AB0334 Very high titer of anti-citrullinated protein antibodies is associated with the achievement of clinical remission by abatacept in biologic-naïve patients with rheumatoid arthritis (the abroad study)

Background:In the idividuals with genetic and enviromental risk factors, immune events at mucosal surfaces occur and may precede systemic autoimmunity. Anti-citrullinated protein antibodies (ACPA) are present in the serum for an average of 3-5 years prior to the onset of rheumatoid arthritis (RA) during an asymptomatic period. In ACPA-positivite individuals, the additional presence of RA-related risk factors appears to add significant power for the development of RA. To date, there have been few reports in which clinical courses of ACPA-positive asymptomatic individuals were investigated prospectively.Objectives:To observe the clinical time course of ACPA-positive healthy population for the development of RA.Methods:Healthy volunteers without joint pain or stiffness, who attended the comprehensive health screening of our hospital, were enrolled in this prospective observational study. The serum ACPA levels were quantified by Ig-G anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay with levels > 4.4 U/mL considered positive. ACPA-positive subjects were followed by rheumatologists of our department clinically or a questionnaire sent by mail for screening to detect arthritis.Results:5,971 healthy individuals without joint symptons were included. Ninty-two (1.5%) were positive for ACPA. Of these, 19 (20.7%) developed RA and two were suspected as RA by mail questionnaire. Their average age were 58-years, and women were 68%. The average duration between the date of serum sampling and diagnosis was 10.7 months. ACPA-positive individuals who developed to RA had higher serum ACPA and Ig-M rheumatoid factor levels than ACPA-positive individuals who did not (P value by Mann-Whitney U test: 0.002, 0.005, respectively).Conclusion:Among ACPA-positive asymptomatic individuals, 20% developed RA. The higher titer of ACPA and Ig-M rheumatoid factor levels are risk factors for devoloping RA.Disclosure of Interests:None declared

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AB0144 PREDICTIVE FACTORS OF SUSTAINED CLINICAL REMISSION IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3555 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1099.2-1099

Author(s):

R. Fakhfakh ◽

N. El Amri ◽

K. Baccouche ◽

H. Zeglaoui ◽

E. Bouajina

Keyword(s):

