapy were categorized as cs group. All the groups were investigated retrospectively.　Results: 100% of patients achieved clinical remission (CR) in the M group. 77% patients achieved CR in the b group. 69% patients achieved CR in the cs group. Patients can consult with a nurse when the rheumatologist is absent from clinic, and this occurred with 25 patients from M group, 31 from b group and 44 from cs group. Fifty two of these consultations were for medication, 13 consulted about side-effects, and the other 35 for miscellaneous reasons. Of all of the patients, 29 were settled by nurse, 31 were received consultation by a rheumatologist, 35 were seen by an orthopedist, and 5 were referred to a cooperate hospital. There were no cases leading to severe adverse events.　Conclusion: In institutions where a rheumatologist is not permanently stationed, diversified medical treatment is possible. The key aspect of the nurses’ role in this case is to provide accurate and timely information and consultations to the patients.

[Patient] a 70-year-old man [Chief complaints] fever, headache, cervicodynia [Clinical history] A 70-year-old man presented to hospital with two months of fever, headache and cervicodynia. Giant cell arteritis (GCA) was strongly doubted due to temporal artery tenderness, advanced age, a new-onset headache and increased erythrocyte sedimentation rate. However FDG-PET CT is known to be useful for the diagnosis of GCA, it did not show any abnormal uptake in the vascular walls in this case. The contrast-enhanced MRI revealed lateral enhancement of the branches of superficial temporal artery without stenosis in the T1-weighted fat suppression images, which is consistent with GCA. The patient was started on daily high-dose prednisone (1mg/kg/day) , and clinical and laboratory findings were improved rapidly. Bilateral biopsy of temporal arteries performed immediately prior to the treatment showed giant cell arteritis. [Discussion] FDG-PET CT is known to be extremely effective for the diagnosis of GCA. The sensitivity and specificity of FDG-PET CT for the diagnosis of GCA are 89.5% and 97.7%, respectively. We experienced the case of GCA without positive FDG-PET CT findings whereas contrast-enhanced MRI showed positive findings. We present the case with a review of the literature.