Arthritis In Japan Research Articles

Overview of the Treatment Goal, the Method of Evaluating Disease Activity/Physical Function, Activities of Daily Living, and Traditional Care for Systemic or Articular Juvenile Idiopathic Arthritis in Japan.

Juvenile idiopathic arthritis (JIA) is a chronic arthritis of unknown cause that develops in patients younger than 16 years of age and persists for at least 6 weeks. It is an important cause of short- and long-term physical and mental impairments in children. The goal of treatment for JIA is remission. A T2T (treatment-to-target) has been proposed and practiced as a means of achieving remission. The method of evaluating the disease activity of JIA depends on the disease type. For systemic JIA, disease activity is determined by comprehensively considering joint findings, systemic inflammatory findings, changes in inflammatory and synovitis markers, imaging findings, and other factors. For articular JIA other than systemic JIA, the Juvenile Arthritis Disease Activity Score (JADAS-27) is used to evaluate disease activity. The CHAQ (Childhood Health Assessment Questionnaire) and the Japanese version of the modified Rankin Scale (mRS) are mainly used to assess the physical function and ADL. The CHAQ is a global standard assessment method with the advantage that it can be transitioned to the HAQ used in adults, making it useful for international comparisons. The mRS is used to classify the severity of JIA as a chronic disease, and is an indispensable evaluation method in the specific disease procedure in Japan. It is necessary to have pediatric-specific knowledge of growth and development and routine childhood immunizations and to consider transition support tailored to the patient's situation. Ultimately, the goal is to foster the patient's independence and to provide an uninterrupted follow-up in the adult care department. Continuous follow-up will be provided during the schooling (and later, employment) period, and the relationship with the patient will be tailored to their developmental stage. It is also important to understand and communicate the importance of contraception and the drugs that cannot be used during pregnancy.

Impact of Bone Mineral Density and Bone Structural Properties on Postmenopausal Women With Rheumatoid Arthritis in Japan: A Cross-Sectional Study.

Introduction There has been no study on bone structural properties in postmenopausal women with rheumatoid arthritis (RA) in Japan. This study investigated bone mineral density (BMD) and bone structural properties in Japanese postmenopausal women with RA. Methods The study had a cross-sectional design and included 119 postmenopausal women aged 50-80 years with RA symptoms for more than five years. BMD, trabecular bone score (TBS), and results of hip structure analysis (HSA) were measured on dual-energy X-ray absorptiometry scans. The control group consisted of 288 women aged 50-80 years without RA. The RA group and control group using bisphosphonates were compared after propensity score matching for age, body mass index, and fracture history. Women in the RA group were also compared according to the use of glucocorticoids (GCs). Results After the propensity matching score, there were no other significant differences in BMD, TBS, and HSA parameters between the RA group and the control group. In the RA group, the TBS was lower in patients on GCs than those not on GCs (1.272 vs 1.313, p=0.008). There were no other significant differences in BMD and HSA parameters between patients in the RA group according to the use of GCs. Conclusion Although there were no differences in BMD, the TBS was lower in patients on GCs than those not on GCs in the RA group. It is thus important for physicians who administer GCs to treat patients with RA to be aware of not only BMD but also TBS.

A preliminary survey of rheumatologists on the management of late-onset rheumatoid arthritis in Japan.

Objectives We investigated the current perspectives regarding the management of late-onset rheumatoid arthritis (LORA) among rheumatologists in clinical practice. Methods This study was performed in October 2021, and included 65 rheumatologists certified by the Japan College of Rheumatology, who were administered questionnaires (including multiple choice and descriptive formulae) regarding the management of LORA. We aggregated and analyzed the responses. Results All 65 rheumatologists responded to the survey; 47 (72%) answered that >50% of newly diagnosed patients were aged ≥65 years, 42 (65%) answered that achievement of remission or low disease activity was the treatment goal, and 40 (62%) considered patient safety to be the highest priority. Most rheumatologists are concerned about the management of conditions other than RA, such as comorbidities, financial constraints, and life circumstances that interfere with standard or recommended treatment implementation. Conclusion This preliminary survey highlighted various rheumatologists' perspectives regarding the management of LORA.

