Circulating miR-145 as a marker of therapeutic response to anti-TNF therapy in patients with ankylosing spondylitis

Circulating miRNAs appear promising therapeutic and prognostic biomarkers. We aimed to investigate the predictive value of circulating miRNAs on the disease outcome following anti-TNF therapy in patients with ankylosing spondylitis (AS). Our study included 19 AS patients assessed at baseline (M0), after three (M3) and twelve months (M12) of therapy. Total RNA was isolated from plasma. A comprehensive analysis of 380 miRNAs using TaqMan Low Density Array (TLDA) was followed by a single assay validation of selected miRNAs. All AS patients had high baseline disease activity and an excellent response to anti-TNF therapy at M3 and M12. TLDA analysis revealed the dysregulation of 17 circulating miRNAs, including miR-145. Single assay validation confirmed that miR-145 is significantly downregulated at M3 compared to baseline. The decrease in the levels of miR-145 from M0 to M3 negatively correlated with the change in BASDAI from M0 to M3; and positively correlated with disease activity improvement from M3 to M12 as per BASDAI and ASDAS. The predictive value of the early change in miR-145 and levels of miR-145 at M3 were further validated by Receiver operating curves analysis. We show that the early change in circulating miR-145 may be a predictor for the future outcome of AS patients treated with TNF inhibitors. Patients with a more significant decrease in miR-145 levels may show further significant improvement of disease activity after 12 months. Monitoring the expression of miR-145 in plasma in AS patients may, therefore, influence our therapeutic decision-making.

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Disease activity assessment in rheumatoid arthritis

Oxford Textbook of Rheumatoid Arthritis ◽

10.1093/med/9780198831433.003.0015 ◽

2020 ◽

pp. 161-168

Author(s):

Josef Smolen

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Joint Pain ◽

Joint Stiffness ◽

Treat To Target ◽

Therapeutic Decision ◽

Activity Assessment ◽

Disease Modifying ◽

Therapeutic Decision Making ◽

Disease Activity Assessment

The major clinical hallmarks of rheumatoid arthritis (RA) are articular swelling, joint pain, and morning joint stiffness. Disease activity assessment is pivotal when following patients with RA throughout the course of their disease, and especially when assessing improvement or deterioration upon institution of the necessary therapies. To prevent an adverse outcome, it is essential to diagnose the disease early and to start treatment with disease-modifying antirheumatic drugs (DMARDs) immediately after diagnosis. Adhering to the treat-to-target approach, which is a central strategy irrespective of the type of treatment available and the therapy applied, requires consistency in using validated composite measures of disease activity. Rather than a mere matter of using specific therapies, it is also a matter of using tools for disease activity assessment to guide therapeutic decision-making. This enables offering and achieving the best possible outcomes for RA patients.

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Concomitant Diagnosis of Fibromyalgia and Ankylosing Spondylitis: Relation to Clinical Features and Plasma Pentraxin -3 Level.

Current Rheumatology Reviews ◽

10.2174/1573397117666210114110823 ◽

2021 ◽

Vol 17 ◽

Author(s):

