Clinical Usefulness of T-Cell Receptor Vß Repertoire Analysis for Differentiating Multisystem Inflammatory Syndrome in Japanese Children From Toxic Shock Syndrome and Kawasaki Disease.

The specific expansion of T-cell receptor ß chain variable region (TCR-Vß21.3 + ) CD4 + and CD8 + T cells was observed in Japanese patients with multisystem inflammatory syndrome in children. In contrast, these findings were not observed in patients with toxic shock syndrome and Kawasaki disease. T-cell receptor ß chain variable region repertoire analysis to detect specific expansion of Vß21.3 + T cells might be useful for differentiating multisystem inflammatory syndrome in children from toxic shock syndrome and Kawasaki disease.

Risk factors for intolerance of oral 5-aminosalicylic acid preparations in pediatric ulcerative colitis.

BACKGROUND: No previous study of Japanese children with ulcerative colitis (UC) has reported the risk factors for intolerance of 5-aminosalicylic acid (5-ASA). We aimed to identify risk factors for intolerance of oral 5-ASA preparations in pediatric UC. METHODS: Patients with childhood-onset UC who were seen at our hospital between November 2003 and March 2020 were investigated. Intolerance of 5-ASA was defined as having clinical symptoms (pyrexia, abdominal pain, diarrhea, bloody stool) that worsened after starting oral administration of 5-ASA and improved after discontinuation of 5-ASA. Patient sex, age, body size, laboratory data, pediatric UC activity index scores, and colonoscopy-based determinations of the extent and severity of the affected lesion at initiation of 5-ASA of intolerant and tolerant groups were compared. RESULTS: Fifteen patients were in the intolerant group, and 37 were in the tolerant group. The leukocyte count, C-reactive protein level, and erythrocyte sedimentation rate were significantly higher in the intolerant group than the tolerant group; the albumin level in the intolerant group was significantly lower. All intolerant patients and 68% of tolerant patients had pancolitis (Paris classification E4). Patients with a large, affected area (Paris classifications E3 and E4) more frequently had intolerance to 5-ASA than patients with a small lesion. The cumulative Mayo endoscopic subscore (cMES), which is the sum of MES scores for six regions of the large intestine, was significantly higher in the intolerant group. CONCLUSIONS: Pediatric UC patients with more intense inflammation and a large lesion could have an increased risk of intolerance for 5-ASA.

Safety and efficacy of vedolizumab in pediatric patients with ulcerative colitis: multicenter study in Japan.

BACKGROUND: Vedolizumab (VDZ) is a humanized monoclonal antibody that binds to α4ß7 integrin expressed in T-lymphocytes and is gut selective. Few studies have evaluated the safety and efficacy of VDZ in pediatric ulcerative colitis (UC) patients, especially from Asia. METHODS: A longitudinal multicenter retrospective study was conducted at 10 Japanese tertiary medical institutions. Patients aged ≤18 years old who received VDZ for UC between January 2019 and July 2021 were enrolled. Information on the clinical characteristics, prior/concomitant treatment, and safety during the observation period was collected. RESULTS: The data obtained from 48 patients (males, n = 30; females, n = 18) were analyzed. The median age at VDZ induction was 14 (range 4-18) years old. VDZ was indicated in 73% of patients as switching from previous biologics due to primary failure, loss of response, and adverse events (AEs) and was the first biologic in 27%. Remission was achieved or maintained at weeks 14, 30, and 54 in 79.2%, 75.0%, and 65.8% of patients, respectively. There were no significant differences between the number of previous biologics exposures and VDZ effectiveness. The hematocrit, serum albumin concentrations, and erythrocyte sedimentation rate (ESR) at baseline differed significantly by VDZ effectiveness. Nine AEs, including infusion reaction, were noted in seven (14.3%) patients. There were no severe AEs related to VDZ administration. CONCLUSIONS: VDZ was safe and effective in children with UC. The hematocrit, albumin, and ESR at VDZ initiation might be predictors for VDZ effectiveness. VDZ may be an important option for pediatric patients and can be used as an alternative to immunomodulators.

Clinical significance of serum cytokine profiles for differentiating between Kawasaki disease and its mimickers.

