British Society For Rheumatology Biologics Register For Rheumatoid Arthritis Research Articles

E039 Association between ethnicity and initial response to TNF inhibitors in people with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

Abstract Background/Aims Little is known about the association between ethnicity and response to TNF inhibitors (TNFi) in people with rheumatoid arthritis (RA). This study examines the association between self-reported ethnicity and DAS28 response after 6 months of treatment in patients starting their first TNFi using data from the British Society for Rheumatology Biologics Register for RA. Methods 14133 RA patients with self-reported ethnicity starting their first TNFi were included. Due to a very low proportion of non-white patients, ethnicity was divided into white or non-white for analysis. Outcomes included the change in disease activity using DAS28, the proportion of patients who achieved DAS28 remission and EULAR response at month 6. Adjusted regression models appropriate to outcome were used to compare between the two groups. Multiple imputation was used to account for missing data. Results Of 14133 patients starting TNFi with recorded ethnicity, only 607 (4.3%) recorded themselves as non-white (389 Asian, 134 Black, 57 Mixed ethnicity and 27 other) (Table). At start of TNFi, non-white patients were younger (non-white vs. white: mean 51 vs. 57 years; p < 0.001), with shorter disease duration (median 8 vs. 10 years; p < 0.001), higher proportion of females (86% vs. 76%; p < 0.001) and fewer current cigarette smokers (9% vs. 20%; p < 0.001). Non-white patients had lesser improvement in DAS28 at month 6 (adjusted regression coefficient (95% confidence interval (95%CI)): 0.3 (0.04-0.5)). However, using the white patients as a reference, non-white patients were not associated with the achievement of DAS28 remission (adjusted odds ratio (95%CI): 0.7 (0.5-1.1)) or EULAR response (aOR (95%CI): 0.8 (0.7-1.0)) at month 6. Conclusion Recruitment to the BSRBR-RA of non-white patients was exceptionally low compared to expected population distribution - the reasons for this are not immediately evident. Among those recruited, there were no significant differences observed in initial treatment response although non-white patients were younger, more likely to be female, had shorter disease duration and less likely to be smokers. Further evaluation into ways to both increase representativeness in our national RA treatment register and influence of ethnic differences on longer term outcomes with biologic therapies is warranted. Disclosure M. Tsoi: None. R.S. Andev: Other; R.S.A. reports speaker fees from Novartis. L. Kearsley-Fleet: None. K. Watson: None. S. Dubey: Honoraria; S.D. reports honoraria from Boehringer Ingelheim. Other; S.D. reports speaker fees from Janssen. K. Kumar: None. A. Moorthy: Honoraria; A.M. reports honoraria from Eli-Lilly and UCB. Other; A.M. reports speaker fees from Novartis and Galapagos. M. Gupta: None. A.O. Adebajo: None. K.L. Hyrich: Honoraria; K.L.H. reports honoraria from Abbvie. Grants/research support; K.L.M reports grant income from Pfizer and BMS.

OA14b Etanercept originator versus its biosimilar (SB4) for the treatment of rheumatoid arthritis. Are they truly similar?

Abstract Background/Aims Etanercept biosimilar SB4 (ETN-B) showed comparable efficacy to its biologic originator (ETN-O) among biologic-naïve patients with rheumatoid arthritis (RA) in randomised controlled trials. Subsequently, a nationwide guideline in the United Kingdom (UK) obligated the prescription of biosimilars in 2016, resulting in significant cost-savings to the NHS. However, real-world evidence comparing ETN-O and ETN-B is limited. This analysis aims to compare the effectiveness of ETN-O versus ETN-B amongst biologic-naïve patients with RA treated in routine clinical practice in the UK. Methods The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective observational cohort study. This analysis included patients starting their first biologic (ETN-O or ETN-B), recruited since 2010, with at least one follow-up. Baseline data are collected at start of therapy, including patient demographics and disease activity. Follow-up data are collected six monthly for the first three years and annually thereafter, including changes in disease activity and anti-rheumatic therapy. Key outcomes assessed were change in Disease Activity Score for 28-joints (DAS28), DAS28 remission, EULAR treatment response, change in Health Assessment Questionnaire (HAQ), and minimal clinically important difference (MCID) in HAQ. Drug retention was explored using Kaplan-Meier and Cox-regression analyses, along with reasons for treatment withdrawal. Multiple imputation was used to account for missing data and confounding by indication was accounted for using propensity-decile adjustment. Results This analysis included 1927 patients with RA starting their first biologic therapy: 996 (52%) ETN-O and 931 (48%) ETN-B. At six-months, change in DAS28 and HAQ were similar between therapies (Table). There were no differences in key imputed propensity adjusted outcomes (odds ratio [95% confidence interval]): DAS28 remission: 0.90 (0.7-1.1, p = 0.3); MCID in HAQ: 0.86 (0.7-1.1, p = 0.3) and EULAR treatment response: 0.96 (0.8-1.2, p = 0.8). One-year retention rates were 69% (95% CI: 66-72) for ETN-O and 70% (95% CI: 67-73) for ETN-B and the main reasons for treatment withdrawal were adverse events and ineffectiveness for both drugs. Conclusion This analysis is the first to our knowledge to show similar outcomes amongst biologic-naïve patients with RA treated with either ETN-O or ETN-B using real-world data, which brings further evidence for similarity between the drugs. Disclosure A. Rokad: None. L. Kearsley-Fleet: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

