Line bDMARDs Research Articles

Impact of conventional and biological disease-modifying anti-rheumatic drugs on arterial lesions in Takayasu arteritis.

The definition of Takayasu arteritis (TAK) remission and disease activity is still unclear. Vascular imaging is an essential tool for following-up patients. Herein, we aimed to compare the evolution of vascular lesions (ie vessel wall thickening and stenosis) under conventional disease-modifying anti-rheumatic drugs (cDMARDs) relatively to biological DMARDs (bDMARDs) in TAK patients followed with the same CT angiography modalities. We compared 75 lines of therapy in TAK patients who received cDMARDs (n = 40 lines) and bDMARDs (n = 35 lines) using CT angiography. We established 1-3 main target vessels with vessel wall thickening and/or stenosis. Every targeted vessel had its thickness and its lumen diameter measured at the initiation of immunosuppressive treatment and at 12 months. We observed an overall reduction of arterial wall thickness in 73% of cases and 31% had >25% of wall thickness relative decrease. Using a linear mixed effects model, first line immunosuppressive therapy (p= 0.012) and bDMARDs relatively to cDMARDs (p= 0.026) were independently associated with vessel wall thickness reduction in TAK. Thirty-eight percent of the stenotic vessels had a > 25% relative increase in lumen diameter under immunosuppressive therapy. The relative increase >25% in lumen diameter was noted in 56% vs 17% with bDMARDs compared with cDMARDs. Immunosuppressive treatments can reduce arterial wall thickness and widen lumen diameter in TAK. bDMARDs seems to be more effective than cDMARDs to improve arterial lesions in TAK.

OA01 No difference in risk of myocardial infarction among patients receiving either IL6 or TNF inhibitors for rheumatoid arthritis

Abstract Background/Aims Interleukin 6 inhibitors (IL-6i) can increase LDL cholesterol levels, which raises concerns about the risk of myocardial infarction (MI) in patients with rheumatoid arthritis (RA) receiving this therapy. This study aims to compare the risk of MI between people with RA in the UK clinical setting receiving IL-6i or tumour necrosis factor inhibitors (TNFi) overall or by line of therapy (LoT). Methods Patients with RA registered between 01/10/2001 and 27/05/2022 with BSRBR-RA starting IL-6i or TNFi treatments were included. Occurrence of MI was identified from clinical follow-up forms and through cause of death reported by the national UK death register. Only those MIs occurring whilst the patient was actively receiving drug were included. The risk of MI in patients receiving IL6i compared to TNFi was compared using Cox regression, adjusted for baseline co-variates using propensity scores (PS, see Table 1). Follow-up commenced at the start of the drug of interest and patients were censored at occurrence of MI, death, discontinuation of therapy or last follow-up visit, whichever came first. Multiple imputation was used for missing data. To account for known differences in LoT use of TNFi and IL6i (with IL6i more likely as a later line bDMARD), overall analyses adjusted for LoT in PS and secondary analyses by LoT were conducted. Direct switches between originator to biosimilars were considered the same treatment. Results A total of 29,596 IL6i or TNFi treatments in 20,725 patients were included (3,098 IL-6i; 26,498 TNFi), representing 153,913 person-years of exposure. Compared to patients receiving TNFi, patients starting IL-6i treatment were older, had longer disease duration, less likely to use methotrexate and steroids, and had more comorbidities. During follow-up, 372 MIs occurred, 27 on IL-6i and 345 on TNFi, with an overall lower crude rate of MI in patients receiving IL6i compared to TNFi. After PS adjustment, the risk of MI was not significantly different between the two treatment overall (HR 0.77, 95% CI 0.48-1.24) or when stratified by LoT (Table 1). Conclusion This study could not identify any difference in risk of MI between IL-6i and TNFi treatment after patient characteristics and LoT were considered. Disclosure Z. Tian: None. L. Kearsley-Fleet: None. K. Lauper: Honoraria; Celltrion, Pfizer, Viatris, Galapagos. S. Haughton: None. K. Watson: None. M. Lunt: None. J. Mclaughlin: None. A. Verma: None. K.L. Hyrich: Honoraria; Abbvie. Grants/research support; Pfizer, BMS.

