Lupus clinical trial eligibility in a real-world setting: results from the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR)

ObjectiveTo quantify how well phase III randomised clinical trials in both SLE and lupus nephritis (LN) represents a real-world SLE cohort.MethodsLiterature reviews were performed of major published phase III SLE (n=12) and LN (n=6) clinical trials (ClinicalTrials.gov). Inclusion and exclusion criteria common across these trials were collated for non-renal SLE or LN trials, and applied to patients recruited to the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR) starting either biological or standard-of-care (SOC) therapies.ResultsWe recruited 837 patients to the BILAG-BR from September 2010 to June 2018, starting either SOC (n=125, 15%) or a biological medication (n=712, 85%). Active LN, defined as a BILAG A in the renal domain occurred in 20% (n=166). Overall, 530 (63%) patients were ineligible to participate in non-renal SLE clinical trials and 72 (43%) patients with active LN would be ineligible for LN trials. The most common reasons for ineligibility from the non-renal lupus trials included active renal involvement (n=166, 20%) and low disease activity (n=114, 15%). For LN trials, the most common exclusion met was pre-existing renal impairment (n=15, 9%). Patients with fewer comorbidities were more likely to be eligible to participate in non-renal SLE trials.ConclusionsIn this national register of patients with moderate-to-severe SLE, nearly two-thirds would not be eligible for recruitment to key SLE clinical trials nor would almost half of those with active LN. Eligibility criteria may excessively constrain enrolment and thus, how we can generalise trial results in a real-world setting.

O17 Effectiveness of rituximab in the treatment of neuro-psychiatric SLE: results from the British Isles Lupus Assessment Group Biologics Register

Background/Aims Neuro-psychiatric (NP) involvement in systemic lupus erythematosus (SLE) can occur in 56.3% cases. Rituximab (RTX) has been demonstrated to be safe and efficacious in the treatment of refractory SLE although there is limited evidence for its use in NP-SLE. We aim to describe the baseline characteristics and short-term effectiveness of RTX in patients treated for NP-SLE within the British Isles Lupus Assessment Group Biologics Register (BILAG-BR). Methods Patients with active NP involvement; scoring BILAG A or B and/or on SLEDAI-2K were included. Baseline characteristics, disease activity and oral steroid dose pre and 5 - 9 months post-treatment were analysed. Paired Wilcoxon-Signed-Ranked Test was used to determine changes in disease activity scores and steroid dose. Results We identified 74 patients of whom 61 (82%) were female and 48 (74%) Caucasian. Median age [interquartile range (IQR)] was 45.5 years [37 - 58] and disease duration 11.5 years [7 - 18.8]. 68 patients had active disease on BILAG (A = 34, B = 34) with 6 scoring on SLEDAI-2K only. The majority (n = 71/74, 96%) had at least one other organ involved. Central nervous system (CNS) disease occurred in 45/65 (69%) cases, 12/65 (18%) had peripheral nervous system (PNS) disease and 8/65 (12%) CNS/PNS overlap. Anti-Ro was the commonest identified antibody (n = 26/57, 46%) and 42 of 59 (71%) patients had a raised anti-dsDNA and/or low complement. The majority (n = 64/74, 86%) were taking glucocorticoids and median prednisolone dose was 15mg [IQR 10 - 20]. Pre and post-RTX BILAG, total SLEDAI-2K and oral steroid dose were available in 50, 57 and 27 patients respectively. Following RTX, patients with NP BILAG A or B reduced from 50 to 11 (p < 0.0001). 4 of the 6 patients with NP-SLE on SLEDAI-2K alone, improved. Total median SLEDAI-2K score reduced from 12 [IQR 14 - 18] to 2 [IQR 0 - 4] (p < 0.0001). Median steroid dose reduced from 15mg [IQR 11.3 - 25] to 10mg [IQR 6.9 - 18.8] (p = 0.009). For 53 patients, active CNS, PNS and overlap disease reduced from 37 (70%) to 6 (11%), 10 (19%) to 3 (6%) and 6 (11%) to 4 (8%) respectively. In 9 patients treated with concomitant CYC, none had persistent NP disease. In contrast, 11 of 41 patients who had RTX alone had persistent NP disease. Conclusion RTX use is associated with improvement in NP-SLE with reduction in oral steroid dose. Concomitant CYC may enhance the level of improvement seen with RTX. Large scale studies are therefore warranted to establish the effectiveness of RTX alone or in combination with CYC in the treatment of NP-SLE. Disclosure T. David: None. R. Hum: None. E. Sutton: None. B. Parker: None. E. McCarthy: None. I. Bruce: None.

