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IntroductionPost-traumatic stress disorder (PTSD) is a disabling psychiatric condition that affects a significant minority of young people exposed to traumatic events. Effective face-to-face psychological treatments for PTSD exist. However, most young people with PTSD do not receive evidence-based treatment. Remotely delivered digital interventions have potential to significantly improve treatment accessibility. Digital interventions have been successfully employed for young people with depression and anxiety, and for adults with PTSD. However, digital interventions to treat PTSD in young people have not been evaluated. The Online PTSD Treatment for Young People & Carers (OPTYC) trial will evaluate the feasibility, acceptability and initial indications of clinical efficacy of a novel internet-delivered Cognitive Therapy for treatment of PTSD in young people (iCT-PTSD-YP).Methods and analysisThis protocol describes a two-arm, parallel-groups, single-blind (outcome assessor), early-stage randomised controlled trial, comparing iCT-PTSD-YP with a waiting list (WL) comparator. N=34 adolescents (12–17 years old), whose primary problem is PTSD after exposure to a single traumatic event, will be recruited from 14 NHS Child and Adolescent Mental Health Services in London and southeast England, from secondary schools and primary care in the same region, or via self-referral from anywhere in the UK using the study website. Individual patient-level randomisation will allocate participants in a 1:1 ratio, randomised using minimisation according to sex and baseline symptom severity. The primary study outcomes are data on feasibility and acceptability, including recruitment, adherence, retention and adverse events (AEs). The primary clinical outcome is PTSD diagnosis 16 weeks post-randomisation. Secondary clinical outcomes include continuous measures of PTSD, anxiety and depression symptoms. Regression analyses will provide preliminary estimates of the effect of iCT-PTSD-YP on PTSD diagnosis, symptoms of PTSD, anxiety and depression relative to WL. Process-outcome evaluation will consider which mechanisms mediate recovery. Qualitative interviews with young people, families and therapists will evaluate acceptability.Ethics and disseminationThe study was approved by a UK Health Research Authority Research Ethics Committee (19/LO/1354). For participants aged under 16, informed consent will be provided by carers and the young person will be asked for their assent; participants aged 16 years or older can provide informed consent without their parent or caregiver’s involvement. Findings will be disseminated broadly to participants, healthcare professionals, the public and other relevant groups. Study findings will be published in peer-reviewed journals.Trial registration numberISRCTN16876240.

Aim: TNF inhibitor drugs are a treatment option for rheumatoid arthritis, but response is not universal. Response is typically measured using the composite 4-component (4C) disease activity score 28 (DAS28) which contains more subjective measures. This study used a validated 2-component (2C) DAS28 score to determine whether SNPs associated with response were replicated in the UK population. Materials & methods: A literature review identified TNF inhibitor response SNPs. Linear regression was conducted to replicate associations with 4C or 2C-DAS28 response. Results: Eighteen independent SNPs were analyzed in 1828 patients. One and four associations with 4C and 2C-DAS28 response respectively were identified (p ≤ 0.05). Conclusion: Further genetic associations were replicated using the 2C-DAS28 which may reflect the objective nature of 2C-AS28.

Objectives: To determine whether using a re‐weighted disease activity score that better reflects joint synovitis, the 2‐component DAS28 (2C‐DAS28), based on 28‐swollen joint count and C‐reactive protein, produces more clinically relevant treatment outcome trajectories compared with the standard 4 component DAS28 (4C‐DAS28). Methods: Latent class mixed modelling (LCMM) of response to biologic treatment was applied to 2,991 patients with RA about to commence bDMARD treatment from the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate (BRAGGSS) cohort using both 4C‐DAS28 and 2C‐DAS28 as outcomes. Identified patient groups with similar trajectories were compared in terms of pre‐treatment baseline characteristics – including disability, comorbidities ‐ and follow‐up characteristics – including anti‐drug antibody (ADAb) events, adherence to treatments and blood drug levels, We compared the trajectories obtained using the 4C and 2C scores to determine which characteristics were better captured by the 2CDAS28 compared with the 4C‐DAS28 trajectories. Results: Using the 4C‐DAS28 we identified 3 trajectory groups, which is consistent with previous reports. We show that the 4C‐DAS28 captures information relating to depression. Using the 2C‐DAS28, 7 trajectory groups were identified; among them, distinct groups of non‐responders had a higher incidence of respiratory comorbidities and a higher proportion of ADAb events. We also identified a group of participants for which the 2C‐DAS28 disease activity score remained relatively low and which was enriched for patients who were non‐adherent to treatment. This highlights the utility of both the 4C and 2C‐DAS28 for monitoring different components of disease activity. Conclusions: Here we show that the 2C‐DAS28 modified disease activity score defines important biological and clinical phenotypes associated with treatment outcome in RA and characterizes important underlying response mechanisms to biologic drugs.

Objectives: Identifying blood-based biomarkers that predict treatment response in RA is a clinical priority. We investigated differential DNA methylation as a candidate biomarker of response for the first-line drug used in RA, MTX. Methods: DNA methylation was measured in DNA samples from individuals recruited to the Rheumatoid Arthritis Medication Study. Differentially methylated positions were compared between whole blood samples collected at baseline and at 4 weeks from patients who, by 6 months, had a good (n = 34) or poor response (n = 34) to MTX using linear modelling, adjusting for gender, age, cell composition, baseline 28-joint disease activity score (DAS28) and smoking status. Analyses also compared methylation with changes in DAS28 and changes in swollen joint count and tender joint count, and changes in CRP over the initial 6 months after MTX commencement. Differentially methylated positions showing significant differences with any response parameter were tested using pyrosequencing in an independent group of 100 patients from the Rheumatoid Arthritis Medication Study. Results: In the discovery group, two CpG sites showed methylation changes at 4 weeks associated with clinical EULAR response by 6 months. Significant changes in methylation for three differentially methylated positions associated with change in tender joint counts, three with change in swollen joint count and a further four with change in CRP. Of the 12 CpGs, four showed replicated association in an independent dataset of samples from the Rheumatoid Arthritis Medication Study. Conclusion: These data represent an advance on current practice by contributing to a personalized medicine strategy allowing an escalation or change in therapy as early as 4 weeks.