Difficult-to-treat rheumatoid arthritis（D2T RA）is a new concept that refers to patients with RA whose symptoms have not improved after several treatments, resulting in a high patient and economic burden. The European League of Rheumatology（EULAR）defined D2T RA as having all three criteria:（1）a history of treatment failure, （2）characterization of active/symptomatic disease, and（3）clinical perception. D2T RA is reported to occur in around 5-10% of RA patients, and patients continue to suffer from symptoms that directly affect their social life, ability to work, and quality of life, as well as incurring higher annual medical costs than non-D2T RA patients. The clinical background that might influence D2T RA includes complications such as respiratory and cardiovascular problems, pain syndromes such as fibromyalgia and osteoarthritis, smoking, obesity, and depression. Patient education, physical exercise, psychological interventions, enhanced patient care, and enhanced communication with health care professionals are the basis of treatment, and each patient needs to optimize treatment through drug selection based on past drug history and mode of action, and orthopedic interventions.

［Objective］

We retrospectively compared the efficacy and safety between two major Janus kinase inhibitors（JAK-i）administered to patients with rheumatoid arthritis.

［Methods］

RA patients to whom JAK-i were administered and followed up for 12 months or more were tracked. Patients were divided into two groups according to the JAK-i used: Tofacitinib（TOF）and Baricitinib（BAR）. Their clinical parameters were statistically compared from baseline to 12 months after baseline. Statistical significance was determined to be less than 5%.

［Results］

A total of 53 cases were studied. These included 22 TOF and 31 BAR. Female distributions were 72.7% and 71.0%. Average values of age, disease duration, anti-cyclic citrullinated polypeptide antibodies, rheumatoid factor（RF）titer, Sharp/van der Heijde Score（SHS）, DAS28-CRP, HAQ-DI, pain VAS, and MMP-3 in the TOF and the BAR were 69.1 and 69.4, 5.5 and 7.5 years, 311.2 and 456.5U/L, 179.1 and 279.5IU/L, 50.2 and 69.1, 3.48 and 3.26, 0.773 and 0.726, 39.7 and 31.0mm, and 189.1 and 141.3ng/mL, respectively. There was no significant difference in the parameters between the two groups. However, as a sub-analysis, DAS28-CRP in the sub-group with a disease duration of 10 years or more and with SHS of 100 or more decreased significantly than in the lesser group for each parameter in the TOF. Though no significant difference was demonstrated, eGFR in BAR tends to decrease after baseline compared to that in TOF.

［Conclusions］

As characteristics in action differ for each JAK-i, the appropriate drug should be chosen based on these drug characteristics.

［Objectives］ To assess the effectiveness and safety of Igratimod（IGU）in rheumatoid arthritis（RA）.

［Methods］ Two hundred eighty-eight RA patients had been treated with IGU in our hospital from October 2012 to January 2018, and 261 of them continued IGU for more than three months. We divided them into some groups; under 75 years old and 75 years old or higher, those treated with methotrexate（MTX）and without MTX, and those treated with biologics（BIO）and without BIO. We investigated the retention rate, adverse events（AEs）and clinical response over 2 years.

［Results］ The mean DAS28-ESR/SDAI at 2 years was 2.7/5.9, which significantly decreased from the baseline. The EULAR moderate response rates by under or over 75 years old at 2 years were 66.2% and 68.3%, and ACR20 response rates were 46.0% and 42.4%, respectively. The EULAR moderate response rates by with or without MTX at 2 years were 68.1% and 64.2%, and ACR20 response rates were 46.6% and 42.5%, respectively. Similarly, the EULAR moderate response rates by with or without biologics at 2 years were 57.0% and 69.9%, and ACR20 response rates were 37.0% and 48.0%, respectively. The incidence rate of AEs was 18.5% among the 288 patients and the skin eruption was the most frequent. The retention rate at 2 years was 81.1%.

［Conclusion］ These data indicate IGU therapy is effective and safe regardless of age, and the use of MTX and BIO.

Purpose: The purpose of this study was to elucidate the actual cognitive function of elderly rheumatoid arthritis（RA）outpatients using the Revised Hasegawa Dementia Scale（HDS-R）and to subsequently evaluate the medication adherence in patients suspected of having dementia according to the HDS-R.

Methods: Thirty-eight RA outpatients were requested to provide responses to the HDS-R. For those patients suspected of having dementia based on the results of the HDS-R，we performed case studies related to medication adherence by collecting data on disease duration，medical history，Steinbrocker stage/class，therapeutic course，family structure，and other factors from patients’ medical records.

Results: The patient’s mean age was 76.1±5.5 years. Four patients（10.5%）scored ≤20 points on the HDS-R and were thus suspected of having dementia. Of these four patients，two（18 points）were self-managing their oral medications，while the other two（17 and 2 points）had family members managing their medications.

Conclusion: The proportion of RA outpatients from our hospital’s rheumatology department suspected of having dementia was slightly lower than that of the national population.

Even if the patient’s HDS-R score is low，medication adherence may be maintained by appropriate interventions for the patient or their family.

