Minimal clinically important difference of the juvenile arthritis disease activity score
Benedetta Schiappapietra1,2, Sergio Davi'2, Federica Mongini2, Luisa Giannone2, Cecilia Bava2, Maria Giannina Alpigiani2, Alberto Martini2, Angelo Ravelli1,2, Alessandro Consolaro1,2
1UNIVERSITA' DI GENOVA, GENOVA, Italy;2Pediatria II, IRCCS G.GASLINI, GENOVA, Italy
Presenting author:Benedetta Schiappapietra Pediatric Rheumatology2017,15(Suppl 1):P268
Introduction:An established approach to the measurement of dis-
ease activity in juvenile idiopathic arthritis (JIA) is based on the Ju- venile Arthritis Disease Activity Score (JADAS). The JADAS consists of 4 variables: physician global rating of overall disease activity; parent/ child ratings of wellbeing; count of active joints, assessed in 71 (JADAS71), 27 (JADAS27) or 10 (JADAS10) joints; and erythrocyte sedimentation rate (ESR). The instrument score is yielded by making the arithmetical sum of the scores of the 4 items. The JADAS has been shown to be feasible and to have good metrologic properties. Moreover, a 3-variable version of the JADAS, which does not include the acute phase reactant, was found to correlate closely with the ori- ginal tool (clinical JADAS, cJADAS).
Objectives: To define the minimal clinically important differences
(MCID) of all JADAS versions for worsening and improvement using both parent and physician perspectives.
Methods:Changes in the JADAS scores in consecutive visits were cal- culated in a dataset of 1,874 visits of JIA patients seen at the study Unit. Both parent and attending physician were asked to rate in a 5- point Likert scale if the patient was much worsened, slightly wors- ened, stable, slightly improved, much improved from previous visit. Those visits in which patient was subjectively rated by parents or by the physician as slightly worsened or slightly improved were retained. Subsequent visits with a time interval of more than 6 months were not retained; each patient could contribute for no more than 1 visit for improvement and 1 visit for worsening for each assessor. MCID were defined as the median changes of the JADAS scores of individual patients who had a minimal important improve- ment or worsening between visits.
Results:Table shows calculated MCID for all JADAS versions accord- ing to parents and physician.
Conclusion:MCID for all JADAS and cJADAS versions were defined
according to parent and physician perspective. Differently from the results of previous study, the clinically important change of the score was smaller for improvement than for worsening for both parents and physicians. Parents required a minor change in the score than physician to define both improvement and worsening.
Disclosure of Interest None Declared.
P269
Influence of FokI vitamin D receptor (VDR) and TNFα-308 tumor necrosis factor gene polymorphism on long term disease outcome in juvenile idiopathic arthritis (JIA)
Dragana S. Lazarevic1, Jelena Vojinovic1, 2, Gordana Susic3, Jelena Basic4 1
Pediatric Rheumatology, CLINIC OF PEDIATRICS, CLINICAL CENTER NIS, Nis, Serbia;2Faculty of Medicine, University of Nis, Nis, Serbia;3Institute of Rheumatology, Belgrade, Serbia;4Institute for Biochemistry, Faculty of Medicine, University of Niš, Nis, Serbia
Presenting author:Dragana S. Lazarevic Pediatric Rheumatology2017,15(Suppl 1):P269
Introduction: Genetic contribution of TNFα-308 promoter and FokI
Vitamin D receptor gene polymorphism on response to biological treatment is not yet well established.
Objectives:To investigate possible influence of tumor necrosis factor alpha (TNFα-308) and FokI Vitamin D receptor (VDR) gene poly- morphism on long term disease outcome in JIA patients treated with biologics.
Methods:We have retrospectively analysed data from our registry of JIA patients treated with biologics in whome 6 years follow-up data could be obtained and genomic DNA extracted to test TNFά–308 promoter and FokI VDR polymorphism. Disease activity was evalu- ated by ACR Pedi core set criteria for inactive disease.
