Objectives To investigate the courses and outcomes of pregnancies involving JIA patients who were exposed to DMARDs. Methods In the Juvenile arthritis MTX/Biologics long-term Observation study, pregnant patients or male patients with pregnant partners were identified. Standardized patient interviews were conducted, and the course and outcome of pregnancy were assessed. Prospectively collected physician- and patient-reported data were also considered in the analysis. Results The study sample included 152 pregnancies in 98 women with JIA and 39 pregnancies involving 21 male patients as partners. The majority of patients had polyarticular-onset/-course JIA (61%). The average age of patients at first pregnancy was 24.1 (4.5) years, and their mean disease duration was 13.8 (5.9) years. Patients had been exposed to DMARDs for 9.5 (5.6) years, and 90% of these patients had received biologics before. Half of the pregnancies occurred during DMARD exposure, mostly with etanercept. Significant differences in pregnancy outcomes between DMARD-exposed and -unexposed pregnancies were not observed. Spontaneous abortion (13.1%) and congenital anomaly (3.6%) rates were not suggestive of increased risk compared with expected background rates. However, the rates of premature birth (12.3%) and caesarean section (37.7%) were slightly above those in the German birthing population. The disease activity of female patients remained relatively stable in pregnancy, with mean cJADAS-10 scores of 5.3, 7.1 and 5.6 in each trimester, respectively. Conclusion Young adults with JIA often become pregnant or become fathers of children while still being treated with DMARDs. Data suggest no increased risk of major adverse pregnancy outcomes.

Pregnancy outcomes in DMARD-exposed patients with juvenile idiopathic arthritis-results from a JIA biologic registry.

OBJECTIVE

Antibodies to cyclic citrullinated peptides (anti-CCP) in rheumatoid arthritis (RA) can express the inherently autoreactive gene VH4–34, detected using the rat monoclonal antibody 9G4. Patients with the polyarticular subtype of juvenile idiopathic arthritis (JIA) share some but not all of the features of adult patients with RA. This study was undertaken to compare serologic findings for rheumatoid factor (RF), anti-CCP, and 9G4-expressing anti-CCP in a large JIA cohort with a cohort of adult RA patients.

METHODS:


Serum from 88 patients with polyarticular JIA, 29 patients with enthesitis-related arthritis, 38 patients with extended oligoarthritis, 31 adolescent controls, 35 patients with RA, and 30 adult controls were tested for RF, for IgG, IgA, and IgM anti-CCP, and for 9G4-expressing anti-CCP by enzyme-linked immunosorbent assay. Total serum 9G4-positive IgM was also measured.
RESULTS:

Of 65 patients with RF-negative polyarticular JIA, 4 (6.2%) were IgG anti-CCP positive. Sera from 20 of 23 patients with RF-positive polyarticular JIA (87.0%), 24 of 35 patients with RA (68.6%), and 1 patient with extended oligoarthritis contained IgG anti-CCP. IgA and IgM anti-CCP levels were lower in the adolescent group (P < 0.01). Levels of 9G4-expressing anti-CCP were higher in patients with RF-positive polyarticular JIA than in those with RF-negative polyarticular JIA (P < 0.0001). Median levels of 9G4-expressing anti-CCP in patients with RF-positive polyarticular JIA and those with RA did not differ. Expression of 9G4 on serum total IgM was greater in patients with RF-positive polyarticular JIA than other adolescent groups (P < 0.01), but similar to adult RF-positive RA.
CONCLUSION:
In healthy individuals, 9G4-positive B cells comprise 5–10% of the peripheral blood pool but serum immunoglobulins utilizing VH4–34 are disproportionately low. The idiotope recognized by 9G4 was detected on anti-CCP antibodies in >80% of patients with RF-positive polyarticular JIA. VH4–34 usage by anti-CCP in both JIA and RA patients suggest elicitation of these autoantibodies through shared pathogenic B cell selection processes.

/pdf/antibodies-to-cyclic-citrullinated-peptides-in-patients-with-1fh3jle1pb.pdf

Antibodies to Cyclic Citrullinated Peptides in Patients With Juvenile Idiopathic Arthritis and Patients With Rheumatoid Arthritis: Shared Expression of the Inherently Autoreactive 9G4 Idiotype

The vast amount of research published on clinical areas can make awareness of current data difficult. Systematic literature reviews (SLR) are performed in order to identify, appraise and summarise the available evidence relating to specific clinical questions, and form the basis of the process used to produce clinical guidelines. This thesis describes the different processes used to produce guidelines using SLR. It includes a review of the literature on imaging in the management of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) as examples. To perform the RA review, key clinical questions were generated on the role of imaging in RA, which included the use of conventional radiography (CR),ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT),dual-emission X-ray absorptiometry (DXA), digital X-ray radiogrammetry (DXR), scintigraphy and positron emission tomography (PET). A comprehensive SLR was then performed resulting in recommendations on the role of imaging in making a diagnosis of RA, detecting inflammation and damage, predicting outcome and response to treatment, monitoring disease activity, progression and remission. A similar process was used to produce recommendations in the management of JIA;however the lack of quality data meant that ‘points to consider’ were created. The thesis also considers the quality of existing recommendations with potential areas for improvement discussed. It concludes with a discussion of the overall benefit of guidelines.

