Challenges Nurses Face in Providing Care for Patients with Juvenile Idiopathic Arthritis.

OBJECTIVES: This study aimed at identifying challenges nurses face in caring for patients with juvenile idiopathic arthritis (JIA) in Japan. METHODS: Nurses certified by the Japan Rheumatism Foundation were asked to describe their challenges with caring for JIA patients. Data was analyzed using qualitative content analysis. RESULTS: Responses were collected from 89 participants. 58 issues were identified from 40 participants with experience caring for JIA patients. Sixteen categories emerged, grouped into five challenges: communication, understanding, expertise, system, and collaboration. Care for JIA patients included different challenges from adult patients with rheumatoid arthritis, such as complicated patient-parent relationships, inadequate patient independence and insufficient patient information. Moreover, 76 issues from 49 participants with no experience were identified. Seven categories emerged, grouped into two challenges: expertise and opportunity. Issues included in expertise between both groups were similar. Even with no experience caring for JIA patients, nurses recognized the importance of acquiring knowledge. CONCLUSION: This is the first study in Japan regarding the difficulties nurses face in caring for JIA patients. Multidisciplinary team care and a comprehensive understanding of the patient journey, including relationships with guardians, acquaintances, and healthcare providers, is crucial to improve treatment outcome and overall patient quality of life.

Challenges faced by nurses engaged in rheumatology care in Japan.

OBJECTIVES: This study aimed to identify the challenges faced by nurses engaged in rheumatology care in Japan. METHODS: We conducted a questionnaire survey of nurses in Japan in 2020 on challenges experienced in rheumatology care. The participants were nurses certified by the Japan Rheumatism Foundation. Participants' answers were coded and categorized based on relevant phrases and words. Content analysis was performed on the findings. RESULTS: Responses were collected from 162 participants, and a total of 228 issues were identified. Eighteen categories with 56 subcategories emerged from the data analysis, which were grouped into five types of challenges: (1) communication, (2) understanding, (3) expertise, (4) system, and (5) collaboration. In particular, the results highlighted deficiencies in needs-based multidisciplinary team care. CONCLUSION: This study elucidated issues experienced by rheumatology nurses in clinical settings in Japan. Furthermore, this investigation revealed the necessity of patient-centered multidisciplinary team care, including health professionals, patients, and other relevant individuals. This study provided practical directions to facilitate the implementation of effective care focused on improving patients' quality of life.

Psychological support and patient-centered care for patients with rheumatoid arthritis: Nurses' opinions and practice in Japan.

AIM: To investigate nurses' opinions and practices regarding psychological support and patient-centered care (PCC) for patients with rheumatoid arthritis. METHOD: Registered nurses engaged in rheumatic care in Japan were asked to complete the questionnaire regarding nurses' perceived necessity, understanding, and implementation of psychological support, and six patient supports related to PCC, using a seven-point Likert scale. Correlation on practice between psychological support and PCC was evaluated. RESULTS: A total of 53 nurses participated. Nurses indicated high necessity of providing psychological support, whereas implementation was statistically significantly lower than necessity and motivation. Nurses' answers showed significantly lower implementation compared with understanding regarding basic concepts of psychological support: listening, empathy, acceptance, open questions, and closed questions. Most nurses (54.7%) sometimes provided psychological support, followed by often (34.0%), always (5.7%), and not at all (5.6%). Perceived necessity of PCC was rated high. However, its implementation was significantly lower than necessity for all evaluated cares, such as patients' need-based support and support to patients' families, related to PCC. Positive correlations were observed between the implementation of psychological support and PCC. Nurses stressed the importance of psychological support for patient education and shared decision-making. CONCLUSION: This preliminary study indicated that most nurses considered psychological support and PCC necessary, but their implementation was relatively low. As psychological support is also crucial to shared decision-making, in addition to PCC, barriers to its implementation should be addressed to improve patients' outcomes and quality of life.

Elevating the role of carers in rheumatoid arthritis management in the Asia-Pacific region.