OA14a Outcomes after switching from etanercept originator to its biosimilar (SB4) for the treatment of rheumatoid arthritis

Abstract Background/Aims Following the etanercept biosimilar SB4 (ETN-B) launch in the UK in 2016, nationwide guidelines encourage patients switch from the biologic originator (ETN-O) to ETN-B, known as non-medical switching (NMS). However, the long-term implications of NMS have not yet been analysed nationally among patients with rheumatoid arthritis (RA). This analysis aims to evaluate treatment outcomes and drug retention after patients with RA are switched from ETN-O to ETN-B in routine clinical practice in the UK. Methods The British Society for Rheumatology Biologics Register for RA (BSRBR-RA) is a prospective observational cohort study. This analysis included all patients who switched from ETN-O to ETN-B since 2016. Disease activity was assessed at the time of switch and after six months. Key outcomes included change in disease activity (DAS28), DAS28 remission and EULAR treatment response. Drug retention was analysed using Kaplan-Meier and treatment withdrawal reasons were explored for all patients who switched to ETN-B, as well as (1) patients who switched-back to ETN-O, (2) patients who changed to a non-ETN biologic, (3) patients discontinuing all biologic therapy. Multiple imputation was used to account for missing data. Results 1160 patients with RA switched from ETN-O to ETN-B. Of the 919 (79%) with available DAS28 data, there was no change in six-month DAS28 score following switch (median: 0, IQR: -0.8, 0.7). After a median follow-up of 1.8 years (IQR: 1.0, 2.3), most patients remained on ETN-B (N = 844, 73%) with the main treatment withdrawal reason being ineffectiveness (N = 139, 44%). Among those who discontinued ETN-B, 133 (11%) patients switched-back to ETN-O and 98 (8%) patients changed to a non-ETN biologic; both primarily due to ineffectiveness (Table). Lastly, 85 (7%) patients discontinued all biologic therapy mainly due to adverse events (N = 50, 59%). Conclusion This analysis has demonstrated sustained effectiveness after switching from ETN-O to ETN-B using real-world nationwide data. Among the sub-cohorts of patients who discontinued ETN-B, differences were observed regarding the frequency and reasons for treatment withdrawal. These results will support UK rheumatologists and patients with treatment decisions, assist quality improvement projects to reduce drug withdrawals and refine biologic treatment delivery in the UK. Disclosure A. Rokad: None. L. Kearsley-Fleet: None. K. Watson: None. M. Lunt: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

Nonserious Infections in Patients With Rheumatoid Arthritis: Results From the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis.

To describe the frequency and predictors of nonserious infections (NSI) and compare incidence across biologic agents within the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA). The BSRBR-RA is a prospective observational cohort study. An NSI was defined as an infection that did not require hospitalization or intravenous therapy. Infections were captured from clinician questionnaires and patient diaries. Individuals were considered "at risk" from the date of initiation of biologic treatment for up to 3 years. Drug exposure was defined by agent: tumor necrosis factor inhibitor (TNFi), interleukin-6 (IL-6) inhibitor, B cell depletion (rituximab), or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) alone. A multiple-failure Cox model was used with multivariable adjustment. Missing data were addressed using multiple imputation. There were 17,304 NSI in 8,145 patients, with an event rate of 27.0 per person per year (95% confidence interval [95% CI] 26.6-27.4). Increasing age, female sex, comorbidity burden, glucocorticoid therapy, higher Disease Activity Score in 28 joints, and higher Health Assessment Questionnaire disability index were associated with an increased risk of NSI. There was a significant reduction in NSI risk with csDMARDs compared to biologic treatments. Compared to TNFi, IL-6 inhibition and rituximab were associated with a higher NSI risk (adjusted hazard ratio 1.45 [95% CI 1.29-1.63] and adjusted hazard ratio 1.28 [95% CI 1.14-1.45], respectively), while the csDMARD cohort had a lower risk (adjusted hazard ratio 0.64 [95% CI 0.59-0.70]). Within the TNFi class, adalimumab was associated with a higher NSI risk than etanercept (adjusted hazard ratio 1.11 [95% CI 1.05-1.17]). NSI occur frequently in RA, and predictors mirror those reported with serious infections. All biologics are associated with a greater risk of NSI, with differences observed between agents. While unmeasured confounding must be considered, the magnitude of effect is large, and a relationship between NSI and targeted immunomodulatory therapy likely exists.