Results:We have evaluated 78 JIA patients in whom there was not
significant distribution difference of TNFα-308and FokI Vitamin D re- ceptor (VDR) gene polymorphism among different JIA subtypes. Pa- tients with the -308 GG (p = 0,004) and GA (p = 0,026) genotype achieved clinical response significantly more frequently than those Table 21 (abstract P268).See text for description
JADAS10 JADAS27 JADAS71 cJADAS10 cJADAS27 cJADAS71
Improvement Parent -2.7 -2.5 -2.7 -2.5 -2 -2.5
Physician -4 -3.5 -4.5 -3.5 -3.5 -4
Worsening Parent 3.6 3 3.6 3.3 3 3.3
with the -308 AA genotype after 36 month of follow up period. Patients with the FF(p = 0,006) and Ff (p = 0,036) genotypes had a reduction of disease activity and more frequently reached clinical re- sponse to biologics with respect to the ff genotypeat the end of the observational period.
There was no influence of distribution of the -308 TNF-αon achieving remission, but there was different distribution of FokI polymorphism on possibility to achieve remission at the end of the observational period. Patients resistant to biologics had significantly more frequent ff genotype, while those achieved remission had significantly more frequent Ff genotype (Χ2= 6,52, p = 0,038). In univariate uncondi- tional logistic regression analysis positive clinical predictor of achieving remission after 24 months under biologics was low dose of steroids (OR 0,749, p = 0,025), while genetic determinats were insuffitient predictors of disease outcome.
Conclusion: JIA patients carrying the TNFα-308 AA genotype and
those with VDR ff genotype are associated with a poorer response to biological treatment. The present study is the first to demonstrate that patients with Ff genotype and low dose of steroids have better chance to achieve remission.
Disclosure of Interest None Declared.
P270
Disease activity and damage in juvenile idiopathic arthritis: comparison between“methotrexate”and“biologic”eras Gabriella Giancane1, Valentina Muratore1, Valentina Marzetti1, Neus Quilis1, Belen Serrano Benavente1, Alessandra Alongi1, Adele Civino2, Lorenzo Quartulli2, Alessandro Consolaro1, Alberto Martini1, Angelo Ravelli1
1Pediatria II, Reumatologia, Istituto Giannina Gaslini, Genoa, Italy;2UOC Pediatria, AO "Card.G.Panico", Tricase, Italy
Presenting author:Gabriella Giancane Pediatric Rheumatology2017,15(Suppl 1):P270
Introduction:The introduction of biologic agents at the beginning
of the 2000s has represented a major advance in the manage- ment of juvenile idiopathic arthritis (JIA). These medications have been shown to be effective in a sizeable proportion of patients refractory or intolerant to methotrexate. However, in order to document the impact of the recent therapeutic progress on the prognosis of JIA there is the need to compare the long-term out- comes achieved with previous therapies with those obtained with the newer medications.
Objectives:To compare the level of disease activity and the amount of articular and extra-articular damage between patients treated in the“methotrexate”and“biologic”eras.
Methods:Data for the“methotrexate”era were extracted from a pre- vious study on disease outcome in 310 patients with disease onset before 2002 and disease duration of ≥5 years (Solari et al. A&R 2008;59:1571-9). Data for the“biologic” era were obtained with the present study by examining all consecutive patients with JIA who had disease onset between January 2002 and June 2011 and a dis- ease duration of ≥5 years. Outcome assessments included joint counts, physician global assessment of overall disease activity on a visual analog scale, Juvenile Arthritis Disease Activity Score-10 (JADAS10), Juvenile Arthritis Multidimensional Assessment Report
(JAMAR) completed by a parent, and acute phase reactants. The
amount of articular and extra-articular damage was assessed through the Juvenile Arthritis Damage Index (JADI).
Results: Demographic and clinical features of patients seen in the
two study periods were overall comparable. As compared to the older sample, patients treated more recently had received more fre- quently methotrexate (84.2 vs 64.5%) and biologic medications (61.8% vs 11.3%), and had undergone more commonly intra-articular corticosteroid injections (98% vs 79%). The comparison of disease ac- tivity and damage between the two cohorts is presented in the table. All items of articular and extra-articular JADI were decreased in the recent sample, with the exception of temporo-mandibular damage
and leg-length discrepancy, whose frequency was comparable in the two datasets.
Conclusion:Compared with patients treated in the “methotrexate”
era, those treated in the“biologic”era have a higher frequency of in- active disease and less articular and extra-articular damage. These findings highlight the improvement in disease outlook achieved with the newer therapeutic modalities.
Disclosure of Interest None Declared.