Rheumatoid Arthritis ◽

Predictive Factors ◽

Clinical Remission ◽

Power Doppler ◽

Health Assessment ◽

Sustained Remission ◽

Sharp Score ◽

Remission Criteria ◽

Ultrasound Parameters

Background:Sustained remission (SR) is an ultimate treatment goal in the management of patients with rheumatoid arthritis (RA) (1) and is associated with better RA prognosis, reflected by the quality of life, physical function and radiographic progression (2).Objectives:To investigate the prevalence and predictors of SR in RA patients.Methods:A longitudinal prospective study of patients with RA. At the inclusion, the patients were in remission DAS28 ESR≤ 2.6 for at least 6 months. A B-mode and power doppler (PD) ultrasound of 42 joints and 20 tendons was performed. Synovial hypertrophy (SH) and tenosynovitis in B-mode and PD were defined and scored from 0 to 3 using the OMERACT. The CDAI, SDAI, Boolean remission criteria, the health assessment questionnaire (HAQ) and the radiological Sharp score were calculated. Then, the DAS28 erythrocyte sedimentation rate (ESR) was evaluated at 6 and 12 months. SR was defined as the persistence of a DAS28 ESR≤2.6 at 6 or 12 months without any change in RA therapy during the follow-up. Unstable remission (UR) was defined either as DAS28 ESR > 2.6 at 6 or 12 months or an increase in RA therapy because of a relapse during the follow-up.Results:At baseline, thirty-seven patients were included. At 6 and 12 months, 28 and 24 patients completed follow-up, respectively. In decreasing order, Boolean remission (92.2%), DAS28ESRremission (85.7%), SDAI remission (85%) and CDAI remission (83.3%) achieved SR at 6 months. At 12 months, SR was found in 100% in Boolean remission, 87.5% in SDAI remission, 86.7% in CDAI remission and in 79.7% in DAS28 ESR remission. At 6 months, only the ESR (17mm/1h in SR versus 32 mm/1h in UR, p=0.04) was associated with SR. The disease duration, remission duration, swollen and tender joints, DAS28ESR, HAQ, rheumatoid factor, radiological Sharp score and ultrasound parameters weren’t associated with SR. At 12 months, the squeeze test (15% in SR vs 80% in UR, P=0.01), the ESR (15 mm/1h in SR versus 30 mm/1h in UR, p=0.03), the Boolean remission (61.1% in SR versus 0% in UR, p=0.04) and the DAS28ESR (mean: 1.8 in SR versus 2.5 in UR, P=0.01) were associated with SR. However, no association was found with radiological Sharp score and ultrasound parameters. On multivariate analysis, the ESR (OR=1.13, CI95%=1.01-1.2, p=0.03) and the Squeeze test (OR=21.3, CI95%=1.7-263, p=0.01) were predictors of SR, at 12 months.Conclusion:At 6 and 12 months, 79.7%-85.7% of patients in DAS28 ESR remission achieved sustained remission, respectively. Boolean and DAS28 ESR remission were associated with SR. Unlike DAS28 ESR, Boolean remission seems to reflect more the SR. The squeeze test and the ESR were predictors’ factor. However, the radiological and the ultrasound parameters didn’t show any association.References:[1]Ajeganova S, Huizinga T. Sustained remission in rheumatoid arthritis: latest evidence and clinical considerations. Ther Adv Musculoskelet Dis. 2017;9(10):249-62.[2]Xie W, Li J, Zhang X, Sun X, Zhang Z. Sustained clinical remission of rheumatoid arthritis and its predictive factors in an unselected adult Chinese population from 2009 to 2018. Int J Rheum Dis. 2019;22(9):1670-8.Disclosure of Interests:None declared

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ASSOCIATIONS BETWEEN SERUM ANTIBODIES TO PERIODONTAL PATHOGENS AND PRECLINICAL PHASES OF RHEUMATOID ARTHRITIS

Rheumatology ◽

10.1093/rheumatology/keab097 ◽

2021 ◽

Author(s):

Daniel Manoil ◽

Delphine S Courvoisier ◽

Benoit Gilbert ◽

Burkhard Möller ◽

Ulrich A Walker ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Primary Outcome ◽

Signs And Symptoms ◽

Serum Levels ◽

Study Cohort ◽

Periodontal Pathogens ◽

Serum Antibodies ◽

Current Smoking ◽

Clinical Arthritis ◽

Citrullinated Protein

Abstract Objectives To examine whether serum antibodies against selected periodontal pathogens are associated with early symptoms of rheumatoid arthritis (RA) development in healthy individuals at risk of developing the disease. Methods Within an ongoing study cohort of first-degree relatives of patients with RA (RA-FDRs), we selected four groups corresponding to specific preclinical phases of RA development (n = 201). (1) RA-FDR controls without signs and symptoms of arthritis nor RA-related autoimmunity (n = 51); (2) RA-FDRs with RA-related autoimmunity (n = 51); (3) RA-FDRs with inflammatory arthralgias without clinical arthritis (n = 51); (4) RA-FDRs who have presented at least one swollen joint (“unclassified arthritis”) (n = 48). Groups were matched for smoking, age, sex and shared epitope status. The primary outcome was IgG serum levels against five selected periodontal pathogens and one commensal oral species assessed using validated-in-house ELISA assays. Associations between IgG measurements and preclinical phases of RA development were examined using Kruskal-Wallis or Mann-Whitney tests (α = 0.05). Results None of the IgGs directed against individual periodontal pathogens significantly differed between the four groups of RA-FDRs. Further analyses of cumulated IgG levels into bacterial clusters representative of periodontal infections, revealed significantly higher IgG titers against periodontopathogens in anti-citrullinated protein antibodies (ACPA)-positive RA-FDRs (p = 0.015). Current smoking displayed a marked trend towards reduced IgG titers against periodontopathogens. Conclusion Our results do not suggest an association between serum IgG titers against individual periodontal pathogens and specific preclinical phases of RA development. However, associations between cumulative IgG titers against periodontopathogens and the presence of ACPAs suggest a synergistic contribution of periodontopathogens to ACPA development.

