AB0240 PREDICTORS OF RESPONSE TO BIOLOGIC AGENTS IN RHEUMATOID ARTHRITIS

Background:In rheumatoid arthritis (RA), the ‘treat-to-target’ therapeutic approach imposes rigorous control of disease activity. Although biological agents have been shown to be effective, these therapies fail sometimes to achieve therapeutic goals.Objectives:In this study we tried to determine predictive factors of good therapeutic response to biologic disease-modifying antirheumatic drugs (bDMARD).Methods:This is a retrospective study including 374 Tunisian patients who received their first biotherapy between 2014 and 2016. Categorical variables were reported in numbers and percentages, while quantitative variables were expressed by mean with standard deviations. The univariate analysis was performed using the student t-test or the Chi2 test. Multivariate analysis was performed by binary logistic regression.Results:Average age of our cohort was 55 ± 12.5 years with a female predominance of 87.2%. The average duration of RA was 11.7 ± 6.7 years. Rheumatoid factors were positive in 79% and ACPA were positive in 72% of cases. After the introduction of biotherapy, low disease activity (LDA) or remission was achieved in 55% of cases (206 patients).No statistically significant difference between biotherapy responder and non-responder groups for age (55.7 vs. 54.7 years; p = 0.44), gender (Female: 86.5% vs. 88.7%; p = 0.08) and disease duration (12 years vs. 11.4 years; p = 0.41). A significant difference between the two groups was found for the positivity of rheumatoid factors (76.4% vs. 88.9%; p = 0.004), methotrexate’s association (65% vs. 53.4%; p = 0.02) and corticosteroids’ use (50% vs. 66.5%; p < 0.001).Positive predictive factors of remission or LDA by biotherapy were female sex (Odds Ratio = 2.2; p = 0.026), presence of rheumatoid factors (Odds Ratio = 2.64; p = 0.001), association with methotrexate (Odds Ratio = 1.69; p = 0.028). Whereas, corticosteroid use (OR = 0.41; p < 10-3) was a negative predictor of disease control by bDMARDs.Conclusion:Achieving LDA low level or even remission is currently achievable with biological treatments. Certain factors need to be studied in order to optimize RA treatment and adapt the right bDMARD for each patient.Disclosure of Interests:None declared

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Anti-carbamylated Protein Antibodies and Serum Level of 14-3-3 Protein for Early Detection of Rheumatoid Arthritis Patient in Correlation with Rheumatoid Factor, Anti-CCP Antibodies, Disease Activity and Joint Damage using High Frequency Musculoskeletal Ultrasound

Applied Clinical Research Clinical Trials and Regulatory Affairs ◽

10.2174/2213476x07666200120111549 ◽

2020 ◽

Vol 7 (2) ◽

pp. 141-153

Author(s):

Sahar A. Ahmed ◽

Enas M. Darwish ◽

Walaa A. Attya ◽

Mai Samir ◽

Mennatallah Elsayed ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Rheumatoid Factor ◽

Disease Activity Score ◽

Joint Damage ◽

Musculoskeletal Ultrasound ◽

Activity Score ◽

Das 28 ◽

Significant Difference ◽

Hands And Feet

Background: Rheumatoid arthritis (RA) is a common progressive chronic inflammatory autoimmune disease which affects mostly small joints, causing pain, swelling, deformity, and disability. Although progress has been made in exploring RA nature, still there is a lot to know about the disease pathogenesis, diagnosis, and treatment. Aim of the Work: To investigate the role of serum anti-carbamylated protein antibodies and 14-3-3η in the diagnosis of RA compared to rheumatoid factor (RF), anti-CCP antibodies, and highfrequency musculoskeletal ultrasound used to assess the disease activity and joint damage. Methods: Serum anti-carbamylated protein antibodies and 14-3-3η were measured using ELISA in 61 RA patients and 26 normal controls. RA Disease Activity Score (DAS 28), X-ray and musculoskeletal ultrasound (hands and feet), carotid ultrasound (Intima-Media Thickness IMT) were used in assessing the RA disease. Results: Anti-carbamylated protein antibodies were significantly elevated in RA patients 4.5 (4.1- 8.9 U⁄ml) compared to the control 3.2(1.9- 4.3 U⁄ml) (p< 0.001) but 14-3-3η showed no significant difference. There was a significant positive correlation between anti-carbamylated protein antibodies, 14-3-3η levels and disease activity score assessed by DAS 28, increased IMT measured by carotid duplex, total synovitis and total erosion score were assessed by musculoskeletal ultrasound. There was no correlation between RF and anti-CCP antibodies. Anti-carbamylated protein antibodies were found to have 66.7% sensitivity and 85.2% specificity in RA diagnosis, while 14- 3-3η had 51.9% sensitivity and 72.1% specificity. Conclusion: Anti-carbamylated protein antibodies and 14-3-3η have a high sensitivity and specificity in RA diagnosis and had a correlation with the disease activity and joint damage.