P271
Development and initial validation of the parent and child versions of the JADAS
Giedre Januskeviciute1, Pieter van Dijkhuizen2, Valentina Muratore2, Gabriella Giancane2, Benedetta Schiappapietra2, Alberto Martini2, Angelo Ravelli2, Alessandro Consolaro2
1
Klaipeda Children's Hospital, Klaipeda, Lithuania,2Istituto Giannina Gaslini, Genoa, Italy
Presenting author:Giedre Januskeviciute Pediatric Rheumatology2017,15(Suppl 1):P271
Introduction: Increasing attention is being paid to parent-/child-re- ported outcomes in juvenile idiopathic arthritis (JIA). Incorporation of these measures in patient assessment is deemed important as they reflect the parent's and children’s perception of the disease course and effectiveness of therapeutic interventions.
Objectives:To develop and to validate a composite parent-centered
and child-centered versions of the JADAS, named parJADAS and chi- JADAS, respectively.
Methods:The parJADAS and chiJADAS include 4 measures: 1) parent/
child assessment of disease activity; 2) assessment of pain intensity; 3) self/proxy assessment of joint disease; 4) assessment of morning stiff- ness (MS). Disease activity and pain are assessed on a 21-numbered cir- cle VAS (0 = best and 10 = worst). The active joint count is based on the count of any swollen or painful joint, irrespective of its type, up to a maximum of 10 joints. MS duration is assessed on a Likert scale, ran- ging from no MS (0 points) to > 2 hours of MS (10 points).
Validation was conducted on a dataset of 602 children with JIA who underwent 1749 visits at study unit. To account for repeated mea- surements in a single patient, construct validity was assessed by cal- culating between-subject and within-subject correlations of parJADAS and chiJADAS with JADAS10, cJADAS10, physician global assessment of disease activity, the number of active joints, parent/ child rating of overall well-being and erythrocyte sedimentation rate (ESR). Discriminant ability was evaluated by comparing parJADAS and chiJADAS levels between patients with active or inactive disease Table 22 (abstract P270).Comparison of disease activity and damage between the“methotrexate”and“biologic”eras
“Methotrexate”era£ (n = 310) N. (%) “Biologic”era (n =152) N. (%) Patients with no active joints 92 (29.8) 96 (63.2) Patients with no restricted joints 126 (40.8) 101 (66.5) Patients with physician global assessment = 0 89 (29.6) 94 (61.8) Patients with inactive disease on JADAS10 64 (20.6) 40 (26.3) Patients with inactive disease on cJADAS10 73 (23.5) 62 (40.8) Functional ability score = 0 155 (51.3)$
83 (54.6)§ Patients with JADI-articular = 0 204 (65.8) 124 (81.6) Patients with JADI-extraarticular = 0 229 (73.9) 128 (84.2)
£
Data from Solari et al A&R 2008;59:1571-9;$
assessed with CHAQ;§
assessed with JAFS; JADAS-10: Juvenile Arthritis Disease Activity Score-10;JADIJuvenile Arthritis Damage Index
according to current criteria, and between patients who were satis- fied or not satisfied with disease outcome. Sensitivity to change was tested using standardized response mean (SRM) in 2 subsequent visits performed no more than 6 months apart. Internal consistency was assessed by means of Cronbach‘s alpha coefficient and inter-rater reli- ability was assessed using the intraclass correlation coefficient (ICC). Results: Between-subject correlations of parJADAS and chiJADAS were high (>0.70) with JADAS10, cJADAS10, parent/child rating of overall well- being, and moderate (0.40-0.70) with the other measurements. Moreover, in the same subject, changes over time of the parJADAS and chiJADAS corresponded to changes in disease activity, as indicated by high within- subject correlations with JADAS10, cJADAS10, physician global assess- ment of disease activity, parent/child rating of overall well-being, and ac- tive joint count. Both parJADAS and chiJADAS discriminated well between inactive and active disease and between satisfied and not satis- fied patients (p < 0.001). The responsiveness to clinical change of parJA- DAS was good (SRM = 0.84). The internal consistency was satisfactory, with Cronbach‘s alpha >0.80 for both parJADAS and chiJADAS. The inter- rater reliability between the parJADAS and the chiJADAS measured at the same visit was high, with ICC 0.92 (95% CI 0.90-0.93).
Conclusion:The parJADAS and chiJADAS were found to be valid and
reliable for assessment of disease activity in JIA and may, therefore, be suitable for use in clinical practice, observational studies, and therapeutic trials. Both scores may potentially surrogate physician as- sessments when these are not available.
