Cryopyrin-associated periodic fever syndrome (CAPS) is a highly debilitating disorder, which is characterized by unregulated interleukin-1β production driven by autosomal dominantly inherited ...mutations in the
NLRP3
gene. Patients with CAPS often present with early-onset episodes of fever and rash. These patients also present with variable systemic signs and symptoms, such as arthritis, sensorineural hearing loss, chronic aseptic meningitis, and skeletal abnormalities, but minimal gastrointestinal symptoms. Recently, effective therapies for CAPS targeted against interleukin-1 have become available. We report a case of a young Japanese woman with CAPS who developed inflammatory bowel disease during canakinumab therapy. The patient had colostomy after intestinal perforation and changed canakinumab to infliximab. To the best of our knowledge, this is the first report of a case of inflammatory bowel disease secondary to CAPS complicated by gastrointestinal symptoms and arthritis which canakinumab could not control. Patients with CAPS who have symptoms that cannot be controlled by canakinumab should be considered for possible co-morbidities.
The transition from pediatric to adult healthcare systems has recently received worldwide attention. Surveys of the attitudes of Japanese non-pediatric rheumatologists regarding transitional care ...were conducted.
Non-pediatric rheumatologists among councilors of the Japan College of Rheumatology were enrolled in the surveys. Experiences of adult patients with childhood-onset rheumatic diseases, ideal medical care for these patients, and factors that made the transition to adult care difficult were examined via e-mail.
Overall, 201 non-pediatric rheumatologists (21.2%) responded to the surveys. Ninety-one percent had previous experience with patients with childhood-onset rheumatic disorders. Transition to non-pediatric institutes was supported by about 90% of respondents. However, only 32% of non-pediatric rheumatologists had no hesitation about caring for adults with childhood-onset rheumatology disorders. Two main factors prevented smooth transitions to non-pediatric care: inadequacy of non-pediatric care (57%) and lack of independence from parents/family (53%). The majority of non-pediatric rheumatologists hesitated about medical care for patients with autoinflammatory syndromes, whereas they became familiar with articular juvenile idiopathic arthritis without hesitation (86.6%); 93% of respondents requested more opportunities to learn about pediatric rheumatology disorders.
Sharing additional knowledge about pediatric rheumatology within the non-pediatric rheumatology field is required.
Objective: To perform a postmarketing surveillance study evaluating the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis (RA).
Methods: Safety and effectiveness ...data were collected for all RA patients (at 772 sites) treated with intravenous abatacept between September 2010 and June 2011. Patients were treated by the approved dosing regimen according to the package insert. Treatment effectiveness was evaluated at baseline and at weeks 4, 12, and 24 using Disease Activity Score 28 (DAS28) according to erythrocyte sedimentation rate or serum C-reactive protein concentrations.
Results: Overall, 3882 and 3016 abatacept-naïve RA patients were included in safety and effectiveness analyses, respectively. Adverse drug reactions (ADRs) were reported for 15.66% of patients and serious ADRs were detected for 2.52% of patients. The incidence of serious infections was 1.03% and these were mainly attributed to different types of bacterial pneumonia. Disease activity improved significantly over 6 months. Separate multivariate analysis identified predictors of severe ADR, and severe infections and factors predictive of clinically meaningful DAS28 improvement after 6 months of treatment with abatacept.
Conclusions: Abatacept was efficacious and well tolerated in a clinical setting. No new safety concerns were detected.
Birth weight is continuously decreasing in Japan since food satiation has become a problem in recent years. The present study aimed to develop and examine the reliability and validity of a scale for ...the assessment of risk factors for low birth weight in infants born at term.
A self-administered postal questionnaire survey comprising a low birth weight risk assessment scale was conducted on mothers with children of nursery school or kindergarten age. After item analysis (scale), factor structure was confirmed by an exploratory factor analysis using the main factor method promax rotation. The reliability of this scale was confirmed by Cronbach's α coefficient and Item-Total correlation. The validity was confirmed by known-groups validity and internal validity.
The responses of 630 mothers (valid response rate, 18.5%) were analyzed. Factor analysis (principal factor analysis and promax rotation) obtained an optimal scale comprising 25 items in the following nine factors: "guidance at each checkup," "adequate rest," "support from husband," "effects on the fetus," "support from society," "support from family," "effects of minor troubles," "good lifestyle habits," and "fall risk and lifestyle changes." The overall Cronbach's α coefficient for the scale was 0.701. Known-groups validity examination revealed significant differences in scale scores of birth weight, birth history, and maternal smoking status.
The scale demonstrated internal consistency, construct validity, and known-groups validity, indicating that it can be used as an indicator of low birth weight risk. In the future, this scale may be included in medical questionnaires as part of health guidance for pregnant women at a risk of delivering low birth weight children.
We evaluated the long-term (52 weeks) safety and effectiveness of iguratimod (IGU) in patients with rheumatoid arthritis (RA).
This multicenter, prospective, observational study included all ...evaluable RA patients who received IGU since its market launch in 2012. We evaluated adverse events (AEs); adverse drug reactions (ADRs); ADRs of special interest, including liver and renal dysfunctions, interstitial lung disease, gastrointestinal and blood disorders, and infection; and change in Disease Activity Score 28-C-reactive protein (DAS28-CRP) at week 52.