Predictors of extra-articular manifestations in axial spondyloarthritis and their influence on TNF-inhibitor prescribing patterns: results from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis

ObjectivesExtra-articular manifestations (EAMs) are important systemic features of axial spondyloarthritis (axSpA), which may influence the choice of tumour necrosis factor-inhibitor (TNFi). We examined the cumulative incidence and predictors of EAMs and the influence of these on first TNFi choice in a ‘real-world’ cohort of patients with axSpA.MethodsClinical and patient-reported outcomes of 2420 patients with axSpA from 83 centres were collected by the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis. Lifestyle factors for EAMs (acute anterior uveitis (AAU), inflammatory bowel diseases (IBD), psoriasis) were compared with those without EAMs. Also, the association between pretreatment EAMs and choice of first TNFi (adalimumab, etanercept, certolizumab) was analysed.ResultsAAU was directly associated with human leukocyte antigen (HLA)-B27 (incidence rate ratio (IRR) 1.95, 95% CI 1.40 to 2.73) and inversely associated with ever-smoking (IRR=0.71, 95% CI 0.55 to 0.92). For both psoriasis and IBD, there was an inverse relationship with HLA-B27 (IRR 0.54, 95% CI 0.36 to 0.79 and IRR 0.63, 95% CI 0.43 to 0.91, respectively). A diagnosis of either AAU (OR 3.79, 95% CI 2.11 to 6.80) or IBD (OR 5.50, 95% CI 2.09 to 14.46) was associated with preference for adalimumab versus others. In contrast, a diagnosis of either AAU (OR 0.14, 95% CI 0.06 to 0.33) or IBD (OR 0.17, 95% CI 0.05 to 0.57) was associated with less preference for etanercept over other TNFi.ConclusionThe higher occurrence of AAU and lower occurrence of psoriasis and IBD in HLA-B27-positive patients with axSpA are consistent with current pathophysiology. Patients with previous AAU and IBD are more likely to be prescribed adalimumab and less likely to receive etanercept, consistent with the superior efficacy of monoclonal TNFi for these indications. Future work will determine whether EAMs influence TNFi survival, or effectiveness, and whether this varies between agents.

