OBJECTIVES:Whilst biologic therapy is used for Behçet's syndrome of all subtypes refractory to first-line immunomodulation, there has been an absence of high-quality evidence and no predictive biomarkers to optimally inform choice. BIO-BEHÇET'S was a randomized, controlled, head-to-head clinical trial comparing the two most frequently used biologics in active refractory Behçet's. METHODS:This was a Bayesian-designed, pragmatic, standard of care, two-arm, parallel head-to-head trial at four UK centres. Patients with active disease were randomized to infliximab or IFN-α2a, and received follow-up with symptom-directed examination at weeks 12 and 24. The primary outcome was the Behçet's Disease Activity Index (BDAI) at 12 weeks. Secondary outcomes included BDAI at 24 weeks and significant improvement in individual organ systems, including ocular symptoms, oral and genital ulcers, arthritis pain, quality of life, disease activity and steroid use. Biomarkers were also investigated but are reported elsewhere. RESULTS:Seventy-nine patients were recruited. Both treatments were equally effective, with a mean difference of 0.13 in BDAI (80% confidence interval: -0.19, 0.46). No significant differences were observed for secondary outcomes, though there were clinically significant within-group reductions for each over time. A modest steroid-sparing effect was observed, with complete cessation of steroids in 20% and 44% of those randomized to infliximab and IFN-α2a, respectively. There was a trend for minor benefit in favour of infliximab in terms of tolerability and persistence. CONCLUSION:In this first reported, high-quality, head-to-head trial of two biologics in Behçet's, both infliximab and IFN-α2a showed comparable short-term clinical efficacy and safety in refractory active disease of all subtypes. TRIAL REGISTRATION:EudraCT: 2014-005390-36; ISRCTN: ISRCTN49793874.

Background and Objectives:Biologic therapy has been used for Behçet's Syndrome after first-line immunomodulation, but in the absence of high-quality evidence or predictive biomarkers. BIO-BEHÇET'S was a randomized controlled clinical trial to compare the two most widely used biologics for Behçet's Syndrome at that time, infliximab versus interferon-α2a, and identify potential biomarkers for response. Methods:A total of 79 patients with active Behçet's Syndrome were randomized to either infliximab (REMICADE) or interferon-α2a (ROFERON) according to the UK national treatment pathway, and follow-up with symptom-directed examination undertaken at Weeks 12 and 24. The head-to-head trial included an exploratory analysis on the potential role of single nucleotide polymorphisms (SNPs) and urinary metabolomic to act as biomarkers for drug response. Genotypic analysis was performed to determine whether four SNPs in IFNL3 and IFNL4 - selected based on known effects - impacted primary and secondary outcomes. For metabolomic analyses, urine samples were analyzed by nuclear magnetic resonance spectroscopy and principal component analysis. Results:Genetic data suggested potential association between outcomes and carriage of rs4803221 or rs7248668 variants in the IFNL3 (IL-28B) gene locus for interferon-α2a patients; however, with the relatively small sample, statistical significance was lost when corrected for multiple testing. Metabolomic analysis identified potential markers of metabolic response to infliximab. Conclusion:BIO-BEHÇET'S suggests there is potential for a novel metabolomic biomarker that can identify response to infliximab in patients with Behçet's Syndrome. Further work will characterize the appropriate metabolite (s) from existing samples to inform future prospective trials to study this in more detail clinically.