OBJECTIVES: To investigate the clinical significance of serum cytokine profiles for differentiating between Kawasaki disease (KD) and its mimickers. METHODS: Patients with KD, including complete KD, KD shock syndrome (KDSS), and KD with macrophage activation syndrome (KD-MAS), and its mimickers, including multisystem inflammatory syndrome in children, toxic shock syndrome, and Yersinia pseudotuberculosis infection, were enrolled. Serum levels of interleukin (IL)-6, soluble tumor necrosis factor receptor type II (sTNF-RII), IL-10, IL-18, and chemokine (C-X-C motif) ligand 9 (CXCL9) were measured using enzyme-linked immunosorbent assay and compared them with clinical manifestations. RESULTS: Serum IL-6, sTNF-RII, and IL-10 levels were significantly elevated in patients with KDSS. Serum IL-18 levels were substantially elevated in patients with KD-MAS. Patients with KD-MAS and KD mimickers had significantly elevated serum CXCL9 levels compared with those with complete KD. Area under the receiver operating characteristic curve analysis showed that serum IL-6 was the most useful for differentiating KDSS from the others, IL-18 and CXCL9 for KD-MAS from complete KD, and CXCL9 for KD mimickers from complete KD and KD-MAS. CONCLUSION: Serum cytokine profiles may be useful for differentiating between KD and its mimickers.

International cohort of 382 children with lupus nephritis - presentation, treatment and outcome at 24 months.

BACKGROUND: Children with lupus have a higher chance of nephritis and worse kidney outcome than adult patients. METHODS: We retrospectively analyzed clinical presentation, treatment and 24-month kidney outcome in a cohort of 382 patients (≤ 18 years old) with lupus nephritis (LN) class ≥ III diagnosed and treated in the last 10 years in 23 international centers. RESULTS: The mean age at onset was 11 years 9 months and 72.8% were females. Fifty-seven percent and 34% achieved complete and partial remission at 24-month follow-up, respectively. Patients with LN class III achieved complete remission more often than those with classes IV or V (mixed and pure). Only 89 of 351 patients maintained stable complete kidney remission from the 6th to 24th months of follow-up. eGFR ≥ 90 ml/min/1.73 m2 at diagnosis and biopsy class III were predictive of stable kidney remission. The youngest and the oldest age quartiles (2y-9y, 5m) (14y, 2m-18y,2m) showed lower rates of stable remission (17% and 20.7%, respectively) compared to the two other age groups (29.9% and 33.7%), while there was no difference in gender. No difference in achieving stable remission was found between children who received mycophenolate or cyclophosphamide as induction treatment. CONCLUSION: Our data show that the rate of complete remission in patients with LN is still not high enough. Severe kidney involvement at diagnosis was the most important risk factor for not achieving stable remission while different induction treatments did not impact outcome. Randomized treatment trials involving children and adolescents with LN are needed to improve outcome for these children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Analysis of the ratio of urinary beta-2-microglobulin to total protein concentration in children with isolated tubulointerstitial disease.

BACKGROUND: Proteinuria is broadly classified into glomerular and tubular proteinuria. Urinary beta-2-microglobulin (ß2-MG) is known as a marker for detecting tubulointerstitial diseases. However, tubulointerstitial damage can also lead to an increase in urinary ß2-MG level in some patients with glomerular diseases. This study aimed to determine the ratio of urinary ß2-MG to total protein (TP) concentration in patients with both isolated tubulointerstitial and glomerular disease. METHODS: This multicenter, retrospective study included children with Dent disease or lupus nephritis in five facilities. Their urinary ß2-MG levels were > 1000 µg/L. Urinary ß2-MG and TP concentrations were obtained, and the ratio of urinary ß2-MG to TP concentration (µg/mg) was calculated. The Mann-Whitney U test was performed to compare this ratio between these children. The optimal cutoff value of the ratio for considering the presence of glomerular disease was obtained from the receiver operating characteristic (ROC) curve. RESULTS: We obtained information on 23 children with Dent disease and 14 children with lupus nephritis. The median ratios of urinary ß2-MG to TP concentrations in children with Dent disease and lupus nephritis were 84.85 and 1.59, respectively. The ROC curve yielded the optimal cutoff value of this ratio for distinguishing between these diseases, and the cutoff value was found to be 22.3. CONCLUSION: In children with tubulointerstitial diseases, the urinary ß2-MG concentration may be approximately 8.5% of the TP concentration. The possibility of presenting with glomerular disease should be considered in patients with a ratio of urinary ß2-MG to TP concentration of < 22.3 (µg/mg).

