Objectives: Vaccination of systemic lupus erythematosus patients with non-live vaccines may decrease vaccine-preventable infections and mortalities. In the present study, we aimed to compare the ...immunogenicity and safety of inactivated hepatitis A vaccination in childhood-onset systemic lupus erythematosus and healthy subjects. Methods: A total of 30 childhood-onset systemic lupus erythematosus and 39 healthy participants who were seronegative for hepatitis A received two doses of the hepatitis A vaccine in a 0- and 6-month schedule. Hepatitis A virus (HAV) IgG antibodies were measured before vaccination and 7 months after the vaccination. Results: Although anti-HAV IgG antibody titers after vaccination were found to be somewhat lower in children with systemic lupus erythematosus than that of the healthy subjects (p < 0.05), the difference in seroconversion rate was insignificant between childhood-onset systemic lupus erythematosus patients (n = 24/30, 80%) and healthy controls (n = 33/39, 84.6%). There was no increase in median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K scores and anti-ds DNA levels after the vaccination procedure. Seroconversion rates in childhood-onset systemic lupus erythematosus patients were not affected by medication, high disease activity (SLEDAI-2K >6) and anti-ds DNA positivity. None of the patients experienced any flare or adverse reaction throughout the study. Conclusions: According to these results, we conclude that inactivated hepatitis A vaccine is safe and well tolerated in childhood-onset systemic lupus erythematosus patients, with no adverse events or increase in activity. Immunogenicity to the hepatitis A vaccine was adequate, with a seropositivity rate of 80%.
Background:Low immunoglobulin (Ig) levels can occur after rituximab treatment, but the clinical significance is not completely understood. Not all patients (pts) who develop low Ig levels after ...rituximab are at an increased risk of serious infection (SI), but factors such as pre-existing low Ig levels, prior biologic therapies, history of SI and other disease and age-related factors may increase the risk.Objectives:To assess the risk of SI in pediatric pts with prolonged low IgG or IgM serum concentrations following rituximab treatment for GPA or MPA in a global clinical trial.Methods:In the Phase 2a PePRS study (WA25615), pts aged ≥ 2 to ≤ 18 yrs with GPA or MPA received 4 weekly intravenous rituximab infusions of 375 mg/m2 body surface area and concomitant oral glucocorticoid taper. After 6 months, pts could receive further rituximab and/or other immunosuppressants at the investigator’s discretion during a minimum 12-month follow-up phase. Pts with IgG/IgM levels below age-specific reference ranges at baseline were excluded. Ig levels were measured every 4-12 wks. SI occurrence was assessed during/after low IgG or IgM. Prolonged low Ig was defined as IgG or IgM levels < lower limit of normal (LLN) reference range for age for a ≥ 4-month period.Results:All 25 pts completed 4 weekly rituximab infusions and the 6-month Remission Induction Phase; 24/25 pts completed ≥ 18 months of follow-up. 17 pts received additional rituximab treatment on or after Month 6. 11 pts received concomitant immunosuppressants (cyclophosphamide, azathioprine, mycophenolate mofetil) during the study. All pts had a decrease in IgG and IgM mostly after the first rituximab infusion. There was no consistent trend in IgG or IgM levels over time and no clear relationship between low IgG or IgM levels and the number of follow-up rituximab treatments. 18 pts (72%) had prolonged low IgG ≥ 4 months, of whom 5 had IgG levels < LLN at screening and/or baseline; in 7 pts, IgG levels returned to within normal range by study end. During or after prolonged low IgG, 6/18 pts experienced a total of 7 SIs. Three pts received treatment with intravenous Ig. 19 pts (76%) had prolonged low IgM, of whom 5 had IgM levels < LLN at screening and/or baseline. During or after prolonged low IgM levels, 6/19 pts experienced a total of 8 SIs. There were no deaths or study discontinuation due to SI. All pts with prolonged low IgG or IgM had past and/or concomitant treatment with steroids and/or immunosuppressants as potential contributory factors. Analysis of SI onset in relation to timing of low Ig was limited due to protocol-defined time points for Ig assessments.Conclusion:In pediatric pts with GPA/MPA treated with rituximab, there was no consistent pattern in IgG or IgM levels over time. The majority of pts with prolonged low IgG or IgM did not experience any SIs; no increase in the number of SIs was observed over time or with multiple rituximab