A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan.

Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis. This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs. A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low. Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.

Peficitinib alleviated acute lung injury by blocking glycolysis through JAK3/STAT3 pathway

Peficitinib is a selective Janus kinase (JAK3) inhibitor recently developed and approved for the treatment of rheumatoid arthritis in Japan. Glycolysis in macrophages could induce NOD-like receptor (NLR) family and pyrin domain-containing protein 3 (NLRP3) inflammasome activation, thus resulting in pyroptosis and acute lung injury (ALI). The aim of our study was to investigate whether Peficitinib could alleviate lipopolysaccharide (LPS)-induced ALI by inhibiting NLRP3 inflammasome activation. Wild type C57BL/6J mice were intraperitoneally injected with Peficitinib (5 or 10 mg·kg−1·day−1) for 7 consecutive days before LPS injection. The results showed that Peficitinib pretreatment significantly relieved LPS-induced pulmonary edema, inflammation, and apoptosis. NLRP3 inflammasome and glycolysis in murine lung tissues challenged with LPS were also blocked by Peficitinib. Furthermore, we found that the activation of JAK3/signal transducer and activator of transcription 3 (STAT3) was also suppressed by Peficitinib in mice with ALI. However, in Jak3 knockout mice, Peficitinib did not show obvious protective effects after LPS injection. In vitro experiments further showed that Jak3 overexpression completely abolished Peficitinib-elicited inhibitory effects on pyroptosis and glycolysis in LPS-induced RAW264.7 macrophages. Finally, we unveiled that LPS-induced activation of JAK3/STAT3 was mediated by toll-like receptor 4 (TLR4) in RAW264.7 macrophages. Collectively, our study proved that Peficitinib could protect against ALI by blocking JAK3-mediated glycolysis and pyroptosis in macrophages, which may serve as a promising candidate against ALI in the future.

Evaluation of medication withdrawal in patients with non-systemic juvenile idiopathic arthritis in Japan using a web-based survey.

Although treatments for juvenile idiopathic arthritis (JIA) have seen considerable advancements, there remains a lack of clear guidelines on withdrawing medications. This study aimed to investigate the current strategies for discontinuing non-systemic JIA treatment. A web-based questionnaire was distributed to members of the Pediatric Rheumatology Association of Japan. According to 126 responses, the most significant factors influencing JIA treatment tapering were the duration of clinically inactive disease, medication toxicity, and a history of arthritis flares. Respondents were often cautious about discontinuing medication if symptoms, e.g. 'morning stiffness' or 'intermittent joint pain', persisted. Among subtypes, oligoarticular JIA was more amenable to treatment tapering, whereas rheumatoid factor-positive polyarticular JIA proved less amenable. Most respondents started medication tapering after a continuous clinical inactive duration exceeding 12 months, and >50% of them required >6 months to achieve treatment discontinuation. Additionally, 40% of the respondents consistently underwent imaging before treatment tapering. The relative risks of treatment continuation and withdrawal should be considered, and decisions should be made accordingly. To obtain improved understanding of and more robust evidence for the optimal strategies for safely discontinuing JIA treatment, it is crucial to continue investigations including long-term outcomes.