OP0285 TOWARDS IMPLEMENTING THE OMOP CDM ACROSS FIVE EUROPEAN BIOLOGIC REGISTRIES

Background:The Observational and Medical Outcomes Partnerships (OMOP) common data model (CDM) provides a framework for standardising health data.Objectives:To map national biologic registry data collected from different European countries to the OMOP CDM.Methods:Five biologic registries are currently being mapped to the OMOP CDM: 1) the Czech biologics register (ATTRA), 2) Registro Español de Acontecimientos Adversos de Terapias Biológicas en Enfermedades Reumáticas (BIOBADASER), 3) British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA), 4) German biologics register ‘Rheumatoid arthritis observation of biologic therapy’ (RABBIT), and 5) Swiss register ’Swiss Clinical Quality Management in Rheumatic Diseases’ (SCQM).Data collected at baseline are being mapped first. Details that uniquely identify individuals are mapped to the person table, with the observation_period table defining the time a person may have had clinical events recorded. Baseline comorbidities are mapped to the condition_occurrence CDM table, while baseline medications are mapped to the drug_exposure CDM table. This mapping is summarised in Figure 1.Figure 1.Overview of initial mappingResults:A total of 64,901 individuals are included in the 5 registries being mapped to the OMOP CDM, see table 1. The number of unique baseline conditions being mapped range from 17 in BSRBR-RA to 108 in RABBIT, while the number of baseline medications range from 26 in ATTRA to 802 in BSRBR-RA. Those registries which captured more comorbidities or medications generally allowed for these to be inputted as free text.Table 1.Summary of initial code mappingRegistryNumber of individualsNumber of mapped baseline conditionsNumber of mapped baseline medicationsATTRA5,3262626BIOBADASER6,4963051BSRBR-RA21,69517802RABBIT13,06210878SCQM18,3222633Conclusion:Due to differences in study design and data capture, the baseline information captured on comorbidities and drugs across registries varies greatly. However, these data have been mapped and mapping biologic registry data to the OMOP CDM is feasible. The adoption of the OMOP CDM will facilitate collaboration across registries and allow for multi-database studies which include data from both biologic registries and other sources of health data which have been mapped to the CDM.Disclosure of Interests:Edward Burn: None declared, Lianne Kearsley-Fleet: None declared, Kimme Hyrich Grant/research support from: Pfizer, UCB, BMS, Speakers bureau: Abbvie, Martin Schaefer: None declared, Doreen Huschek: None declared, Anja Strangfeld Speakers bureau: AbbVie, BMS, Pfizer, Roche, Sanofi-Aventis, Jakub Zavada Speakers bureau: Abbvie, UCB, Sanofi, Elli-Lilly, Novartis, Zentiva, Accord, Markéta Lagová: None declared, Delphine Courvoisier: None declared, Christoph Tellenbach: None declared, Kim Lauper: None declared, Carlos Sánchez-Piedra: None declared, Nuria Montero: None declared, Jesús-Tomás Sanchez-Costa: None declared, Daniel Prieto-Alhambra Grant/research support from: Professor Prieto-Alhambra has received research Grants from AMGEN, UCB Biopharma and Les Laboratoires Servier, Consultant of: DPA’s department has received fees for consultancy services from UCB Biopharma, Speakers bureau: DPA’s department has received fees for speaker and advisory board membership services from Amgen

O26 Non-serious infections in patients with RA: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Background Patients with rheumatoid arthritis (RA) are at an increased risk of infection. Most attention has been given to serious infections, but these are the tip of the iceberg. Non-serious infections (NSI) are far more frequent, and although not life-threatening, have potential to impact treatment outcomes (drug survival) and quality of life. Our objective was to describe frequency of NSI and compare incidence of NSI by biologic drug within the British Society for Rheumatology Biologics Register (BSRBR-RA). Methods The BSRBR-RA is a prospective observational cohort study. NSI was identified as not requiring hospitalisation, intravenous therapy or leading to disability or death. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered ‘at risk’ from the date of commencing biologic treatment for 3 years. Drug exposure was defined by agent; TNF inhibitor, IL-6 inhibitor, anti-CD20 or csDMARD only. To account for a high frequency of events, a multiple-failure Cox model was used. Multivariable adjustment included age, gender, DAS28-ESR, HAQ-DI, disease duration, smoking, steroid usage, year recruited to BSRBR-RA, line of biologic therapy and cumulative infection number. Results There were 17,304 NSI in 10,099 patients, with an event rate of 27.0 per year (95% CI 26.6 to 27.4). Increasing age, female gender, comorbidity burden, corticosteroid therapy, DAS28 and HAQ-DI were associated with an increased risk of NSI. The rate of NSI was numerically lowest with csDMARDs. Compared to TNFi, IL-6 inhibitor had a higher risk of NSI, whilst the csDMARD cohort had a lower risk. Between the TNFi agents, adalimumab had a higher risk than etanercept (Table 1). Conclusion These results confirm that NSI is a frequent occurrence for patients, which historically has received little attention in research literature. The data suggest biologics increase the risk of NSI, especially IL-6 inhibition. Whilst unmeasured confounding must be considered, the magnitude of effects are large and it seems likely that a causal link between targeted immunosuppression and NSI risk exists. Further research is needed to understand the impact of NSI on clinical outcomes including drug survival and quality of life. Disclosures K. Bechman: None. K. Halai: None. S. Norton: None. A.P. Cope: None. K.L. Hyrich: Honoraria; AbbVie paid to the institution and grant income from Pfizer and Bristol-Myers Squibb for activities outside of this work. J.B. Galloway: Honoraria; for speaking or attending conferences from AbbVie, Bristol-Myers Squibb, Celgene, Janssen, Pfizer and Union Chimique Belge.