O27 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

Abstract Background In 2017, a new class of oral disease modifying anti-rheumatic drugs (DMARDs), janus kinase inhibitors (JAKi), were licensed for rheumatoid arthritis (RA): baricitinib and tofacitinib. In the UK, they are approved for use in patients with high disease activity with or without methotrexate, following failure of conventional synthetic (cs) DMARDs or biologic DMARDs, the latter when rituximab is contraindicated. As a new therapy option, it is currently unclear how and when these drugs are being prescribed in patients with RA. This analysis aims to describe the characteristics of patients starting JAKi and registered with the BSRBR-RA. Methods The BSRBR-RA aims to capture exposure and outcome data in patients with RA receiving biologics, biosimilars and targeted synthetic DMARDs. At the start of therapy, demographic and clinical data, including past treatment data, are collected. Characteristics of all patients receiving a JAKi for the first time with data recorded in the BSRBR-RA up to 31/03/2019 are described. Results To 31/03/2019, 698 patients in the BSRBR-RA have been treated with a JAKi; 596 patients baricitinib and 110 tofacitinib (Table 1). A quarter of patients received a JAKi with no prior biologic exposure; 148 (25%) baricitinib and 16 (15%) tofacitinib. Of these, 15% had a prior malignancy history. Of those with prior biologic exposure, the median number of previous biologics was 3 (IQR 2-4), the majority had prior TNFi (91%) or rituximab (51%), and 50% were receiving concurrent methotrexate. Conclusion To date, more patients have been recruited starting baricitinib than tofacitinib, likely owing to the later licensing of tofacitinib. Two groups are emerging with a quarter of patients receiving JAKi immediately after csDMARDs and a majority as a later stage alternative following multiple biologics. Further recruitment and follow-up patients will allow for analysis of real-world safety and effectiveness, but differences in patient characteristics will need to be considered in any comparative effectiveness analyses. Disclosures L. Kearsley-Fleet None. R. Davies None. K. Watson None. M. Lunt None. K.L. Hyrich Honoraria; AbbVie. Grants/research support; UCB, Pfizer, BMS.

064 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

064 Early experience with JAK inhibitor prescribing in the UK: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

O19 The association of biologic drug-levels with infection risk: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

O19 The association of biologic drug-levels with infection risk: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

243 Long‐term risk of serious infections in patients with rheumatoid arthritis treated with rituximab: five year data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR‐RA)

243 Long‐term risk of serious infections in patients with rheumatoid arthritis treated with rituximab: five year data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR‐RA)

Serious infection across biologic-treated patients with rheumatoid arthritis: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

ObjectivesTo compare the incidence of serious infection (SI) across biologic drugs used to treat rheumatoid arthritis (RA) using data from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis...

Association Between Ischemic Stroke and Tumor Necrosis Factor Inhibitor Therapy in Patients With Rheumatoid Arthritis.

ObjectivePatients with rheumatoid arthritis (RA) are at an increased risk of ischemic stroke. Tumor necrosis factor inhibitors (TNFi) may influence risk and mortality after ischemic stroke by reducing inflammation. This study was undertaken to examine the association of TNFi with the risk of incident ischemic stroke and with 30‐day and 1‐year mortality after ischemic stroke.MethodsPatients with RA starting therapy with TNFi and a biologics‐naive comparator group treated with synthetic disease‐modifying antirheumatic drugs (DMARDs) only were recruited to the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis from 2001 to 2009. Patients were followed up via clinical and patient questionnaires as well as the national death register. Incident strokes were classified as ischemic if brain imaging reports suggested ischemia or if ischemic stroke was reported as the underlying cause of death on a death certificate. Patients with a previous stroke were excluded. Risk of ischemic stroke was compared between patients receiving synthetic DMARDs only and those ever‐exposed to TNFi using a Cox proportional hazards regression model adjusted for potential confounders. Mortality after ischemic stroke was compared between synthetic DMARD–treated patients and TNFi‐treated patients using logistic regression, adjusted for age and sex.ResultsTo April 2010, 127 verified incident ischemic strokes (21 in 3,271 synthetic DMARD–treated patients and 106 in 11,642 TNFi‐treated patients) occurred during 11,973 and 61,226 person‐years of observation, respectively (incidence rate 175 versus 173 per 100,000 person‐years). After adjustment for confounders, there was no association between ever‐exposure to TNFi and ischemic stroke (hazard ratio 0.99 [95% confidence interval (95% CI) 0.54–1.81]). Mortality 30 days or 1 year after ischemic stroke was not associated with concurrent TNFi exposure (odds ratio 0.18 [95% CI 0.03–1.21] and 0.60 [95% CI 0.16–2.28], respectively).ConclusionExposure to TNFi does not appear to influence the occurrence of ischemic stroke in the medium term in patients with RA. The impact on mortality after ischemic stroke remains inconclusive.