P282 ANA seroconversion during prior anti-TNF therapy abolishes anti-CCP antibody positivity as a predictor of abatacept retention in rheumatoid arthritis

Abstract Background/Aims Few long-term drug survival analyses have been reported for patients with rheumatoid arthritis (RA) treated with abatacept. Here we report a machine learning approach to investigate drug-survival of abatacept over 5 years in RA patients. Methods We performed a retrospective observational study on a tertiary hospital dataset of RA patients who started abatacept between January 2008 and December 2020. Time to abatacept discontinuation over 5 years was estimated using Kaplan-Meier survival analyses. A multivariate cox-proportional hazard model to predict abatacept discontinuation was chosen by random survival forest and partial least regression. Results A total of 112 RA patients (81% female, mean age 58.1 [SD 13.5] years) received abatacept. Mean disease duration was 18.3 months (SD 13.6). More than half (65/112) were co-prescribed at least one conventional synthetic DMARD (csDMARD). Methotrexate was the most frequently concomitant csDMARD (n = 37), followed by hydroxychloroquine (n = 23), sulfasalazine (n = 15), and leflunomide (n = 7). 42 (37.5%) patients were treated with glucocorticoids (intermittent or continuous) with abatacept. Abatacept was mostly used as 4th (n = 29) and 3rd line (n = 24) bDMARD, but 19 patients received abatacept as their first line bDMARD. 75 (67%) patients were rheumatoid factor (RF) positive and 73 (65.2%) were anti-citrullinated protein antibody (ACPA) positive. Anti-nuclear antibody (ANA) was positive (≥1:80) in 25 patients (pre-biologics) and 18 seroconverted to previously exposed anti-TNF (ANA seroconversion group). Abatacept was discontinued in 54 patients (48.2%); 19 (35.2%) due to an adverse event and 35 (64.8%) due to loss of efficacy. Overall, the median time to discontinuation of abatacept was 3.8 years. Multivariate cox-proportional hazard model revealed that ACPA positivity was associated with reduced risk of abatacept discontinuation with HR of 0.56 (95% CI 0.32-0.95,p=0.03) compared to the ACPA-negative group. In contrast, the ANA seroconversion group demonstrated worse retention of abatacept with HR of 2.67 (95% CI 1.39-5.16, p = 0.0033) compared to ANA-negative patients. Kaplan-Meier analysis demonstrated that in the ANA seroconversion group, retention of abatacept was significantly inferior to pre-anti-TNF ANA positive patients (p = 0.0084) and ANA-negative patients (p = 0.0041). ACPA positivity was associated with better survival only in the non-ANA seroconverted group with HR of 0.54 (95% CI 0.29-0.92, p = 0.041), after adjusted by propensity score. Combining abatacept with any csDMARDs reduced the risk of abatacept discontinuation with HR of 0.57 (95% CI 0.33-0.98, p = 0.043) after adjusting by propensity score. No statistical difference was found between first-line, second-line, or any subsequent chronology of use of abatacept. Conclusion Our data suggest that previous ANA seroconversion occurring whilst on anti-TNF therapy reduces subsequent abatacept retention and cancels out the protective effect of anti-CCP positivity. The mechanism through which this occurs is unclear and further prospective and mechanistic studies are needed to validate these findings. Disclosure J. Kimpton: None. M. Shipa: Grants/research support; MS is funded by Versus Arthritis. S. Yeoh: Grants/research support; SY is funded by the Royal College of Physicians, Rosetrees Trust, NIHR University College London Hospitals Biomedical Research Centre, UCLH Charities, and Versus Arthritis. E. Hawkins: None. M. Ehrenstein: Grants/research support; ME is supported (in part) by the University College London Hospital Biomedical Research Centre.

