Objectives. To study the association between disease severity at first presentation to paediatric rheumatology (PRh) and length of time since symptom onset in children recruited to the Childhood Arthritis Prospective Study.Methods. Children ≤16 yrs with inflammatory arthritis persisting ≥2 weeks were recruited from five UK hospitals. Data including demographics, disease features, Childhood Health Assessment Questionnaire (CHAQ), physician and parent global assessment and blood tests were collected at the first appointment with PRh (baseline). The association between symptom duration (defined as time from first reported symptom onset to presentation at PRh) and baseline disease characteristics was evaluated using non-parametric descriptive statistics and multivariable logistic regression analyses.Results. Five hundred and seven children (65% female) were included: median age at onset was 6.8 yrs. Two hundred and thirty-three had oligoarthritis, 68 had RF-negative polyarthritis, 27 had systemic onset arthritis and 29 had arthritis that was not JIA. The median symptom duration was 4.6 months. Median symptom duration was shortest for children presenting with systemic arthritis (1.6 months) and longest for those with PsA (8.6 months). Children with a longer duration of symptoms were older and had higher median active joint counts but lower median ESR. Symptom duration did not correlate with CHAQ score at presentation.Conclusions. Children who have systemic arthritis had the shortest delay to PRh presumably because they are profoundly unwell. Children with joint pain/stiffness but normal ESR had longer delays suggesting that if blood tests do not indicate inflammation, the diagnosis of JIA may be overlooked.

Objective: To describe the occurrence of baseline comorbidity in subjects with active rheumatoid arthritis starting treatment with biological agents. Such data are necessary to interpret the reported occurrence of adverse events following treatment. Methods: Baseline comorbidity was recorded in a large national cohort of patients with rheumatoid arthritis newly starting biological agents. The distribution of the number and types of comorbidities is presented. Results: In all, 7818 patients treated with biological agents (infliximab 3332, etanercept 3302, adalimumab 1059, anakinra 132) were included in the analysis. Comorbidity was common, with 58% of patients having at least one comorbid condition and 25% having more than one. The most frequent comorbid conditions were hypertension, depression, peptic ulcer disease, and respiratory disease. Conclusions: In routine use, patients treated with biological agents have high levels of baseline comorbidity, which should influence the interpretation of reported adverse events.

Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.

In this real-world cohort of patients with systemic JIA receiving tocilizumab or anakinra, approximately half achieved a minimal disease state by one year. Treatment responses appeared similar between the two therapies albeit with better persistence observed with tocilizumab.

ObjectivesRituximab (RTX) may be a treatment option for children and young people with JIA, although it is not licensed for this indication. The aim of this study was to describe RTX use and outcomes among children with JIA.MethodsThis analysis included all JIA patients within the UK Biologics for Children with Rheumatic Diseases study starting RTX. Disease activity was assessed at RTX start and at follow-up. The total number of courses each patient received was assessed. Serious infections and infusion reactions occurring following RTX were reported.ResultsForty-one JIA patients starting RTX were included, the majority with polyarthritis: polyarthritis RF negative [n = 14 (35%)], polyarthritis RF positive [n = 13 (33%)] and extended oligoarthritis [n = 9 (23%)]. Most were female (80%) with a median age of 15 years [interquartile range (IQR) 12–16] and a median disease duration of 9 years (IQR 5–11). The median improvement in the clinical Juvenile Arthritis Disease Activity Score (cJADAS; three-variable 71-joint JADAS) from RTX start was 9 units (n = 7; IQR −14–2). More than half reported more than one course of RTX. The median time between each course was 219 days (IQR 198–315). During follow-up, 17 (41%) patients reported switching to another biologic, including tocilizumab (n = 8), abatacept (n = 6) and TNF inhibitor (n = 3). Three patients (7%) reported a serious infection on RTX (rate of first serious infection 6.2/100 person-years). Four patients (10%) reported an infusion reaction.ConclusionsThis real-world cohort of children with JIA, the majority with polyarticular or extended oligoarticular JIA, showed RTX may be an effective treatment option for children who do not respond to TNF inhibitor, with a low rate of serious infections on treatment.