Background While biologic therapy, typically with infliximab or Roferon, was used for Behçet syndrome after first-line immunosuppressants, no high-quality randomised trials or predictive biomarkers were available. Objective To undertake a randomised controlled clinical trial of infliximab versus Roferon in Behçet syndrome and identify potential biomarkers for response. Design Pragmatic, standard of care, single-masked, randomised, two-arm, parallel head-to-head trial, with exploratory study on potential role of interferon lambda 3 and interferon lambda 4 single nucleotide polymorphisms and urinary metabolomics biomarkers. Setting Three national UK Behçet syndrome centres and allied clinics. Participants Patients with active Behçet syndrome, fulfilling International Study Group 1990 criteria, with inadequate response to or intolerance of first-line treatment. Intervention Randomisation to infliximab (5 mg/kg intravenous infusion) or Roferon (subcutaneous injection), utilising the UK Behçet syndrome drug pathway protocol. Outcomes Primary outcome: modified Behçet’s disease activity index at 12 weeks of therapy. Secondary outcomes: (1) modified Behçet’s disease activity index score at 24 weeks and (2) significant improvement at 12 and 24 weeks from baseline in vitreous haze and best corrected visual acuity change, oral ulcer severity score, number of genital ulcers, arthritis pain, adverse events, reduction in dose of glucocorticoid, quality-of-life scores and Physician’s Global Assessment of disease activity. Sample size Utilising a Bayesian analysis of covariance model (80% credible interval), initial sample size was 45/arm (Bayesian power 90%). With an anticipated 10% dropout rate, 100 patients were to be recruited. Following recommendations to reduce the overall length of the trial, this was revised down to 80 patients (36 in each arm, allowing for 10% dropout): 80% equi-tailed credibility interval, Bayesian power 88%. In total, 79 patients were eventually recruited for the study. Methods Patients with refractory active Behçet syndrome underwent stratified block randomisation, based on randomly permuted blocks with random block sizes of two and four, allocating treatment to either infliximab or Roferon. Follow up with symptom-directed examination at weeks 12 and 24 according to standard of care. Analysis of the primary end point was undertaken using a Bayesian analysis of covariance approach. Informative priors for the anticipated treatment effect were derived from a cohort of six international experts prior to the start of the study. Results In this first prospective head-to-head randomised controlled clinical trial of two biologic drugs in Behçet syndrome, both infliximab and Roferon were equally effective [mean difference (80% credibility interval) = 0.13 (–0.19 to 0.46)], with a trend for minor benefit in favour of infliximab in terms of tolerability and treatment persistence. Genetic data suggested a potential association between patient outcome and carriage of either rs4803221 or rs7248668 variants in the interferon lambda 3 (interleukin 28B) gene locus in the Roferon-treated arm. However, with the relatively small sample size, statistical significance of the association was lost when correcting for multiple tests. Metabolomic analysis identified potential markers of a metabolic response to treatment with infliximab. Limitations Single-masked design. Slow recruitment with fewer patients recruited in total, limiting the strength of analysis for secondary outcomes and mechanistic studies. Conclusion We report clinical efficacy in both infliximab and Roferon in refractory active Behçet syndrome, together with the potential for a novel metabolomic biomarker identifying response to infliximab. Future work Further work will characterise the appropriate metabolite(s) from existing samples to inform future prospective trials to study this in more detail clinically. The efficacy of Roferon in Behçet syndrome may support future manufacture of this drug. Trial registration This trial is registered as EudraCT Number: 2014-005390-36; ISRCTN49793874. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/205/46) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 17. See the NIHR Funding and Awards website for further award information. Plain language summary Behçet syndrome, a very rare disease in the UK, causes major illness. Yet without high-quality, randomised, controlled trials, choosing treatment is somewhat hit and miss. We set up a randomised controlled clinical trial to study the two most widely used biologic drugs in Behçet syndrome, infliximab and Roferon, head-to-head and searched for potential blood and urinary markers for response. Patients with active Behçet syndrome, in the United Kingdom national Behçet syndrome centres and allied clinics, who had not responded to or could not tolerate first-line treatment were randomised