AIM: Carers may offer valuable insight into the true health status of patients with rheumatoid arthritis (RA). This multinational, multi-stakeholder, exploratory study in Australia, China and Japan aimed to enrich our understanding of the role and potential impact of carers on RA management. METHOD: This study used a 2-phase sequential mixed methods approach involving 3 key stakeholder groups: rheumatologists, RA patients and carers. The first phase involved an in-depth qualitative exploratory survey (n = 30), which informed the development of the subsequent quantitative validation survey (n = 908). In both phases, patients and carers provided self-assessments of disease and support parameters. RESULTS: In the qualitative phase, patients usually understated the amount of physical support required, compared to carers. Rheumatologists underestimated the amount of physical and emotional care required, compared to carers and patients; however, in the quantitative phase, rheumatologists overestimated the level of support provided by carers. Levels of support provided by carers increased as disease severity increased. Active participation of carers in clinical consultations and treatment decision-making was deemed important by 55% of all patients and 82% of all carers. All stakeholders believed carers' insights into the physical and emotional conditions of patients were useful and should be considered in clinical decision-making. Over 95% of rheumatologists reported soliciting input from the carer. CONCLUSION: Carers provide valuable input that can give clinicians greater insight into the patients' physical and emotional states, and treatment adherence. Development of standardized carer-reported outcomes that correlate with patient-reported outcomes and clinical parameters will ensure clinical meaningfulness and external validity.

Survey on attitudes regarding EULAR recommendations for the role of nurses involved in medical care of patients with chronic inflammatory arthritis in Japan.

OBJECTIVE: We seek to evaluate the opinions of nurses and doctors in Japan regarding EULAR recommendations for nurses' roles in the management of chronic inflammatory arthritis. METHODS: This is a cross-sectional survey within Japan. We randomly selected nurses and doctors engaged in consultation of patients with rheumatoid arthritis (RA) and assessed their agreement and opinions on the feasibility of implementing EULAR recommendations, including potential barriers. RESULTS: 431 nurses and 128 doctors completed the questionnaire. For both nurses and doctors, levels of feasibility showed statistically significant lower results compared with those of agreement for all items. When compared between nurses and doctors, agreement showed no statistically significant differences, while nurses' answers were statistically significant lower for feasibility. Insufficient time, staff and knowledge, lack of established procedures and facilities, and lack of an education system for nurses were cited as barriers to the feasibility of implementing EULAR recommendations. CONCLUSIONS: This is the first survey within Japan evaluating opinions regarding EULAR recommendations for nurses' roles. We found that while agreement was high, feasibility was generally believed to be low. We recommend further research and collaboration between medical professionals in order to implement these recommendations in Japan.

Psychological state is related to the remission of the Boolean-based definition of patient global assessment in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate whether the psychological state is related to the Boolean-based definition of patient global assessment (PGA) remission in patients with rheumatoid arthritis (RA). METHODS: Patients with RA who met the criteria of swollen joint count (SJC) ≤ 1, tender joint count (TJC) ≤ 1 and C-reactive protein (CRP) ≤ 1 were divided into two groups, PGA remission group (PGA ≤ 1 cm) and non-remission group (PGA > 1 cm). Anxiety was evaluated utilizing the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), while depression was evaluated with HADS-Depression (HADS-D) and the Center for Epidemiologic Studies Depression Scale (CES-D). Comparison analyses were done between the PGA remission and non-remission groups in HADS-A, HADS-D and CES-D. RESULTS: Seventy-eight patients met the criteria for SJC ≤ 1, TJC ≤ 1 and CRP ≤ 1. There were no significant differences between the PGA remission group (n = 45) and the non-remission group (n = 33) in age, sex, disease duration and Steinbrocker's class and stage. HADS-A, HADS-D and CES-D scores were significantly lower in the PGA remission group. CONCLUSIONS: Patients with RA who did not meet the PGA remission criteria despite good disease condition were in a poorer psychological state than those who satisfied the Boolean-based definition of clinical remission. Psychological support might be effective for improvement of PGA, resulting in the attainment of true remission.

Improvement of health status evaluated by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36) in patients with rheumatoid arthritis treated with tocilizumab.