treatments. While no firm conclusions can be made on a possible relationship between prolonged low IgG or IgM and risk of SI following rituximab due to study limitations (low pt numbers, lack of placebo comparator), these observations are consistent with the known rituximab safety profile in adult pts with GPA/MPA.Disclosure of Interests:Simone Melega Shareholder of: F. Hoffmann-La Roche, Employee of: F. Hoffmann-La Roche, Paul Brogan Grant/research support from: Roche, Novartis, SOBI, Chemocentryx, Novimmune, Consultant of: Roche, SOBI, UCB, Novartis, Speakers bureau: Roche, SOBI, UCB, Novartis, Gavin Cleary Speakers bureau: AbbVie, Aimee Hersh: None declared, Ozgur Kasapcopur: None declared, Satyapal Rangaraj: None declared, Rae Yeung Consultant of: AbbVie, Novartis, Speakers bureau: AbbVie, Novartis, Andrew Zeft: None declared, Jennifer Cooper Employee of: Genentech, Inc., Pooneh Pordeli Shareholder of: Roche, Employee of: Roche, Petra Kirchner Shareholder of: Roche, Employee of: Roche, Patricia Lehane Shareholder of: Roche, Employee of: Roche
BackgroundJuvenile scleroderma (JS) is a rarely seen chronic connective tissue disorder. According to organ involvement, the disease is divided into two main forms: systemic and localized. Localized ...scleroderma (JLS) is characterized with sclerosis of the skin but internal organs involvement is not expected. Juvenile systemic sclerosis (JSS) is characterized by both cutaneous and internal organ involvement. Clinical features are insidious and it can take years until complete clinical picture develops.ObjectivesThe aim of the study was to investigate main demographic and clinical characteristics of patients with JS, followed up at our department. Additionally, we aim to share our experience of this rare condition.MethodsPatients with JS were included in cross-sectional study. Demographic data were taken from disease history of patients. Clinical features, laboratory results and treatment options were evaluated at last clinical visit.ResultsA totally of 46 patients were included in the study: 40 (86,9%) female, 6 (13%) male. The mean age of patients was 14±3 years, mean age at disease onset was 9,1±4,23 years and the mean age at diagnosis was 10,2±3,4 years. Twenty six patients (56,5%) were diagnosed with JSS and 20 (43,4%) had JLS. Skin involvement and peripheral vasculopathy were the most common clinical features. Musculoskeletal involvement takes a second place. Gastro-intestinal (GIS) involvement was present only in systemic sclerosis group. Six patients (13%) had lung fibrosis. Pulmonary hypertension was found in 6,5% of all JS patients but its percentage was higher among patients with JSS (11,5%). None of patients had neurological and renal involvement. All JSS patients were positive while 40% of JLS patients were negative for ANA. Anti Scl 70 antibody was positive only among patients with JSS. Combination of MTX+corticosteroids was used in 15 patients (32,6%). Vasoactive agent was added in therapy of 20 patients (43,5%) which all belong to JSS group. While 31 patients were in remission (67,4%), 15 (32,6%) had active disease in last visit. All patients with active disease belonged to systemic group.ConclusionsJuvenile scleroderma is rarely seen multisystemic disease. Unlike adults, cardiovascular and pulmonary involvement is uncommon among children. Early diagnosis, regular follow up and appropriate treatment are of high importance in clinical course and disease prognosis.ReferencesZulian F, Cuffaro G, Sperotto F. Scleroderma in children: an update. Curr Opin Rheumatol 2013;25:643–50.Foeldvari I. New developments in juvenile systemic and localized scleroderma. Rheum Dis Clin N Am 2013;39: 905–20.Hedrich CM, Fiebig B, Hahn G, Suttorp M, Gahr M. Presentations and treatment of childhood scleroderma: localized scleroderma, eosinophilic fasciitis, systemic sclerosis, and graft-versus-host disease. Clin Pediatr 2011;50: 604–14.Adrovic A, Oztunc F,Barut K, Koka A, Gojak R, Sahin S, et al. The frequency of pulmonary hypertension in patients with juvenile scleroderma. Bosn J Basic Med Sci. 2015;15:30–5.Disclosure of InterestNone declared
Background:
Enthesitis-related arthritis (ERA) and juvenile psoriatic arthritis (JPsA) are two ILAR categories of juvenile idiopathic arthritis (JIA) and represent paediatric correlates of axial ...spondyloarthritis (axSpA) and adult psoriatic arthritis (PsA), respectively.
1,2
Secukinumab (SEC) has demonstrated efficacy and safety in adult patients (pts) with PsA, ankylosing spondylitis and non-radiographic axSpA.
3-5
Objectives:
Evaluate efficacy and safety of SEC using a flare prevention design in pts with active ERA and JPsA.