Trends in treatment for patients with late-onset rheumatoid arthritis in Japan: Data from the NinJa study

ABSTRACT Objectives Our objective was to investigate trends in the treatment of patients with late-onset rheumatoid arthritis (LORA) using data from the National Database of Rheumatic Diseases in Japan (NinJa). Methods Patients registered in the National Database of Rheumatic Diseases in Japan were classified according to the disease onset: at <65 years (young-onset rheumatoid arthritis); at 65–74 years (early LORA); and at ≥75 years (late LORA). Chronological changes in the treatment and disease activity were compared. Results A total of 7178, 13,171, 15,295, and 15,943 patients were evaluated in 2010, 2013, 2016, and 2019, respectively. In all groups, the use of methotrexate gradually decreased, whereas that of biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) increased; the use of tumor necrosis factor inhibitors decreased, whereas that of non-tumor necrosis factor inhibitors increased. LORA was characterized by more single DMARD use and less methotrexate and biological/targeted synthetic DMARD use. Tumor necrosis factor inhibitors and interleukin-6 inhibitors were used less frequently, whereas abatacept was utilized more frequently in late versus early LORA. Conventional synthetic DMARD (excluding methotrexate) and glucocorticoid use was higher in late versus early LORA. Conclusions This analysis revealed chronological changes in the treatment of LORA in Japan. Differences between early and late LORA suggest that patients are not a homogeneous population.

A cross-sectional questionnaire survey involving physicians for the clarification of the diagnosis and current status of therapeutic intervention of psoriatic arthritis in Japan.

Patients with psoriatic arthritis (PsA) often experience comorbid, irreversible joint destruction, therefore early diagnosis and treatment of PsA are important. The diagnosis requires a comprehensive assessment, which includes an interview, a physical examination, a visual examination of the skin and nails, a blood test, and an imaging test. To clarify how patients with PsA are actually diagnosed and how physicians collaborate among clinical departments, we conducted a web-based questionnaire survey of 500 physicians (dermatologists, rheumatologists, and orthopedists) frequently involved in PsA treatment in Japan. The survey showed that those patients are rarely confirmed to have axial arthritis, peripheral arthritis, enthesitis, or dactylitis by general dermatology practitioners (GP dermatologists). Overall, <60% of patients suspected of having PsA underwent PsA examination by GP dermatologists more than once every 6 months; this percentage is lower than that of patients who underwent PsA examination by rheumatologists and orthopedists. The Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire is the most commonly used for PsA screening. However, users of PASE were only 11.0%, 25.3%, 14.8%, and 24.1% of GP dermatologists, attending dermatologists in hospitals (HP dermatologists), rheumatologists, and orthopedists, respectively. While >80% of HP dermatologists, rheumatologists, and orthopedists used imaging tests (ultrasound, X-ray, and magnetic resonance imaging) for PsA screening, only 40% of GP dermatologists performed imaging tests. Regarding the demands on the healthcare environment of PsA treatment, early diagnosis and treatment for PsA are crucial in every clinical department. The present study showed that GP dermatologists rarely perform imaging tests or confirm a PsA diagnosis, thus patients may miss out on appropriate treatment through collaboration among clinical departments and step-up therapy. Because patients with PsA present diverse comorbid clinical symptoms, early diagnosis, including routine imaging tests, and appropriate treatment in collaboration with other experts are necessary.

Healthcare resource utilisation andeconomic burden ofpatients with adequate andinadequate responses to biological andtargeted synthetic disease-modifying antirheumatic drugs forrheumatoid arthritis inJapan.

To compare healthcare resource utilisation (HCRU) and direct costs between responders versus non-responders to advanced therapies for rheumatoid arthritis (RA). Patients initiating ≥1 advanced therapy (October 2018 - September 2019) with ≥1 RA claim (6-month pre-index period), ≥2 RA claims (any period), and ≥12 months follow-up were identified from the Medical Data Vision claims database. HCRU and all-cause and RA-related costs [direct medical, emergency department (ED), laboratory, and pharmacy] were compared between responders and non-responders. Adjusted incidence rate ratios (IRRs) for HCRU or cost were calculated via multivariable analyses. Among 2446 patients [non-responders (n = 1817); responders (n = 629)], non-responders had significantly longer hospitalisation days [IRR: 1.8 (95% CI: 1.2 - 2.6)], and significantly more ED visits [2.5 (1.5 - 4.2)] and prescriptions [1.1 (1.1 - 1.2)]. Mean all-cause hospital/outpatient medical costs were significantly higher for non-responders [1.4 (1.3 - 1.6), ¥530,895 versus ¥357,009 ($3992 versus $2684) for responders; ¥173,886 ($1307) difference]; RA-related medical costs showed a similar trend [¥351,306 vs ¥253,030 ($2641 vs $1902); ¥98,276 ($739) difference]. No differences between responders and non-responders were observed in mean all-cause and RA-related pharmacy costs. Non-responders to advanced therapies had greater HCRU and all-cause/RA-related direct costs as compared with responders, suggesting a need for more effective RA therapies to reduce the economic burden associated with non-response.