Disclosure of Interest None Declared.
P272
Adult outcomes in a large cohort of childhood-onset SLE patients: fertility and pregnancies–the CHILL-NL study
N. Groot1, W. van Dijk1, I. E. M. Bultink1, M. Bijl1, R. J. E. M. Dolhain1, Y. K. O. Teng1, E. Zirkzee1, K. de Leeuw1, R. Fritsch-Stork1, S. S. M. Kamphuis1 1Sophia Children's Hospital - Erasmus University Medical Centre, Rotterdam, Netherlands
Presenting author:N. Groot
Pediatric Rheumatology2017,15(Suppl 1):P272
Introduction:Systemic lupus erythematosus (SLE) is a rare, lifelong autoimmune disease. Childhood-onset SLE (cSLE) often has its onset during puberty, and is thought to be more severe than SLE. Informa- tion regarding long term outcomes like fertility and pregnancies is scarce for this population.
Objectives:To investigate effects of cSLE on family planning, fertility and pregnancies in a large cohort of 101 female adults with cSLE. Methods:Adults with cSLE and SLE were seen for a single study visit. In- formation regarding family planning, fertility and pregnancies were assessed by structured questionnaires and checked with medical records. Results:We studied a cohort of 101 female cSLE patients with median age at study visit of 33 years and median disease duration of 20 years. 26% of patients felt that effects of cSLE limited them in their sexuality. Two third of the patients found the disease to be a restrictive factor in wanting children. They feared complications during pregnancy (51%) and during labour (30%), and problems with raising children (34%). 29% of patients feared their children would be diagnosed with SLE. A total of 85 pregnancies were reported in 36 cSLE patients (median 2 preg- nancies per female), of whom 22% had a history of cyclophosphamide use. Remarkably, time to pregnancy was not delayed, as it was 12 months or less in all but three patients. The 85 pregnancies resulted in 63 live births (76%), 13 miscarriages (15%), and 5 induced abortions (6%). The miscarriage rate in this group was comparable to that of healthy Dutch women.
An impressive 37% of the 67 pregnancies with a duration of at least 20 weeks had a complicated course. Four pregnancies (6%) resulted in stillbirth, where only 0,9% of pregnancies have this outcome in healthy Dutch women. Other complications were pregnancy induced hyperten- sion, pre-eclampsia/HELLP, preterm birth (median gestational age of 31 weeks) and placental abruption. The frequency of pregnancy compli- cations was higher in cSLE than in SLE and the Dutch female population. Conclusion:Family planning is affected in a substantial percentage of females with cSLE. Multiple issues complicated their wish to have
children. In this cohort, fertility did not seem to be impaired as no delay was found in the time to pregnancy. In contrast, the frequency of pregnancy complications including stillbirth was remarkably high in cSLE patients.
Disclosure of Interest None Declared.
P273
Adult outcomes in a large cohort of childhood-onset SLE patients:
education and work participation–the CHILL-NL study
Noortje Groot, A. Kardolus, I. E. M. Bultink, M. Bijl, R. J. E. M. Dolhain, Y. K. O. Teng, E. Zirkzee, K. de Leeuw, R. Fritsch-Stork, S. S. M. Kamphuis Sophia Children's Hospital - Erasmus University Medical Centre, Rotterdam, Netherlands
Presenting author:Noortje Groot Pediatric Rheumatology2017,15(Suppl 1):P273
Introduction: Systemic lupus erythematosus (SLE) is a rare auto-
immune disease which can affect any organ system. Childhood-onset SLE (cSLE) is thought to be more severe than SLE, with more major Table 23 (abstract P272).Patient characteristics and pregnancy characteristics cSLE: n = 101 SLE n = 37 p* Ethnicity White 71% 68% Non White (%) 29% 32%
Age at study visit (median (range)) 33 (18–65)*
38 (25–76)*
0.003 Age at diagnosis in yrs (median (range)) 14 (5–17)* 26 (18–63)* 0.000 Disease duration in yrs (median (range)) 20 (1–55) 12 (1–34) 0.000 Current SLEDAI-2 K score (median (range)) 4 (0–14) 5 (0–10) SDI-score (median (range)) 1 (0–8) 1 (0–7) Patients with SLICC-DI≥1 60% (61/40) 57% (21/37) cSLE restrictive in pregnancy wish 66% (63/96) 69% (25/36) Patients ever pregnant (after diagnosis of SLE) 36% (36/
101)
41% (9/22) With history of cyclophosphamide use 22% (8/36) 22% (2/9) Time to first pregnancy, months
(median(range))
2 (0–84) 1 (0–12) n.s. Age at first pregnancy, yrs(median(range)) 27 (18–36) 30 (22–32) n.s.
