Cytokines are central to the pathogenesis of rheumatoid arthritis（RA）. In addition to existing anti-rheumatic drugs, the use of biologics that target cytokines and other factors has made RA a disease in which remission can be achieved. Janus kinase（JAK）inhibitors have become an option for the treatment of RA and are expected to be effective in RA refractory to pre-existing treatment tools. In addition, the indications for the use of JAK inhibitors have been expanded to include diseases and conditions other than RA, such as inflammatory bowel disease and pneumonia due to the novel coronavirus disease（COVID-19）, and clinical trials are underway for systemic lupus erythematosus, psoriatic arthritis, and ankylosing spondylitis. The incidence of herpes zoster（HZ）with JAK inhibitors is elevated, especially in Japanese population, so it is important to accumulate clinical data. The recombinant herpes zoster vaccine may reduce the risk of HZ, but there are numbers of questions regarding its appropriate use. Recent trial with a JAK inhibitor has pointed out the possibility of an increased risk of malignancy, major cardiovascular events, and venous thromboembolism. The most immediate issue seems to be the vaccination against COVID-19 under the use of JAK inhibitors, for which recommendations have been made, but no policy has been established. In this paper, we will present the latest information on these issues and discuss measures to resolve them.

Familial Mediterranean fever（FMF）is an autoinflammatory disease which repeats fever and serosa-like symptoms periodically. Accumulation of cases diagnosed as FMF by genetic analysis is advanced. We report a genetically diagnosed FMF case who demonstrated gastrointestinal symptoms periodically from the age of 15 years. Although diagnosis and treatment have been difficult in gynecology and gastroenterology, we made a diagnosis of FMF by genetic analysis and clinical efficacy of colchicine. Although the family has no history for similar case, genetic test revealed that the patient who was a minor at onset has M694I heterozygote of exon 10 of MEFV gene, which is prevalent in typical FMF cases. Her asymptomatic father was also found to have the M694I heterozygote. There were many isolated cases in Japan, and as in the case of the father in this instance, it is possible that many FMF patients may be latent. The patient as well as her asymptomatic mother demonstrated the presence of E148Q heterozygote in exon2 of MEFV gene that have been reported to show allele frequencies as high as 16-23% in normal individuals. Compared to overseas cases, delayed onset of FMF and milder symptoms have been prevalent in Japan. Therefore, it is under evaluation whether it is necessary to actively carry out genetic testing for parents of FMF patients.

[Objective] We evaluated the effectiveness and safety of sarilumab in rheumatoid arthritis（RA）in clinical practice.

[Methods] Thirty-five RA patients who initiated sarilumab from February 2018 to September 2019 were enrolled, and we reviewed the change of clinical disease activity index（CDAI）, and safety for 24 weeks after initiation of sarilumab retrospectively.

[Results] Mean age was 60.3 ± 17.5 years old, duration of RA was 12.5 ± 9.3 years, CDAI was 26.2 ± 10.8, concomitant use of methotrexate（MTX）was 62.9% at baseline. Six patients were biologic and Janus kinase inhibitor-naïve, and 29 patients had been experienced at least one biologic or targeted synthetic disease-modifying antirheumatic drugs. CDAI rapidly decreased to 17.2 at two weeks, and finally decreased to 10.9 ± 9.2 at 24 weeks. The effectiveness of sarilumab was not changed in patients without concomitant use of MTX or in patients whose treatment were switched from tocilizumab. Body mass index（BMI）did not influence treatment response to sarilumab. There were seven adverse events. The most common of them were infections. The number of patients who discontinued sarilumab was nine. The most common reason was ineffectiveness.

  The study analyzed and identified structural relationships among rheumatology nursing competencies of certified RA nurses.

  Two hundred twenty-seven certified RA nurses listed on the Japan Rheumatism Foundation’s web site were surveyed on the “RA Nurse Core Competency Scale” we developed（2018, Kanzaki et al.）. The results of this previous study were used for secondary analysis to develop a structural model.

  A hypothetical model was created with five factors of nursing competencies: “knowledge and skill regarding RA”, “listening attitude”, “practices and techniques to support self-care”, “support for patients under treatment”, and “smooth rheumatology care provision”. Then, confirmatory factor analysis was performed by structural equation modeling.

  The results showed that “knowledge and skill regarding RA” was the core factor, giving direct influence to each of the other four; “listening attitude” mediated reinforcement of “support for patients under treatment” and “smooth rheumatology care provision”; and “practices and techniques to support self-care” mediated reinforcement of “support for patients under treatment”.

  As relationships among the five factors of RA nursing competencies were identified by structural equation modeling, we propose the structural model could be used for RA nurses as an educational intervention and for determination of its effects.

We report a 77-year-old man with rheumatoid meningitis. He came to the hospital because he had difficulty in walking and communication. His brain magnetic resonance imaging（MRI）showed increased fluid attenuated inversion recovery（FLAIR）signals in his right cerebral hemisphere cortex, and contrasting effects along the cerebral sulcus and surface were detected. Although he presented no joint symptoms, he was diagnosed with rheumatoid meningitis based on the positivity of RF and anti-CCP antibody in his cerebrospinal fluid and seurm, and the pathology of cerebral biopsy. After the initiation of corticosteroid therapy, the titer of anti-CCP antibody in his cerebrospinal fluids were decreased in accordance with the change of the clinical course. Anti-CCP antibody in the cerebrospinal fluids was a helpful biomarker in diagnosis and assessment of the severity of rheumatoid meningitis.