to either infliximab infusions or Roferon injections. The primary outcome was modified Behçet’s disease activity index at 12 weeks of therapy. Secondary outcomes included modified Behçet’s disease activity index at 24 weeks and significant improvements in individual organs, quality of life and Physician’s Global Assessments of activity at 12 and 24 weeks. Initial assessment suggested 100 patients were required for a statistically meaningful outcome but was revised down to 80 following recommendations to shorten the trial. In this first prospective head-to-head randomised controlled clinical trial of two biologics in Behçet syndrome, both drugs worked equally well. There was a non-significant trend for minor benefits of infliximab in terms of tolerability and treatment persistence. Genetic data suggested a potential association between patient outcome and carriage of either rs4803221 or rs7248668 variants in the interferon lambda 3 (interleukin 28B) gene locus in the Roferon arm, but statistical significance was lost with the relatively small sample size. Metabolomics analysis identified potential markers of a metabolic response to infliximab. The limitations of the study included the single-masked design: patients (but not clinicians) were aware of their treatment, and fewer patients were studied than planned. This limited the strength of analysis for secondary outcomes and mechanistic studies. We now plan to characterise the metabolite(s) from existing samples to design future trials to study if there can be effective targeting of treatment in Behçet syndrome. Scientific summary Background Behçet syndrome (BS), a multisystem inflammatory vasculitis, is infrequent in the UK, but it has the potential to cause significant morbidity and mortality. The evidence base supporting biologic treatment, which is used for active disease after failure of standard immunosuppression or when prognosis is poor, is largely based on uncontrolled studies. At the time of the trial, the UK National guideline for therapy of Behçet’s indicated that either the tumour necrosis factor alpha inhibitor infliximab or the interferon alpha drug Roferon could be employed as treatment for patients following failure of first-line treatment with standard immunomodulators. The Bio Behçet’s trial was conceived to exploit the opportunity of the three UK National Centres of Excellence for Behçet’s and associated satellite centres to undertake the first randomised clinical trial to compare infliximab and Roferon as treatment for BS, together with an exploratory analysis of potential genomic and metabolomic biomarkers of therapeutic response. Methods The Bio Behçet’s trial is a pragmatic, standard of care, single-masked, randomised, two-arm, parallel trial comparing the efficacies of infliximab and Roferon employed after failure of first-line therapy in BS. Patients with BS, diagnosed according to the International Study Group 1990 criteria, with active disease who had failed to respond to, or were intolerant of, first-line treatment of BS with topical steroids or small-molecule immunosuppressants were randomised to treatment with either infliximab (Remicade) 5 mg/kg intravenous infusions or Roferon subcutaneous injection (in variable dose), utilising the treatment protocol for each of these drugs in normal clinical care as detailed in the BS drugs pathway for England. The trial utilised a Bayesian design utilising priors informed by a small survey of international experts in BS. Utilising a Bayesian analysis of covariance model, with an 80% credible interval, a sample size of 45 patients per arm was deemed appropriate and gave a Bayesian power of 90%. Allowing for an anticipated 10% dropout rate, 100 patients were planned to be recruited but reduced to 80 following recommendations to reduce the overall length of the trial. Allowing for a 10% dropout rate, estimates of study power based on 72 evaluable patients (36 on each arm) and an 80% credible interval a Bayesian power of 88% was obtained. Between June 2016 and February 2020, 161 patients were screened, and 79 patients were randomised. The intention-to-treat analysis was restricted to 37 subjects allocated to infliximab and 37 to Roferon. Based on previous work with hepatitis C infection and response to interferon therapy and given the role of the innate immune system in the pathogenesis of BS, we examined interferon lambda 3 (IFNL3) and interferon lambda 4 (IFNL4) single nucleotide polymorphisms (SNPs) as biomarkers of response to treatment with alpha interferon and/or infliximab in BS. We also examined the potential for urine metabolomics to act as biomarkers for drug response. The primary outcome was a modified version of the Behçet’s disease activity index (mBDAI) after 3 months of therapy. Secondary outcomes comprised mBDAI score after 6 months of therapy and significant improvement in organ systems after 3 and 6 