Birth, aging, illness and death remain eternal themes that human beings cannot avoid, no matter how the environment surrounding them changes. Any person gets illness, and any illness have the characteristic of chronicity. In other words, we are already living with long-term illnesses. If what modern society demands is to work efficiently, make a profit, and live actively and positively, illness or disability may make it impossible to work as efficiently as before, or to spend every day time actively. When that happens, we lose some of the characteristics that make us socially acceptable, our qualities differ from those of others, and we cannot live up to the expectations of society. At that time, the person becomes a being neglected from the accepted state, which leads to stigma. In some cases, we may not be able to find value in our existence and may be deeply saddened and socially isolated. However, it is not only illnesses and disabilities that cause us to encounter such unforeseen events in life, but also the experience of various crises that occur in our daily lives, and we experience the resilience of each and every one of us in these situations. We will continue to walk the daily life beyond that. In this paper, I would like to consider psychosocial support for RA based on self-stigma and resilience as a force to overcome it.

In Japan, 8 biological disease-modifying antirheumatic drugs（bDMARDs）are available for rheumatoid arthritis（RA）.

1. Infliximab（IFX）

IFX is a chimeric anti-TNF antibody. Used intravenously, it works rapidly. Dose escalation and shortening of the interval are approved and effective for patients with high disease activity（HDA）. A bio-free condition（BF）can be introduced.

2. Etanercept（ETN）

ETN is a soluble TNF receptor that can be used by elderly patients since its half-life is short and immunosuppression may be mitigated by discontinuation. ETN can be used by female patients who desire pregnancy.

3. Adalimumab（ADA）

ADA is a fully humanized anti-TNF antibody, however, combination with methotrexate（MTX）is desirable. Early introduction followed by BF can be achieved.

4. Tocilizumab（TCZ）

TCZ is an anti-IL-6 receptor antibody that works well without MTX. Masking of the signs and symptoms of infection can occur and should be considered.

5. Abatacept（ABT）

ABT is a selective T cell co-stimulatory modulator that works well（albeit a little slowly）without MTX. ABT is a safe bDMARDs and can be used by patients with interstitial pneumonia.

6. Golimumab（GLM）

GLM is a fully humanized anti-TNF antibody that works well without MTX. It works slowly but secondary failure is rare due to its low immunogenicity.

7. Certolizumab pegol（CZP）

CZP is a polyethylene glycolated anti-TNF antibody. It does not pass though the placenta and is rarely excreted in breast milk. It can be used by female patients who desire pregnancy. Since CZP works well without MTX and early introduction is approved, we use it for elderly-onset patients with HDA.

8. Sarilumab（SAR）

SAR is a second anti-IL-6 receptor antibody that works well without MTX. We use SAR when patients exhibit secondary failure or side effects with TCZ.

European League Against Rheumatism（EULAR）describes the situation before the onset of RA as follows: ①“Individual at risk on the basis of genetic and environmental risk factors with no identifiable laboratory abnormalities and no symptoms or signs of inflammatory arthritis”, ②“Individual at risk of RA on the basis of laboratory abnormalities（eg, ACPA, RF positivity with no symptoms or signs of inflammatory arthritis”, ③“Individual at risk on the basis of symptoms of inflammatory arthritis（eg, arthralgia/morning stiffness）but no clinical or imaging evidence of synovitis”, ④“Individuals with synovitis on imaging but no clinically apparent inflammatory arthritis”, ⑤“Individual with clinically apparent inflammatory arthritis not yet fulfilling classification criteria for RA”. Thus, EULAR proposes to express these with“Pre-RA”, “Pre-clinical RA”, “Inflammatory arthralgia”, “Autoantibody-positive arthralgia”, and“Undifferentiated arthritis”. Considering the “window of opportunity” and “treat-to-target” in RA treatment, it is necessary to grasp the pathological conditions before the onset of RA as accurately as possible and predict the “risk of developing RA” in each individual as accurately as possible. Accordingly, these are the extremely important research themes that is directly linked to the introduction of（ultra）early treatment toward inflammatory arthritis patients in the near future.

Rheumatoid arthritis（RA）is one of most common autoimmune diseases with multifactorial etiology. With the advent of molecular-targeted drugs, complete suppression of disease has become a realistic goal. For that purpose, early diagnosis and appropriate treatment selection based on the pathological status of the individual patient are important. Genome-wide association studies have identified more than a hundred disease risk loci, and it is expected that the pathophysiology of patients at the onset stage can be evaluated by utilizing these genetic factors. In this review, I will discuss whether 1）HLA-DRB1 polymorphism, which is the largest genetic factor in RA, and 2）polygenic risk score（PRS）, which evaluates the accumulation of genetic factors, can be used for pathological evaluation around disease onset.