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AB0235 RITUXIMAB (BIOSIMILAR) IN RHEUMATOID ARTHRITIS: CLINICAL & IMMUNOLOGICAL RESPONSE TO VARYING DOSES- EXPERIENCES FROM A TERTIARY CARE CENTER IN SOUTH INDIA

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3794 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1143.2-1144

Author(s):

J. Antony ◽

R. Sankaralingam ◽

R. Maheshwari ◽

B. Chilukuri ◽

S. Chinnadurai

Keyword(s):

Rheumatoid Arthritis ◽

Computed Tomography ◽

Interstitial Lung Disease ◽

Complete Remission ◽

Lung Disease ◽

Clinical Remission ◽

Clinical Indication ◽

Fixed Dose ◽

Double Negative ◽

Lung Involvement

Background:Rituximab (RTX) is a chimeric monoclonal antibody against CD20. There is a paucity of studies done with RTX biosimilars. This is a Retrospective and Observational study from January 2018 to December 2019 done in the Department of Clinical Immunology & Rheumatology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India.Objectives:1.To find the effects of varying doses of RTX in attaining clinical remission in RA.2.To find if CD19, CD20 & IgG help in identifying impending flare & if these levels help in deciding the timing of the next dose of RTX.Methods:Rheumatoid arthritis (RA) cases who were given Rituximab from January 2018 were selected. Clinical Response at 6 & 12 months & wherever feasible at 18 & 24 months was assessed by Simplified Disease Activity index (SDAI). RTX initial dose was given at 0 and 14 days followed by fixed dose at six months interval.CD19, CD20 B cell count, IgG levels were tested in patients in whom it was feasible at baseline & 6 months (select patients at 12,18 &24 months). Patients were divided in to 5 groups (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and (500mg & 1g). Patients were divided into three clinical groups, (DMARD naïve, DMARD resistant & Interstitial Lung disease (ILD) [Lung involvement>20% in Computed Tomography (CT)]) and two treatment groups (500mg & 1g) based on clinical indication for RTX and dose of RTX, respectively. In patients with ILD, CT scan & FVC were compared at baseline & 12 months.Results:29 patients (seropositive 28 (RF/Anti CCP/BOTH+VE), seronegative 1) were given RTX for RA over a 2-year period of which 12 had CD19, CD20 & IgG tested. Mean SDAI reduction from baseline to 6 months post treatment was 30%, 32% & 14% while complete remission (SDAI<3.3) was attained in 100%, 18% & 20% in DMARD naïve, DMARD resistant & ILD groups, respectively. CD19, CD20 & IgG reduced from 18.6%, 18.4% & 18.53g/L to 3.7%,3.7% & 9.7g/L respectively FVC improved from 62.4% to 67% at 12. The percentage of patients with lung involvement >20% reduced from 53.3% to 46.7%. Flare was observed in one patient who received 500mg RTX. CD19, CD20 & IgG levels increased from 7.9%, 8% & 9.8g/L to 27%, 25% & 13g/L respectively. 3 patients in the 1g group were followed up at 12,18 & 24 months. In these patients there were no flares or worsening symptoms. 1 patient was double negative for RF & Anti CCP and this patient did not attain clinical remission even after 2 doses of 1g RTX.Conclusion:[1]Patients with early arthritis (diagnosis made within 1 year) and who were DMARD naïve had an excellent response to Rituximab.[2]Complete remission was observed in more patients the 1g compared to 500mg group.[3]Reduction in CD19 & CD20 was associated with significant reduction in the SDAI score.[4]There was no significant reduction of CD19 & CD20 with 500mg dose of Rituximab where either a partial remission or mild flare was observed.[5]There was reduction in the lung involvement to less than 20%(CT) in few patients with 1g dose.[6]Double negative Rheumatoid arthritis poorly responded to Rituximab.[7]The positive effects of 1g Rituximab could be noted up to 24 months.[8]Flare of RA was associated with significant increase in CD19 & CD20.Disclosure of Interests:None declared