months (week 12 and week 24 visits) assessed by: reduction in vitreous haze using the SUN consensus group grading scale and best corrected visual acuity change [using the logarithm of the minimal angle of resolution (LogMAR) chart at 4 m] from baseline; change in oral ulcer severity score; change in number of genital ulcers; arthritis pain (10 cm Likert scale); adverse events (AEs) in each group; reduction in dose of prednisolone (or equivalent glucocorticoid) at 3 months (week 12 visit); reduction in dose of prednisolone (or equivalent glucocorticoid) at 6 months (week 24 visit); quality-of-life (QoL) scores at 3 and 6 months (week 12 and week 24 visits) and Physician’s Global Assessment of disease activity at 3 and 6 months (week 12 and week 24 visits). Results Baseline characteristics of the two treatment arms did not differ significantly by sex, ethnic profile, baseline disease characteristics and steroid use. For the primary outcome measure, change in mBDAI between baseline and 3 months (and as a secondary outcome between baseline and 6 months) did not differ significantly between the two treatments [mean difference (80% CrI) = 0.13 (–0.19 to 0.46)]. A significantly higher proportion of patients randomised to Roferon swapped away from their randomised treatment compared to those randomised to infliximab treatment (Roferon 11 of 37, infliximab 3 of 37; p = 0.0104). The clinician’s overall perception of disease activity indicated a reduction in disease activity for most patients between baseline and 3 months and between baseline and 6 months, with a median reduction of −2.0 (infliximab) and −1.0 (Roferon) at 3 months and −3.0 (infliximab) and −2.0 (alpha interferon) at 6 months. There was a small but significant difference in favour of infliximab compared to Roferon at both 3 and 6 months (p < 0.05). There were no significant differences between the two treatments at 3 or 6 months for secondary outcome measures, including oral ulcer activity score, genital ulcer activity score and Likert pain score, though, for each of these secondary outcome measures, there were important clinically significant within-group reductions over time at 3 and 6 months. There were no important differences between the two treatments for QoL measures. A modest steroid-sparing effect was observed for each treatment. In total, 46 patients reported 270 Aes. There were a greater number of AEs observed on Roferon (p < 0.001). Eight serious adverse events (SAEs) from five patients were reported across the study. One patient on the infliximab arm reported four SAEs [hypertension (×2), bacterial urinary tract infection and blood pressure inadequately controlled]. In total, three patients (six events) were reported on the infliximab arm, and two patients (two events) were reported on the Roferon arm. There were no suspected drug interactions and no suspected unexpected serious adverse reactions (SUSARS) reported in the study. The genetic data suggest the possibility of an association between response to treatment and carriage of either rs4803221 or rs7248668 variants in the IFNL3 (interleukin 28B) gene locus only for the alpha interferon-treated arm, in line with association between these two SNPs and Roferon treatment outcome in hepatitis C. These results must be treated with caution due to small numbers in responder subgroups. There were no baseline differences in metabolomic analysis between the patients before randomisation, indicating no major confounding factors that may have influenced response to a particular treatment. Comparison of 24-week urine samples from responders and non-responders to the same drug using principal component analysis revealed, for infliximab, one specific bin of metabolites that remained significantly different comparing responders to non-responders. This effect was weaker for Roferon, but further study will be required to identify individual metabolites and the associated metabolic pathways responsible for these results. Conclusion Using a Bayesian trial design, in this first randomised controlled study comparing infliximab with Roferon when used after primary treatment failure, both were found to be effective and largely equivalent, with minor benefits favouring infliximab in terms of efficacy and tolerability. Mechanistic studies utilising genomics and metabolomics to identify predictors of response to treatment revealed opportunities for further study based on our initial findings. The UK National Behçet’s Centres of Excellence and associated satellite centres can be an effective resource to support clinical trials in the management of BS. Trial registration This trial is registered as EudraCT Number: 2014-005390-36; ISRCTN49793874. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 12/205/46) and is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 17. See the NIHR Funding and Awards website for further award information.