Treatment for macrophage activation syndrome associated with systemic juvenile idiopathic arthritis in Japan.

OBJECTIVES: To clarify how pediatric rheumatologists treat systemic juvenile idiopathic arthritis (s-JIA) associated macrophage activation syndrome (MAS) in the real world and to assess the efficacy and safety of dexamethasone palmitate (DEX-P) in the treatment of s-JIA-associated MAS. METHODS: This multicenter, retrospective study was conducted at 13 pediatric rheumatology institutes in Japan. This study included 28 patients with s-JIA-associated MAS. Clinical findings, such as treatment details and adverse events, were evaluated. RESULTS: Methylprednisolone (mPSL) pulse therapy was selected as the first-line treatment in more than half of the patients with MAS. Cyclosporine A (CsA) was used as first-line therapy in combination with corticosteroids in half of the patients with MAS. DEX-P and/or CsA were selected as the second-line therapy in 63% of patients with corticosteroid-resistant MAS. Plasma exchange was selected as the third-line therapy for DEX-P and CsA-resistant MAS. All patients improved and there were no characteristically severe adverse events associated with DEX-P. CONCLUSIONS: The first-line treatment for MAS in Japan is mPSL pulse therapy and/or CyA. DEX-P could be an effective and safe therapeutic option for patients with corticosteroid-resistant MAS.

Clinical outcome of ulcerative colitis with severe onset in children: a multicenter prospective cohort study.

BACKGROUND: As best practices for treating children with severe-onset ulcerative colitis remain controversial in the era of biologic agents, we prospectively investigated treatments and outcomes in a multicenter cohort. METHODS: Using a Web-based data registry maintained in Japan between October 2012 and March 2020, we compared management and treatment outcomes in an S1 group defined by a Pediatric Ulcerative Colitis Activity Index of 65 or more points at diagnosis with those in an S0 group defined by an index value below 65. RESULTS: Three hundred one children with ulcerative colitis treated at 21 institutions were included, with follow-up for 3.6 ± 1.9 years. Among them, 75 (25.0%) were in S1; their age at diagnosis was 12.3 ± 2.9 years, and 93% had pancolitis. Colectomy free rates in S1 were 89% after 1 year, 79% after 2, and 74% after 5, significantly lower than for S0 (P = 0.0003). Calcineurin inhibitors and biologic agents, respectively, were given to 53% and 56% of S1 patients, significantly more than for S0 patients (P < 0.0001). Among S1 patients treated with calcineurin inhibitors when steroids failed, 23% required neither biologic agents nor colectomy, similarly to the S0 group (P = 0.46). CONCLUSIONS: Children with severe ulcerative colitis are likely to require powerful agents such as calcineurin inhibitors and biologic agents; sometimes colectomy ultimately proves necessary. Need for biologic agents in steroid-resistant patients might be reduced to an extent by interposing a therapeutic trial of CI rather than turning to biologic agents or colectomy immediately.

The dynamics of laboratory markers reflecting cytokine overproduction in macrophage activation syndrome complicated with systemic juvenile idiopathic arthritis.

OBJECTIVES: To validate the correlation between laboratory markers reflecting disease activity of macrophage activation syndrome (MAS) and serum cytokine levels and identify the valuable laboratory markers that change over time for a prompt MAS diagnosis. METHODS: Serum cytokine levels were determined by enzyme-linked immunosorbent assay and compared with laboratory markers reflecting MAS disease activity.The changes in values were evaluated from the acute phase of systemic juvenile idiopathic arthritis (s-JIA) to MAS diagnosis. RESULTS: CXCL9 was significantly correlated with aspartate aminotransferase (AST), lactate dehydrogenase (LDH), D dimer, and urine ß2 microglobulin levels. sTNF-RII was significantly correlated with platelet counts, AST, LDH, D dimer, and ferritin levels. Significant changes in platelet count, LDH, and D dimer levels were observed. Decreased platelet counts were the most valuable indicator for MAS diagnosis. CONCLUSION: Monitoring the laboratory markers that change over time, particularly decreased platelet counts, was valuable for the prompt MAS diagnosis in s-JIA.