POS1034 RESPONSE TO SEQUENTIAL LINES OF BIOLOGICAL THERAPY IN PSORIATIC ARTHRITIS: A SINGLE CENTRE COHORT STUDY

Background:Biologic interventions using highly specific immuno-modulatory biologic disease-modifying anti-rheumatic drugs (bDMARDs) represent a rapidly developing therapeutic approach to the treatment of Psoriatic Arthritis (PsA). However, despite high rates of response, adverse events, primary and secondary inefficacy are common, and multiple sequential lines of bDMARDs are often required. Data on drug persistence, as a surrogate for response, from national registries indicates switching has become accepted routine practice. One third of patients will fail or discontinue their first biologic with a significant proportion switching on to a 3rd biologic or higher.1-4 Due to a lack of evidence on the response to sequential therapies, individual patients may not have further lines routinely funded after three bDMARDs in the UK. While limiting lines of therapy remains a UK concern, many countries with rationed healthcare systems follow the UK model of drug usage.Objectives:To describe the response to sequential lines of bDMARD therapy prescribed in routine care in a UK single centre cohort.Methods:A retrospective sample of patients with PsA who fulfilled CASPAR criteria and had received at least one bDMARD were taken from the Bath longitudinal cohort for inclusion in the study. Clinical and laboratory variables that constitute physician and patient-reported outcome measures were collected at baseline and after a median (range) follow-up of 3 months (2-5) into their respective therapy line in accordance with the National Institute for Health and Care Excellence (NICE) rules. The mean change with a 95% confidence interval (CI) was used to report the difference between the baseline and follow-up measures. All patients provided consent to use their data collected during routine care, and ethical approval by the local committee was granted.Results:The patients mean age was 57.7 (SD 12.2) with a median (range) disease duration of 14.4 years (9.7 – 23.2). Data was available for 194 patients commencing 1st line bDMARD, 106 (2nd line), 93 (3rd line), 33 (4th line), 12 (5th line), and 9 (6th line and higher) from a total of 759 patients in the cohort. Mean tender and swollen joint count at baseline 1st bDMARD was 7 (SD 4.7) and 22 (SD 14.0), pain visual analogue scale 50 (SD 27.6) and PASI 1.3 (SD 2.2). Reasons for changing biological therapies include lack or loss of efficacy, intolerance, side effects, and comorbidities. Mean levels of joint disease at drug initiation did not diminish with subsequent lines of therapy. Clinical and patient reported outcomes by line of therapy are reported in Figure 1. Clinical responses were greatest to first line bDMARD, however clinically relevant DAPSA improvements were seen up to 5th line. Absolute levels of psoriasis in the cohort were low, however improvement in PASI was achieved across all lines of therapy. Patient and Physician Global Assessments (1-5 on Likert scale) and the Pain Visual analogue score (VAS on 1-10 Likert scale) showed a similar trend with greatest improvement to first line treatment across all lines of therapy.Conclusion:In this study we report the clinical response to sequential lines of bDMARD therapy for active PsA in routine clinical practice. Clinical response was greatest to the first line bDMARD but overall improvement in DAPSA, PASI or pain response did not appear to diminish up to 5th line. Further study in larger cohorts is required to confirm this finding and build on our understanding of clinical response to sequential lines of bDMARD therapy.

The first biological choice in patients with rheumatoid arthritis: data from the Moroccan register of biotherapies.

Introductionthe aim of our study is to determine, from data of the Moroccan register of biotherapies, the factors influencing the choice of the first prescribed biological treatment.Methodscross-sectional multicenter study including rheumatoid arthritis patients who were initiated the first biological treatment either: Rituximab, an anti-TNF, or Tocilizumab. The determinants related to the patient and disease have been gathered. A univariate and then multivariate analysis to determine the factors associated with the choice of the first bDMARDs was realized.Resultsa total of 225 rheumatoid arthritis patients were included in the Moroccan registry. The mean age was 52 ± 11 years, with female predominance 88% (n = 197). The first prescribed biological treatment was Rituximab 74% (n = 166), the second one was Tocilizumab, 13.6% (n = 31) then comes the anti-TNF in 3rd position with 12.4% (n = 28). The factors associated with the choice of Rituximab as the first line bDMARDs prescribed in univariate analysis were: the insurance type, the positivity of the rheumatoid factor. In multivariate analysis, only the insurance type that remains associated with the choice of Rituximab as the first biological drugs. The Tocilizumab was associated with shorter disease duration and was more prescribed as mono-therapy compared to non Tocilizumab group. TNFi was associated with the insurance type.Conclusionour study suggests that Rituximab and TNFi are associated with the type of insurance and Tocilizumab is the most prescribed biologic mono-therapy in RA patients. Further studies are needed to confirm these results.