Abstract Background/Aims Behçet’s Syndrome is considered rare in the UK. Prevalence estimates range from 0.64 to14.61 per 100 000 population. Here we explore validity of HES ICD-10 codes for BS using Birmingham Centre of excellence (BCoE) data as reference. Prevalence, incidence, clinical characteristics and mortality were compared for attendees at the three national Centres of Excellence (CoE) versus non attendees Methods We extracted all patients aged >18 who had a diagnosis for Behçet's Disease in HES between April 2011 and March 2019. A retrospective cross-sectional analysis of medical records (2012 to 2019) was undertaken at BCoE for MDT confirmed BS for validation. A multivariable logistic regression model examined mortality within 3 years following BS diagnosis. Kaplan Meier survival analysis was undertaken comparing CoE attenders versus non-attenders. Chi squared tests assessed significance of the relationship between CoE attendance, demography, symptom categories, infliximab use and mortality within 3 years. To determine the incidence and prevalence rates, we obtained ONS mid-year estimates of England’s adult population for each year from 2011 to 2019. Point prevalence of BS per 100,000 population was calculated per year of study while Incidence was calculated per 100,000 person years for each year of the study period Results 4452 cases of BS including 515 BCoE attendees were identified in HES between 2011 and 2019. 559 BS cases were confirmed between 2012 and 2020 in the BCoE database. BS prevalence and incidence increased from 2.2 to 3.8 and 0.7 to 0.9 per 100,000 respectively between 2011 and 2019. 65.5% of BS cases were female, 84.9% were Caucasian. BS prevalence peaked at ages 40-49 years. HES data only identified 1157/4452 patients attending one of the three national COEs. Male patients with BS were more likely to have ocular, vascular and cardiac characteristics of BS (p < 0.001). Caucasian ethnicity was associated with highest prevalence of genital ulceration, ocular, vascular and neurological BS. 3-year all-cause mortality was higher in the non-COE cohort (6.4%) versus COE attenders (2.6%) (p < 0.001). Overall BS associated mortality at 3 years follow-up was 0.83%, with higher rate noted in males (1.3%). In logistic regression analysis, mortality significantly associated with age >40 years, IMD and Comorbidity. Infliximab reduced risk of mortality (OR 0.51; p 0.037) Conclusion Our study strength includes use of unselected national HES data with potential coding for inpatient and outpatient episodes. Increasing prevalence of BS may be multifactorial (misclassification, improved recognition, migration effects, improved survival). Our study confirms differences in phenotype and mortality between those diagnosed with BS in the England versus endemic regions. Future work will examine primary care datasets (CPRD and linked HES) to evaluate the national prevalence, incidence, phenotype clusters and risk factors for BS and will ultimately facilitate the creation of a National BS Register Disclosure P. Chandratre: None. R. Situnayake: None. B. Coupland: None.

Background Behcet’s disease is a multi-system inflammatory disorder. A small subset of patients with Behcet’s develop relapsing polychondritis which is classified as a separate disease known as Mouth and Genital ulcers with inflamed cartilage (MAGIC syndrome). It has previously been observed that this condition can also affect the cartilaginous tissue in the tracheobronchial tree. Case presentation We present the case of a 44-year-old lady with Behcet’s Disease, Mouth and Genital ulcers with inflamed cartilage (MAGIC) syndrome and an aortic Frozen Elephant Trunk (FET) who presented to hospital with recurrent episodes of left lobar collapse of the lung. During bronchoscopy, we found the presence of multiple inflammatory endobronchial webs occluding segments of the left bronchial tree. Repeated examinations showed evidence that these inflammatory webs were progressing in size, density and location. Furthermore, we noticed herniation of her descending aortic FET into her left bronchial tree forming an aorto-bronchial fistula which was complicated by a graft infection. Her descending aortic FET section was surgically replaced with an open procedure and bronchoscopic interventions attempted to remove the occlusions in her bronchial tree. Despite optimisation of medical management and surgical correction, this patient continued to develop progressive occlusion of her left bronchial tree, resulting in a chronically collapsed left lung. Conclusions A multi-disciplinary team approach is of paramount importance in order to optimally manage patients with Behcet’s disease, balancing immunosuppressive regimens that need close monitoring and titration in the context of potential surgical intervention and the risk for intercurrent infection.