Expert consensus on vaccination in patients with inflammatory bowel disease in Japan.

Immunosuppressive therapies can affect the immune response to or safety of vaccination in patients with inflammatory bowel disease (IBD). The appropriateness of vaccination should be assessed prior to the initiation of IBD treatment because patients with IBD frequently undergo continuous treatment with immunosuppressive drugs. This consensus was developed to support the decision-making process regarding appropriate vaccination for pediatric and adult patients with IBD and physicians by providing critical information according to the published literature and expert consensus about vaccine-preventable diseases (VPDs) [excluding cervical cancer and coronavirus disease 2019 (COVID-19)] in Japan. This consensus includes 19 important clinical questions (CQs) on the following 4 topics: VPDs (6 CQs), live attenuated vaccines (2 CQs), inactivated vaccines (6 CQs), and vaccination for pregnancy, childbirth, and breastfeeding (5 CQs). These topics and CQs were selected under unified consensus by the members of a committee on intractable diseases with support by a Health and Labour Sciences Research Grant. Physicians should provide necessary information on VPDs to their patients with IBD and carefully manage these patients' IBD if various risk factors for the development or worsening of VPDs are present. This consensus will facilitate informed and shared decision-making in daily IBD clinical practice.

Long-term efficacy and safety of canakinumab in the treatment of systemic juvenile idiopathic arthritis in Japanese patients: Results from an open-label Phase III study.

OBJECTIVES: The objective of the study was to report the efficacy and safety of canakinumab treatment in Japanese patients with systemic juvenile idiopathic arthritis (sJIA) over a 48-week study period. METHODS: Patients were administered canakinumab 4 mg/kg (maximum dose 300 mg) every 4 weeks, with no dose adjustments. The key outcome measures included adapted American College of Rheumatology paediatric (aACR pedi) 30/50/70/90/100 response, proportion of patients with inactive disease, and corticosteroid (CS) tapering. RESULTS: In total, 16/19 (84.2%) patients received canakinumab for ≥96 weeks reaching end-of-study (EOS) visit without premature discontinuation. Regardless of the level of joint involvement at baseline, high aACR pedi responses were observed throughout the study; at the EOS, aACR pedi 90/100 response rates were 84.2%/63.2%, respectively. The proportion of patients who successfully tapered CSs at EOS was 66.7% (12/18), of which 10 patients were steroid-free. The most common adverse events were infections (238.3 events/100 patient-years). Serious adverse events were observed in 52.6%. The event (n=1) adjudicated as possible macrophage activation syndrome was preceded by sJIA flare. No deaths were reported. CONCLUSIONS: Canakinumab treatment resulted in a sustained treatment response in sJIA patients over 48 weeks and was associated with CS tapering in majority of patients. No new safety findings were reported.

Association of steroid administration with larger coronary artery abnormalities in patients with Kawasaki disease.

We sought to elucidate the risk profiles of patients with Kawasaki disease who developed coronary artery abnormalities through a retrospective analysis with special reference to steroid treatment. Demographics of the patients were obtained from medical records, and characteristics of the coronary artery abnormalities were evaluated by echocardiography and coronary angiography, which included number, location, size, and length of coronary artery abnormalities (we evaluated by cardiac catheterisation with the American Heart Association classification with segments). We divided the patients into two groups based on steroid use and compared their characteristics and the complications of coronary artery abnormalities and cardiac events. A total of 29 patients were diagnosed with coronary artery abnormalities by echocardiography and coronary angiography during the study period (24 male; median age, 24 months [range: 2-84 months]). Eighteen patients were treated with aspirin and intravenous immunoglobulin (63%, non-steroid group), whereas 11 received aspirin and intravenous immunoglobulin plus steroids (37%, steroid group). No significant differences were found in the number and location of coronary artery abnormalities between the steroid and non-steroid groups. However, the size and number of segments for coronary artery abnormalities were significantly larger and shorter, respectively, in the steroid group (z-score: non-steroid group 6.3 versus steroid group 8.7; p < 0.01). The coronary artery abnormality segments under steroid use were also shorter (non-steroid group versus steroid group, two segments versus one segment; p = 0.02). Coronary artery abnormality size was larger in patients who used steroids than that of non-steroids. This study showed that steroid use significantly affected coronary artery abnormality size in patients with Kawasaki disease. However, cardiac complications from coronary artery abnormalities and cardiac events were comparable between the steroid and non-steroid groups. Further prospective, multicentre studies are needed to confirm these findings.