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AB0189 ASSESSMENT OF POWER DOPPLER SYNOVITIS IN RHEUMATOID ARTHRITIS PATIENTS WITH CLINICAL REMISSION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.6064 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1394.2-1394

Author(s):

R. Fakhfakh ◽

N. El Amri ◽

K. Baccouche ◽

H. Zeglaoui ◽

E. Bouajina

Keyword(s):

Rheumatoid Arthritis ◽

Functional Capacity ◽

Clinical Remission ◽

Power Doppler ◽

Health Assessment ◽

Disease Flare ◽

Synovial Hypertrophy ◽

The Mean ◽

Grade 3 ◽

Subclinical Synovitis

Background:Ultrasound-detected synovitis, mainly synovial Doppler signal, has shown predictive value in relation to radiographic damage progression and disease flare or relapse in rheumatoid arthritis (RA) patients with clinical remission.Objectives:The aim of the study was to analyze the correlation between power Doppler scores and clinical/laboratory and radiographic data in clinical remission RA patients.Methods:Cross-sectional study including patients with RA in clinical remission defined by: DAS28ESR ≤ 2.6, without disease flare or changes in therapy in the previous 6 months. Each patient underwent ultrasound: B-mode and PD assessments of 36 joints and 20 tendons in the Rheumatology Department over a period of 6 month. Synovitis and tenosynovitis were defined and scored according to the Outcome Measures in Rheumatology Clinical Trials (OMERACT). Radiological measurements included the modified Sharp/van der Heijde method (SHS). Functional capacity was assessed by the Health Assessment Questionnaire (HAQ).Results:Thirty two patients were enrolled, the mean age was 53.7±13.4 and 75% were female. The mean disease duration was 15 years ± 8.8. Subclinical synovitis were the most frequent in wrist (56.3%), 2ndmetacarpophalangeal joints (28.1%) and 2ndmetatarsophalangeal joints (29%). The mean subclinical synovitis/ tenosynovitis numbers was 4±3.1 per patient. Synovial hypertrophy and B mode tenosynovitis were detected in 93.8%: 71.3% had a grade = 2 and 9.8% had a grade= 3. Total B mode score was correlated only with the SHS score in the feet (r: 0.4, p: 0.03). PD signal was detected in 62.5% of patients: 37.5% had a grade =2 and 9.4% had a grade= 3. Total PD score was correlated with DAS28 (r:0.42, p:0.02), the SHS score in the hands (r:0.39, p:0.03) and in the feet (r:0.5, p:0.007), synovial hypertrophy (r:0.6, p:0.0001) and HAQ (r:0.32, p:0.06). No correlation was found with CDAI, SDAI, swollen joint counts, tender joint counts, patient global health assessment, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor and anti-cyclic citrullinated peptide, biologic treatment.Conclusion:Synovial hypertrophy and PD signal were frequent in RA remission. PD signal was associated with RA activity, radiologic damage and functional capacity.References:[1]Yan Geng & Jingjing Han & Xuerong Deng and al. Presence of power Doppler synovitis in rheumatoid arthritis patients with synthetic and/or biological disease-modifying anti-rheumatic drug-induced clinical remission: experience from a Chinese cohort. Clinical Rheumatology 2014. DOI 10.1007/s10067-014-2634-yDisclosure of Interests:None declared