P246 Predicting non-response to biologic therapy amongst patients with axSpA: results from the British Society for Rheumatology Biologics Register

Background Biologic therapies have transformed treatment for axial spondyloarthritis (axSpA). However, although studies report overall benefits, these are average effects. There remains a subset of patients in whom response is not achieved. Here, we aimed to identify characteristics of patients who may need additional therapeutic approaches to optimise outcome. Methods The British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) is a prospective cohort of axSpA patients recruited from 83 centres across Great Britain. All patients were biologic-naïve at recruitment, however those in the “biologic” cohort commenced a biologic therapy shortly thereafter, or during follow-up. Clinical data was collected from medical records, and socio-economic/patient reported outcomes via questionnaires. Response was assessed at first follow-up, between 10 weeks and 9 months from therapy commencement, and defined in four ways: ASAS20 and ASAS40 criteria, ≥1.1 reduction in ASDAS, and achieving moderate/inactive ASDAS (<2.1). Factors associated with non-response were assessed by logistic regression and parsimonious models identified using stepwise methods. The ability to predict non-response was assessed by positive predictive value (PPV). Results 335 biologic participants provided information at a median follow-up of 14 weeks (inter-quartile range (IQR) 12-17). Median age was 47 years (IQR 36-56), 69% were male and 61% met AS modified New York criteria. The proportion meeting response varied by criteria: ASAS20 52%, ASAS40 33%, ASDAS reduction 47% and ASDAS <2.1 35%. Socio-economic circumstances predicted non-response, specifically (in all models) work status and (in some models) fewer years of education (Table 1). Poorer mental health and high number of co-morbidities was associated with non-response across multiple (but not all) outcomes, while body mass index, enthesitis and gender were included in models for a single outcome. Disease-specific factors were largely not associated with non-response. All models demonstrated a good level of fit and were effective at predicting non-response (PPV 65%-77%). Conclusion We have identified factors which predict non-response to biologic therapy, some of which may be modifiable and others which identify patients who are unlikely to benefit from biologic therapy alone. In such patients additional/alternative treatment strategies should be considered to maximise the benefits which others gain from biologic therapy. Disclosures L.E. Dean None. E. Pathan Other; E.P. has recieved salary funding from Jansen (2019) and Merck (2018). G.T. Jones None. G.J. Macfarlane None.

P249 Working with axSpA: a qualitative study using the British Society for Rheumatology Biologics Register

Background We have previously reported that axSpA patients living in rural areas report a greater impact of their disease on work productivity. Whilst rural dwellers were more likely to work in a physical job and work part-time, it is unclear how features of the disease, job type and work environment interact to influence presenteeism (work disability). We aimed to explore experiences of work and factors influencing the ability to work optimally in individuals with axSpA. Methods 30 semi-structured telephone interviews were conducted from a subset of patients drawn from the British Society for Rheumatology Biologics Register for Ankylosing Spondylitis (BSRBR-AS) registry. Individuals were purposively sampled across a range of ages, area of residence (urban and rural), occupations (sedentary and manual), employment status and stage of working life, from diverse geographical regions in the UK. The topic guide explored experiences of living with AxSpA, work, health care and impact of AxSpA on family, financial and social life over time. Interviews were audio-recorded and transcribed. Data was analysed using an iterative thematic approach, supported by NVivo 12 qualitative data analysis software. Results Factors influencing presenteeism are considered under three themes; occupation, individual and workplace. Occupation: The extent to which jobs permitted flexibility, in terms of what, when and how tasks were done, was important. Dichotomous classifications of job type as sedentary or manual were unhelpful. Participants, especially in public facing jobs, reported an obligation to attend work even when feeling unwell. Individual: Work was important in terms of self-identity and providing social interactions as well as financial security. However, fatigue, reduced mobility, chronic pain and medication affected physical and mental function at work. Individuals did not discuss work issues with their rheumatologist, who tended to focus on disease management. Workplace: Support from work colleagues and immediate line managers was critically important, over and above organisational policies. However, AxSpA was often misunderstood, for example, as ‘a bad back.’ Flexible working practices e.g. home-working enabled individuals to continue to work, when they would otherwise have been unable to. Adaptations to driving and commuting to work were common. Some employers permitted adjustments to working practices or time off for appointments, whereas others were inflexible. Sickness monitoring procedures were often perceived to be punitive, rather than supportive. Conclusion The relationship between job type, work environment and work disability is nuanced and complex. Existing measures of work do not accurately reflect what people actually do, the challenges they face, or the benefits of work. Flexibility in terms of what, when and how tasks are done is important. There is significant variation in support offered by employers. Healthcare professionals can do more to support individuals to work well and educate employers. Disclosures R.J. Hollick None.