Methods:
This 2-yr study consisted of an open-label (OL) s.c. SEC (75/150 mg in pts <50/ ≥50 kg) at baseline (BL), and at Weeks (Wk) 1, 2, 3, 4, 8 and 12 in treatment-period (TP) 1. Responder pts who achieved at least JIA ACR 30 response at Wk 12 were randomised into the double-blinded TP2 to continue SEC or placebo (PBO) q4w until a disease flare, or up to Wk 100. Pts (aged 2 to <18 yrs) classified as ERA or JPsA according to ILAR criteria of ≥6 months duration with active disease were included. Primary endpoint was time to flare in TP2 and key secondary endpoints were JIA ACR 30/50/70/90/100, inactive disease, JADAS, enthesitis count and safety. Analysis of time to flare in TP2 included proportion of disease flare, Kaplan-Meier (KM) estimate of median time to flare in days, hazard ratio (95% CI) from Cox model, and
P
-value for the Stratified log-rank test. KM estimates of the probability to disease flare by treatment groups in TP2 were plotted against days. Observed data were used in all analyses. Post-hoc analyses using non-responder imputation (NRI) were performed for JIA ACR 30/50/70/90/100 responses.
Results:
86/97 (89%) pts were enrolled in the OL period TP1 (mean age, 13.1 yrs; female, 33.7%; ERA, n=52; JPsA, n=34). At BL, mean JADAS-27 score was 15.1 and enthesitis count was 2.6. At the end of TP1, 90.4% (75/83) of pts achieved JIA ACR 30 and 69.9% (58/83) achieved JIA ACR 70. There were 21 and 10 flares in TP2, respectively in PBO and SEC treated pts with a significantly longer time to flare and 72% risk of flare reduction in SEC treatment vs PBO (HR: 0.28; 95% CI: 0.13–0.63;
P
<0.001) (Figure 1). JIA ACR responses, disease activity and enthesitis count are reported in Table 1. NRI analyses showed that 87.2%, 83.7%, 67.4%, 38.4% and 24.4% of pts achieved JIA ACR 30/50/70/90/100, respectively. Rates of adverse events (AEs; 91.7% vs 92.1%) and serious AEs (14.6% vs 10.5%) in SEC and PBO groups were comparable in the entire TP. No new safety signals were observed.
Table 1.
Efficacy of secukinumab in Treatment Periods 1 and 2 (Key secondary endpoints)
Efficacy Outcomes, %
TP1
TP2
¥
SEC (N=83
)
^
SEC (N=37
)
PBO (N=37
)
P
-value
JIA ACR 30
90.4
89.2
64.9
0.014
JIA ACR 50
86.7
78.4
62.2
0.152
JIA ACR 70
69.9
67.6
43.2
0.042
JIA ACR 90
39.8
51.4
40.5
0.431
JIA ACR 100
25.3
43.2
37.8
0.745
Inactive disease
#
36.1
47.2
37.8
0.500
JADAS-27, mean (SD)
15.1 (7.2)
14.6 (8.1)
13.3 (5.8)
NA
Enthesitis count, mean change from BL (SD)
−1.8 (2.3)
−2.1 (2.0)
−1.9 (1.2)
NA
P
-values: Cochran-Mantel-Haenszel test, adjusted for analysis factors: JIA category (ERA/ JPsA) and MTX use at BL
¥
The N numbers are values at the end of TP2
^
Efficacy outcomes (%) in TP1 calculated in patients with evaluable data at Wk 12 (N=83)
#
Inactive disease: Definition adapted from JIA ACR criteria of Wallace et al., 2011. N=36 for SEC at the end of TP2
JADAS, Juvenile Arthritis Disease Activity Score; N, total number of patients in the treatment group; NA, data not available
Figure 1.
Time to flare in Treatment Period 2 (Primary Endpoint)
Conclusion:
In children and adolescents with ERA and JPsA, efficacy of SEC was demonstrated with a significantly longer time to flare vs PBO with sustained improvement of signs and symptoms up to Wk 104 and a favourable safety profile.
References:
1Colbert RA.
Nat Rev Rheumatol
. 2010;6:477–85.
2Martini A, et al.
J Rheumatol
. 2019;46:190–7.
3McInnes IB, et al.
Lancet
. 2015;386:1137–46.
4Baeten D, et al.
N Engl J Med
. 2015;373:2534–48.
5Deodhar A, et al.
Arthritis Rheumatol
. 2021;73:110–20.