Drug-specific risk, and associated factors, of vasculitis-like events in patients exposed to tumour necrosis factor alpha inhibitor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA)

BackgroundThe association between TNF inhibitors and vasculitis-like events, possibly secondary to induction of autoantibodies, has been well reported. However, the incidence, drug-specific differences, and associated factors have been poorly characterised. The aim of this study was to assess the drug-specific risk, and associated factors, of vasculitis-like events in patients with rheumatoid arthritis treated with TNF inhibitors and non-biologic disease modifying antirheumatic drugs (nbDMARDs). MethodsThis analysis included two cohorts from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis (BSRBR-RA) recruited from Oct 1, 2001, to May 31, 2015: patients starting first TNF inhibitors (adalimumab, etanercept, infliximab, certolizumab) and a comparison cohort receiving nbDMARDs. After identification of vasculitis-like events, additional information from hospital consultants was sought for verification. The risk of an event was compared between the two cohorts with Cox proportional hazard models, adjusted using propensity scores (inverse probability of treatment weighting). FindingsThere were 95 incident vasculitis-like events (14 in 3640 patients on nbDMARD, 81 in 12 745 patients starting first TNF inhibitors) with 20 365 and 52 428 patient-years of follow-up generating crude incidence rates of 7 per 10 000 and 16 per 10 000 person-years, respectively. After adjustment, the hazard ratio (HR) of vasculitis-like events in patients on TNF inhibitors versus nbDMARD was 1·3 (95% CI 0·4–4·0). Drug specific HRs were highest in patients on infliximab (HR 2·7, 95% CI 1·4–5·2) and etanercept (2·6, 1·4–4·8), but these associations were not significant after adjustment. Factors associated with vasculitis-like events included baseline disease activity (HR 1·4, 95% CI 1·2–1·7), rheumatoid factor positive status (1·8, 1·2–2·8), health assessment questionnaire score (1·7, 1·2–2·3), and sulfasalazine use (0·6, 0·3–0·9). InterpretationIn one of the largest registers of patients receiving biological drugs, the absolute risk of vasculitis-like events was low, irrespective of whether patients received TNF inhibitors or nbDMARDs. There were no significant differences in risk between TNF inhibitors after adjustment. Higher baseline disease activity and seropositive status were associated with higher rates of vasculitis events, whereas baseline sulfasalazine use was associated with lower rates. To our knowledge, this is the first study to date to assess the risk of this outcome in a prospective, observational cohort. FundingMedical Research Council.

Biologic treatment response among adults with juvenile idiopathic arthritis: results from the British Society for Rheumatology Biologics Register.

Objective. To describe the use of and response to biologic therapies commenced in adults with JIA.Methods. Patients with arthritis onset <16 years were identified from the British Society for Rheumatology Biologics Register for rheumatoid arthritis (BSRBR-RA) and stratified into ILAR JIA subtypes. Patterns of biologic use and treatment persistence were explored, with disability levels (HAQ) and remission rates [28-Joint Disease Activity Score (DAS28)] evaluated at 6 and 12 months.Results. Arthritis with an onset of <16 years was confirmed in 225 patients and the ILAR subtype was determined in 154 (68%). Only 58 (26%) patients had a diagnosis of JIA recorded in the BSRBR-RA. The median age at biologic commencement was 31 years [interquartile range (IQR) 23–39] and 76% were female. The biologic therapies were etanercept (49%), infliximab (28%), adalimumab (22%) and anakinra (1%). Fifty per cent of patients received more than one biologic during follow-up (2 agents, n = 64; ≥3 agents, n = 49). Treatment persistence at 1 year was 78% (95% CI 71%, 82%), falling to 42% (95% CI 34%, 49%) at 5 years. Both the HAQ and DAS28 improved significantly at 6 months, with 21% and 28% of patients in remission (DAS28 < 2.6) at 6 and 12 months, respectively.Conclusion. This study describes patterns and identifies outcomes of biologic use in a national cohort of adults with JIA. With no national guidance currently available in this area, the choice of first biologic was inconsistent, although treatment outcomes were good. These data confirm that biologic therapies are an important treatment option in adults with active JIA in adulthood.