Discontinuation of methotrexate in rheumatoid arthritis patients achieving clinical remission by treatment with upadacitinib plus methotrexate (DOPPLER study)

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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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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Prevalence of ultrasound-detected residual synovitis and risk of relapse and structural progression in rheumatoid arthritis patients in clinical remission: a systematic review and meta-analysis

Rheumatology ◽

10.1093/rheumatology/keu217 ◽

2014 ◽

Vol 53 (11) ◽

pp. 2110-2118 ◽

Cited By ~ 71

Author(s):

Huong Nguyen ◽

Adeline Ruyssen-Witrand ◽

Frédérique Gandjbakhch ◽

Arnaud Constantin ◽

Violaine Foltz ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systematic Review ◽

Clinical Remission ◽

Meta Analysis ◽

Structural Progression ◽

Risk Of Relapse

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OP0217 Ultrasound-Detected Synovitis and Tenosynovitis Independently Associate with Flare in Patients with Rheumatoid Arthritis in Clinical Remission

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.4927 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 153.1-153 ◽

Cited By ~ 1

Author(s):

E. Bellis ◽

C.A. Scirè ◽

G. Carrara ◽

A. Adinolfi ◽

A. Batticciotto ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Remission

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Patients with Rheumatoid Arthritis in Clinical Remission Manifest Persistent Joint Inflammation on Histology and Imaging Studies

The Journal of Rheumatology ◽

10.3899/jrheum.140411 ◽

2014 ◽

Vol 41 (11) ◽

pp. 2153-2160 ◽

Cited By ~ 26

Author(s):

Allen Anandarajah ◽

Ralf Thiele ◽

Ellen Giampoli ◽

Johnny Monu ◽

Gwy-Suk Seo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Clinical Remission ◽

Severe Disease ◽

Joint Inflammation ◽

Imaging Studies ◽

American College Of Rheumatology ◽

Remission Criteria ◽

Magnetic Resonance Imaging Mri ◽

Active Inflammation

Objective.The purpose of our study was to test the hypothesis that synovitis on magnetic resonance imaging (MRI) and ultrasound (US) observed in patients with rheumatoid arthritis (RA) who meet remission criteria reflects active inflammation on histopathology.Methods.We analyzed 15 synovial specimens obtained during surgical procedures from 14 patients with RA in clinical remission as defined by the American College of Rheumatology criteria. Histological specimens were scored for hyperplasia of synovial lining and synovial stroma, inflammation, lymphoid follicles, and vascularity. The histology scores were classified as minimal, mild, moderate, or severe disease activity. US and MRI performed within a 4-month period of surgery were scored for disease activity. The correlation between histology and imaging scores was examined.Results.Four of 14 patients were receiving anti-tumor necrosis factor (TNF) therapy, 4 were receiving methotrexate (MTX) alone, 4 were taking MTX and hydroxychloroquine (HCQ), and 1 was taking HCQ and sulfasalazine. Four specimens had severe, 6 moderate, 3 mild, and 2 minimal disease activity on histology. Three of 4 specimens with minimal and mild histology were observed in subjects receiving anti-TNF therapy. Synovitis was noted on greyscale in 80% of joints and Doppler signal in 60%. MRI demonstrated synovitis and bone marrow edema in 86% of images. Positive but not significant correlations were noted between histology and synovitis scores on US.Conclusion.Despite clinical remission, histology and imaging studies documented a persistently active disease state that may explain the mechanism for radiographic progression.

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