Disclosure of Interests:
Nicolino Ruperto Consultant of: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Grant/research support from: BMS, Eli-Lilly, GlaxoSmithKline, F Hoffmann-La Roche, Janssen, Novartis, Pfizer, Sobi, Speakers bureau: Ablynx, Astrazeneca-Medimmune, Bayer, Biogen, Boehringer, Bristol Myers and Squibb, Celgene, Eli-Lilly, EMD Serono, Glaxo Smith and Kline, Hoffmann-La Roche, Janssen, Merck, Novartis, Pfizer, R-Pharma, Sinergie, Sobi and UCB, Ivan Foeldvari Consultant of: Novartis, Speakers bureau: Novartis, Ekaterina Alexeeva Grant/research support from: Novartis, Pfizer, Sanofi, MSD, AMGEN, Eli Lilly, Roche, Speakers bureau: Novartis, Pfizer, Sanofi, MSD, AMGEN, Eli Lilly, Roche, NURAY AKTAY AYAZ: None declared, Inmaculada Calvo Consultant of: Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia, Speakers bureau: Sobi, Novartis, Abbvie, GlaxoSmithKline, Pfizer, Amgen, Clementia, Ozgur KASAPCOPUR: None declared, Vyacheslav Chasnyk: None declared, Markus Hufnagel Grant/research support from: Astellas, F. Hoffmann-La Roche, Novartis, Zbigniew Żuber: None declared, Grant Schulert Consultant of: Sobi, Novartis, Seza Ozen: None declared, Artem Popov: None declared, Athimalaipet Ramanan Speakers bureau: Roche, Sobi, Eli Lilly, UCB, Novartis, Christiaan Scott: None declared, Betül Sözeri: None declared, Elena Zholobova Grant/research support from: Pfizer, Novartis, Speakers bureau: Abbvie, Pfizer, Roche, Novartis, Xuan Zhu Employee of: Novartis, sarah whelan Employee of: Novartis, Shareholder of: Novartis, Luminita Pricop Employee of: Novartis, Shareholder of: Novartis, Angelo Ravelli Consultant of: Abbvie, Bristol-Myers Squibb, Pfizer, Hoffmann-LaRoche, Novartis, Centocor, Angelini Holding, Reckitt Benckiser, Speakers bureau: Abbvie, Bristol-Myers Squibb, Pfizer, Hoffmann-LaRoche, Novartis, Centocor, Angelini Holding, Reckitt Benckiser, Alberto Martini Consultant of: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Speakers bureau: Eli Lilly, EMD Serono, Janssen, Novartis, Pfizer, Abbvie, Daniel J Lovell Consultant of: AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Takeda, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie, Forest Research, Speakers bureau: AstraZeneca, Wyeth, Amgen, Abbott, Pfizer, Hoffmann-La Roche, Novartis, UBC, Takeda, Janssen, GlaxoSmithKline, Boehringer Ingelheim, Celgene, Bristol Myers Squibb, AbbVie, Forest Research, Hermine Brunner Consultant of: Aurina, AbbVie, Astra Zeneca-Medimmune, Biogen, Boehringer, Bristol-Myers Squibb, Celgene, Eli Lilly, EMD Serono, GlaxoSmithKline, F. Hoffmann-La Roche, Merck, Novartis, R-Pharm, Sanofi, Pfizer, Grant/research support from: Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, F. Hoffmann-La Roche, Janssen, Novartis, and Pfizer, Speakers bureau: Pfizer, Roche and GlaxoSmithKline
BackgroundFamilial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease characterised with fever, recurrent episodes of self-limiting polyserositis and arthritis. FMF ...arthritis is generally acute monoarthritis especially in the larger joints of the lower extremities, healing without a sequelae. However some of the patients develop different type of chronic arthritis, predominantly oligoarticular juvenile idiopathic arthritis (JIA) and juvenile pondyloarthropathies (JSpA). Studies on JSpA among childhood FMF patients are spare.ObjectivesTo evaluate frequency of JSpA in a large childhood FMF cohort. Furthermore, we aimed to define main characteristics of JSpA among childhood FMF patients.MethodsA total of 320 juvenile FMF patients were blindly questioned according to recently proposed criteria for JSpA by 3 researchers (EO, DS, ET) that were previously educated for FMF and JSpA. A standardised case report form was prepared and completed for each patient. This form was including demographic data, clinical features, MEFV mutation and treatment. Patients fulfilled the JSpA criteria and were classified as probable JSpA. Afterwards, an expert in paediatric rheumatology (OK) reevaluated the classified patients and some of them were confirmed to be a definite while some of them were accepted as potential JSpA patients.ResultsAs a result, 37 patients (11.5%) were initially classified as potential JSpA. Furthermore, 32 (10%) of them were accepted as definite and 5 (1.5%) patients as probable JSpA in childhood FMF. Demographic, clinical and treatment data of definitive JSPA patients are shown in Table I. The most frequent MEFV mutation among JSPA patients was M694V (63.33%).Table I. Demographic, clinical and genetic features of childhood FMF patients.FMF +Definite JSPAFMF +Probable JSPAFMF patients without JIA and JSpAFMF+JIA (except ERA or JSpA) Patients, n32526815Female, n (%)10 (31.25%)1 (20%)148 (55.22%)10 (66.66%)Age of disease onset, mean±SD years7.19±3.685.60±4.934.91±3.404.93±3.32Age at study, mean±SD years14.84±3.7013.40±1.6712.51±4.4310.73±3.57Family History of FMF, n (%)15 (46.87%)1 (20%)132 (49.25%)6 (40%)Colchicine resistance in FMF patients, n(%)2 (6.25%)014 (5.22%)1 (6.66%)M694V mutation n(%)Homozygote, n(%)Heterozygote, n(%)Compound heterozygote, n(%)NA, n(%)19/30 (63.33%)7 (36.84%)5 (26.31%)7 (36.84%)2 (6.25%)3 (60%)2 (66.66%)1 (33.33%)00148/245 (60.40%)51 (34.45%)54 (36.48%)43 (29.05%)23 (8.58%)11 (73.33%)8 (72.72%)2 (18.18%)1 (9.09%)0Disease onset over 6 years,n (%) years26 (81.25%)5 (100%)6 (40%)Oligorthritis, n(%)21 (65.62%)1 (20%)14 (93.33%)Inflammatory back pain, n(%)17/32 (53.12%)3/5 (60%)0Enthesopathy22/32 (68.75%)3/5 (60%)0Sacroiliitis14/21 (66.66%)0/1 (0)0/5 (0)ConclusionsArticular involvement compatible with JSpA could be seen in childhood FMF patients. Spondyloarthropathy was detected in 10% of childhood FMF cases. The M694V mutation is the most common MEFV mutation among JSpA patients with FMF. JSpA should be considered in childhood FMF patients, especially in those chronic arthritis, axial involvement and enthesopathy.Reference1 Adrovic A, Sezen M, Barut K, et al. The performance of classification criteria for juvenile spondyloarthropathies. Rheumatol Int2017;37:2013–2018.Disclosure of InterestNone declared
BackgroundTransitional care is a purposeful, planed movement of adolescence and young adults with chronic condition from childhood- to adult-oriented health care systems. Well-organised, systematic ...transitional health care is of high importance for providing the continuous medical treatment and for reaching optimal outcomes. Up to date, there is no unique, consensus-based model for patients’ transition from childhood- to adult oriented health care centres in Turkey.ObjectivesWe aimed to assess the transitional care among patients with juvenile onset rheumatologic disease in referral tertiary centre in Turkey.MethodsThe transitional policlinic is held once per month at the department for paediatric rheumatology, consisting of 2 adult and 4 paediatric rheumatologist. A total of 147 patients have undergone the transitional care in the time period from May 2014 to December 2017. Patient s were called by telephone, by two different investigators (EP, OK). Thirty-three (22%) patients were not reached and 17 (11%) of theme were excluded from the study due to short post-transitional period (<6 months). Consequently, 97 (66%) patients have been reached and included in the study. Data on demographic, clinical and socio-economic features and experience with transitional practice were collected by using a structured questionnaire, which was fulfilled during the phone conversation between investigator and patient.ResultsA total of 147 patients (79 (54%) females) underwent transition process and 97 of them were included in the study. There was no statistically significant difference between different patients groups regarding the age of transition. The education levels of patients were as following: university 60 (61.9%), high-school 21 (21.6%), middle-school 13 (13.4%), primary school 3 (3.1%). Majority of patients was single at the time of study (79 (81.4%) patients) while only 18 (18.6%) patients were married; half of them being child owner. At the time of study, 44 (30%) patients were employed and mean age at employment was 19.06±3.1 years. Most of patients had health insurance at the time of study (94 (96.9%)). Seventy-one (73.2%) patients continued their regular follow up at adult department while 26 (25.8%) patients discontinued medical treatment. The most common reasons for cessation of follow up were the work/school absence (20 (76.9%)), followed by patients’ personal reasons (2 (7.6%)) and dissatisfaction with adult clinic services (4 (15.5%)). Most of patients reported satisfaction with transition process: 96 (99%).Abstract AB1079 – Table 1n=97 Female, n (%)58 (59.7%)Age at transition, mean±SD21.4±1.4 yearsAge at study mean±SD22.8±1.8 yearsJIA26 (26.8%)FMF60 (61.8%)ConnectiveTissueDisease7 (7%)Vasculitis4 (4%)ConclusionsThis is the first Turkish model of transitional care among patients with chronic rheumatic disease. Well-organised transitional health care is of crucial importance for the continuous and optimal health care of adolescents and young adults with chronic rheumatic disease. Further studies with higher number of patients would reveal the relevance of described transitional care model.Reference1 - Foster HE, Minden K, Clemente D, et al. EULAR/PReS standards and recommendations for the transitional care of young people with juvenile-onset rheumatic diseases. Ann Rheum Dis. 2017;76:639–646.Disclosure of InterestNone declared
Background:
The Composite Response Index in Systemic Sclerosis (CRISS) was developed by Dinesh Khanna as a response measure in patients with adult systemic sclerosis. CRISS aims to capture the ...complexity of systemic sclerosis and to provide a sensitive measure for change in disease activity. The CRISS score is based on a two-step approach. First, significant disease worsening or new-onset organ damage is defined as non-responsiveness. In patients who did not fulfill the criteria of part one, a probability of improvement is calculated for each patient based the Rodnan Skin Score (mRSS), percent predicted forced vital capacity (FVC%), patient and physician global assessments (PGA), and the Health Assessment Questionnaire Disability Index (HAQ-DI). A probability of 0.6 or higher indicates improvement.