OP0014 COMPARISON OF ANTERIOR UVEITIS OCCURRENCE DURING TREATMENT WITH SECUKINUMAB, ADALIMUMAB, INFLIXIMAB AND ETANERCEPT IN SPONDYLOARTHRITIS

Background:Randomized controlled trials indicate that compared to tumor necrosis factor inhibitors (TNFi), secukinumab (SEC) has similar efficacy regarding axial inflammation in spondyloarthritis (SpA), better efficacy regarding cutaneous psoriasis, but is inferior in inflammatory bowel disease (IBD). However, the efficacy of SEC compared to TNFi in anterior uveitis (AU) has not been extensively studied.Objectives:To compare the occurrence of AU in patients with SpA treated with SEC, adalimumab (ADA), infliximab (IFX) or etanercept (ETN), in clinical practice.Methods:Patients with ankylosing spondylitis or undifferentiated SpA starting either SEC, ADA, IFX or ETN, in 2015 through 2017, were identified in the Swedish Rheumatology Quality register, and were linked to the national patient register for identification of AU. AU-flares were defined as the number of visits with an AU diagnosis, separated by a ≥60 days penalty interval, within ophthalmology outpatient care, during the respective bDMARD treatment.Follow-up started at the bDMARD initiation, and ended at the first of Dec 31st2017, death, emigration or discontinuation date of the bDMARD.To assess and accommodate treatment channeling, crude incidence rates for AU-flares were determined (A) for all bDMARD treatment starts, (B) excluding patients with an AU diagnosis during the year prior to the bDMARD start, and (C) in addition, excluding all first line bDMARD treatment starts.Hazard ratios (HR) for time until a first on-treatment AU diagnosis were estimated using Cox regression (ADA=reference), adjusted for sex, age, and any history of AU, and estimating robust confidence intervals to account for the individuals contributing multiple lines of treatment.Results:In total, 2,684 patients (52% women) contributed 3,255 treatment initiations. SEC was less frequently used as first line bDMARD and there was channeling of patients with previous AU, towards treatment with ADA, and away from ETN (Table 1). Further, AU occurred almost exclusively in patients with a pre-treatment history of AU (data not shown).Table 1.AnalysisTreat-ment starts, NPrevious AU1Age at treat-ment start, mean (sd)N Previous bDMARD, medianHR (95% CI) for first AU-diagnosisAU flares, NFollow-up2, yearsA. All treatment starts, N=3255SEC33321%48 (13)22.0 (1.2-3.3)52241ADA87234%44 (12)1Ref175973IFX71421%43 (14)00.9 (0.6-1.4)68677ETN133617%44 (14)00.9 (0.7-1.3)1021290B. Excluding patients with prior AU within 1 year before treatment start, N=2907SEC30413%47 (13)23.1 (1.4-7.3)10212ADA71119%44 (13)1Ref18792IFX63311%43 (14)01.0 (0.4-2.3)8599ETN125912%44 (14)01.8 (1.0-3.4)431204C. Excluding patients with prior AU within 1 year before treatment start and first line bDMARD, N=1288SEC28414%48 (13)22.5 (1.0-6.2)10198ADA37418%45 (13)1Ref11384IFX18512%45 (14)21.3 (0.4-4.0)4166ETN44517%47 (14)11.9 (0.9-4.0)234391) Anterior uveitis between 2001 and treatment start; 2) Total follow-up time for analyses of incidence rate.The incidence rates of AU-flares were higher for SEC and ETN compared to ADA and IFX, in the analyses (B, C) accommodating for channeling, figure 1.Compared to ADA, the adjusted HRs of a first on-treatment AU-diagnosis were also higher for SEC and ETA, Table 1.Conclusion:In clinical practice, SEC and ETN are associated with a higher incidence of AU than ADA and INF, suggesting a poorer protective effect of SEC and ETN against AU. These preliminary results should be interpreted in light of pronounced treatment channeling, which was only partly accommodated for.Disclosure of Interests:Ulf Lindström: None declared, Karin Bengtsson: None declared, Tor Olofsson: None declared, Daniela Di Giuseppe: None declared, Bente Glintborg Grant/research support from: Grants from Pfizer, Biogen and Abbvie, Helena Forsblad-d’Elia Grant/research support from: Unrestricted grant from Novartis., Consultant of: Advisory Board Fees from Sandoz, Novartis, and Abbvie, Lennart T.H. Jacobsson Consultant of: AbbVie, Eli Lilly, Janssen, Novartis and Pfizer, Johan Askling Grant/research support from: JA acts or has acted as PI for agreements between Karolinska Institutet and the following entities, mainly in the context of the ARTIS national safety monitoring programme of immunomodulators in rheumatology: Abbvie, BMS, Eli Lilly, Merck, MSD, Pfizer, Roche, Samsung Bioepis, Sanofi, and UCB Pharma