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POS1234 IMPACT OF THE CHANGE IN ADMINISTRATION ROUTE OF TOCILIZUMAB AND ABATACEPT, DUE TO THE COVID-19 LOCKDOWN ON DISEASE ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3126 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 900.1-900

Author(s):

L. Diebold ◽

T. Wirth ◽

V. Pradel ◽

N. Balandraud ◽

E. Fockens ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Physical Activity ◽

Disease Activity ◽

Univariate Analysis ◽

Route Of Administration ◽

Anxiety And Depression ◽

Administration Route ◽

Factors Associated ◽

The Impact

Background:Among therapeutics used to treat rheumatoid arthritis (RA), Tocilizumab (TCZ) and Abatacept (ABA) are both biologic agents that can be delivered subcutaneously (SC) or intravenously (IV). During the first COVID-19 lockdown in France, all patients treated with IV TCZ or IV ABA were offered the option to switch to SC administration.Objectives:The primary aim was to assess the impact of changing the route of administration on the disease activity. The second aim was to assess whether the return to IV route at the patient’s request was associated with disease activity variation, flares, anxiety, depression and low physical activity during the lockdown.Methods:We conducted a prospective monocentric observational study. Eligibility criteria: Adult ≥ 18 years old, RA treated with IV TCZ or IV ABA with a stable dose ≥3 months, change in administration route (from IV to SC) between March 16, 2020, and April 17, 2020. The following data were collected at baseline and 6 months later (M6): demographics, RA characteristics, treatment, history of previous SC treatment, disease activity (DAS28), self-administered questionnaires on flares, RA life repercussions, physical activity, anxiety and depression (FLARE, RAID, Ricci &Gagnon, HAD).The primary outcome was the proportion of patients with a DAS28 variation>1.2 at M6. Analyses: Chi2-test for quantitative variables and Mann-Whitney test for qualitative variables. Factors associated with return to IV route identification was performed with univariate and multivariate analysis.Results:Among the 84 patients who were offered to switch their treatment route of administration, 13 refused to change their treatment. Among the 71 who switched (48 TCZ, 23 ABA), 58 had a M6 follow-up visit (13 lost of follow-up) and DAS28 was available for 49 patients at M6. Main baseline characteristics: female 81%, mean age 62.7, mean disease duration: 16.0, ACPA positive: 72.4%, mean DAS28: 2.01, previously treated with SC TCZ or ABA: 17%.At M6, the mean DAS28 variation was 0.18 ± 0.15. Ten (12.2%) patients had a DAS28 worsening>1.2 (ABA: 5/17 [29.4%] and TCZ: 5/32 [15.6%], p= 0.152) and 19 patients (32.8%) had a DAS28 worsening>0.6 (ABA: 11/17 [64.7%] and TCZ: 8/32 [25.0%], p= 0.007).At M6, 41 patients (77.4%) were back to IV route (26 TCZ, 15 ABA) at their request. The proportion of patients with a DAS28 worsening>1.2 and>0.6 in the groups return to IV versus SC maintenance were 22.5%, 42.5% versus 11.1% and 22.2% (p=0.4), respectively. The univariate analysis identified the following factors associated with the return to IV route: HAD depression score (12 vs 41, p=0.009), HAS anxiety score (12 vs 41, p=0.047) and corticosteroid use (70% vs 100%, p=0.021), in the SC maintenance vs return to IV, respectively.Conclusion:The change of administration route of TCZ and ABA during the first COVID-19 lockdown was infrequently associated with a worsening of RA disease. However, the great majority of the patients (77.4%) request to return to IV route, even without disease activity worsening. This nocebo effect was associated with higher anxiety and depression scores.Disclosure of Interests:None declared

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POS0305 PHYSICIAN AND PATIENT ATTITUDES TOWARDS TREAT-TO-TARGET, ITS IMPLEMENTATION AND STATED TREATMENT GOALS IN PATIENTS WITH RHEUMATOID ARTHRITIS IN A REAL-WORLD SETTING ACROSS EUROPE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.893 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 378-379

Author(s):