Objectives:
The objective of this study was to validate the CRISS in a prospectively followed cohort of patients with juvenile systemic sclerosis (jSSc).
Methods:
Data from the prospective international inception cohort for jSSc was used to validate the CRISS. Patients with an available 12-months follow-up were included in the analyses. Clinically improvement was defined by the anchor question about improvement (much better or little better versus almost the same, little worse or much worse) in patients overall health due to scleroderma since the last visit provided by the treating physician.
Results:
Forty seven jSSc patients were included in the analysis. 74.2% had diffuse subtype. The physician rated the disease as improved in 34 patients (72.3%) since the last visit. No patient had a renal crisis or new onset of left ventricular failure during the 12-months follow-up. Three patients (3.4%) each had a new onset or worsening of lung fibrosis and new onset of pulmonary arterial hypertension. In total, 6 patients resulted in a rating of not improved based on the CRISS in part I. The mRSSS, FVC%, CHAQ and PGA significantly improved during the 12-months follow-up in patients who were rated as improved. The predicted probability based on the CRISS algorithm resulted in an area under curve of 0.77 predicting the anchor question of improvement. In summary, 33 (70.0%) patients were correctly classified by the adult CRISS score resulting in an overall area under curve of 0.7.
Conclusion:
The CRISS score was evaluated in a pediatric jSSc cohort for the first time. It showed a good performance. However, it seems that the formula of part II of the CRISS score needs a calibration to pediatric jSSc patients.
Disclosure of Interests:
Jens Klotsche: None declared, Ivan Foeldvari Consultant of: Novartis, Ozgur Kasapcopur: None declared, Amra Adrovic: None declared, Kathryn Torok: None declared, Valda Stanevicha: None declared, Jordi Anton Grant/research support from: grants from Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Grant/research support from: Pfizer, abbvie, Novartis, Sobi. Gebro, Roche, Novimmune, Sanofi, Lilly, Amgen, Consultant of: Novartis, Sobi, Pfizer, abbvie, Consultant of: Novartis, Sobi, Pfizer, abbvie, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, Speakers bureau: abbvie, Pfizer, Roche, Novartis, Sobi, Gebro, edoardo marrani: None declared, Maria T. Terreri: None declared, Flávio R. Sztajnbok: None declared, Cristina Battagliotti: None declared, Lillemor Berntson Consultant of: paid by Abbvie as a consultant, Speakers bureau: paid by Abbvie for giving speaches about JIA, Despina Eleftheriou: None declared, Gerd Horneff Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Farzana Nuruzzaman: None declared, Nicola Helmus: None declared
BackgroundFever and the fear of febrile seizure risk in parents are a common reason that lead parents to seek care in childhood emergency departments. The most frequently seen periodic fever ...syndromes in Turkey are periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome and familial Mediterranean fever (FMF). There is lack of data regarding the frequency of febrile seizures in periodic fever syndromes.ObjectivesTo document the frequency of febrile seizure in patients with Familial Mediterranean Fever and PFAPA syndrome.MethodsPatients with FMF and PFAPA, who were diagnosed according to Turkish paediatric FMF diagnostic criteria and Marshall criteria, were enrolled to the study. Past medical history of all subjects from postnatal six months to 6 years of age were assessed in terms of febrile seizure. Clinical, demographic and laboratory data of both patient groups were obtained from patient files. The frequency of febrile seizure in both disease groups was compared with the prevalence in healthy children of a previous Turkish study.ResultsA total of 417 FMF and 157 PFAPA subjects were recruited to the study with a female frequency of 49.9% and 42.8%, respectively. The mean age of the FMF and PFAPA patients at study time was 12.4±4.5 years and 5.3±2.1 years, respectively. The mean age at disease onset was 5.1±3.8 (IQR: 2–7) years in FMF group, whereas it was 21±16.5 months (IQR: 10–30) in PFAPA group. The frequency of febrile seizure in FMF and PFAPA syndrome was similar (8.4% versus 8.6%, p>0.05). Among the subjects with febrile seizure, 42.9% (n=15) in