Assessment of type I interferon signatures in undifferentiated inflammatory diseases: A Japanese multicenter experience.

Purpose: Upregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature. Methods: The type I IFN signature was measured in patients' whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature. Results: A total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling. Conclusions: Half of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.

Evaluation of the European League Against Rheumatism/American College of Rheumatology-2019 classification criteria in patients with childhood-onset systemic lupus erythematosus: a single-center retrospective study.

This study aimed to compare the sensitivity and specificity of the European League Against Rheumatism/American College of Rheumatology-2019 (EULAR/ACR-2019) classification criteria with prior classification schemes for patients with childhood-onset systemic lupus erythematosus (cSLE). This single-center retrospective study examined 53 patients with cSLE and 53 patients having antinuclear antibody (ANA) titers ≥ 1:80 but not cSLE as controls. Sensitivity and specificity were calculated for the EULAR/ACR-2019 criteria, original criteria reported earlier in 2019, the ACR-1997 criteria, and the Systemic Lupus International Collaborating Clinics-2012 (SLICC-2012) criteria. The frequency of positivity in the cSLE group for each item of the EULAR/ACR-2019, ACR-1997, and SLICC-2012 criteria was determined. Characteristics of the misclassified patients were also investigated. All patients with cSLE had ANA titers ≥ 1:80. The non-SLE diagnoses included juvenile idiopathic inflammatory myopathies, primary Sjögren's syndrome (pSS), juvenile idiopathic arthritis, systemic sclerosis, mixed connective tissue disease (MCTD), and others. Sensitivities of the EULAR/ACR-2019 criteria, the original criteria, the ACR-1997 criteria, and the SLICC-2012 criteria were 100%, 100%, 86.8%, and 100%, respectively; the specificities were 84.9%, 92.5%, 98.1%, and 88.7%, respectively. In the cSLE group, the items of the SLE-specific antibody (100%), complement (98.1%), hematological (94.3%), and renal (84.9%) domains were frequently observed in the EULAR/ACR-2019 criteria. The EULAR/ACR-2019 criteria misclassified patient controls more frequently, especially those with MCTD or pSS, as having SLE than the previous criteria. The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity; the weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be more appropriate for the classification of SLE in a pediatric population. Key Points • The EULAR/ACR-2019 criteria for cSLE had high sensitivity but low specificity. • The EULAR/ACR-2019 criteria more frequently misclassified non-SLE patients who did not have SLE, especially those with MCTD or pSS, as having SLE than the previous criteria in patients with childhood onset. • The weighted scoring of the original criteria reported earlier in 2019 may confer higher specificity and be a more appropriate classification of SLE for a pediatric population.

Defining renal remission in an international cohort of 248 children and adolescents with lupus nephritis.

OBJECTIVE: We studied the rate of remission of LN in an international cohort of 248 children and adolescents with biopsy-proven LN. Five different definitions from scientific studies and the definitions recommended by the ACR and Kidney Disease: Improving Global Outcomes were used. METHODS: Anonymized clinical data in patients with biopsy-proven LN class ≥III (International Society of Nephrology/Royal Pathology Society) diagnosed and treated in the last 10 years in 23 international centres from 10 countries were collected. We compared the rate of patients in complete and partial remission applying the different definitions. RESULTS: The mean age at diagnosis was 11 years and 4 months, and 177 were females. The number of patients in complete and partial remission varied a great deal between the different definitions. At 24 months, between 50% and 78.8% of the patients were in full remission as defined by the different criteria. The number of patients in partial remission was low, between 2.3% and 25%. No difference in achieved remission was found between boys and girls or between children and adolescents (P > 0.05). Patients with East Asian ethnicity reached remission more often than other ethnicities (P = 0.03-0.0008). Patients treated in high-income countries showed a higher percentage of complete remission at 12 and 24 months (P = 0.002-0.000001). CONCLUSION: The rate of children and adolescents with LN achieving remission varied hugely with the definition used. Our results give important information for long-awaited treatment studies in children and young people.

Impact of Ventricular Assist Device-Specific Infections on Post-Heart Transplant Infections: A Retrospective Single-Center Study.