OBJECTIVE: To evaluate the improvement of health status in patients with rheumatoid arthritis (RA) treated with tocilizumab. METHODS: Thirty-nine patients were treated with 8 mg/kg tocilizumab every 4 weeks for 24 weeks. Disease activity was assessed by Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI). Improvement of health status was assessed by Arthritis Impact Measurement Scale 2 (AIMS-2) and Short Form-36 (SF-36). RESULTS: Tocilizumab improved CDAI and SDAI significantly at week 4 compared with at baseline. In the components of AIMS-2, "physical score", "symptom" and "affect" improved significantly at week 4 compared with at baseline, while "social interaction" did not improve significantly during 24 weeks of tocilizumab therapy. Similarly in SF-36, "bodily pain", "general health", "vitality" and "mental health" improved significantly at week 4. The most correlative component of AIMS-2 with CDAI was "symptom", while "social interaction" did not correlate with CDAI during tocilizumab treatment. CONCLUSION: The time-course diversity in improvement of health status should be considered to provide proper healthcare when treated with tocilizumab.

A case report of a patient with rheumatoid arthritis complicated with Mycobacterium avium during tocilizumab treatment.

A female patient with rheumatoid arthritis (RA) suffered from Mycobacterium avium (M. avium) infection during tocilizumab treatment. Tocilizumab was discontinued and she was treated with a recommended chemotherapy, resulting in improvement of M. avium. Tocilizumab retreatment did not aggravate M. avium infection, and radiographic abnormalities improved over 1 year after cessation of the recommended therapy. Tocilizumab may be one candidate for intractable RA patients with M. avium if any biologic is required.

A case report of a patient with refractory adult-onset Still's disease who was successfully treated with tocilizumab over 6 years.

Interleukin-6 overproduction is pathologically involved in adult onset Still's disease (AOSD). We successfully treated a man with refractory AOSD utilizing tocilizumab. Tocilizumab was discontinued after 15 doses due to intestinal bleeding, but the efficacy was sustained over 21 months. Tocilizumab was readministered safely upon recurrence and showed similar efficacy over 6 years. Corticosteroid and NSAIDs could be discontinued and intestinal bleeding was no more observed. Tocilizumab can be a therapeutic option for AOSD.

Mechanisms and pathologic significances in increase in serum interleukin-6 (IL-6) and soluble IL-6 receptor after administration of an anti-IL-6 receptor antibody, tocilizumab, in patients with rheumatoid arthritis and Castleman disease.

Interleukin-6 (IL-6) plays pathologic roles in immune-inflammatory diseases such as rheumatoid arthritis (RA) and Castleman disease. By inhibiting IL-6 receptors (IL-6Rs), tocilizumab (a humanized anti-IL-6R antibody) ameliorates the symptoms of these diseases and normalizes acute-phase proteins, including C-reactive protein (CRP). We found that tocilizumab treatment increased serum levels of IL-6 and soluble IL-6R (sIL-6R). To investigate the pathologic significance of these increases, we analyzed the kinetics of serum IL-6 and sIL-6R and the proportion of sIL-6R saturated with tocilizumab after tocilizumab administration in patients with RA and Castleman disease and then compared the results with the CRP values. Serum IL-6 and sIL-6R markedly increased after tocilizumab administration in both RA and Castleman disease. As long as free tocilizumab was detectable, sIL-6R was saturated with tocilizumab and IL-6 signaling was completely inhibited. We concluded that it is likely that sIL-6R increased because its elimination half-life was prolonged by the formation of tocilizumab/sIL-6R immune complex, and that free serum IL-6 increased because IL-6R-mediated consumption of IL-6 was inhibited by the unavailability of tocilizumab-free IL-6R. We also concluded that the increased level of free IL-6 during tocilizumab treatment closely reflects the actual endogenous IL-6 production and true disease activity.

Successful treatment of a patient with Takayasu arteritis using a humanized anti-interleukin-6 receptor antibody.

Takayasu arteritis (TA) is a chronic inflammatory disease that involves the aorta and its major branches. Since overproduction of interleukin-6 (IL-6) seems to play a pathogenic role in TA, we used the anti-IL-6 receptor (IL-6R) antibody tocilizumab to treat a 20-year-old woman with refractory active TA complicated by ulcerative colitis (UC). Treatment with tocilizumab improved the clinical manifestations of TA and the abnormal laboratory findings in this patient and ameliorated the activity of UC. These results indicate that IL-6R inhibition with tocilizumab might be a future treatment option for TA.

Anti-interleukin-6 receptor antibody therapy in rheumatic diseases.