B. Fautrel ◽

R. Caporali ◽

E. Holdsworth ◽

B. Donaghy ◽

M. Khalid ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Real World ◽

Current Treatment ◽

High Disease Activity ◽

Clinical State ◽

Treat To Target ◽

Treatment Goals ◽

Research Support ◽

Reduction Of Pain

Background:The principles of treat to target (T2T) include defining an appropriate treatment target, assessed at pre-defined intervals, with a commitment to changing therapeutic approach if the target is not met (1). T2T is recommended as a key strategy for the treatment of rheumatoid arthritis (RA).Objectives:To explore attitudes towards T2T, its implementation and stated treatment goals among physicians and their patients with RA.Methods:The Adelphi RA Disease Specific Programme™ was a large, quantitative, point-in-time survey conducted amongst rheumatologists (n=296) and their consulting patients with RA (n=3042) in Europe (France, Germany, Italy, Spain, UK) between Q4 2019–Q3 2020. Physicians were recruited via publicly available lists, completing an online survey and medical record extraction for their next 10–12 consecutive patients. The same patients were invited to voluntarily complete a self-report questionnaire (n=1098, 36% response), collecting data on attitudes towards T2T and treatment goals.Results:Physicians reported that 76% of patients were in remission (DAS28: <2.6) or had low disease activity (DAS28: 2.6 – 3.2), and 24% had moderate-high disease activity (DAS28: >3.2). Patient mean age was 53.0 years (SD 14.0), mean time since diagnosis was 7.2 years (SD 7.2). The proportion of patients currently receiving an advanced therapy (AT; defined as biologic or targeted synthetic DMARD) was 68%, of whom 70% were on a first line AT. No difference was observed between disease activity groups.In the physician survey, 86% of physicians stated they followed T2T principals in at least some of their RA patients, and would utilize a T2T approach in RA patients with moderate-high disease activity (61%), the most uncontrolled patients (37%) and those who do not respond well to initial therapy (34%). In this sample of real-world RA patients, 66% were reported by physicians to be on a T2T plan at the time of data collection. The most common physician-reported targets were remission (DAS28: <2.6) (75%), improvement of quality of life (QoL) (41%) and reduction of pain (31%), with 85% of physicians perceiving these treatment goals were fully or partially met. The most stated reasons for not implementing T2T was physician preference not to adjust current treatment (34%), patient preference not to adjust current treatment (23%), and there are no achievable goals for this patient (16%).Overall, 29% of patients reported they were involved in setting their T2T goals, while 34% stated their T2T goals were set by their physicians only, and 29% perceived no T2T goal had been set (n=620). The most common overall T2T goals from the patient perspective were remission (61%), controlling symptoms (41%), and reducing impact on QoL (34%). Of those patients who acknowledged a T2T goal had been set (n=407), 77% reported their T2T goal was fully or partially achieved.Of 719 patients who had moderate-high disease activity, 57% were on a T2T plan, with 46% of physicians perceiving these treatment goals were fully or partially met. The most common physician-stated reason for not implementing T2T was a lack of achievable targets (29%).Conclusion:Rheumatologists in this study reported a strong belief in T2T. The most common physician-set T2T goals were remission, improvement of QoL and reduction of pain, corresponding with T2T goals as reported by patients. However, a third of patients in this cohort were not aware of a defined T2T objective in their management, which may be a result of a perceived lack of achievable goals by physicians. It may be desirable to promote more patient involvement in defining achievable targets amongst those with moderate-high disease activity who despite best efforts may not reach a clinical state of remission. Further research is needed to identify and understand goals important to RA patients.References:[1]van Vollenhoven R. Treat-to-target in rheumatoid arthritis - are we there yet? Nat Rev Rheumatol. 2019;15(3):180-6.Acknowledgements:This study was funded by Galapagos NV, Belgium.Medical writing support was provided by Gary Sidgwick, PhD (Adelphi Real World, Bollington, UK) and editorial support was provided by Debbie Sherwood, BSc, CMPP (Aspire Scientific, Bollington, UK), both funded by Galapagos NV.Disclosure of Interests:Bruno Fautrel Consultant of: AbbVie, Amgen, Biogen, BMS, Celgene, Celltrion, Fresenius Kabi, Gilead, Janssen, Lilly, Medac, MSD, Mylan, NORDIC Pharma, Novartis, Pfizer, Roche, Sandoz, Sanofi-Genzyme, SOBI, UCB, Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Roberto Caporali Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Celltrion, Galapagos, Gilead, Lilly, Pfizer, Roche, UCB, Sanofi, Fresenius Kabi, Samsung Bioepis, MSD, Consultant of: Galapagos, Gilead, Lilly, Janssen, MSD, Elizabeth Holdsworth Employee of: Adelphi Real World, Bethany Donaghy Employee of: Adelphi Real World, Mona Khalid Shareholder of: Galapagos, Employee of: Galapagos, Mark Moore Shareholder of: Gilead Sciences, Speakers bureau: Gilead Sciences (only as employee), Paid instructor for: Gilead Sciences (only as employee), Consultant of: Gilead Sciences (only as employee), Grant/research support from: Gilead Sciences (only as employee), Employee of: Gilead Sciences, and previously Sanofi and AstraZeneca, Katrien Van Beneden Shareholder of: Galapagos, Employee of: Galapagos, Yves Piette Consultant of: AbbVie, Amgen, Galapagos, Grünenthal and Sandoz, Grant/research support from: Amgen, Mylan and UCB, Susana Romero-Yuste Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Grunenthal, Kern Pharma, Lilly, Roche, Sandoz, Sanofi, UCB, Janssen, Consultant of: AbbVie, Biogen, Fresenius, Galapagos, Gebro, Janssen, Lilly, Grant/research support from: Bristol Myers Squibb, MSD, Novartis, Pfizer, Jasper Broen Shareholder of: Pharming Group, Consultant of: Galapagos, Gilead, Novartis, Peter C. Taylor Consultant of: AbbVie, Biogen, Galapagos, Gilead, GlaxoSmithKline, Janssen, Lilly, Pfizer, Roche, Sanofi, Nordic Pharma, Fresenius, UCB, Grant/research support from: Celgene, Galapagos, Gilead, Lilly

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AB0655 RHEUMATOID ARTHRITIS ACTIVITY BEFORE AND AFTER COVID-19 LOCKDOWN PERIOD

