Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA).
...This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434.
Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 29% of 72 patients) than with placebo (37 53% of 70 patients; hazard ratio 0·46, 95% CI 0·27–0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study.
The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections.
Pfizer.
The socioeconomic effects of rheumatic fever (RF) in Brazil, including direct and indirect costs to patients and their families and to society, are largely unknown. We evaluated the utilization of ...resources and costs related to RF in a tertiary center caring for low income patients in the city of São Paulo, Brazil.
One hundred patients with RF, younger than 18 yrs, with followup of at least one year, were sequentially selected to provide complete information on a questionnaire. Additional data were collected from patients' charts. The utilization of resources was evaluated for each patient throughout the entire disease course. Costs were determined for patients and their families as well as for the society, using variables from 3 different systems: the national public health system, used by most lower income groups; the Brazilian Medical Association, which regulates charges and fees utilized by health plans and insurance companies; and costs charged by private practitioners, paid directly by patients.
The RF population studied belonged to a low socioeconomic level. The mean monthly family income was $625.20 US. The mean disease duration was 3.9 yrs (range 1-10). Patients had a total of 1657 medical consultations, 22 hospital admissions, and 4 admissions to intensive care unit. Work absenteeism among parents was calculated as 22.9%, equivalent to 901 days of missed work; about 5% of the parents lost their jobs. Patients showed a high rate of school failure (22%). Considering the public system as a reference, direct, indirect, and total costs to society per 100 patients throughout the entire disease duration were $105,860 US ($271/patient/yr), $18,803 US ($48/patient/yr), and $124,663 US (US $319/patient/yr), respectively. When health care plan and private systems were taken as reference, the total costs were $423,550 US and $684,351 US, respectively.
RF and rheumatic heart disease have an important socioeconomic impact in Brazil; costs of RF made up roughly 1.3% of annual family income. The estimated annual cost of RF for society in Brazil is $51,144,347.00 US.
To present a national guideline for ophthalmologic care and surveillance of juvenile idiopathic arthritis-associated uveitis (JIA-uveitis).
Review article based on medical literature and the ...experience of an Expert Committee composed of members of the Brazilian Society of Pediatric Ophthalmology/Brazilian Council of Ophthalmology and the Brazilian Society of Pediatrics/Brazilian Society of Rheumatology. Studies with a high level of evidence were selected by searching the PubMed/Medline database. The final document was approved by the experts.
The main recommendations are that children/adolescents with JIA should undergo screening according to their risk factors. Ophthalmological checkups should also consider ocular inflammation and therapy. Topical glucocorticoids should be the first line of therapy, with systemic glucocorticoids acting as bridge treatments in severe uveitis. Methotrexate should be the first-line systemic therapy and anti-tumor necrosis factor (anti-TNF alpha) the second for uncontrolled uveitis.
This evidence-based guideline for JIA-uveitis will be useful for both ophthalmology and rheumatology practice.
Objective
The objective of this study was to compare demographic data, clinical/laboratorial features and disease activity at diagnosis in three different groups with distinct time intervals between ...onset of signs/symptoms and disease diagnosis.
Methods
A multicenter study was performed in 1555 childhood-onset systemic lupus erythematosus (American College of Rheumatology criteria) patients from 27 pediatric rheumatology services. Patients were divided into three childhood-onset systemic lupus erythematosus groups: A: short time interval to diagnosis (<1 month); B: intermediate time interval (≥1 and <3 months); and C: long time interval (≥3 months). An investigator meeting was held to define the protocol. Demographic data, SLICC classification criteria and SLEDAI-2 K were evaluated.
Results
The number of patients in each group was: A = 60 (4%); B = 522 (33.5%); and C = 973 (62.5%). The median age at diagnosis (11.1 (4.2–17) vs. 12 (1.9–17.7) vs. 12.5 (3–18) years, P = 0.025) was significantly lower in group A compared with groups B and C. The median number of diagnostic criteria according to SLICC (7 (4–12) vs. 6 (4–13) vs. 6 (4–12), P < 0.0001) and SLEDAI-2 K (18 (6–57) vs. 16 (2–63) vs. 13 (1–49), P < 0.0001) were significantly higher in group A than the other two groups. The frequency of oral ulcers in the palate (25% vs. 15% vs. 11%, P = 0.003), pleuritis (25% vs. 24% vs. 14%, P < 0.0001), nephritis (52% vs. 47% vs. 40%, P = 0.009), neuropsychiatric manifestations (22% vs. 13% vs. 10%, P = 0.008), thrombocytopenia (32% vs. 18% vs. 19%, P = 0.037), leucopenia/lymphopenia (65% vs. 46% vs. 40%, P < 0.0001) and anti-dsDNA antibodies (79% vs. 66% vs. 61%, P = 0.01) were significantly higher in group A compared with the other groups. In contrast, group C had a less severe disease characterized by higher frequencies of synovitis (61% vs. 66% vs. 71%, P = 0.032) and lower frequencies of serositis (37% vs. 33% vs. 25%, P = 0.002), proteinuria >500 mg/day (48% vs. 45% vs. 36%, P = 0.002) and low complement levels (81% vs. 81% vs. 71%, P < 0.0001) compared with groups A or B.