Financial Conflicts of Interest Among the Authors of the Clinical Practice Guidelines for Rheumatoid Arthritis in Japan.

Objective To assess the financial relationships between pharmaceutical companies and authors of the 2020 Japan College of Rheumatology Clinical Practice Guidelines (CPG) for the Management of Rheumatoid Arthritis and to evaluate the quality of evidence supporting the guideline recommendations. Methods This retrospective study evaluated financial relationships between all 27 authors of the CPGand pharmaceutical companies in Japan. Personal payments from pharmaceutical companies to these authors between 2016 and 2020 were extracted from publicly disclosed databases for each pharmaceutical company. The quality of the evidence supporting the CPG recommendations was also assessed. Results All 27 authors received personal payments from pharmaceutical companies, totaling $3,683,048 over five years. The median and mean payments per author were $101,624 and $136,409, respectively. Speaking compensations accounted for more than 80% of all personal payments. More than 77.8% (21 authors), 66.7% (18 authors), and 51.9% (14 authors) received more than $10,000, $50,000, and $100,000 in total payments over the five years, respectively. Nevertheless, these financial relationships between the CPG authors and pharmaceutical companies were not disclosed. More than 81.8% of the CPG recommendations were supported by low- or very-low-quality evidence. Of the strong recommendations, 66.7% were supported by low- or very-low-quality evidence. Conclusion Even though all CPG authors received substantial amounts of personal payments from pharmaceutical companies, these conflictsof interest(COIs) were not disclosed in the CPG. These findings underscore the urgent need for policy interventions to enhance transparency, integrity, and reliability in the development of CPGs in Japan.

Six-month safety andeffectiveness oftofacitinib inpatients with rheumatoid arthritis inJapan: Interim analysis ofpost-marketing surveillance.

We evaluated the real-world safety/effectiveness of tofacitinib, an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA), in patients with RA in Japan registered in a post-marketing surveillance study. This interim analysis included data from July 2013 to December 2018. Adverse events (AEs), serious AEs (SAEs), Simplified Disease Activity Index (SDAI)/Clinical Disease Activity Index (CDAI)/Disease Activity Score in 28 joints, erythrocyte sedimentation rate [DAS28-4(ESR)] scores, and rates of SDAI/CDAI/DAS28-4(ESR)-defined remission and low disease activity were analysed using 6 months of data. Risk factors for serious infections were assessed by multivariable analyses. Safety and disease activity were evaluated in 6866 and 6649 patients, respectively. Overall, 32.73%/7.37% of patients reported AEs/SAEs. Clinically important AEs with tofacitinib included serious infections/infestations [3.13% of patients; incidence rate (IR; patients with events) 6.91/100 patient-years (PY)], herpes zoster (3.63%; IR 8.02/100 PY), and malignancies (0.68%; IR 1.45/100 PY). SDAI/CDAI/DAS28-4(ESR) scores and remission/low disease activity rates improved over 6 months. Male sex, older age, Steinbrocker's stage IV, history of infection, and diabetes mellitus at baseline were independent risk factors for serious infection. In patients with RA receiving tofacitinib in Japan, safety was consistent with the reported profile, and disease activity improved over 6 months. NCT01932372.