The current study aimed to evaluate the reliability and validity of the Body Image Assessment Tool（BIAT）in Japanese patients with rheumatoid arthritis（RA）. A total of 265 outpatients（non-surgical group）and inpatients（surgical group）with RA and 62 healthy hospital staff members were asked to complete the BIAT questionnaire. To assess reliability, baseline data from 265 patients were used for the internally consistency, and baseline and 3-week data from 62 patients in the healthy group and baseline, 6-month, and 1-year data from 76 patients in the non-surgical group were used for the test-retest method. The validity of BIAT as a clinical assessment was evaluated using. BDI-II（Beck Depression Inventory-II）as an existing assessment method. 265 patients with RA were grouped into remission, low disease activity, moderate disease activity, and high disease activity groups based on DAS28-CRP, and the association with BIAT was examined. We also examined whether there was a difference in BIAT between the non-surgical and surgical groups. BIAT was highly consistent, with alpha coefficients above 0.8 in both the overall assessment and the assessment of each construct. The overall BIAT score showed a significant negative correlation（r=-0.64, P<0.001）with the BDI-II. BIAT tended to be lower in patients with higher disease activity. Interestingly, patients of the surgical group showed worse BI disturbance than those of the non-operative group. In conclusion, BIAT was a highly consistent and stable assessment tool, and can be applicable for Japanese patients with RA.

Objective: To analyze the efficacy of continuous erythropoietin receptor activator（CERA）in rheumatoid arthritis（RA）with chronic kidney disease（CKD）.

Methods: Among the 37 patients with RA who received CERA, 11 died within 12 months. Twenty-six patients（M 2, F 24）were followed up more than 12 months.

Results: Patients were 77.4 ± 7.0 years old, and the disease duration was 17.9 ± 14.5 years. The mean blood urea nitrogen was 25.8 ± 10.6 mg/dl, serum creatinine（Cr）was 1.2 ± 0.5 mg/dl, and the estimated glomerular filtration rate was 41.6 ± 16.0 ml/min/1.73 m². The serum iron and ferritin levels were not low, and the unsaturated iron binding capacity did not increase. The mean corpuscle volume did not decrease, and the serum erythropoietin level did not increase. Using CERA（43.1 ± 21.4μg/month）, hemoglobin（Hb）increased from 8.70 ± 1.1 g/dl to 10.0 ± 1.2 g/dl（p<0.001）. In patients without iron preparation and/or intensification of RA treatment（n=15）, Hb also increased from 9.1 ± 0.8 g/dl to 10.1 ± 1.2 g/dl（p=0.028）. Eight patients were able to discontinue CERA, and while 3 of them re-started CERA, 1 eventually discontinued CERA again.

Conclusion: Even with low Cr levels, CERA should be performed in RA patients when CKD is suspected.

Super elderly-onset rheumatoid arthritis（RA）is difficult to treat because of aging and complications. We herein report a case of super elderly-onset RA: 91-year-old female with RA. She came to our hospital with pain and swelling of the bilateral wrists，pain of the bilateral shoulder and knee joints, and difficulty in walking. Her anti-CCP antibody and rheumatoid factor were positive. She was diagnosed with RA and had been treated with bDMARDs. Her symptoms were once relieved, however, flared up after 6-month treatment. Also, J-HAQ, in this case, showed little improvement after the treatment. The treatment goal in super elderly-onset RA patients should be considered separately from non-elderly.

Objectives: To investigate drug retention rates of TNF inhibitors in bio-naïve patients with rheumatoid arthritis（RA）and causes of discontinuation and of which characteristic predictors in daily practice.

Methods: Using clinical data from the SUNSET registry, drug retention rates were examined by Kaplan-Meier’s method. Predictors of the various causes of discontinuation, such as remission, lack of effectiveness and toxic adverse events, were investigated using multivariate analysis.

Results: Four hundred fifty-five RA patients were analyzed. The overall drug retention rate of TNF-inhibitors at 3 years after treatment was 34.5%. Cumulative incidence rates of discontinuation due to remission, lack of effectiveness and toxic adverse events at 3 years were 13.7%, 21.6% and 20.6%, respectively. In multivariate analysis, low disease activity using clinical disease activity index（CDAI）at 3 months and achievement of CDAI 50 at 6 months correlated positively with discontinuation due to remission, and etanercept, treatment starting from 2003 to 2007 and high CRP level correlated negatively. High CRP levels, high-dose methotrexate concomitant and high-dose oral steroids were risk factors for discontinuation due to lack of effectiveness. Elderly onset was associated with a greater risk of drug discontinuation due to toxic adverse events.

Conclusion: Cumulative incidence rates of lack of effectiveness and toxic adverse events are not drug related but are related to patient characteristics. Considering the factors related to discontinuation due to remission, it is suggested that therapeutic strategies for early RA patients have been changed.