BackgroundBiosimilars, biopharmaceuticals assessed by regulatory agencies to have efficacy and safety similar to their reference products, were introduced to the UK market in February 2015 for rheumatoid arthritis (RA). Most research on RA biosimilars has been done in the context of clinical trials, but real world data are lacking. No national mandate exists in the UK to switch all patients from originator to biosimilars, but there are regional variations.ObjectivesThis analysis aims to describe the characteristics of the first UK patients starting RA biosimilars registered with the British Society for Rheumatology Biologics Register for RA (BSRBR-RA).MethodsSince 03/08/2015, the BSRBR-RA has captured data on patients starting biosimilars available in the UK: infliximab (Inflectra and Remsima) and etanercept (Benepali). At biosimilar start, information is captured from the hospital including demographic and clinical data, previous biologic exposure and if switching therapies, the reason for switch (as a tick box and free text). Follow-up data, including disease activity, occurrence of adverse events and changes to treatment is captured 6-monthly for 3 years and annually thereafter. Descriptive data are presented.ResultsTo 15/12/2016, 417 RA patients were recruited to the BSRBR-RA at point of starting a biosimilar for whom data were available for analysis on 414 participants: 47 (11%) Inflectra, 78 (19%) Remsima and 289 (70%) Benepali. Of these, 138 started a biosimilar as first biologic, 242 switched directly from the originator product and 34 switched from an alternative biologic (Table). Patients switching from the originator did so after a median (IQR) of 6.7 (3.0–9.5) years and the majority had low disease activity (median DAS28 2.7 (IQR 2.0–3.9)). The switch reason was reported in 33% of patients, with cost listed as the main reason and “trust policy” included in 63% of 30 free text comments. Six-month follow-up data were available in 41 patients. Three patients on Remsima and 1 patient on Inflectra reported drug hypersensitivity reactions (rash, pruritus, hyperpigmentation), and 18% (6/34) of patients experienced a deterioration in their DAS28 of >1.2 after 6 months.ConclusionsThis preliminary study gives an early review of biosimilar use in the UK, showing that these drugs are used in patients with active disease as both first-line and subsequent-line biologics. Many patients with low disease activity are also being switched from originators primarily for cost reasons. Outcome data are limited but data capture will continue and updated reports from the BSRBR-RA will continue to be presented.Disclosure of InterestNone declared

Background:Tocilizumab is an IL-6 receptor humanised monoclonal antibody treatment option in rheumatoid arthritis (RA) who have not responded or are intolerant of disease modifying anti-rheumatic drugs (DMARDs) or other biologics. Tocilizumab was available initially as an intravenous (IV) preparation, dosed according to weight, and more recently as a subcutaneous (SC) preparation given at 162mg/weekly irrespective of bodyweight.Obesity is highly prevalent in RA and there has been concern that starting or switching patients to SC tocilizumab could reduce its effectiveness in those patients with a higher body weight when compared to IV tocilizumab.Objectives:To investigate the relationship between bodyweight and DAS28 response at 6 months in tocilizumab naïve RA patients starting IV or SC tocilizumab.Methods:The study population comprised RA subjects recruited to the BSRBR-RA up to 30/11/2018 commencing IV or SC tocilizumab for the first time. Patients had to be tocilizumab naïve and have at least one six monthly study follow-up recorded after starting tocilizumab. Baseline characteristics at point of starting tocilizumab are described. Linear regression, fully adjusted for relevant confounders, was used to investigate the relationship between change in DAS28 score from baseline to six months and body weight per ten kilograms (kg), and in a separate analysis, as BMI category. Multiple imputation was used to handle missing data.Results:1241 patients starting tocilizumab (902 IV, 339 SC) were eligible for analysis. The median age was 59 years, majority were female, and had median disease duration of 11 years at baseline. Over seventy percent had prior biologic exposure. Median weight was 77kg for IV and 76kg for SC starters, and the majority of patients were categorised as normal weight (30% IV, 37% SC) or pre-obesity (31% IV & SC) according to BMI. Median DAS28 score was 5.8 (IV) and 5.5 (SC) at start of treatment with median improvement after 6-months of 1.50 and 2.02 units respectively. The fully adjusted linear regression model showed no association between body weight or BMI and change in DAS28 score at six months for patients starting IV or SC tocilizumab. (Table).TableBaseline VariableIntravenous TCZ patients (n=902)Subcutaneous TCZ patients (n=339)Age, median (IQR)58 (50-67)60 (51-70)Gender, n (%) female708 (78)233 (74)Disease duration, median (IQR) years11 (4-21)11 (4-21)DAS28 score, median (IQR)5.8 (5.1-6.6)5.5 (4.7-6.5)Change in DAS28 score, median (IQR)-1.50 (-3.10 - -0.23)-2.02 (-3.72- -0.37)Weight in KGs, median (IQR)77 (64-91)76 (64-88)Change in DAS28, coefficient (95% CI)Body weight per 10kgs*0.04 (-0.01-0.09)-0.005 (-0.11-0.10)BMI category*Normal weightrefrefUnderweight-0.41 (-1.27-0.46)0.08 (-1.62-1.77)Pre-obesity-0.26 (-0.57-0.05)0.02 (-0.44-0.48)Obesity class I, II & III-0.03 (-0.35-0.29)0.08 (-0.40-0.55)*Fully adjusted for age, gender, disease duration, baseline DAS28 score, baseline HAQ score, co-morbidities, and number of previous biologicsConclusion:Data from this study show that body weight does not appear to affect initial response to IV or SC tocilizumab. This is reassuring given that patients are likely to be given SC tocilizumab due to ease of administration and reduced hospital costs.Disclosure of Interests:Rebecca Davies: None declared, Arani Vivekanantham: None declared, Mark Lunt: None declared, Kath Watson: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, James Bluett: None declared