FMF group and 30.8% (n=4) in PFAPA group underwent electroencephalography. The EEG result of all subjects were reported to be normal. While 8 subjects with febrile seizure (22.9%) in FMF group required anticonvulsant therapy, 2 patients (15.4%) in PFAPA group used anticonvulsant treatment. Among the PFAPA subjects with febrile seizure (n=13), 53.9% (n=7) underwent tonsillectomy. Thereafter, 85.7% (n=6) of the patients with tonsillectomy never experienced a febrile seizure.Both the FMF and PFAPA syndrome group were found to have a higher frequency of febrile seizure compared with the healthy subjects of the previous Turkish study (FMF versus healthy children: 8.4% versus 3.2%) (PFAPA syndrome versus healthy children: 8.6% versus 3.2%); and this was statistically significant (p<0.001). However, the frequency of febrile seizure in FMF did not differ from the patients with PFAPA syndrome (8.4% versus 8.6%, p>0.05).ConclusionsCompared to the healthy children, the frequency of febrile seizure in FMF and PFAPA syndrome was significantly increased. The recurrent fever, which is the main shared manifestation of these two diseases, is possibly a trigger for febrile seizure. This increased frequency of febrile seizure in both periodic syndrome seems to be a result of recurrent fever, other than a neurologic involvement of the FMF itself.References1 Barut K, Sahin S, Adrovic A, Sinoplu AB, Yucel G, Pamuk G, et al. Familial Mediterranean fever in childhood: a single-center experience. Rheumatology international2018;38(1):67–74.2 Yakinci C, Kutlu NO, Durmaz Y, Karabiber H, Egri M. Prevalence of febrile seizure in 3637 children of primary school age in the province of Malatya. Turk J Trop Pediatr2000;46:249–50.Disclosure of InterestNone declared
BackgroundProgressive systemic sclerosis (PSSc) has been known to affect mainly adults of 30–50 years of age. Juvenile –onset has been reported to be rare and studies comparing clinical differences ...between juvenile-onset and adult onset form have been limited.1 These studies were coming from European and North American countries.1–2 As there would be also effects of ethnic differences, we aimed to assess clinical differences between the two forms of pSSc of paediatric and adult rheumatology centres of a tertiary centre, in Turkey.MethodsAdult onset patients were defined as those who were registered and followed as ‘scleroderma’ at the departments of adult and paediatric rheumatology at Cerrahpasa Medical Faculty, Istanbul, between 2005 and 2017. Only those with at least 2 follow-up visits were included. Patients’s charts were re-evaluated retrospectively.Abstract AB0764 – Table 1Adult onset, n=137Juvenile onset, n=26P Age at disease onset, mean±SD38.6±13.410.1±4.3-Age at diagnosis, mean±SD43.6±14.011.4±3.2-Follow-up duration, med. IQR, years5 2.0–7.04 2.5–6.0NSMale/Female20/1172/24NSFamilial history of chronic inflammatory diseases, n (%)20 (14.6)4 (15.4)NSSclerodactyly, n (%)128 (93.4)25 (96.2)NSRaynaud phenomenon, n (%)135 (98.5)24 (92.3)NSDigital ulcers, n (%)55 (41.4)14 (54.0)0.001Interstitial lung disease, n (%)71 (52.2)6 (24.0)0.009PAH, n (%)20 (14.9)00.045Arrhythmia/heart failure, n (%)14 (10.4)1 (4.0)NSJoint involvement, n (%)20 (14.9)13 (50.0)<0.001Skleletal muscle involvement/myopathy n (%)10 (7.5)7 (28.0)0.002Gastrointestinal system involvement, n (%)42 (31.8)8 (32.0)NSArterial hypertension, n (%)24 (18.2)00.015ANA positivity, n (%)119 (93.0)18 (75.0)0.007DMARD use, n (%)90 (65.7)25 (96.2)0.002Vasodilators, n (%)113 (82.5)13 (50.0)<0.001ResultsThere were 140 patients with scleroderma in the adult outpatient clinic records and 51 in the paediatric clinic records. Of these patients, 3 (2%) adults and 25 (49%) paediatric patients had localised scleroderma (p<0.001). We studied the remaining patients (adults: n=137, juvenile: n=26) who had systemic pattern. Male/female ratio, median follow-up duration, familial history of chronic inflammatory diseases and the frequency of sclerodactyly, digital ulcers, Raynaud phenomenon, arrhythmia/heart failure and gastrointestinal involvement were similar between two groups (table 1). The frequency of interstitial lung disease, pulmonary artery hypertension, and serum ANA positivity were significantly more common in the adult onset group. Whereas joint and muscle involvements were significantly more common among juvenile onset patients. DMARD use was significantly more common in the juvenile group while the use of vasodilators was more frequent among adults1ConclusionsOur results are online with previous reports: juvenile onset patients seem to have a milder form of disease. Major organ involvement as defined interstitial lung disease and pulmonary artery hypertension was more common among adult onset patients. On the other hand, as expected, joint involvement and myopathy were major causes of morbidity in the juvenile group. Contrary to that previously reported, cardiac involvement was not common in the juvenile group.References1 Scalapino K, J Rheumatol. 