Conclusions
Our large Brazilian multicenter study demonstrated that for most childhood-onset systemic lupus erythematosus patients, diagnosis is delayed probably due to mild disease onset. Conversely, the minority has a very short time interval to diagnosis and a presentation with a more severe and active multisystemic condition.
BackgroundJuvenile systemic scleroderma (jSSc) is an orphan disease with an estimated prevalence of around 3 per 1 000 000 children. There are no studies which evaluated prospectively the patient ...related outcomes in these patients. We report the data from juvenile scleroderma inception cohort (jSSc) regarding organ involvement and patient related outcomes.MethodsThe jSSc is a prospective cohort of jSSc patients. Patients were enrolled who were diagnosed with jSSc, had a jSSc onset age under 16 years and were younger as age of 18 years at the time of inclusion. The patients are prospectively assessed every 6 months according to a standardised protocol. Patients with available 12 months follow up data were included in the analyses.ResultsCurrently 100 patients are followed in the jSSc cohort. 51 of them had available 12 months follow up data. Among those patients 37 (72.5%) had diffuse and 14 (27.5%) limited subtype. Mean age of onset of disease was 9.5 (±4.1) years and the mean disease duration at time of inclusion was 3.1 years (±3.2). The proportion of patients treated with DMARD increased from 74.5% to 88% at 12 months follow up. 86% were ANA positive at both assessments. Anti-scl70 positivity increased from 38% to 42%. Anticentromere antibody positivity was 2.4% at both assessments. Mean modified skin score decreased from 17.7 to 14.3 (p=0.151) Raynaud phenomenon occurred in 86% at enrolment and increased up to 88% at 12 months follow up. Nailfold capillary changes occurred around 70% at both assessments, but number of patients with active ulceration decreased from 28% to 16% (p=0.148). The number of patients with decreased FVC (FVC under 80%) decreased from 40.5% to 32% (p=0.497). The number of patients with pulmonary hypertension remained around 10%. No renal crisis or hypertension were reported. The gastrointestinal involvement was around 40% at both assessments. The number of patients with swollen joints decreased from 24% to 10% (p=0.06). The number of patients with muscle weakness decreased significantly from 33% to 9% (p=0.016), parallel to the number of patients with elevated CK values which decreased from 27% to 12% (p=0.074). All patient related outcomes, like global disease activity (p=0.048), global disease damage (p=0.05), Raynaud activity (p=0.003) and ulceration activity (p=0.001) improved significantly over 12 months. Physician assessed global disease activity (p=0.003) and ulceration activity (p=0.001) also improved significantly.ConclusionsOur data show, that jSSc patients over a 12 months disease course stayed quite stable or improved regarding organ involvement. But patient and physician related outcomes regarding activity assessment improved significantly.Disclosure of InterestNone declared
BackgroundJuvenile systemic scleroderma (jSSc) is an orphan disease, with an estimated prevalence of 3 per 1000 000 children. Most jSSc patients primarily present with Raynaud phenomenon (RP). We ...investigated in our patient of the juvenile scleroderma inception cohort, how fare patients with (RP+) and without (RP-) RP differed in their clinical presentation at enrolment.MethodsThe jSSc is a prospective cohort of jSSc patients. Patients were enrolled who were diagnosed with jSSc, had a jSSc onset age under 16 years and were younger as age of 18 years at the time of inclusion. The patients are prospectively assessed every 6 months according to a standardised protocol. We reviewed the organ involvement pattern of our patients currently followed in the cohort.Results100 patients are currently followed in the cohort and 89 (89%) of them had RP. The female/male ratio was lower in the RP +group, 3.7:1 compared to 4.5:1(p=0.808). Diffuse subtype was more common in the RP +group, 72% compared to 63%. Mean age of onset of first non- Raynaud symptomatic was 10.4 years in both groups. Mean disease duration was slightly higher in the RP +group, 3.4 compared to 2.2 years. ANA positivity was higher in the RP +group, 88% compared to 70% (p=0.48). Anti-Scl70 was 34% in the RP +and 20% in the RP-group (p=0.34). Interestingly 7% of RP +but none of the RP +were anti-centromere positive. The mean modified skin score was lower in RP +group (mean of 14.8 compared to 17.0). There were