A Real-World Claims Database Study Assessing Long-Term Persistence with Golimumab Treatment in Patients with Rheumatoid Arthritis in Japan.

The persistence of golimumab (GLM) treatment in Japanese patients with rheumatoid arthritis (RA) has been evaluated previously, but evidence of long-term real-world use is lacking. This study assessed the long-term persistence of GLM use, its influencing factors, and impact of prior medications in patients with RA in actual clinical practice in Japan. This is a retrospective cohort study of patients with RA using data from a hospital insurance claims database in Japan. The identified patients were stratified as only GLM treatment (naïve), had one biological disease-modifying anti-rheumatic drug (bDMARD)/Janus kinase (JAK) inhibitor treatment prior to GLM [switch(1)] and had at least two bDMARDs/JAK prior to GLM treatment [switch(≥ 2)]. Patient characteristics were evaluated using descriptive statistics. Kaplan-Meier survival and Cox regression methods were used to analyze GLM persistence at 1, 3, 5, and 7years and the associated factors. Treatment differences were compared using a log-rank test. GLM persistence rate in the naïve group was 58.8%, 32.1%, 21.4%, and 11.4% at 1, 3, 5, and 7years, respectively. Overall persistence rates in the naïve group were higher than in switch groups. Higher GLM persistence was observed among patients aged 61-75years and those concomitantly using methotrexate (MTX). Also, women were less likely to discontinue treatment compared to men. Higher Charlson Comorbidity Index score, initial GLM dose of 100mg, and switch from bDMARDs/JAK inhibitor were related to a lower persistence rate. As a prior medication, infliximab showed the longest persistence for subsequent GLM, and using this as a reference, tocilizumab, sarilumab, and tofacitinib subgroups had significantly shorter persistence, respectively (p = 0.001, 0.025, 0.041). This study presents the long-term real-world results for persistence of GLM and its potential determinants. These most recent and long-term observations demonstrated that GLM and other bDMARDs continue to benefit patients with RA in Japan.

A retrospective, longitudinal study of rheumatoid arthritis treatment patterns with Janus kinase inhibitors and other disease-modifying antirheumatic drugs in Japan.

There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis treatment in Japan. The aim of this study was to identify disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan. This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with rheumatoid arthritis diagnosis were enrolled 2016-19, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic DMARDs; tumour necrosis factor alpha inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis. Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other conventional synthetic DMARDs, and tumour necrosis factor alpha inhibitors. The total number of JAKi prescriptions increased approximately 8-fold during 2016-19. Most (61.1%) patients who received JAKis had prior MTX or tumour necrosis factor alpha inhibitor treatment. The duration of JAKi treatment was longer than for biologics and other conventional synthetic DMARDs and comparable to that of MTX. The sequence of drug class prescriptions for rheumatoid arthritis in Japan during 2016-19 followed clinical guidelines. Over this period, JAKis were increasingly used as a second-line treatment following MTX.

Number needed to treat and cost per responder of Janus kinase inhibitors approved for the treatment of moderate-to-severe rheumatoid arthritis in Japan.

This study evaluated the effectiveness and cost-effectiveness of baricitinib, tofacitinib, and upadacitinib regimens, compared to conventional synthetic disease-modifying antirheumatic drug (csDMARD) alone, among Japanese patients with moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to csDMARD, measured in terms of number needed to treat (NNT) and cost per responder (CPR). Efficacy data were derived from two recent network meta-analyses among global and Japanese population. The cost perspective was that of the Japanese Health Service. Both NNT and CPR were based on disease activity score for 28 joints with C-reactive protein (DAS28-CRP) remission and American College of Rheumatology (ACR) 20/50/70 at 12 and 24 weeks. Over 12 weeks, the median NNT and the median CPR to achieve DAS28-CRP remission were 4.3 and JPY 1,799,696 [USD 16,361], respectively, for upadacitinib 15 mg + csDMARD. The equivalent results were 6.0 and JPY 2,691,684 [USD 24,470] for baricitinib 4 mg + csDMARD and 5.6 and JPY 2,507,152 [USD 22,792] for tofacitinib 5 mg + csDMARD. Similar rankings were observed at 24 weeks and for other outcomes. Upadacitinib 15 mg was associated with the lowest NNT and CPR among the three Janus kinase inhibitors used in treatment regimens for Japanese patients with moderate-to-severe RA inadequately responsive to csDMARD.