2006.2 Ingegnoli F, Microvasc Res. 2015.Disclosure of InterestNone declared
BackgroundRituximab in combination with glucocorticoids (GC) is approved to treat adult patients (pts) with GPA or MPA; however, limited data exist on the safety and efficacy of rituximab in ...paediatric pts with these potentially life- and organ-threatening diseases.ObjectivesTo report the interim safety, pharmacokinetics (PK) and exploratory efficacy data from the 6 month remission induction phase of a Phase IIa international, open-label, 18 month clinical study of rituximab in paediatric pts with GPA or MPA.MethodsPts aged ≥2 to≤18 years with newly diagnosed or relapsing GPA/MPA received 4 intravenous (IV) rituximab infusions of 375 mg/m2 body surface area (BSA) on Days 1, 8, 15 and 22 with concomitant GC 1 mg/kg/day (max 60 mg/day) tapered to 0.2 mg/kg/day minimum (max 10 mg/day) by Month 6. All pts received 3 doses of pulse IV methylprednisolone (30 mg/kg/day, max 1 g/day) prior to first rituximab infusion and mandatory prophylaxis for Pneumocystis jiroveci infection. Pts were also pre-medicated with acetaminophen and an antihistamine, 1 hour before each rituximab infusion. Adverse events (AEs) and laboratory data were measured at each study visit (1, 2, 4 and 6 months). Plasma samples for PK analysis were collected throughout the study; clearance and area under the curve (AUC) were calculated using population PK modelling from the RAVE study of rituximab in adult pts with GPA/MPA.1 For exploratory efficacy assessment, the Paediatric Vasculitis Activity Score (PVAS) was measured at each study visit.ResultsOf the 25 pts enrolled, 19 (76%) had GPA and 6 (25%) had MPA (median range age 146–17 years; 80% female). Median (range) disease duration was 0.5 (0.2–0.72) months; 2 pts had received prior cyclophosphamide therapy. All received 4/4 rituximab infusions and completed the 6 month induction phase. By Month 6, all pts had experienced ≥1 AE. The most common AEs by system organ class were infections and infestations in 16 pts (64%). AE terms reported in ≥3 pts are listed in the table 1. Eleven serious AEs occurred in 7 pts (28%), including 3 serious infections (viral gastroenteritis, one lower and one upper respiratory tract infection). 32% of pts had ≥1 infusion related reaction (IRR). No serious IRRs or deaths were reported. The relationship between AUC and BSA was flat and comparable to adult pts. A total of 13 pts (52%) achieved remission by 6 months, defined as PVAS of 0 and GC dose 0.2 mg/kg/day (max 10 mg/day) or PVAS of 0 on 2 consecutive readings≥4 weeks apart irrespective of GC dose.Abstract OP0332 – Table 1Adverse events reported in ≥3 patientsConclusionsIn the initial 6 months of this first global clinical trial of rituximab in paediatric pts with GPA/MPA, rituximab was generally safe and well tolerated. The overall safety profile and PK parameters were comparable to adults with GPA/MPA. No new safety signals were observed. However, the study size and interim nature of the analysis limit firm conclusions. The clinical trial and additional efficacy, PK and safety analyses are ongoing.Reference1 Stone, et al. NEJM2010;363:221–32.AcknowledgementsThis study is funded by F. Hoffmann-La Roche.Disclosure of InterestP. Brogan Grant/research support from: Roche, SOBI, Novartis, Chemocentryx, Consultant for: Roche, SOBI, UCB, Speakers bureau: SOBI, Novartis, G. Cleary Speakers bureau: AbbVie, O. Kasapcopur: None declared, S. Rangaraj: None declared, R. Yeung Consultant for: Novartis, Eli Lilly, P. Brunetta Shareholder of: Roche, Employee of: Genentech, Inc., J. Cooper Employee of: Genentech, Inc., P. Pordeli Employee of: Roche, P. Lehane Employee of: Roche
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