BACKGROUND: Patients with a ventricular assist device (VAD) who are awaiting heart transplant (HTx) are susceptible to infections. Such infections, especially at the site of the VAD, may increase the risk of severe post-transplant infections and mortality. Information on the characteristics of VAD-specific infections and outcomes in HTx recipients after prolonged periods of LVAD therapy is scarce. PURPOSE: We aimed to assess the impact of active VAD-specific infections on the incidence of early post-transplant infections and patient survival. METHODS: We conducted a retrospective review of adult HTx cases at our center between April 2011 and October 2020. Informed consent was waived due to study design. A total of 86 patients were included in this study, among whom 94.2% (n = 81) were bridged with a VAD, and the median VAD support period was 1089 days. RESULTS: Patients with active VAD-specific infections were significantly more likely to develop severe acute mediastinitis [odds ratio (OR) 14.8, 95% confidence interval (CI) 4.83-45.4, P < .01]. Active VAD infections were significantly related to increased length of intensive care unit stay (22.1 days vs 13.0 days, P = .016) and longer mechanical ventilation periods (324.7 hours vs 113.2 hours, P = .03). The 30-day survival rates for patients with and without post-transplant infections were 100% and 97.1%, respectively. CONCLUSION: Compared to other risk factors, the presence of active VAD-specific infections increases the risk of early post-heart transplant infections and morbidity, without affecting mortality.

[The Strength of the Sense of Shame of the Aged in Care Scenes: Comparison Between Whether or not There is Anyone Else Around Them].

Medical staff in a hospital or nursing facility should take care of aged individuals with dignity and respect. We conducted a survey on aged individuals to derive under what care circumstances they had a sense of shame, using 12 illustrations, drawn by ourselves, which were common daily care scenes where nurses and patients meet. This survey was conducted at 4 care facilities in A prefecture, Japan. The number of surveyed persons was 43, with the following exclusion criteria: over 60 years old, more than third level of care needed, and non suspected of having dementia. We got the following results from the answers of 41 persons: 1. When elder persons are surrounded by people other than the care staff, they feel more of a sense of shame than when alone; 2. They feel more sense of shame when they use a wheelchair than when they use crutches; 3. They do not feel much shame when they get a bed-bath, even if other persons are there; and 4. Male patients feel more shame than females when they meet their family. These results suggest that elderly patients feel a stronger sense of shame when they are seen by others than when they are seen by care staff. The result 2 suggests that the use of a wheelchair exposes their physical weakness to others. Males feel a stronger sense of shame when they show a weakness in their gender role. We conclude that the sense of shame of aged individuals in daily life scenes in a care facility depends on their gender and whether or not they are surrounded by other persons.

Efficacy and safety of canakinumab in systemic juvenile idiopathic arthritis: 48-week results from an open-label phase III study in Japanese patients.

OBJECTIVES: To assess the efficacy and safety of canakinumab in Japanese patients with systemic juvenile idiopathic arthritis (sJIA). METHODS: This was an open-label, single-arm active treatment study. sJIA patients, aged ≥2 to <20 years, were administered canakinumab 4 mg/kg every 4 weeks for ≤48 weeks. The co-primary endpoints were the proportion of patients who achieved an adapted American College of Rheumatology pediatric (ACR pedi) 30 criteria at week 8, and the proportion of patients who successfully tapered corticosteroids at week 28. Herein, the efficacy and safety results up to 48 weeks are reported. RESULTS: Of the 19 patients enrolled, 15 (78.9%) had previously used tocilizumab. All patients achieved ACR pedi 30 at week 8 and 73.7% (14/19) successfully tapered corticosteroids at week 28. At week 48, ACR pedi 50/70/90/100 responses were achieved by 100.0%/100.0%/87.5%/68.8% of patients. The most common adverse events (AEs) were infections (271.6 patient-years), 42.1% (8/19) patients had serious AEs. Two potential cases of macrophage activation syndrome were identified. No deaths were reported. CONCLUSION: Canakinumab was efficacious in Japanese patients with sJIA and was associated with substantial corticosteroid dose reduction in the majority of patients. The safety profile of canakinumab was consistent with that observed from previous studies. CLINICALTRIALS.GOV (IDENTIFIER: NCT02396212).