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.576 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1360.1-1360

Author(s):

M. Jordhani ◽

D. Ruci ◽

F. Skana ◽

E. Memlika

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Musculoskeletal Diseases ◽

Statistical Tests ◽

Laboratory Data ◽

World Population ◽

Chronic Patients ◽

Das 28 ◽

Significant Difference ◽

Before And After

Background:The COVID-19 global pandemic has had a great impact on world population due to morbidity, mortality and restriction measures in order to stop the progression of COVID-19.Patients with rheumatic and musculoskeletic diseases, and especially rheumatoid arthritis (RA) patients, being one of the vulnerable classes of chronic patients, were recommended to follow the government’s rules1.Objectives:The aim of this study was to evaluate DAS-28-ESR in patients with rheumatoid arthritis before and after lockdown period.Methods:This is a multi-center observational study including 85 patients which were evaluated before and after lockdown for their disease activity score according to DAS-28-ESR score. They had been diagnosed with rheumatoid arthritis more than 5 years ago. A thorough physical examination was performed before and after the lockdown period. It included examination of tender and swollen joints and patient’s global health. They were completed with all required laboratory data, including erythrosedimentation rate. For a more accurate calculation, DAS-28-ESR was used in an electronic version. Patients with other inflammatory or infective diseases were excluded from the study. All data were statistically evaluated using statistical tests such as t-student test.Results:The first group (the one before lockdown) had an average DAS-28-ESR of 4.7 while after the lockdown period, the average DAS-28-ESR was 5.16.After statistically evaluating all data, it was found that there exists a significant difference between DAS-28-ESR score before and after COVID-19 lockdown (p=0.0011).Conclusion:Our study showed that lockdown period due to COVID-19 pandemic, has aggravated disease activity in patients with Rheumatoid Arthritis. This may be consequence of various causes such as physical inactivity and difficulty to follow-up or to take the medication properly.References:[1]Landewé RB, Machado PM, Kroon F, et al, EULAR provisional recommendations for the management of rheumatic and musculoskeletal diseases in the context of SARS-CoV-2, Annals of the Rheumatic Diseases 2020;79:851-858.Disclosure of Interests:None declared.

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AB1119 U9: A NOVEL CLINICALLY ORIENTED ULTRASONOGRAPHIC SCALE AS A USEFUL MARKER FOR MONITORING THERAPEUTIC RESPONSE IN RHEUMATOID ARTHRITIS (MULTI CENTERS STUDY)

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2733 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1848.2-1849

Author(s):

M. A. Mortada ◽

H. Eitta ◽

R. Elmallah ◽

A. Radwan ◽

A. Elsaman

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Laboratory ◽

Pearson Correlation ◽

Response To Treatment ◽

P Value ◽

Clinical Parameters ◽

Biologic Dmards ◽

Das 28 ◽

Significant Difference

Background:Musculoskeletal Ultrasonography (MSUS) is now a widely used tool for monitoring of rheumatoid arthritis (RA). Although there are many proposed sets of composite scores, a fixed set of joints may not be an ideal tool to assess a disease like RA, which affects many joints and tendons in different presentations. In previous study (1) U9 score was proven to be correlated with disease activity parameters.Objectives:To determine whether US assessment using U9 score is useful for monitoring response to treatment for RA or not?Methods:A prospective, multicenter study were conducted in period from July 2019 to December 2019. All recruited RA patients were subjected to: Disease activity assessment by clinical disease activity indices (CDAI and DAS28 ESR). Functional status assessment by (HAQ) and ultrasonographic assessment using U9 score which include 8 joints (bilateral wrists,2ndMCP,3RDMCP and knees) plus most clinically affected joint or tendon (one joint or one tendon). Most clinically affected joints from 48 joints. Any affected tendons could be choosing. All targeted joints were evaluated according to EULAR guidlines and by EULAR/ OMERACT combined score (0-3). Targeted tendons were scored (0-3).All patients received their treatment (biologic and non biologic DMARDs) according to the decision of the treating physicians. No specific therapy is needed. CDAI and DAS28 ESR, HAQ and U9 score were repeated after 3 months to detect the response to change after receiving the therapy.Results:One hundred and forty patients (23.6% were male) with mean age 39.26±11.30 were recruited from 4 tertiary referral university hospitals.There was a significant difference (<0.001) between the first and second visits as regards clinical, laboratory and ultrasonographic parameters. DAS 28 decreased form (5.29±1.21) to (3.95±0.99), ESR decreased from (42.12±15.24) to (26.84±12.32), HAQ2 improved from (0.652±0.350) to (0.510±0.237) and U9 total US score decreased from (13.56±5.18) to (8.02±4.28).There was significant correlation between U9 ultrasonographic score and clinical parameters at both visits (table 1).Table 1.correlation between U9 ultrasonographic score and clinical parameters.U9 at 1stvisitU9 at 2ndvisitDAS-28Pearson Correlation(P value)0.806<0.0010.790<0.001CDAIPearson Correlation(P value)0.787<0.0010.773<0.001HAQPearson Correlation(P value)0.431<0.0010.317<0.001We found that the most suitable cut-off value of U9 score to predict high disease activity was 11.5 (sensitivity 85.7% and specificity 80.6%), cut off value for moderate disease activity was 5.5(sensitivity 83.2% and specificity 88%) and cut off value for low disease activity was 3.5 (sensitivity of 83.3% and specificity 57.1%). These results are summarized in the following table:Conclusion:U9 ultrasonographic score is very useful method for evaluating the monitoring the response of treatment.References:[1]Mortada, et al. Annals of the Rheumatic Diseases 2019;78:1009.Disclosure of Interests:None declared