In patients with rheumatoid arthritis（RA）who underwent small joint surgery such as on finger and wrist joints, we sometimes recognize cases with dissatisfaction even if their clinical outcomes are good. This study evaluated patient reported outcome of the finger and wrist surgery for RA patients using Japanese version of the decision regret scale（DRS）which is used to measure patient’s regret for the health care decisions. Thirty-two surgeries were involved in this study. In approximately 60% of the surgeries, patients expressed complete satisfaction, on the other hand, there were 3 cases who were judged as regret for the surgery by DRS. In cases with MCP finger joint arthroplasty, significant negative correlation was observed between DRS and general satisfaction, function, and appearance, however, no correlation was observed with appearance in the other cases. From the results of this study, many of the patients who underwent MCP finger joint arthroplasty regard both function and appearance as important, on the other hand, patients with other surgery value function above appearance.

Objective: To study the effect of an educational intervention program designed to improve the “listening-attitude” competence of rheumatoid arthritis（RA）nurses. Methods: A quasi-experimental intervention study design. Participants were RA nurses working in hospitals for RA in- and/or outpatients. An intervention group comprised of 77 RA nurses who joined the study after receiving listening-attitude training for interview skill development. In the study，they practiced their interviewing skills with at least one or more RA inpatients or outpatients after the training. A non-intervention group comprised 60 RA nurses who were randomly selected from the 1657 nurses listed on the Japan Rheumatism Foundation. The five factors and 23 items of the “RA Nurse Core Competency Scale”（Kanzaki et al.，2018）were used for measurement. Results: Using the RA Nurse Core Competency Scale，the intervention group of 63 nurses and the non-intervention group of 46 nurses were compared. The intervention group showed significantly higher scores at the beginning of the study for two factors out of five: factors 3，“smooth rheumatology care provision”，and 4，“practices and techniques to support self-care”. Therefore，the general linear model was applied in order to analyze score increase of each group. In the final between-subjects comparison，the main effects were again factors 3 and 4，“smooth rheumatology care provision（p=0.011）” and “practices and techniques to support self-care（p<0.01）”. Conclusion: Our intervention program designed to strengthen RA nurses’ listening attitude did improve their “listening-attitude” competence.

Case 1: The patient was a 69-year-old man with rheumatoid arthritis. He had diabetes mellitus and started insulin. He achieved clinical remission（CR）with etanercept（ETN, 50mg/week）. He started sitagliptin and discontinued insulin. ETN lost its efficacy and golimumab was started, but since it was not effective, tocilizumab（TCZ, 162mg/2 weeks）was started and he achieved a CR again, which was maintained for 7 years. When TCZ lost its efficacy, sarilumab（SAR, 200mg/2 weeks）was started. Along with the amelioration of the patient’s RA activity, his hemoglobin A1c value improved.

Case 2: The patient was a 56-year-old man with RA. He maintained low disease activity with disease-modifying antirheumatic drugs including methotrexate（MTX, 16mg/week）and adalimumab（ADA, 40mg/2 weeks）, but he stopped all treatment due to financial reasons. One year later, he experienced a RA flare-up and visited our rheumatic center again. Considering the medical cost, MTX（16mg/week）, prednisolone（5mg/day）, and TCZ（162mg/2 weeks）were started. However, he developed severe vertigo with TCZ, and SAR（150mg/2 weeks, then 200mg/2 weeks）was started. This was effective and was not associated with side effects. SAR was effective for secondary failure and for overcoming the side effects of TCZ.

A 33-year-old woman was diagnosed with systemic lupus erythematosus, and her renal biopsy showed class V. She was started on prednisolone, and her serology was in remission. However, proteinuria did not improve and it progressed to nephrotic syndrome. The electron microscopy of renal tissue showed podocyte damage. The patient was started on tacrolimus and ACE inhibitors, and the proteinuria improved. Both drugs have been reported to be useful in stabilizing podocyte structure, and early intervention with these drugs may be essential in patients with podocytosis.

  With the recent increase in the scale of human genome research and the development of genetic statistical methods, much progress has been made in the genome analysis of rheumatoid arthritis. Genome-wide association studies（GWASs）of rheumatoid arthritis have previously reported that more than 100 loci were significantly associated with the risk of rheumatoid arthritis. Because most of the disease-sensitive SNPs identified by GWAS are located in non-coding regions, it is often difficult to interpret their biological significance. Our group demonstrated trans-omics analysis by integrating the results of GWASs and epigenetic data, which clarified certain inflammatory cell types that were significantly associated with the risk of rheumatoid arthritis. It has been also known that in rheumatoid arthritis, the human microbiome was involved in the etiology and progression of the rheumatoid arthritis. Our group demonstrated metagenome-wide association analysis（MWAS）of the gut microbiome by using whole-genome shotgun sequencing and found association among the human genome, the gut microbiome, and rheumatoid arthritis. Furthermore, in recent years, the application to personalized medicine by using human genomics is attracting attention. Polygenic risk score（PRS）predicts disease risk based on SNPs identified by GWAS. Our group analyzed the data of international biobanks of approximately 670,000 participants and identified the biomarker associated with human lifespan.