ACTIVE TB AFTER THE USE OF TOCILIZUMAB FOR COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Tocilizumab is a humanized anti-IL-6 receptor antibody and inhibits the binding of IL-6 to its receptors, associated with Th17 and Th22 cell differentiation which is critical for anti-mycobacterial activity. It is commonly used in patients with active rheumatoid arthritis. During the COVID-19 pandemic, tocilizumab has been widely used in severe COVID-19 infection with elevated markers of systemic inflammation. We report a case of active tuberculosis after the use of tocilizumab for COVID-19 pneumonia. CASE PRESENTATION: An 80-year-old Asian female with hypertension, coronary artery disease presented to the emergency department(ED) due to a one-day duration of fever, cough, and altered mental status. About three months prior to presentation, she had COVID-19 pneumonia requiring prolong hospitalization which was complicated by acute respiratory distress syndrome. She received tocilizumab, remdesivir, steroids and hydroxychloroquine for COVID-19 infection. Following the hospital stay, she was discharged to a long-term acute care facility, and then went home. She is originally from China and moved to the United States 50 years ago. In the ED she was febrile (100.4°F) and hypoxemic, subsequently placed on 4L of nasal cannula. The laboratory data was remarkable for leukocytosis and lactic acidosis. The chest radiograph showed bilateral reticular nodular patchy opacities. The patient was admitted and empiric antibiotics were started for possible pneumonia. Despite this treatment, her respiratory status deteriorated and she was intubated on day 4, with CT chest (figure1) revealing innumerable bilateral micronodules with centrilobular distribution and tree-in-bud opacities. There were also 2 large cavitary lesions in the right upper lobe. The sputum specimen was sent, which returned positive for Acid-Fast Bacillus. In addition, Mycobacterium tuberculosis PCR on sputum was positive. Therefore, the first-line anti-tuberculosis agents including rifampin, isoniazid, pyrazinamide, and ethambutol were started. The Mycobacterium tuberculosis Complex was isolated on sputum 3 weeks later. DISCUSSION: The data from clinical trials indicate that the use of tocilizumab is associated with a very low or absent risk of tuberculosis reactivation. However, this case highlights the judicious use of tocilizumab in patients who are at high risk of exposure or reactivation such as immigrants from endemic regions, IV drug users and health care workers, etc. In our case, the patient had other factors including severe COVID-18 infection, use of steroids, prolonged hospital stay, and malnutrition which might compromise the immune system, and predispose to active tuberculosis. CONCLUSIONS: We suggest that tests be performed to rule out latent tuberculosis in selected patients prior to tocilizumab use and monitor all patients for active tuberculosis during treatment. REFERENCE #1: Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol. 2008;180(3):1962-70. REFERENCE #2: Cantini F, Nannini C, Niccoli L, Petrone L, Ippolito G, Goletti D. Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics. Mediators Inflamm. 2017;2017:8909834. REFERENCE #3: Koike T, Harigai M, Inokuma S, Ishiguro N, Ryu J, Takeuchi T, et al. Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann Rheum Dis. 2011;70(12):2148-51. DISCLOSURES: No relevant relationships by Goutham Dronavalli, source=Web Response No relevant relationships by Sungryong Noh, source=Web Response

Overlapping Features in Kawasaki Disease-Related Arthritis and Systemic-Onset Juvenile Idiopathic Arthritis: A Nationwide Study in Japan.