Abstract Background/Aims Behçet’s disease (BD) is a rare multisystem auto-inflammatory disorder. In England the incidence is estimated between 0.38 per 100,000 in the population, however, the actual incidence of BD in U.K. is unknown. The prevalence is estimated to be 14.61 (95% CI 13.35-15.88) per 100 000 population in 2017 but the read codes from the THIN network were not validated, thereby potentially causing an overestimate. The study aims to understand the epidemiology of BD in England using primary and secondary data Methods 1. Annual incidence rate per million person years will be calculated stratified by age, gender and ethnicity 2. Point prevalence will be calculated at the midpoint of the study stratified by age, gender and ethnicity 3. Establish phenotypes and their clusters 4. To identify treatments and outcomes of BD (multi-system morbidity and mortality) 5. The time to diagnosis 6. Equity of access to biologic treatment for BD 7. Identify risk factors for BD. Case ascertainment sources include primary care data from Clinical Practice Research Datalink and secondary care data from the CRPD linked Hospital Episode Statistics. In order to validate the diagnosis of BD in CRPD, data will be triangulated by scrutinising the HES within Sandwell & West Birmingham Hospitals NHS Trust. A list of ICD-10 codes for BD, its complications and treatments needing admission will be used to identify those with BD. The findings will be compared and contrasted to the data from the Birmingham Centre of Excellence using the same codes. The validity of the HES data will be ascertained by comparing proportions of diagnostic and treatment codes within the two data sets. Results We have conducted a pilot study of the clinical characteristics of those with BD treated at the Birmingham Centre of Excellence between July 2012 and July 2018. The average age of this group was 44 years (SD 11.5). 109 patients were male (36.8%) and 199 (67.2%) were Caucasian. Men presented at a younger age ( 41.9 years compared with 45.2 years for females) and were less likely to experience genital ulceration and musculoskeletal symptoms. 96 (32.4%) patients were currently receiving or had previously received monoclonal antibody therapy. Men on average had a higher Transformed Index score of 7(3-8) (p = 0.0025) and younger age (OR 0.96; 95% CI 0.93-100) and being female (OR 0.30; 95% CI 0.12-0.69) were associated with lower disease activity. Conclusion To our knowledge, this is the largest population based study of the incidence and prevalence of BD in the UK. It will also be the first study in BD to ascertain diagnostic validity by scrutinising routinely collected clinical data and to describe disease evolution over time in order to better design health services to cater to these needs. Disclosure P. Chandratre: None. J. Chandan: None. M. Hunjan: None. N. Trudgill: None. R. Moots: None. F. Fortune: None. R. Situnayake: None.

Objectives: To measure health utilities Time Trade-Off (TTO) and Standard Gamble (SG) in Behcet's disease (BD), and explore the interrelationships with EQ-5D-5L, disease activity, depression, anxiety and fatigue. Methods: TTO, SG, EQ-5D-5L, EQ VAS, depression (PHQ-9), anxiety (GAD-7) and fatigue (MAF) questionnaires were administered to 103 adult BD patients. Disease activity was assessed using the Behcet's Disease Activity Index (BDAI). Results: Mean TTO was 0.72 +/- SD 0.27, mean SG 0.70 +/- SD 0.34, and mean EQ-5D-5L 0.519 +/- SD 0.315. Moderate to severe depression was identified in 55.2%, moderate to severe anxiety in 35.1% and moderate to high fatigue in 97.7% patients. TTO correlated with SG (p < 0.01), EQ-5D-5L (p < 0.01) and negatively correlated with depression (p < 0.01), anxiety (p < 0.01) and fatigue (p < 0.01). Multiple linear regression showed SG was the only predictor of TTO (p = 0.002). Cluster analysis revealed one cluster where psychological factors rather than disease activity may have influenced TTO and SG scores. Conclusion: TTO and SG show that BD patients would on average forgo 28% of their remaining life or run a 30% risk of death to avoid the condition. Complex interrelationships with depression, anxiety and fatigue appear to play an important role in their decision making.