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POS0460 ASSOCIATION OF ANTI-CITRULLINATED PROTEIN ANTIBODIES OF IgA SUBCLASSES WITH SUSTAINED REMISSION AND FLARE IN RHEUMATOID ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2004 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 461-461

Author(s):

M. V. Sokolova ◽

J. Rech ◽

M. Hagen ◽

G. Schett ◽

U. Steffen (née Harre)

Keyword(s):

Rheumatoid Arthritis ◽

Enzyme Linked Immunosorbent Assay ◽

Sustained Remission ◽

Das28 Score ◽

Effector Functions ◽

Conventional Dmards ◽

The Impact ◽

Citrullinated Protein ◽

Iga Subclasses ◽

Over Time

Background:Understanding key mechanisms of flare development and sustained remission is one of the acute goals in modern rheumatology. Anti-citrullinated protein antibodies (ACPA) are the most abundant and specific autoantibodies in rheumatoid arthritis (RA) patients. However, the impact of ACPA of IgA isotype is poorly defined. IgA ACPA were previously shown to have a higher percentage of IgA2 in comparison to total IgA; and a correlation between IgA2% ACPA with the DAS28 score was observed in a previous study [1]. Of note, IgA1 and IgA2 were shown to exhibit different effector functions, with IgA2 being pro-inflammatory, which might be the background for its role in RA [1].Objectives:We aimed to investigate, whether IgA ACPA could be used as a predictive factor for flare development in RA; and to look further into the changes in IgA ACPA levels in patients remaining in stable remission versus patients developing flare.Methods:We analysed serum of 111 patients from a multicentre randomized controlled trial ‘RETRO’. The study observational period was 12 months. Patients in the trial had to be in stable remission (DAS28-ESR<2.6) for a minimum of 6 months and were randomized into 3 different treatment arms: continuation of treatment, tapering by 50% or a gradual tapering until discontinuation [2]. IgA ACPA concentrations were measured with an enzyme-linked immunosorbent assay on CCP2-pre-coated plates.Results:60% of patients had IgG-ACPA. IgA ACPA levels were higher among the IgG-ACPA-positive patients (median 4.7 versus 2.24 µg/ml, p<0.0001). Baseline IgA1 and 2 ACPA levels were not different between patients who had a flare later on in the study period and those remaining in remission, showing no predictive value for flare development. However, the percentage of IgA2 in ACPA was correlating with the first registered DAS28 after flare (r=0.36, p=0.046). After the 12 months study period, IgA2 ACPA as well as IgA2% ACPA decreased significantly in patients who remained in stable remission by 17.5% (median, p<0.0001) and 13.6% (p=0.0006), respectively. By contrast, there was no significant change in IgA2 ACPA levels over time in patients who developed a flare. IgA1 ACPA levels remained stable over time. Disease management strategies did not seem to influence IgA ACPA levels in a specific way, as baseline levels were similar between patients on biological and conventional DMARDs and changes in levels after 12 months did not depend on the assignment to either of the study arms.Conclusion:Neither IgA1 nor IgA2 ACPA levels were predictive of flare development or associated with treatment strategies (though rituximab, JAK-inhibitors and abatacept were not amongst treatment options). However, in patients remaining in sustained remission after 1 year a decrease in IgA2 and IgA2% ACPA was observed and IgA2% ACPA was associated with DAS28 score registered after flare. This could be an indication towards ACPA of IgA2 isotype contributing to the severity of flare, alongside other factors, and its reduction being associated with a prolonged state of remission.References:[1]Steffen U, Koeleman CA, Sokolova MV, et al. IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun 11, 120 (2020).[2]Haschka J, Englbrecht M, Hueber AJ, et al. Relapse rates in patients with rheumatoid arthritis in stable remission tapering or stopping antirheumatic therapy: interim results from the prospective randomised controlled RETRO study. Ann Rheum Dis. 75:45-51 (2016).Disclosure of Interests:None declared

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