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SAT0581 SERIOUS INFECTION RATES WITH BIOLOGICAL DISEASE MODIFYING ANTI-RHEUMATIC AGENTS (bDMARDs) AND PREDISPOSING FACTORS: A 5-YEAR RETROSPECTIVE REVIEW

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.1137 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1249.1-1250

Author(s):

K. Celkys ◽

J. Ly ◽

M. Soden

Keyword(s):

Rheumatoid Arthritis ◽

Real World ◽

Retrospective Review ◽

Total Duration ◽

Predisposing Factors ◽

Baseline Risk ◽

Categorical Variables ◽

Significant Difference ◽

Disease Modifying ◽

Tract Infections

Background:Biological and targeted synthetic disease modifying anti-rheumatic agents (bDMARDs) increase the risk of serious infections (SIs), however there is limited ‘real-world’ evidence comparing the relative risk of SI for individual bDMARDs. (1,2)Objectives:This study examines the rates of SIs in a non-select Australian Northern Queensland (NQ) cohort of patients with various rheumatic diseases receiving treatment with a bDMARD, to define predisposing factors and directly compare the bDMARDs.Methods:A retrospective review was performed for all patients who received a bDMARD through the Townsville Hospital Rheumatology Department over the 5-year period between June 2013 and May 2018. Episodes of a SI were defined as infection requiring admission or use of intravenous antibiotics. For each bDMARD the rate of SI per 100 patient years (PYs) was calculated and patient demographics and comorbidities were analysed. Between group differences were assessed using independent samples t-tests or ANOVA. Where assumptions were violated, Mann-Whitney U tests or Kruskal-Wallis tests were used. For categorical variables, chi-square tests were used, except when assumptions were violated when Fisher’s Exact tests were used.Results:296 patients received bDMARDs with an overall SI rate of 11.7/100PYs. There was no significant difference in presence of SI by disease type with 24% of patients with rheumatoid arthritis versus 19% with psoriatic arthritis, 14% with ankylosing spondylitis and 29% with “other” (X2=3.11; df=3; p=0.37). Respiratory tract infections were the most common infection (46%) followed by skin and soft tissue infections (23%). The highest incidence rate of SI occurred with rituximab (29.72 SI/100PYs) followed by certolizumab (22.50 SI/100PYs) and tocilizumab (15.00 SI/100PYs). Duration of time on a bDMARD, disease duration and use of methotrexate or leflunomide were not shown to significantly increase the risk of SI for the entire cohort. The characteristics which were shown to significantly increase SI rates were; prednisone use, increasing age, chronic pulmonary comorbidity and specifically in those with rheumatoid arthritis male gender and total duration of bDMARD use.Conclusion:In this real-world NQ cohort of patients treated with a bDMARD for a rheumatic disease, we have identified a number of factors potentially contributing to the risk of the development of SIs. This study provides valuable data on SI rates in an Australian ‘real-world’ cohort that may assist clinicians’ choice of bDMARD in patients with a high baseline risk of infection and highlights the importance of minimising prednisone use in patients on bDMARDs.References:[1]Ramiro S, Sepriano A, Chatzidionysiou K, et al. Safety of synthetic and biological DMARDs: a systematic literature review informing the 2016 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis. 2017;76:1093–1101.[2]Singh J, Wells G, Christensen R, et al. Adverse effects of biologics: a network meta-analysis and Cochrane overview. Cochrane Database Syst Rev. 2011;16:CD008794.Disclosure of Interests: :Kate Celkys: None declared, Jason Ly: None declared, Muriel Soden Speakers bureau: Speaker Fees from Pfizer in 2016

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POS0495 LARGE JOINT DISEASE IN RHEUMATOID ARTHRITIS AND THE ROLE OF RHEUMATOID FACTOR. RESULTS FROM THE EARLY RHEUMATOID ARTHRITIS STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3626 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 480-480

Author(s):

S. S. Zhao ◽

E. Nikiphorou ◽

A. Young ◽

P. Kiely

Keyword(s):