OBJECTIVES The epidemiology of Behçet's disease (BD) has not been well characterized in the UK. Evidence on the risk of cardiovascular disease, thromboembolic disease and mortality in patients with BD compared with the general population is scarce. METHODS We used a large UK primary care database to investigate the epidemiology of BD. A retrospective matched cohort study was used to assess the following outcomes: risk of cardiovascular, thromboembolic disease and mortality. Controls were selected at a 1:4 ratio (age and gender matched). Cox proportional hazard models were used to derive adjusted hazard ratios (aHR). RESULTS The prevalence of BD was 14.61 (95% CI 13.35-15.88) per 100 000 population in 2017. A total of 1281 patients with BD were compared with 5124 age- and gender-matched controls. There was significantly increased risk of ischaemic heart disease [aHR 3.09 (1.28-7.44)], venous thrombosis [aHR 4.80 (2.42-9.54)] and mortality [aHR 1.40 (1.07-1.84)] in patients with BD compared with corresponding controls. Patients with BD were at higher risk of pulmonary embolism compared with corresponding controls at baseline [adjusted odds ratio 4.64 (2.66-8.09), P < 0.0001]. The majority of patients with pulmonary embolism and a diagnosis of BD had pulmonary embolism preceding the diagnosis of BD, not after (87.5%; n = 28/32). CONCLUSION BD has a higher prevalence than previously thought. Physicians should be aware of the increased risk of developing ischaemic heart disease, stroke/transient ischaemic attack and deep venous thrombosis in patients with BD at an earlier age compared with the general population. Risk of embolism in patients with BD might vary across the disease course.

Abstract Introduction Behçet’s Disease (BD) is a complex, multisystem auto-inflammatory disorder. The most frequent manifestations are oral aphthous ulcers, genital ulcers and uveitis. Vascular involvement is less common but one of the major causes of mortality and morbidity. This case highlights the need to consider BD, especially in young, male, patients with arterial abnormalities and the challenges of treatment. Case description A 20-year-old man with a Moroccan father, presented to A&E with abdominal pain, constipation and night sweats, following recurrent admissions with lower abdominal and back pain. On this occasion he was noted to have a CRP of 160 mg/L and a subsequent CT scan of the abdomen showed a 4 cm pseudo-aneurysm arising from the right lateral infrarenal abdominal aorta which was initially repaired with open surgery and a vein graft. This subsequently leaked and so he had further surgery and an EVAR procedure. On further questioning it was noted that he had had frequent mouth ulcers for seven years and also episodes of epididymo-orchitis and folliculitis and the possibility of BD was considered. He was seen in the Birmingham Behçet’s Centre of Excellence and started azathioprine together with oral prednisolone. Six months later he required embolization of a left renal artery pseudoaneurysm and stent-grafting of the same artery. Given these new changes he was commenced on IV cyclophosphamide. Despite six pulses of cyclophosphamide and high doses of prednisolone he continued to have a raised CRP and so was switched to tocilizumab infusions. His inflammatory markers initially improved, but after about two years he attended for an infusion and complained of worsening abdominal pain. At that point it was noted that his inflammatory markers had been intermittently raised over the preceding few months. There had been a few breaks in treatment due to possible infections and non-attendance. A further CT scan was performed that showed disease progression at the distal site of the graft with small new aneurysms. After an MDT discussion it was decided to switch him to infliximab. He has now been on infliximab for over six months and his inflammatory markers have, reassuringly, remained low. Discussion Arterial involvement in BD is relatively uncommon, presenting variably with stenosis, thrombotic occlusions and aneurysms, as the vasculitic process can affect perivascular and endovascular tissues. Aneurysms are typically seen a number of years after the initial diagnosis and are believed to be due to an obliterative endarteritis with inflammation causing destruction of elastic and muscle cells in the media. The aneurysms tend to be more saccular, and the abdominal aorta is more frequently involved than the thoracic aorta or pulmonary artery. In this case the initial surgical procedure was performed prior to the diagnosis of BD, so it was not possible to give something such as cyclophosphamide prior to surgical intervention which would be advised. The EULAR guidelines recommend cyclophosphamide and corticosteroids as first line in treatment in arterial involvement. However, no further guidance is given regarding subsequent immunosuppression if needed. In this case the