P283 Clinical predictors of switching biologic treatment in patients PsA: data from a single centre over 17 years

Abstract Background Management of PsA has included biologic agents (bDMARDs) since the early 2000s, in addition to conventional disease-modifying antirheumatic drugs (csDMARDs). Switching of bDMARD treatment is currently common clinical practice in treatment failure. Our aims were to determine the most prescribed first line bDMARDs, reasons for switching and any clinical factors at baseline that may predict switching in PsA. Methods Data was analysed retrospectively from a cohort of 400 PsA patients followed through from 2002-2019. Statistical analysis was carried out (logistic regression, analysis of variance and descriptive statistics) using SPSS version 22. Results The median age at baseline was 38.4 years (interquartile range [IQR] 29.8 - 53.3 years), 52.5% were female. bDMARDs were started in 220 of the 400 patients (55.0%). Initial therapy was a TNFi in 212 patients (96.3%). The median age of those started on bDMARDs was 33.7 years (IQR 27.5 - 48.2 years), 52.5% were female. The most frequently prescribed was adalimumab (59.5%), followed by etanercept (33.2 %) and infliximab (3.2%). 106 out of the 220 patients (48.2%) were on at least one concomitant csDMARD. 83 patients (37.8%) switched to a second bDMARD; 69 of these (83.1%) switched to a second TNFi. The commonest reasons for switching were primary or secondary inefficacy (61.0%) and adverse events (33.7%). The median duration on the first bDMARD was 11.6 months (IQR 3.8 - 30.1 months). Of the 83 patients who commenced a second bDMARD, 45 (54.2%) switched to a third bDMARD. The median duration on the second bDMARD was 10.0 months (IQR 3.0 - 33.0 months). The main reasons for the second switch were primary or secondary inefficacy (44.4%), adverse events (42.2%) and a combination of the two (11.1%). Patients who switched onto a second bDMARD were more frequently female (57.8%), had longer disease duration (14.01 versus 13.2 years), higher pain scores (84.2 versus 66.0) and higher tender/swollen joint counts compared to non-switchers at baseline. Patients using csDMARDs at baseline were more often responsive to initial bDMARD treatment than those on bDMARD alone (63.2% response versus 45.1%), but this was not statistically significant (p value >0.05). There was no significant change in drug survival of the first bDMARD if the patient was concurrently taking csDMARDS. A high ESR at baseline was associated with increased risk of switching from a second bDMARD to a third (odds ratio 1.20, p = 0.036). Conclusion We found that females, those with longer disease duration, higher subjective elements to disease activity at baseline were more likely to switch from initial bDMARD therapy. A high baseline ESR was associated with switching onto a third line bDMARD. Interestingly, the concurrent use of csDMARDs had no significant effect on the drug survival or efficacy of bDMARD therapy. Disclosures M. Naja None. L. R. Santos None. M. Greenwood None. M. Castelino None.

P282 Outcome for PsA biologic switchers following primary inefficacy of TNFi therapy in a secondary care cohort: sequential TNFi versus switching mode of action

Abstract Background TNFi are the most used first line of biologic disease modifying anti-rheumatic drugs (bDMARDs) in PsA. In primary loss of response (PLR) to TNFi, there is no current evidence that directs the choice of second line bDMARDs. Our aim in this work was to compare drug survival for those who switched to a second TNFi versus alternative agents in real life. Methods Data was analysed retrospectively from a cohort of 400 PsA patients followed through from 2002-2019. Statistical analysis was carried out with descriptive statistics and t-test analysis using SPSS version 22. Results Out of 400 patients, 220 (55.0%) were started on bDMARD treatment. Of these 220, 212 (96.5%) were started on TNFi as initial therapy. PLR was seen in 42 of these patients (19.8%). The median drug survival of initial TNFi therapy was 7.1 months (interquartile range [IQR] 3.6 - 53.4 months). Of the 42 patients with PLR: 32 (76.2%) were switched to a second TNFi; 6 (14.3%) were switched to ustekinumab and 4 (9.5%) were switched to secukinumab. 21 of the 32 patients switched to a second TNFi were subsequently switched onto a third biologic due to treatment failure (65.6%). The median drug survival of the second TNFi in this group was 7.7 months (IQR 3.0 - 26.3 months). 3 out of the 6 (50%) patients who were switched to ustekinumab were then subsequently switched, this was due to primary inefficacy in 66.7% and adverse events in 33.3%. The median drug survival of ustekinumab in this group was 10.0 months (IQR 0.0 - 16.0 months). All 4 patients switched to secukinumab continue on this treatment with no drop outs, giving a median drug survival 12.3 months (IQR 6.5 - 19.5 months). Conclusion Our data suggests that patients with PLR to TNFi in PsA who switched mode of action to IL-17 inhibitor appeared to have better drug survival than subsequent TNFi or IL-12/23 inhibitors. Exploring the clinical biomarkers for those with successful switch to non-TNFi bDMARD in a larger cohort would help with targeting the most appropriate individuals and early disease control. Disclosures M. Naja None. L. R. Santos None. M. Shipa None. G. Mandy None. M. Castelino None.