Environmental factors play a major role in the pathogenesis of rheumatoid arthritis（RA）, accounting for approximately 70% of the disease, and the breakdown of immune tolerance caused by environmental factors is a trigger for the development of RA. The most important environmental factor is smoking. Other factors such as periodontal disease, microbiome, air pollutants, diet, and sex hormones have been implicated in the pathogenesis of RA, and their pathogenesis is gradually being elucidated. Cessation of smoking has been shown to have the potential for risk reduction, although the effects are stronger with quantity and duration. The effects of passive smoking during childhood have also been suggested. It has been suggested that periodontal disease may play a role in the pathogenesis of RA, not only for specific species of bacteria, but also by itself. Air pollutants such as PM2.5 and silica have been reported to cause various health problems, and RA, an autoimmune disease, is no exception. Knowledge of these environmental factors may lead to preventive intervention for people at high risk of RA. “Preventive intervention” in addition to “early diagnosis and early treatment” is essential to truly overcome the disease of RA, and further accumulation of knowledge is expected.

Rheumatoid arthritis（RA）can be defined as a “systemic autoimmune disease characterized by anti-citrullinated protein antibody（ACPA）”. ACPA or rheumatoid factor（RF）may be found in serum more than 10 years before the onset of RA and their positive rate is increasing as the onset of RA approaches, with epitope spreading for ACPA. It is also known that the titers of ACPA and RF are sharply elevated just before the onset of RA. If ACPA is positive, cortical bone damage begins even without RA synovitis, but little abnormalities are observed in the trabecular number and/or thickness. Therefore, activation of inflammatory cytokines is necessary to complete the RA pathology. It is reported that ACPA immune complex is recognized by macrophages via FcγR and enhances the secretion of TNF-α and IL-6. The importance of RF in this setting has been determined. Since ACPA-positive individuals are considered to be in the “pre-RA” state, clinical trials have been reported in which rituximab and abatacept are administered to such individuals to prevent the onset of RA. Thus, autoantibodies may have clinical significance for considering RA “at risk” condition.

In the development of RA, the phase that precedes clinical arthritis is often called “preclinical RA”. In preclinical RA, a wide range of lesions are detected by ultrasound and MRI. Recently, tenosynovitis and peritendinitis, in addition to synovitis and bone erosion, have been recognized as characteristic imaging findings in preclinical RA. These findings that extra-articular lesions can precedes clinical arthritis are considered important, giving insight into the pathogenesis of RA.

Background: Patients with rheumatoid arthritis（RA）are highly affected by environmental factors. Thus, a natural disaster may affect RA activity and functional status. Future patient education could be improved by understanding the life activities and conditions of patients with RA affected by disasters or evacuated to shelters, future patient education could be improved. However, there have been limited reports concerning this issue. Herein we conducted a retrospective cohort study in the disaster area after the July 2018 heavy rain event in western Japan.

Objective: To clarify daily life activities and evacuation behavior of patients with RA affected by natural disasters.

Methods: We conducted a questionnaire survey. Patients with RA who were treated in the Red Cross Matsuyama Hospital living in the area affected by the heavy rain disaster were invited to participate. Self-administered questionnaires were sent by mail to participants in June 2020. Damage-related factors; changes in health, functional, and mental status; and evacuation behaviors were included. Clinical and laboratory data were collected from medical records.

Results: Sixty patients（average age, 67 years; females, 82%; average disease duration, 17 years）responded among 90 patients（response rate, 67%）. Among them, 29 patients were affected by the disaster, and 11 patients evacuated their homes. Functional status decrease, which occurred in 56% of patients, was associated with a higher pre-event modified Health Assessment Questionnaire score. Of the evacuees, 25% found the living environment of the evacuation shelter inconvenient, and 83% did not exercise.

Conclusion: Daily life activities of patients with RA could be affected by a natural disaster. Results from this study can provide information for future pre-event patient education.

Objective: Interstitial lung disease（ILD）is a serious complication that can affect the prognosis for with rheumatoid arthritis（RA）patients, but appropriate treatment has not been established to address this issue. This study aimed to clarify the efficacy and safety of Janus kinase inhibitors （JAKi）in RA patients with ILD.

Methods: This non-interventional observational study included 26 RA patients with ILD complications who were treated with JAKi. ILD was evaluated by changes in computed tomography（CT）scores（fibrosis and ground-glass opacity [GGO]）12 months after JAKi initiation. The safety evaluation items were acute exacerbation of ILD and severe infections requiring hospitalization.

Results: In total, 17 patients were able to continue JAKi for over 12 months, while 9 discontinued. f these 17 patients, 12 patients were analyzed using CT scores. The CT-GGO scores were significantly decreased, but the CT-fibrosis scores remained steady throughout the 12 months. （p=0.037 and p=0.813, respectively）. The DAS28-CRP and prednisolone dosage were significantly decreased from the initiation to 12 months later（p<0.001 and p=0.031, respectively）. Among the 26 patients, no exacerbation of existing ILD and two infections（same patient）requiring hospitalization were observed（6.4/100 person-year）.

Conclusion: Although this study has several limitations, such as a small sample size and limited observation period, the results support that JAKi may be a therapeutic option for RA-ILD patients due to its efficacy for arthritis and safety.