BackgroundMethotrexate (MTX) is the first-line disease modifying anti-rheumatic drug for the treatment of rheumatoid arthritis (RA). However, many patients do not respond adequately or experience adverse effects1,2; therefore, identifying blood-based biomarkers that predict treatment response is a research priority. DNA methylation is an epigenetic marker that modifies but does not alter DNA sequence, and it is thought that MTX may act, at least in part, by inhibiting intracellular methyl donor transfer leading to DNA hypomethylation2.ObjectivesWe aimed to identify differential DNA methylation signatures in whole blood, which may act as biomarkers predictive of response to MTX in patients with RA.MethodsDNA methylation was measured using the HumanMethylation450 BeadChip in DNA samples from individuals recruited to the Rheumatoid Arthritis Medication Study (RAMS), a one year observational study in the UK including patients with RA starting MTX for the first time. In RAMS, demographic and clinical data are collected prior MTX start (baseline) and at 6 months after commencing MTX. DNA was extracted from whole blood samples collected baseline and at 4 weeks from patients who, at 6 months, had a EULAR good response (n=36) or EULAR poor response (n=36) to MTX. Differentially methylated positions (DMPs) between the baseline and 4 weeks, and between good and poor response were identified using linear regression, adjusting for gender, age, cell composition, baseline disease activity score (DAS28), and smoking status. Analyses also compared methylation with changes in DAS28 and the individual DAS28 components over 6 months. DMPs that showed significant differences in the test cohort were selected for replication by pyrosequencing in an independent group of 100 patients with both baseline and 4 week samples.ResultsBased on percentage change in methylation between pre-treatment and following 4 weeks of therapy, two DMPs were significantly associated with response status in samples taken at 4 weeks (p-value <10-5). Three additional DMPs were associated with change in tender joint count, whilst three other DMPs were associated with change in swollen joint count, and a further four DMPs associated with change in C-reactive protein. Of the four DMPs tested to date, hypermethylation at cg23700278 at baseline suggests replicated association with improvement in swollen joint count by 6 months. The nearest gene to the cg23700278 locus is adrenoceptor alpha 2C (ADRA2C), involved in neurotransmission.ConclusionsThese preliminary results suggest DNA methylation may provide a biomarker of MTX response but requires replication in other data sets.References Verstappen SMM et al. (2012) Int. J. Clin. Rheu. 7(5):559–567.Kim Y, et al. (1996) J. Lab.Clin.Med. 128:165–172. Disclosure of InterestNone declared