P244 Determining factors related to poor quality of life in patients with axSpA: results from the British Society for Rheumatology Biologics Register

Background The aim when treating people with axial spondyloarthropathies (axSpA) is to maintain/improve their Quality of Life (QoL), traditionally through reducing disease activity. Previously, the Scotland Registry for Ankylosing Spondylitis (SIRAS) demonstrated, however, that although important, disease activity may not be the only factor influencing QoL. Indeed, function was a better predictor, with fatigue, chronic widespread pain and spinal mobility also important. The aim of the current study was to validate the previous findings in a large nationwide population, and determine if other factors, not collected in the previous study (such as mood and sleep) are also important. Methods The British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) is a prospective cohort of axSpA patients from 83 secondary care centres across Great Britain. Clinical data was collected during routine clinic visits and questionnaires provided patient reported outcomes including: the Ankylosing Spondylitis QoL questionnaire (ASQoL: scored 0 (best) to 18 (worst)), the Bath AS indices for disease & physical activity ((BASDAI/BASFI: scored 0 (best) - 10 (worst)), sleep disturbance (Jenkins: 0 (best) - 20 (worst)), depression (hospital anxiety & depression scales: scored 0 (best) - 21 (worst)) and the modification of the 2010 fibromyalgia criteria (widespread pain index (WPI): scored 0 (best) - 19 (worst) & symptom severity score (SSS): 0 (best) -12 (worst)). Using data collected at BSRBR-AS registration, multivariate linear regression models, predicting ASQoL, were used to validate the previous SIRAS model. Additionally, a de-novo forward stepwise model was developed to assess consistency across both populations and to determine if any additional factors (such as mood and sleep) predicted QoL. Results 1,810 BSRBR-AS participants were eligible for the current study, 67% of whom were male, median age 49 years (interquartile range 38-61). 80% of those tested were HLA-B27 positive and the majority of patients (67%) met the modified New York Criteria for AS. Of the five factors included in the SIRAS model; disease activity, physical function, fatigue and widespread pain remained significantly associated with QoL in the BSRBR-AS study. Spinal mobility was no longer significantly associated. Within the de-novo model eight independent factors predicted ASQoL score: disease activity (coefficient 0.31, 95% (confidence interval 0.14, 0.47)), physical function (0.59 (0.45, 0.73)), depression (HADS: 0.16 (0.09, 0.24)), sleep disturbance (0.08 (0.04, 0.13)), activity impairment (0.04 (0.02, 0.05)), fibromyalgia (SSS: 0.24 (0.13, 0.35), WPI: 0.10 (0.03, 0.17)) and tobacco smoking (vs. non-smoker: 0.66 (0.10, 1.21)). Conclusion Current EULAR guidelines for management of axSpA targeting disease activity and physical function are supported by the current findings which suggest both are consistently important predictors of QoL. However, additional factors such as fatigue, sleep disturbance and mood also contribute to QoL and should be considered additional targets within future axSpA management strategies. Disclosures L.E. Dean None. O. Rotariu None. G.T. Jones None. E. Pathan Other; E.P. has received salary funding from Jansen (2019) and Merck (2018). G.J. Macfarlane None.