Rheumatoid Arthritis ◽

Rheumatoid Factor ◽

Treatment Strategies ◽

Treat To Target ◽

Joint Involvement ◽

Aggressive Treatment ◽

Joint Surgery ◽

Large Joint ◽

Significant Difference ◽

Over Time

Background:Rheumatoid arthritis (RA) is classically described as a symmetric small joint polyarthritis with additional involvement of large joints. There is a paucity of information concerning the time course of damage in large joints, such as shoulder, elbow, hip, knee and ankle, from early to established RA, or of the influence of Rheumatoid Factor (RF) status. There is a historic perception that patients who do not have RF follow a milder less destructive course, which might promote less aggressive treatment strategies in RF-negative patients. The historic nature of the Ealy Rheumatoid Arthritis Study (ERAS) provides a unique opportunity to study RA in the context of less aggressive treatment strategies.Objectives:To examine the progression of large joint involvement from early to established RA in terms of range of movement (ROM) and time to joint surgery, according to the presence of RF.Methods:ERAS was a multi-centre inception cohort of newly diagnosed RA patients (<2 years disease duration, csDMARD naive), recruited from 1985-2001 with yearly follow-up for up to 25 (median 10) years. First line treatment was csDMARD monotherapy with/without steroids, favouring sulphasalazine for the majority. Outcome data was recorded at baseline, at 12 months and then once yearly. Patients were deemed RF negative if all repeated assessments were negative. ROM of individual shoulder, elbow, wrist, hip, knee, ankle and hindfeet joints was collected at 3, 5, 9 and 12-15 years. The rate of progression from normal to any loss of ROM, from years 3 to 14 was modelled using GEE, adjusting for confounders. Radiographs of wrists taken at years 0, 1, 2, 3, 5, 7, 9 were scored according to the Larsen method. Change in the Larsen wrist damage score was modelled using GEE as a continuous variable, while the erosion score was dichotomised into present/absent. Surgical procedure data were obtained by linking to Hospital Episodes Statistics and the National Joint Registry. Time to joint surgery was analysed using multivariable Cox models.Results:A total of 1458 patients from the ERAS cohort were included (66% female, mean age 55 years) and 74% were RF-positive. The prevalence of any loss of ROM, from year 3 through to 14 was highest in the wrist followed by ankle, knee, elbow and hip. The proportion of patients at year 9 with greater than 25% loss of ROM was: wrist 30%, ankle 12%, elbow 7%, knee 7% and hip 5%. Odds of loss of ROM increased over time in all joint regions, at around 7 to 13% per year from year 3 to 14. There was no significant difference between RF-positive and RF-negative patients (see Figure 1). Larsen erosion and damage scores at the wrists progressed in all patients; annual odds of developing any erosions were higher in RF-positives OR 1.28 (95%CI 1.24-1.32) than RF-negatives OR 1.17 (95%CI 1.09-1.26), p 0.013. Time to surgery was similar according to RF-status for the wrist and ankle, but RF-positive cases had a lower hazard of surgery at the elbow (HR 0.37, 0.15-0.90), hip (HR 0.69, 0.48-0.99) and after 10 years at the knee (HR 0.41, 0.25-0.68). Adjustment of the models for Lawrence assessed osteoarthritis of hand and feet radiographs did not influence these results.Figure 1.Odds of progression to any loss of ROM (from no loss of ROM) per year in the overall population and stratified by RF status.Conclusion:Large joints become progressively involved in RA, most frequently affecting the wrist followed by ankle, which is overlooked in some composite disease activity indices. We confirm a higher burden of erosions and damage at the wrists in RF-positive patients, but have not found RF-negative patients to have a better prognosis over time with respect to involvement of other large joints. In contrast RF-negative patients had more joint surgery at the elbow, hip, and knee after 10 years. There is no justification to adopt a less aggressive treatment strategy for RF-negative RA. High vigilance and treat-to-target approaches should be followed irrespective of RF status.Disclosure of Interests:None declared

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AB0115 COMPARISON OF ULTRASOUND FINDINGS BETWEEN TNF INHIBITORS AND NON-TNF INHIBITORS AT FIRST BIOLOGICS IN PATIENTS WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1377 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1086.2-1087

Author(s):