Using systematic literature reviews to develop guidelines for the management of inflammatory arthritis

Pathogenesis of juvenile idiopathic arthritis (JIA) is linked to the IL-23/IL-17 axis. This is of particular interest as new biological drugs targeting this pathway have been developed and may prove a useful treatment. Increased IL-17+CD4+ T cells have been reported in the joints of patients with JIA, but less is known about IL-17 production from other cell types. Innate lymphoid cells (ILC) bridge innate and adaptive immune systems and are sub-divided into 3 types (1,2 and 3), which mirror CD4+T- cell subsets. This thesis aimed to investigate T cell and ILC contribution to the disease phenotype in the joints of patients with JIA. Using a combination of flow cytometry techniques along with multiplex cytokine analysis, qPCR and culture assays this study has assessed the immune phenotype of patients with JIA. Significant enrichments of IL-17A+ CD4+, CD8 and γδ T cells were observed in the synovial fluid of patients compared to blood, which correlated with disease severity. In parallel, a significant difference was seen between relative proportions and functionality of ILC subpopulations in the synovial fluid of patients compared to blood. IL17+ILC3 and IL-22+ILC3 were significantly enriched at the inflamed site. These two ILC3 populations were negatively correlated suggesting interplay between the two groups. Additionally, IL-17+ILC3 were associated with more severe disease. Further exploration of immune cells found a significant enrichment of myeloid DC (mDC), which strongly correlated with IL-22+ILC3 at the inflamed site. It was shown that synovial mDC produce retinoic acid which may contribute to skewing of ILC populations. These data suggest a strong IL-17A signature in JIA patients, which extends beyond the T cell compartment. Therefore, therapies targeting the IL-17/IL-23 axis could also attenuate ILC populations within the inflamed joint. Finally, these data suggest that IL22+ILC3 populations are induced by mDC and may be protective in disease.

Defining the T cell and innate lymphoid cell signature in childhood arthritis

Objectives To redefine criteria for high disease activity (HDA) in JIA, to establish HDA cut-off values for the 10-joint Juvenile Arthritis Disease Activity Score (JADAS10) and clinical JADAS10 (cJADAS10) and to describe the distribution of patients' disease activity levels based on the JADAS cut-off values in the literature. Methods Data on 305 treatment-naive JIA patients were collected from nine paediatric units treating JIA. The median parameters of the JADAS were proposed to be the clinical criteria for HDA. The cut-off values were assessed by using two receiver operating characteristics curve-based methods. The patients were divided into disease activity levels based on currently used JADAS cut-off values. Results We proposed new criteria for HDA. At least three of the following criteria must be satisfied in both disease courses: in oligoarthritis, two or more active joints, ESR above normal, physician global assessment (PGA) of disease activity ≥2 and parent/patient global assessment (PtGA) of well-being ≥2; in polyarthritis, six or more active joints, ESR above normal, PGA of overall disease activity ≥4 and PtGA of well-being ≥2. The HDA cut-off values for JADAS10 (cJADAS) were ≥6.7 (6.7) for oligoarticular and ≥15.3 (14.1) for polyarticular disease. The distribution of the disease activity levels based on the JADAS cut-off values in the literature varied markedly based on which cut-offs were used. Conclusion New clinically derived criteria for HDA in JIA and both JADAS and cJADAS cut-off values for HDA were proposed.

/pdf/defining-new-clinically-derived-criteria-for-high-disease-23f04p6mup.pdf

Defining new clinically derived criteria for high disease activity in non-systemic juvenile idiopathic arthritis: a Finnish multicentre study.

A considerable proportion of children with polyarticular juvenile idiopathic arthritis (polyJIA) experience active disease into adulthood.1 However, there is no validated disease activity measure for adults with polyJIA, and they are often assessed using the disease activity score 28 (DAS28). DAS28 is validated in adults with rheumatoid arthritis (RA), and determines qualification for biological drugs in the UK and other countries.2 ,3 In contrast to the juvenile arthritis disease activity score (JADAS),4 DAS28 does not fully evaluate the pattern of joint involvement often observed in polyJIA. In this study, we compared DAS28 with JADAS-10 in adolescents and adults with polyJIA.

Tender and swollen joint counts out of 28, active joint count of all joints up to a maximum of 10, patient/parent and physician global assessment visual analogue scales were collected from clinics in patients aged ≥10 years with polyJIA (International League of Associations for Rheumatology classification criteria for rheumatoid factor-negative (RhF-ve) or rheumatoid factor-positive (RhF+ve) polyJIA). Erythrocyte sedimentation rate (ESR) values were taken within 30 days before or after assessment. When unavailable, values were taken within 3 months before or after, provided the patient remained stable between the ESR test and assessment. When unavailable within these time periods, patients were excluded from …

https://ard.bmj.com/content/annrheumdis/75/3/635.full.pdf

Juvenile arthritis disease activity score is a better reflector of active disease than the disease activity score 28 in adults with polyarticular juvenile idiopathic arthritis

The rheumatological history

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Juvenile arthritis disease activity score is a better reflector of active disease than the disease activity score 28 in adults with polyarticular juvenile idiopathic arthritis

The rheumatological history