PMS44 COMPARISON OF REAL-WORLD PERSISTENCE OF SUBCUTANEOUSLY ADMINISTERED BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUG THERAPIES AMONG PATIENTS WITH RHEUMATOID ARTHRITIS SWITCHING FROM ANOTHER BIOLOGIC

To compare persistence of subcutaneously administered biologic disease modifying antirheumatic drugs (bDMARDs) in patients with rheumatoid arthritis (RA) as subsequent-line therapy following a failure of first line bDMARDs. US administrative claims data were used to create a longitudinal cohort of adult patients with RA initiating abatacept (n=2,988), adalimumab (n=3,599), certolizumab (n=982), etanercept (n=2,760), golimumab (n=745), or tocilizumab (n=1,630) between 1/1/2012 and 6/30/2017 (initiation date = index). Patients were required to have failed 1st bDMARD to enter study (but could later switch therapy) and to have 6 and 3 months of continuous enrollment pre- and post-index (date of prescription for bDMARD). Those with other autoimmune conditions were excluded from the study. Outcomes were biologic persistence, defined in two alternative ways: 1) number of days between initiation date and last supplied day of last fill (primary); 2) time patients were on bDMARDs until they switched or had a gap >90 days (secondary). Generalized Equation Models were used to compare outcomes for tocilizumab versus other biologics, adjusting for differences in baseline characteristics, accounting for correlation among different bDMARD episodes. There were 10,301 patients with 12,704 bDMARD episodes; mean age 51.0-53.3. Mean [SD] Elixhauser comorbidity scores were significantly higher (p<0.001) for tocilizumab (2.8 [2.3]) compared to abatacept (2.5 [2.2]), adalimumab (2.5 [2.1]), certolizumab (2.4 [2.0]), etanercept (2.4 [2.0]), or golimumab (2.4 [2.2]). Adjusted mean days (95% CI) for primary persistence were: abatacept 324 (313, 335); adalimumab 299 (289, 310); certolizumab 281 (262, 301); etanercept 302 (290, 313); golimumab 303 (281, 326); and tocilizumab 334 (318, 349). Tocilizumab had significantly (p < 0.05) higher persistence compared to other biologics, except abatacept. Results were similar for secondary persistence. Among patients with RA who previously used ≥1 other biologic, tocilizumab-treated patients had similar or statistically significantly better biologic persistence compared with other biologics.

Anti-nuclear antibody development is associated with poor treatment response to biological disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis

BackgroundIt has been well known that TNF-α inhibitor (TNFi) treatment for patients with rheumatoid arthritis (RA) is associated with anti-nuclear antibody (ANA) development. We previously reported that ANA development was associated with poor outcomes of infliximab (IFX) treatment (1). However, no replication studies have been reported to date. In addition, whether the findings are true to general biological disease-modifying anti-rheumatic drugs (bDMARDs) is uncertain. MethodsTo evaluate an association between treatment response and ANA development during bDMARDs treatment in RA and to analyze correlates of ANA development, Japanese RA patients treated with (n = 657) or without (n = 211) bDMARDs as a first line bDMARD were enrolled from a single center cohort. ANA was measured by an indirect immunofluorescence assay at multiple time points of treatment. We analyzed associations between ANA development and insufficient response to treatment. Correlates of ANA development were also analyzed. ResultsANA development (≥2 times baseline levels) at 3 months and at 6–12 months after bDMARDs initiation were significantly associated with insufficient response at 3–12 months (odds ratio (OR)=3.51, p = 0.020) and at 12–24 months (OR = 3.16, p = 0.038), respectively. The associations remained significant after conditioning on the use of each bDMARD. The use of IFX (OR = 6.24, p < 0.001) was a risk for ANA development, and other TNFi showed the same tends as infliximab. On the other hand, non-TNFi bDMARDs were not associated with ANA development. ConclusionsANA development could be a marker of poor treatment response in RA patients undergoing bDMARDs treatment. Undefined factors might influence ANA development and subsequent poor bDMARDs outcome in RA.