T. Okano ◽

T. Koike ◽

K. Inui ◽

K. Mamoto ◽

Y. Yamada ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Disease Duration ◽

Power Doppler ◽

Tnf Inhibitors ◽

Tnf Inhibitor ◽

Significant Difference ◽

The Us ◽

Us Findings ◽

Improvement Ratio

Background:In rheumatoid arthritis (RA), biologics treatment is one of the effective treatment options. Usually, there is no difference in therapeutic effect regardless of which biologics is used, but the effect for joint synovitis is unknown. Recently, ultrasound (US) has played a role of sensitive imaging modality in the diagnosis and follow-up of patients with RA.Objectives:The aim of this study was to compare the improvement of US findings between TNF inhibitors and non-TNF inhibitors at first biologics in patients with RA.Methods:Fifty-four RA patients who started the first biologics from September 2016 to December 2018 were included in this longitudinal study (SPEEDY study, UMIN000028260). All the patients were performed clinical examination, blood test and US examination at baseline, 4, 12, 24, 36 and 52 weeks. A US examination was performed at the bilateral first to fifth metacarpophalangeal (MCP) joints, first interphalangeal (IP) and second to fifth proximal interphalangeal (PIP) joints, wrist joints (three part of radial, medial and ulnar) and first to fifth metatarsophalangeal (MTP) joints, by using HI VISION Ascendus (Hitachi Medical Corporation, Japan) with a multifrequency linear transducer (18-6 MHz). The gray scale (GS) and power Doppler (PD) findings were assessed by the semi-quantitative method (0-3). GS score and PD score (both 0-108 points) were defined as the sum of each score. The change of disease activity and US findings were compared between TNF group and non-TNF group.Results:Among 54 cases, 32 patients were used TNF inhibitor and 22 were non-TNF inhibitor. Age and duration of RA were significantly higher in the non-TNF group, and MTX dose was significantly lower in the non-TNF group. The baseline inflammatory markers tended to be higher in the non-TNF group and the disease activity was also higher in the non-TNF group. However, the US findings showed no significant difference in both GS and PD between two groups at baseline. US improvement ratio was no difference between TNF group and non-TNF group at 4, 12, 24, 36 and 52 weeks in both GS and PD score. Regardless of the type of biologics, patients with long-term disease duration tended to have poor improvement in US synovial fingings.Table 1.Baseline patient and disease characteristicsTNF (n=32)non-TNF (n=22)P valueFemale patients, n (%)21 (65.6)16 (72.7)0.767Age (years)63.5±15.471.0±9.00.030Disease duration (years)6.5±8.213.0±11.70.032CRP (mg/dl)1.8±2.53.0±3.20.170DAS28-ESR5.0±1.45.8±1.20.022GS score26.1±18.831.8±21.10.313PD score17.6±11.423.1±14.60.150Figure 1.GS and PD improvement ratio at 4, 12, 24, 36 and 52 weeksConclusion:There was no difference in the US findings improvement between patients with TNF inhibitor and non-TNF inhibitor at first biologics in patients with RA.References:[1]Grassi W, Okano T, Di Geso L, Filippucci E. Imaging in rheumatoid arthritis: options, uses and optimization. Expert Rev Clin Immunol. 2015;11:1131-46.[2]Nishino A, Kawashiri SY, Koga T, et al. Ultrasonographic Efficacy of Biologic andTargeted Synthetic Disease-ModifyingAntirheumatic Drug Therapy in RheumatoidArthritis From a Multicenter RheumatoidArthritis Ultrasound Prospective Cohort in Japan. Arthritis Care Res (Hoboken). 2018;70:1719-26.Acknowledgements:We wish to thank Atsuko Kamiyama, Tomoko Nakatsuka for clinical assistant, Setsuko Takeda, Emi Yamashita, Yuko Yoshida, Rika Morinaka, Hatsue Ueda and Tomomi Iwahashi for their special efforts as a sonographer and collecting data.Disclosure of Interests:None declared

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POS0492 A MOLECULAR SIGNATURE RESPONSE CLASSIFIER PREDICTS THE LIKELIHOOD OF EULAR NON-RESPONSE TO TNF INHIBITOR THERAPIES IN RA: RESULTS FROM A RETROSPECTIVE COHORT ANALYSIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3396 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 478.2-479

Author(s):