Background: Arthritis may occur after the diagnosis of Kawasaki disease (KD). Most cases are self-limiting; however, some patients require prolonged treatment.Method: To characterize KD-related arthritis, 14 patients who required arthritis treatment within 30 days after the diagnosis of KD were recruited from the 23rd KD survey in Japan. Twenty-six additional patients were included from our tertiary center and literature review cohorts.Results: The estimated prevalence of KD-related arthritis in Japan was 48 per 100,000 KD patients. Patients with KD-related arthritis had an older age at onset (52 vs. 28 months, P = 0.002) and higher rate of intravenous immunoglobulin (IVIG) resistance in comparison to those without arthritis (86 vs. 17%, P < 0.001). Among 40 patients, 18 had arthritis in the acute phase KD (continued fever-onset type) and 22 did in the convalescent phase (interval fever-onset type). Both showed a similar rate of complete KD or IVIG response. Interval-type patients required biologics for arthritis control less frequently (5 vs. 39%, P = 0.02) and had a higher 2-year off-treatment rate (100 vs. 43%, P = 0.009) than continued-type ones. Interval-types showed lower serum ferritin and interleukin-18 levels than continued-types. When continued-types were grouped according to whether or not they required biologics (n = 7 and n = 11, respectively), the former subgroup had higher ferritin and interleukin-18 levels (P = 0.01 and 0.02, respectively). A canonical discriminant analysis differentiated interval-type from continued-type with the combination of age, time to arthritis, and the ferritin and matrix metalloproteinase-3 levels.Conclusion: Arthritis requiring treatment is a rare complication of KD. KD-associated arthritis includes interval-type (KD-reactive) and continued-type (true systemic-onset juvenile idiopathic arthritis [JIA] requiring biologics), and overlapping arthritis, suggesting the pathophysiological continuity of autoinflammation between KD and JIA.

The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan.

IntroductionUpadacitinib is a Janus kinase inhibitor with demonstrated efficacy in patients with rheumatoid arthritis (RA).ObjectiveThe aim of this study was to assess the long-term safety of upadacitinib in patients with active RA from Japan compared with global clinical trial populations.MethodsPooled data in patients enrolled from Japan (the ‘Japanese population’; SELECT-SUNRISE, SELECT-EARLY, and SELECT-MONOTHERAPY) were compared with that from global (Japan and ex-Japan) upadacitinib clinical trial populations and summarized descriptively.ResultsThe Japanese population (mean age 57.0 years; mean RA duration 6.1 years) received upadacitinib 7.5 mg (n = 121), 15 mg (n = 126), and 30 mg (n = 124) once daily, while the global population (mean age 54.8 years; mean RA duration 9.1 years) received upadacitinib 6 mg twice daily/15 mg once daily (n = 2883) and 12 mg twice daily/30 mg once daily (n = 1375). Most patients were female (79.3%). The exposure-adjusted incidence rates (EAIRs) of serious adverse events in the Japanese population were 11.5, 12.2, and 21.2 per 100 patient-years (PY) with upadacitinib 7.5, 15, and 30 mg, respectively. Herpes zoster rates were higher in the Japanese population (7.8, 12.4, and 16.7 per 100 PY with 7.5, 15, and 30 mg, respectively) versus global populations (3.7 and 7.0 per 100 PY with 15 and 30 mg, respectively). Prior herpes zoster was a significant risk factor for herpes zoster.ConclusionsThe safety profile of upadacitinib was generally similar between Japanese and global RA populations, except for higher EAIRs for serious adverse events and infections, including herpes zoster, in the Japanese population.Trial Registration NumbersSELECT-EARLY: NCT02706873; SELECT-NEXT: NCT02675426; SELECT-COMPARE: NCT02629159; SELECT-MONOTHERAPY: NCT02706951; SELECT-BEYOND: NCT02706847; SELECT-SUNRISE: NCT02720523; BALANCE I: NCT01960855; BALANCE II: NCT02066389.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40264-021-01067-x.