Biological treatment in ankylosing spondylitis in the Nordic countries during 2010–2016: a collaboration between five biological registries

Objectives: Large-scale observational cohorts may be used to study the effectiveness and rare side effects of biological disease-modifying anti-rheumatic drugs (bDMARDs) in ankylosing spondylitis (AS), but may be hampered by differences in baseline characteristics and disease activity across countries. We aimed to explore the research infrastructure in the five Nordic countries regarding bDMARD treatment in AS.Method: This observational cohort study was based on data from biological registries in Denmark (DANBIO), Sweden (SRQ/ARTIS), Finland (ROB-FIN), Norway (NOR-DMARD), and Iceland (ICEBIO). Data were collected for the years 2010–2016. Registry coverage, registry inventory (patient characteristics, disease activity measures), and national guidelines for bDMARD prescription in AS were described per country. Incident (first line) and prevalent bDMARD use per capita, country, and year were calculated. In AS patients who started first line bDMARDs during 2010–2016 (n = 4392), baseline characteristics and disease activity measures were retrieved.Results: Registry coverage of bDMARD-treated patients ranged from 60% to 95%. All registries included extensive prospectively collected data at patient level. Guidelines regarding choice of first line drug and prescription patterns varied across countries. During the period 2010–2016 prevalent bDMARD use increased (p < 0.001), whereas incident use tended to decrease (p for trend < 0.004), with large national variations (e.g. 2016 incidence: Iceland 10.7/100 000, Finland 1.7/100 000). Baseline characteristics were similar regarding C-reactive protein, but differed for other variables, including the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (range 3.5–6.3) and Ankylosing Spondylitis Disease Activity Score (ASDAS) (2.7–3.8) (both p < 0.0001).Conclusion: Collaboration across the five Nordic biological registries regarding bDMARD use in AS is feasible but national differences in coverage, prescription patterns, and patient characteristics must be taken into account depending on the scientific question.

Long-term persistence with rituximab in patients with rheumatoid arthritis.

ObjectivesTo investigate the long term persistence of rituximab (RTX) in a large observational RA cohort, investigate persistence of RTX when used as a first or second line biologic DMARD (bDMARD), to characterize subsequent bDMARD treatment following RTX. MethodsPatients with RA starting treatment with RTX (MabThera) between 2008 and 2011 were recruited into the British Society for Rheumatology Biologics Register for RA. Duration of RTX treatment over the first 4 years after initiation was estimated via Kaplan-Meier estimates and the reason for discontinuation was ascertained. Subsequent bDMARD use following RTX discontinuation was characterised. Treatment survival in bDMARD-naïve (first line RTX use) and experienced (second line RTX use) cohorts was described.ResultsOne thousand six hundred and twenty-nine patients were recruited (1371 bDMARD-experienced and 258 bDMARD-naïve). Sixty percent of the whole cohort remained on RTX after 4 years. Ineffectiveness (46%) and death (24%) were the most common reason for RTX discontinuation. RTX discontinuation was associated with RF negativity for the bDMARD-experienced cohort. Of those that discontinued RTX, 46% initiated treatment with another bDMARD, with tocilizumab being the most common.ConclusionThis large study of patients initiating RTX treatment for severe RA found that 60% persisted with treatment after 4 years. This study also identified that RTX is tolerated well when used as a first or second line bDMARD.

THU0168 Monotherapy with Biological Disease-Modifying Anti-Rheumatic Drugs-Data from the Czech Registry Attra

BackgroundThe biological disease-modifying anti-rheumatic drugs (bDMARDs) should be used for the treatment of rheumatoid arthritis (RA) in combination with conventional synthetic DMARDs (csDMARDs). However a significant proportion of patients receive...