L. Zhang ◽

C. van der Tog ◽

A. den Broeder ◽

T. Mellors ◽

E. Connolly-Strong ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Predictive Value ◽

Molecular Signature ◽

Response Criteria ◽

Treat To Target ◽

Inadequate Response ◽

Tnf Inhibitor ◽

Target Setting ◽

The Impact

Background:Following RA treatment recommendations, most people with rheumatoid arthritis (RA) begin targeted therapy with TNF inhibitors (TNFi), even though inadequate response to TNFi therapies is widespread. Treatment changes from one medication to the next are currently fueled by disease-activity measures and eventually result in disease control for most patients; however, this “trial-and-error” approach wastes precious time on ineffective treatments. A delay in reaching treat-to-target goals has a negative effect on patient burden and, possibly, disease progression.1 Useful predictors for TNFi response have been challenging to identify but a specific molecular signature response classifier (MSRC) test was shown to be predictive for inadequate response to TNFi therapies.2 The impact of such identification has the potential to result in improved patient outcomes, but further validation would be welcome, especially for response criteria other than ACR50, and in a stringent treat-to-target setting with lower baseline disease activity.Objectives:To validate the predictive value of the MSRC test in identifying those patients who do not meet EULAR good response criteria after 6 months of TNFi treatment.Methods:Data from a prospective cohort study conducted in the Sint Maartenskliniek (Nijmegen, the Netherlands) of RA patients who started adalimumab or etanercept TNFi as their first biologic were included.3 Baseline RNA samples and clinical assessments were used to identify patients who had a molecular signature1 of non-response to TNFi therapy. Outcomes were calculated at six months using DAS28-CRP-based EULAR good response, and high and low confidence responders and non-responders were identified using Monte Carlo simulation with 2,000 repeats and 70% precision cut off. Outcome measurements were blinded for test results. Treatment switch before 6 months was imputed as non-response. Odds ratios and area under the ROC curve (AUC) assessments were used to evaluate the ability of the MSRC test to predict inadequate response at 6 months against EULAR good response criteria.Results:A total of 68 out of 88 RA patients were identified to have a high-confidence response status and were included in analyses (Table 1). EULAR good response was observed in 45.5% (31/68) of patients. Patients were stratified according to detection of a molecular signature of non-response with an AUC of 0.61. The odds that a patient with the molecular signature of non-response at baseline failed to achieve a EULAR good response at 6 months was four times greater than that of a patient lacking the molecular signature (odds ratio 4.0, 95% confidence interval 1.2-13.3).Table 1.Patient demographicsCharacteristicRA patients (N = 68)Age, median (SD)57 (11)Female, n (%)43 (63.2)CCP positive, n (%)34 (50.0)RF positive, n (%)38 (55.9)Prescribed adalimumab at baseline, n (%)11 (16.2)Prescribed etanercept at baseline, n (%)57 (83.8)Conclusion:In this validation study, the molecular signature of non-response identified patients who did not fulfill the EULAR good response criteria to TNFi therapies. The patient selection process for this study had limitations; additional analysis in an alternative cohort would further verify the performance of the MSRC test. Nevertheless, the test, previously validated for ACR50, now has been validated using EULAR good response in a treat-to-target setting.References:[1]Schipper LG et al, Time to achieve remission determines time to be in remission. Arthritis Res Ther 201[2]Mellors T, et al. Clinical Validation of a Blood-Based Predictive Test for Stratification of Response to Tumor Necrosis Factor Inhibitor Therapies in Rheumatoid Arthritis Patients. Network and Systems Medicine 2020[3]Tweehuysen L et al. Predictive value of ex-vivo drug-inhibited cytokine production for clinical response to biologic DMARD therapy in rheumatoid arthritis. Clin Exp Rheumatol 2019Disclosure of Interests:Lixia Zhang Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Celeste van der Tog: None declared, Alfons den Broeder Consultant of: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Grant/research support from: Abbvie, Amgen, Cellgene, Roche, Biogen, Lilly, Novartis, Celltrion Sanofi, Gilead., Ted Mellors Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Erin Connolly-Strong Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Johanna Withers Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Alex Jones Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation, Viatcheslav Akmaev Shareholder of: Scipher Medicine Corporation, Employee of: Scipher Medicine Corporation

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AB0302 USE OF TNF-INHIBITORS BEFORE, DURING AND THE FIRST YEAR AFTER PREGNANCY AMONG WOMEN WITH RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3622 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1450.2-1450

Author(s):

H. Bjørngaard ◽

H. Koksvik ◽

B. Jakobsen ◽

M. Wallenius

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Post Partum ◽

Tnf Inhibitors ◽

Treat To Target ◽

Inflammatory Rheumatic Diseases ◽

Tnf Inhibitor ◽

Rheumatic Arthritis ◽

Quality Register ◽

In Pregnancy

Background:Treat to target is a goal, also in pregnant women with Rheumatoid arthritis (1). There is increasing evidence on safe use with TNF inhibitors during pregnancy. Adjusted use of TNF inhibitors preconception and throughout pregnancy may stabilize disease activity and prevent flares (2). Low disease activity is also beneficial for the fetus.Objectives:To study the use of TNF-inhibitors among women with Rheumatic arthritis during and after pregnancy.Methods:RevNatus is a Norwegian, nationwide quality register that monitors treatment of inflammatory rheumatic diseases before, during and after pregnancy. Data from RevNatus in the period October 2017 to October 2019 was used to map the use of all types of TNF inhibitors among 208 women with rheumatoid arthritis, diagnosed by the ACR/EULAR criteria. The use of medication was reported at the time of visit in outpatient clinic. The frequency of use of TNF inhibitors registered at seven timepoints from pre-pregnancy to twelve months after delivery.Results:The use of medication was reported at each visit for all the women with rheumatoid arthritis. Most of the women were not using TNF inhibitors before and beyond conception. Most of the women continuing TNF inhibitors beyond conception used certolizumab or etanercept. Adalimumab and infliximab were used in pregnancy (tabell 1).Tabell 1.certoliz-umabetane-rceptadalim-umabgolim-umabinflixi-mabNo TNF-inhibitorBefore pregnancyn=10521% (22)9% (10)3% (3)1% (1)66% (69)1.trimestern=8119% (15)10% (8)71% (58)2.trimestern=8810% (9)10% (9)80% (70)3.trimestern=9111% (10)5% (5)83% (76)6 weeks post partum n=9622% (21)13% (13)1% (1)1% (1)63% (60)6 months post partum n=8824% (21)18% (16)4% (4)1% (1)53% (46)12 months post partum n=8421% (18)17% (15)7% (6)2% (2)53% (43)Conclusion:Most of the women with rheumatic arthritis were not treated with TNF inhibitors before or in pregnancy. Women with rheumatic arthritis that continuing treatment with TNF inhibitors through pregnancy were using certilozumab and etanercept.References:[1]Gotestam Skorpen C, Hoeltzenbein M, Tincani A, Fischer-Betz R, Elefant E, Chambers C, et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. 2016;75(5):795-810.[2]van den Brandt S, Zbinden A, Baeten D, Villiger PM, Ostensen M, Forger F. Risk factors for flare and treatment of disease flares during pregnancy in rheumatoid arthritis and axial spondyloarthritis patients. Arthritis Res Ther. 2017;19(1):64.Disclosure of Interests:None declared

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