Total number of pregnancies 85 19
Miscarriages (<20 weeks) 15% (13/85) 21% (4/19)
Induced Abortion 6% (5/85) 0
Any pregnancy complications > 20 weeks 37% (25/67) 27% (4/15) n.s.
Stillbirth 16% (4/25) 0
Pregnancy induced hypertension 12% (3/25) 0
Pre-eclampsia/HELLP 24% (6/25) 0
Preterm birth(AD < 37 weeks) 20% (5/25) 25% (1/4) Median gestational age(range) 31 wk,28-35 32 wk
Placental abruption 8% (2/25) 25% (1/4)
Other 20% (5/25) 50% (2/4)
if no p-values are given, differences between cSLE and SLE were not statistically significant
organ involvement and higher disease activity. Little is known about the effects of cSLE on education and work.
Objectives:To investigate effects of cSLE on education, career and work participation in a large cohort (n = 106) of adults with cSLE. Methods:Patients were seen by the CHILL-NL (CHILdhood Lupus in the NetherLands) study team for a study visit containing a structured history and physical examination. Education and work status were assessed by val- idated questionnaires. A control group of 38 SLE patients was included. Results:106 cSLE patients (median disease duration 20 yrs) filled in an extensive questionnaire regarding education and work participa- tion. 61% of patients had an SDI of 1 or higher.
Education was affected in 86% of cSLE patients; choice of secondary education was affected for 60%. 58% reported their subsequent choice of career to be affected. When comparing this to the SLE pa- tients, education and career choice were much more affected in cSLE, most logically relating to the early onset of cSLE.
Twenty-seven cSLE patients were students and excluded from analyses regarding work. Despite adjusting their career choice to their disease, 21 of the remaining 79 cSLE patients (27%) had quit their job and 13 (16%) had to reduce their working hours, due to effects of cSLE. Many cSLE pa- tients were unemployed (41%), comparable to the unemployment rate of the SLE patients (45%) but very high compared to the 9% unemployment rate of the Dutch female population. Interestingly, more cSLE patients than SLE patients were work disabled (p = .028), with more partial work disability in the cSLE group (19% cSLE versus 5% SLE). Work disabled cSLE patients were more likely to have damage (SDI≥1, p = .018).
Conclusion:CSLE had great impact on education and career. Despite
an opportunity to adapt education and career choice to the limitations of their disease, work disability for SLE patients was higher than for SLE patients, and more common for cSLE patients with damage. Better con- trol of disease including prevention of disease damage as well as edu- cating patients about their possibilities to find a compatible career are of important to facilitate participation in our community.
Disclosure of Interest None Declared.
P274
Cross-sectional study in mexican-mestizo patients with juvenile idiopathic arthritis (JIA) from two tertiary referal centers in mexico city. Reality of socio-economical and cultural factors contributing to discapacity
Raul Gutiérrez Suárez
Pediatric Rheumatology, Shriner Hospital For Children Mexico City, Mexico, Mexico
Pediatric Rheumatology2017,15(Suppl 1):P274
Introduction:Little is known about socio-economical and cultural
factors contributing to discapacity in Mexican-Mestizo JIA pa- tients. Some studies have found statistically significant higher proportion of poor functional status, low health-related quality of life and discapacity in comparison with children from other coun- tries. Furthermore, in Mexico a period of≥4 years is the mean time to establish an adequate diagnosis; 3 out of 10 children have developed a serious or irreversible disability at diagnosis and 1 out of 3 children have stopped their treatment because their high cost.
Objectives: To assess discapacity related to socio-economical and
cultural factors in Mexican-Mestizo JIA patients from two tertiary referal centers in Mexico City.
Methods:A cross-sectional analytical study was designed in two ter- tiary referal centers in Mexico City. Incident and Prevalent JIA Mexican-Mestizo patients according to ILAR criteria were included.