significantly more nailfold capillary changes (70% compared to 18%, p=0.001) and a higher rate of history of ulceration in the RP +group (49% compared to 20%, p=0.083). Decreased DLCO and FVC <80% was higher in the RP-negative group with 45%/50% compared to 37.5%/31% respectively. Pulmonary hypertension occurred in 7% in the RP +group and there was no case in the RP- group (p=0.335). RP- group had a higher rate of urinary sediment changes 18% compared to 4.5% in the RP +group (p=0.07). No renal crisis or hypertension was reported in neither groups. Gastrointestinal involvement was similar between the two groups with around 35%. Occurrence of swollen joints was similar in both groups as the frequency of muscle weakness with around 20%. The tendon friction rub occurred around 10% in both groups. In the patient related outcomes, there was only a difference in rating of Raynauds activity.ConclusionsThe RP– group differed from RP +group in the clinical presentation at enrolment. The absence of Raynaud phenomenon was associated with a decreased rate of history of ulceration, no occurrence of pulmonary hypertension. Interestingly higher rate of urinary sedimentary changes and no anticentromere positivity was observed in RP- patients.Disclosure of InterestNone declared
Objectives: Our aim was to demonstrate the benefit of whole-body magnetic resonance imaging (WBMRI) as a diagnostic modality in the detection of muscle activity in juvenile dermatomyositis ...(JDM)/polymyositis (JPM) patients and to correlate these findings with clinical evaluation, laboratory examinations, nailfold capillaroscopy (NFC), and muscle biopsy.
Method: Thirty-four patients aged 5.5 to 18.9 years with a diagnosis of JDM/JPM were prospectively evaluated using clinical examination, muscle enzyme determination, the Childhood Myositis Assessment Scale (CMAS), Disease Activity Score (DAS), Manual Muscle Testing (MMT), NFC, and WBMRI. An open muscle biopsy was performed if muscle disease activity was detected on WBMRI.
Results: Disease activity was detected in WBMRI in four (11.7%) patients and confirmed by muscle biopsy. All four patients had elevation of at least one muscle enzyme and NFC showed scleroderma patterns in these patients.
Conclusions: WBMRI allows us to evaluate the extent and symmetry of muscle disease and inflammatory activity. NFC is an important additional examination to assess disease activity.
BackgroundEvans syndrome (ES) is an uncommon manifestation characterized by autoimmune destruction of red cells and platelets and concomitant or sequential appearance of immune thrombocytopenia (ITP) ...and autoimmune hemolytic anemia (AIHA). This involvement has been associated to severe disease activity in adult patients with systemic lupus erythematosus (SLE), particularly at disease onset. However, ES studies in childhood-onset SLE (cSLE) patients have been rarely reported and limited to small populations.ObjectivesThe objective of the present multicenter study was to assess ES in a large cSLE cohort at diagnosis evaluating prevalence, clinical features, laboratory findings and outcomes.MethodsA retrospective multicenter cohort study (Brazilian cSLE group) was performed in 10 Pediatric Rheumatology services including 850 patients with cSLE (ACR criteria). None of them had secondary etiologies of autoimmune cytopenias, such as infections, primary immunodeficiencies and malignancies. Patients were divided in two groups for the assessment of lupus manifestations, laboratory exams and treatment at cSLE diagnosis: patients with ES and patients without ES.ResultsES was observed in 11/850 (1.3%) cSLE patients at diagnosis. The majority of them had hemorrhagic manifestations (58%) and active disease (82%). All patients with ES were hospitalized and none of them died. Comparisons of cSLE patients with and without ES at diagnosis revealed similar frequencies of female gender, multi-organ involvement, autoantibody profile and low complement levels (p>0.05). Patients with ES had a lower frequency of malar rash (9% vs. 53%, p=0.003) and musculoskeletal involvement (18% vs. 69%, p=0.001) than those without this complication. The median of hemoglobin 7.4 (5.4–9.4) vs. 10.3 (3.5–16.4)g/dL, p<0.001 and platelets 27 (15–54) vs. 231 (2–761)x103/mm3, p=0.005 were significantly lower in ES compared to non-ES patients, whereas lymphocytes were significantly higher in ES patients 1.8 (1–2.38) vs. 1.16 (0.07–7)x103/mm3, p<0.001. The frequencies of intravenous methylprednisolone (82% vs. 43%, p=0.013) and intravenous immunoglobulin use (64% vs. 3%, p<0.0001) were