Safety and effectiveness were analyzed in 2666 and 1614 patients, respectively. The incidences of AEs, serious AEs, ADRs, and serious ADRs were 46.92, 7.35, 38.26, and 4.58%, respectively. The incidence of ADRs peaked at approximately 4 weeks of treatment. Subsequently, the ADR incidence did not increase over time. Improvement of RA activity was shown up to week 52.
Long-term treatment with IGU in patients with RA resulted in a tolerable safety profile and an improvement in RA activity. IGU could be considered a useful treatment option for patients with RA.
To assess the efficacy and safety of canakinumab in Japanese patients with systemic juvenile idiopathic arthritis (sJIA).
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.
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.
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.
NCT02396212).
We evaluated the safety and efficacy of tocilizumab in polyarticular-course juvenile idiopathic arthritis (pJIA) with polyarticular or oligoarticular onset. Patients received 8 mg/kg tocilizumab ...every 4 weeks in the open-label studies: initial study (to week 12) and then an extension study (at least 48 weeks). Nineteen patients intractable to conventional methotrexate therapy were enrolled. Seventeen patients had polyarticular-onset pJIA; two had oligoarticular-onset pJIA. Mean age was 11.6 years; mean disease duration 5.3 years. American College of Rheumatology Pediatric (ACR Pedi) 30, 50, 70, and 90 response rates, respectively, were 94.7%, 94.7%, 57.9%, and 10.5% at week 12, and 100%, 94.1%, 88.2%, and 64.7% at week 48. Mean disease activity score (DAS28) remained below the remission level (2.6) from week 24. Administration was discontinued in two patients during the extension study because the ACR Pedi 50 response was judged insufficient (one patient) and antitocilizumab antibodies developed (one patient). Adverse events were generally mild, and the four serious adverse events resolved spontaneously or with treatment. In conclusion, tocilizumab showed early and sustained efficacy and tolerability for treating intractable pJIA, which suggests that it is a promising new treatment for this disease.
Objectives: To investigate the safety, effectiveness, and risk-benefit balance of intravenous abatacept (ABA) in non-elderly (<65 years: NEG) and elderly (≥65 years: EG) rheumatoid arthritis ...patients.
Methods: This sub-analysis of an all-cases postmarketing surveillance in Japan assessed safety in all enrolled patients and effectiveness in those with Disease Activity Score 28 based on C-reactive protein (DAS28-CRP) measurements at ≥2 time points including baseline. Risk-benefit was evaluated based on infections and DAS28-CRP improvement >1.2.
Results: The NEG and EG of the safety analysis set comprised 2,170 and 1,712 patients, respectively; corresponding 6-month ABA retention rates were 80.2% and 77.1%. The NEG had fewer adverse drug reactions (14.5% vs. 17.2%, p = .021) and infections (4.8% vs. 7.2%, p = .002) than the EG. DAS28-CRP changed similarly between groups. The proportion of patients with low-risk/high-benefit and high-risk/low-benefit were 33.1% and 6.9% (NEG) and 29.7% and 9.0% (EG). Low-risk/high-benefit patients were younger, had shorter disease duration and fewer comorbidities, and were with less use of oral glucocorticoid and prior biologics, more use of methotrexate and higher DAS28-CRP than high-risk/low-benefit patients at baseline.
Conclusion: ABA was well tolerated and similarly efficacious in the EG and NEG. Identification of factors related to low-risk/high-benefit may aid appropriate patient selection.
This study was conducted to assess the real-world safety and effectiveness of adalimumab in patients with juvenile idiopathic arthritis (JIA).
In this all-case, postmarketing surveillance study ...(NCT01412021) conducted in Japan, patients receiving adalimumab for JIA affecting multiple joints were observed for 24 weeks. The safety (adverse drug reactions ADRs/serious ADRs) and effectiveness (4-variable Disease Activity Score in 28 joints using erythrocyte sedimentation rate DAS28-4/ESR remission rate) were assessed.
In the safety population (
= 356), 90.3% (65/72; weight, ≥15-<30 kg) of patients received adalimumab 20 mg every 2 weeks (q2w) and 98.3% (236/240; weight ≥30 kg) received 40 mg q2w. Incidence of ADRs and serious ADRs was 29.8% (106/356) and 3.4% (12/356), respectively. Incidence of ADRs was significantly higher in patients aged <15 years vs. ≥15 years (34.6% vs. 21.1%,
= .0072), those with comorbidities vs. without (38.3% vs. 25.7%,
= .0155), and those receiving dose <40 mg q2w vs. ≥40 mg q2w (38.8% vs. 26.9%,
= .0418). DAS28-4/ESR remission rate improved from 21.7% (36/166) at baseline to 74.7% (112/150) at week 24.
Adalimumab was well tolerated and had acceptable safety and effectiveness in patients with JIA in the real-world setting.
Abstract Juvenile dermatomyositis (JDM) is characterized by chronic inflammation of the striated muscle and skin. Although cutaneous ulceration occurs relatively frequently, JDM patients with ...cutaneous ulcerations may have severe and prolonged disease. Herein, we report 2 cases of JDM with axillary skin ulcers. A 1-year-old boy and a 2-year-old girl were referred to our hospital because of muscle weakness and skin ulcers. Both patients fulfilled the diagnostic criteria for dermatomyositis, and had axillary skin ulcers characterized by sharp cut circular lesions. Axillary skin ulcers in JDM are unique in their clinical appearance. Both patients received aggressive immunosuppressive therapy because of disease severity.
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