decision to start tocilizumab was made based on successful use in other patients with vascular Behçet’s disease. Subsequently infliximab was chosen as it has been used more widely in BD including in patients with vascular BD. Biochemically and symptomatically the patient has been well since infliximab was started, but we are currently awaiting a repeat CT scan. This case has also proved challenging as the patient has struggled with the diagnosis and need for frequent hospital appointments. He has had some help from the psychologist available through the Behçet’s service but has continued to DNA appointments and turn up for infusions at times that suit him. We are hopeful that a longer period of stability will also be beneficial from that point of view. Key learning points Vascular is less common than other features of BD but can sometimes be a presenting feature and is a major cause of mortality and morbidity. Unlike the international study group (ISG) criteria for Behçet’s disease the international criteria for Behçet’s disease (ICBD) do include vascular lesions. The possibility of BD needs to be considered, especially in patients presenting with potential vascular involvement. For both aortic and peripheral artery aneurysms the 2018 update of the EULAR guidelines recommend medical treatment with cyclophosphamide and corticosteroids before surgical intervention. If there is ongoing arterial disease activity despite cyclophosphamide anti-TNF and IL6 inhibition can be considered and have shown some success. Endovascular surgery is increasingly being preferred to open surgery, although there is a risk of further aneurysm formation, particularly at graft peripheries. Conflicts of interest The authors have declared no conflicts of interest.

This study reports on the analysis of the application and diagnostic predictability of the revised 2014 ICBD criteria in an unselected cohort of UK patients, and the ensuing organ associations and patterns of disease.

Purpose of reviewThis article discusses recent genetic and epigenetic associations involved in the pathogenesis of Behçet's disease. Recent findingsGenetic studies have supported the strong association of human leukocyte antigen-B and Behçet's disease, and high production of tumour necrosis factor and low production of interleukin (IL)-10, which have led to therapy based on controlling these effects. Polymorphisms that affect the response to pathogens (TLR and FUT2) are leading to increased interest in responses to microbiomes. Inflammation in Behçet's disease results in vascular damage and several single nucleotide polymorphisms in chemokine and adhesion molecules may be involved in this process. Increased levels of inflammatory cytokines including IL-1&bgr; and IL-17 have been linked to altered expression of microRNAs, miR155, miR21 and miR23b. DNA methylation changes in monocytes and lymphocytes have been described that affect the function of these cells. SummaryGenetic and epigenetic changes affecting cells and molecules involved in Behçet's disease offer new pathways for research, including cytoskeletal protein function, that will provide new targets for therapy, and potentially address the ethnic differences seen in validation of gene studies.

OBJECTIVE:The aim of this study was to describe the outcomes and predictors for development of damage in a large inception cohort of SLE patients. METHODS:This was a prospective longitudinal study of a cohort of SLE patients. SLE patients were included if they were recruited within 3 years of achieving the fourth ACR criterion for SLE. Data were collected on disease activity, damage and treatment. Information on death was provided by the Office for National Statistics. The censoring date for analysis was 31 December 2010. A standardized mortality ratio was calculated. Poisson regression was used to determine the incidence rate for damage accrual. Multistate Markov modelling was used to determine predictors for development of damage. RESULTS:There were 382 patients (92.4% females, 51.6% Caucasian, 22% South Asian, 20.7% Afro-Caribbean) with 12 072 assessments and total follow-up of 2958 patient-years. There were 300 items of damage (in 143 patients) and 37 deaths. The overall standardized mortality ratio was 2.0 (95% CI 1.5, 2.8) and the most common causes of death were infection (37.8%), cardiovascular (27%) and malignancy (13.5%). The predictors for damage accrual were higher prior damage, older age at diagnosis, active disease, systemic corticosteroid exposure and CYC exposure. Patients were more likely to develop new damage earlier in their disease than later. Ethnicity was not predictive of damage accrual or death in this cohort. CONCLUSION:SLE patients have premature mortality. Active disease, corticosteroid exposure and CYC exposure were independently associated with the development of damage. Damage accrual is more likely to occur in early disease.