significantly higher in the former group. Current prednisone dose between the two groups was similar 1.1 (0.76–1.5) vs. 1.0 mg/kg/day (0–30), 0.195.ConclusionsOur large multicenter study identified that ES was a rare and severe cSLE manifestation with a difficult diagnosis due to the absence of typical lupus manifestations, often requiring hospitalization and intravenous treatment.Disclosure of InterestG. Lube: None declared, M. Ferriani: None declared, L. Campos: None declared, M. Terreri: None declared, E. Bonfá: None declared, C. Magalhães: None declared, N. Aikawa: None declared, D. Piotto: None declared, O. Peracchi: None declared, M. C. Santos: None declared, S. Appenzeller: None declared, V. Ferriani: None declared, R. Pereira: None declared, C. Silva Grant/research support from: Conselho Nacional de Desenvolvimento Científico e Tecnolόgico (CNPq 302724/2011–7 to CAS), Federico Foundation (to CAS) and by Núcleo de Apoio à Pesquisa “Saúde da Criança e do Adolescente” da USP (NAP-CriAd) to CAS
Background Pediatric Takayasu’s Arteritis (pTA) is a rare granulomatous vasculitis that affects the aorta and its branches. Though cyclophosphamide (CYC) is often used as first line therapy there are ...few studies proving its efficacy (2). Recently, several case series have reported beneficial results with Infliximab (INF) treating adult and pediatric patients with TA (1). Objectives To describe the treatment response to CYC and INF in an American and Brazilian cohort of pTA patients. Methods Retrospective analysis of 23 pediatric Takayasu’s Arteritis patients seen at Children’s Hospital Los Angeles (CHLA) and Universidade Federal de São Paulo – Brazil (Unifesp) from 1990 to 2011. All patients fulfilled the 1990 American College of Rheumatology criteria for TA. Disease activity was assessed by angiographic imaging, markers of inflammation, and clinical findings. Outcome was assessed using a scoring system (-1 = worse, 0 = unchanged, 1 = improved) that was applied to imaging and clinical findings. Results 23 pts (14F:9M), mean age at disease onset 9.0±3.8 yrs were included: 3 patients presented with type IIa, 2 with type IIb, 3 with type III, 2 with type IV, and 13 with type V (1994 International TA Conference criteria). There was a significantly longer time between disease onset and diagnosis in the Unifesp cohort (2.7±2.1 yrs) compared to the CHLA cohort (1.0±4.6 yrs) (p-value 0.027). CYC was used as initial treatment in 17/23 and INF in 2/23 patients. Average time from disease onset to initiation of CYC was 2.6±2.4 yrs and INF 4.1±2.4 yrs. 9/17 patients initially treated with CYC were changed to INF due to disease progression (7) or partial response (2). 7/9 of these patients subsequently clinically improved on INF. The 2 patients initially treated with INF were changed to CYC due to lack of appropriate response. 1 patient worsened on CYC and the other was lost to follow-up. Of the remaining 4 patients who did not receive CYC or INF 1 patient improved on methotrexate, 1 patient was treated with corticosteroids, methotrexate, and cyclosporine, and 2 patients died. The 2 fatalities were Unifesp patients who died prior to treatment with any immunosuppressant medications except corticosteroids. No differences were detected between the inflammatory markers or angiographic progression in the 2 treatment groups at 6, 12, 24, and 48 months. One serious adverse event occurred during CYC (sepsis) but none during treatment with INF. Conclusions Pediatric Takayasu’s Arteritis is difficult to treat and can lead to significant morbidity or mortality. CYC is often used in the treatment of pTA but has many potential side effects. INF was non-inferior to CYC in our study although patient numbers were too low to detect meaningful statistical differences. Use of INF may be an alternative therapeutic option in pediatric patients with TA. References Hoffman GS, et al. Anti-tumor necrosis factor therapy in patients with difficult to treat Takayasu’s arteritis. Arthritis Rheum 2004; 50:2296-304. Ozen S, et al. Takayasu arteritis in children: Preliminary experience with cyclophosphamide induction and corticosteroids followed by methotrexate. J Pediatr 2007; 150:72-6. Disclosure of Interest S. Stern: None Declared, G. Clemente Consultant for: Novartis, A. Reiff Consultant for: Immunex, Wyeth, Amgen, Merck, Abbott, Pfizer, Novartis, & Genentech, M. Ramos: None Declared, K. Marzan: None Declared, M. T. Terreri Consultant for: Novartis, Pfizer, Johnson & Johnsons, & Abbott
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