In the treatment of rheumatic diseases such as rheumatoid arthritis (RA) or systemic onset juvenile idiopathic arthritis (soJIA), new therapies targeting pro-inflammatory cytokines have been developed. IL-6 is a pleiotropic cytokine with a wide range of biological activities including a pro-inflammatory mediator activity. Overproduction of IL-6 has been reported to be pathologically involved in the rheumatic diseases and, therefore, blockade of IL-6 actions may improve the disease. Tocilizumab, a humanized monoclonal antibody against human interleukin-6 receptor (IL-6R), inhibits IL-6 binding to IL-6R and specifically interferes with IL-6 actions. Castleman's disease is an atypical lymphoproliferative disorder caused by the overproduction of IL-6. Tocilizumab therapy improves immunological and hematological abnormalities as well as systemic inflammatory symptoms including wasting. This translational study also confirmed the pathological significance of IL-6 in the disease. RA is a representative autoimmune inflammatory disease characterized by bone and cartilage destruction in multiple joints. Since IL-6 also plays pathological roles in RA, tocilizumab therapy has been introduced to the patients with refractory disease and has shown a strong therapeutic effect. Besides Castleman's disease and RA, tocilizumab has been shown to be effective for patients with soJIA and Crohn's disease. Tocilizumab treatment is generally well tolerated and safe. Therefore, tocilizumab can be a promising therapeutic agent for the rheumatic diseases in which IL-6 overproduction is pathologically involved.

Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease.

Multicentric Castleman disease (MCD) is an atypical lymphoproliferative disorder characterized by systemic lymphadenopathy and constitutional inflammatory symptoms. Dysregulated overproduction of interleukin-6 is responsible for the clinical abnormalities. This multicenter prospective study was undertaken to evaluate the safety and efficacy of a humanized anti-human interleukin-6 (IL-6) receptor monoclonal antibody (MRA) in patients with MCD. We report here results of the first 60 weeks of the study enrolling 28 patients. The initial dosing period consisted of 8 infusions of 8 mg/kg MRA administered biweekly. Adjustments in the dose and treatment interval were allowed for each patient in an extension phase after 16 weeks. Within 16 weeks, treatment with MRA consistently alleviated lymphadenopathy and all the inflammatory parameters. Hemoglobin, albumin, and total cholesterol levels, high-density lipoprotein cholesterol values, and body mass index all increased significantly. In addition, fatigue diminished. Chronic inflammatory symptoms were successfully managed over 60 weeks. In 8 (28.6%) patients, the MRA dose was decreased or the treatment interval was extended without exacerbation. Eleven (73.3%) of 15 patients who had received oral corticosteroids before study entry were able to do well on a reduced corticosteroid dose. Most adverse events were mild to moderate in severity. MRA was tolerated well and significantly alleviated chronic inflammatory symptoms and wasting in patients with MCD.

Anti-interleukin-6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis.

OBJECTIVE: To investigate whether interleukin-6 (IL-6) is a regulator of vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA). METHODS: Serum VEGF levels in RA patients were assayed before and after 8 weeks or 24 weeks of maintenance therapy with humanized anti-IL-6 receptor monoclonal antibody (anti-IL-6R mAb). VEGF secreted by RA synovial fibroblasts cultured in the presence of IL-6, IL-1beta, and/or tumor necrosis factor alpha (TNFalpha) was measured. The inhibitory effect of anti-IL-6R mAb, recombinant IL-1 receptor antagonist (IL-1Ra), and anti-TNFalpha mAb on VEGF production was also examined. RESULTS: Serum VEGF levels in RA patients before anti-IL-6R mAb therapy were significantly higher than those in healthy controls (P < 0.0005). Treatment of RA patients with anti-IL-6R mAb normalized serum VEGF levels. In the in vitro study, IL-6 and IL-1beta each induced a slight amount of VEGF production in synovial cells, but TNFalpha did not. Although VEGF-inducing activity of these cytokines was not remarkable when they were added alone, IL-6 acted synergistically with IL-1beta or TNFalpha to induce VEGF production. There was no synergistic effect between IL-1beta and TNFalpha. In the presence of all of these cytokines, anti-IL-6R mAb eliminated the synergistic effect of IL-6, IL-1beta, and TNFalpha, while IL-1Ra or anti-TNFalpha mAb did not. CONCLUSION: Anti-IL-6R mAb therapy reduced VEGF production in RA. IL-6 is the pivotal cytokine that induces VEGF production in synergy with IL-1beta or TNFalpha, and this may be the mechanism by which IL-6 blockade effectively suppresses VEGF production in synovial fibroblasts.