Early psoriatic arthritis in Japan: Post-hoc analyses from a survey by the Japanese Society of Psoriasis Research.

To determine the characteristics of the early phase of psoriatic arthritis (PsA), we conducted a subanalysis of a retrospective survey of Japanese patients. In this study, we enrolled patients with early onset within either 2years or 1year from onset among the 1282 patients with PsA that had previously been reported. Among the total reported PsA patients, 304 (23.7%) were diagnosed with less than 2years of onset of joint manifestation. The male:female ratio was 1.9:1, mean age at onset of cutaneous psoriasis 40.2years, and that of joint manifestation 50.3years. Age of less than 20years at cutaneous psoriasis onset was observed in 22 cases, while that at joint manifestation was observed in two cases. Plaque-type psoriasis accounted for 90.1%, followed by psoriasis erythroderma (3.9%), pustular psoriasis (3.9%), and nail psoriasis (1.3%). Polyarthritis was the most common joint manifestation (32.9%), followed by distal interphalangeal (DIP) type (29.6%), oligoarthritis type (27.3%), and ankylosing spondylitis type (4.9%). Enthesitis was observed in 27.3% and dactylitis in 61.8%. Biologics were used in 168 cases (55.3%). By contrast, 199 patients (15.5%) were diagnosed within 1year of onset of joint manifestation, among whom polyarthritis was the most common (30.7%). Biologics were used in 50.8%. In conclusion, the present study showed that the frequency of early PsA within 2years of onset accounted for 23.7%, and those within 1year of onset was 15.5% among the Japanese patients with PsA. Polyarthritis was the most common in early PsA patients.

Clinicopathological characteristics of lymphoproliferative disorders in 232 patients with rheumatoid arthritis in Japan: A retrospective, multicenter, descriptive study.

To describe the clinicopathological characteristics of lymphoproliferative disorders (LPDs) in patients with rheumatoid arthritis (RA). In this multicenter case series, we retrospectively reviewed the medical records of RA patients who were newly diagnosed as having LPDs with or without biopsy confirmation between 2000 and 2017 in eight hospitals in Japan. We included 232 patients with LPDs. The median age was 67 years (interquartile range [IQR], 60-73 years), and 77.1% were female. At the time of LPD diagnosis, 94.8% and 62.6% of the patients were methotrexate users and in remission or had low RA disease activity, respectively; lymphadenopathy and extranodal involvement were present in 77.1% and 51.9%, respectively. Major extranodal sites were the lungs and oral/oropharyngeal mucosa. The most common LPD pathological subtype was diffuse large B-cell lymphoma (40.5%), followed by classic Hodgkin lymphoma (10.8%), Epstein-Barr virus-positive mucocutaneous ulcer (7.7%), and reactive lymphoid hyperplasia (6.2%). The clinical and laboratory characteristics varied across the pathological subtypes. LPD occurred mainly in methotrexate users, while RA disease activity did not seem to be associated with LPD development. Although the clinical manifestations vary among pathological subtypes, manifestations of LPD in patients with RA can include lymphadenopathy, extranodal mass, and mucocutaneous ulcer.

Guselkumab in the treatment of moderate-to-severe plaque psoriasis.

Recent advances in our understanding of the immunopathogenesis of psoriasis have resulted in novel therapeutic agents. IL-23, mainly produced by dendritic cells, maintains the differentiation of naive T cells to Th17 cells, the keystone effector cells in psoriasis. The clinical effectiveness of therapeutic agents targeting this cytokine has been demonstrated in moderate-to-severe plaque psoriasis. Guselkumab is the first human antibody against the p40 subunit of the IL-23 receptor approved by the US FDA and the EMA for this indication in adult patients (2017). It has also been approved for treatment of psoriatic arthritis in Japan (April 2018). This article reviews the published data relating to the efficacy and safety of guselkumab for treatment of moderate-to-severe plaque psoriasis.