Eman Baraka ◽

Mona Balata ◽

Shereen Ahmed ◽

Mona El-Blbehisy ◽

Enas Elattar

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Clinical Features ◽

Predictive Value ◽

Disease Duration ◽

Rapid Screening ◽

Disease Assessment ◽

Group I ◽

Diagnostic Certainty ◽

Group Ii

Background: Ankylosing spondylitis (AS) is a chronic systemic inflammatory rheumatic disease that specifically affects the spine and sacroiliac joint. AS diagnosis is often delayed in the clinical practice and this delay may cause the patients to miss the chance of early treatment. Fibromyalgia (FM) is a frequently encountered clinical syndrome, fibromyalgianess is a term used when patients who are diagnosed with inflammatory arthropathies met the criteria for FM syndrome as shown in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome, and AS. Objectives: We aimed primarily to assess the frequency of concomitant diagnosis FM syndrome in AS patients and to study its impact on clinical disease aspects. Secondary, our aim extended as a preliminary pilot study to assess the PTX-3 as a potential marker for the diagnosis of FM syndrome in AS patients. Methods: Plasma PTX-3 in 61 AS patients was compared to 60 matched controls. FM was diagnosed by FM Rapid Screening Tool. Bath AS disease activity index (BASDAI) and AS disease assessment score using C- reactive protein (ASDAS-CRP), Bath AS functional impairment index (BASFI), Bath AS metrology index (BASMI), AS quality of life (ASQoL) scale, Beck Depression Inventory, and Bath AS Radiology Index (BASRI) were assessed. Results: The patients were categorized into two groups according to the concomitant diagnosis of FM syndrome. Group I included 14 (22.9%) AS patients who fulfilled the clinical diagnosis of FM syndrome. Group II included 47 (77.1%) patients without FM syndrome. AS patients with FM (Group I) had significantly(p<0.001) increased an average of ages, disease duration, diagnostic delay of AS, switching of bDMARDs, morning stiffness duration, ASDAS-CRP, BASFI, ASQoL score, BASDAI (p=0.008), and BDI score (p=0.005) compared to AS patients without FM (Group II). PTX-3 levels were significantly (p<0.001) higher in Group I (p<0.001) (median, 0.23; IQR, 0.15-0.41 ng/ml) than Group II (median, 0.13; IQR, 0.035-0.21ng/ml) which showed no significant differences (p>0.05) compared to the controls. PTX-3 levels had significant positive correlations (p<0.05) with disease duration, BASFI, and ASQOl. Age, female sex, switch of biologic, ASDAS -CRP, and PTX-3 were significant predictors of FM in AS patients. Conclusion: These results indicate that concomitant FM is a significant problem in patients with AS and its presence is associated with higher disease activity, impaired function as well as an overall negative impact on QoL. Easy scanning of suspicious cases of FM with FiRST questionnaire can be done in daily practice. PTX-3 is more or less accurate as the clinical features to improve the diagnostic certainty of FM in the presence of AS with a proven sensitivity of 62.3%, a specificity of 90 %, a positive predictive value of 82.75%, and a negative predictive value of 73.9%.

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AB0683 IS THE NEW ASDAS NOMENCLATURE IN LINE WITH THERAPEUTIC DECISION MAKING IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2224 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1637.1-1637

Author(s):

B. Garcia-Magallon ◽

M. D. C. Castro Villegas ◽

R. Rosselló ◽

V. Navarro-Compán

Keyword(s):

Ankylosing Spondylitis ◽

Disease Activity ◽

Disease Activity Score ◽

Axial Spondyloarthritis ◽

Therapeutic Decision ◽

Low Disease Activity ◽

Moderate Disease ◽

Therapeutic Attitude ◽

Very High ◽

Moderate Disease Activity

Background:The Assessment of SpondyloArthritis international Society (ASAS) proposed in 2018 a change in the nomenclature of the Ankylosing Spondylitis Disease Activity Score (ASDAS) for monitoring disease activity in axial spondyloarthritis (axSpA), renaming the previously status of moderate disease activity as low disease activity status, with the presumption that this better reflects the perception that the doctor and the patient have about the disease situation. However, this decision was not data-driven.Objectives:To evaluate the association between the state of low disease activity according to the new ASDAS nomenclature and the therapeutic decision in patients with axSpA.Methods:Longitudinal retrospective study in which patients with axSpA recruited in a secondary hospital were included. All patients with clinical diagnosis of axSpA who started treatment with a first inhibitor of tumor necrosis factor between January 2014 and June 2019 were included. At each follow-up visit, disease activity assessments (including BASDAI and CRP) and the therapeutic decision of the doctor were collected. Later, the ASDAS was calculated and disease status at each visit was classified according to the new nomenclature (inactive, low, high and very high activity). Using descriptive statistics, the association between the disease activity status and the therapeutic decision was evaluated.Results:A total of 304 visits were analyzed in 104 patients with axSpA. Out of these, 57% were women, 47% had a subtype of non-radiographic axSpA and 42% were HLA-B27 positive. The mean (standard deviation) age at diagnosis was 46.9 (12.5) years. In the visits with an ASDAS showing a status of low activity, the therapeutic attitude was not to intensify the treatment in 98.2% of the cases. However, in visits with an ASDAS status of high or very high disease activity, treatment was intensified in 33.7% and 82.8% of cases, respectively.Conclusion:In clinical practice, the status of disease activity initially classified by the ASDAS as moderate disease activity is currently considered to represent low disease activity status based on the therapeutic attitude of following a non-intensification strategy in this situation. These data support the recent change in the nomenclature of disease activity states according to the ASDAS.References:[1]Machado PM, Landewé R, van der Heijde D. Assessment of Spondyloarthritis international Society (ASAS). Ankylosing Spondylitis Disease Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states. Ann Rheum Dis 2018; 77:1539-1540.Figure 1.Association between the state of disease activity according to the new ASDAS nomenclature and the therapeutic decision.Disclosure of Interests:Blanca Garcia-Magallon Consultant of: MSD, Speakers bureau: Pfizer, Amgen, Celgene, MSD, María del Carmen Castro Villegas: None declared, Rosa Rosselló: None declared, Victoria Navarro-Compán Consultant of: Abbvie, Lilly, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Lilly, Novartis, Pfizer, UCB

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AB1150 ECONOMIC IMPACT ASSOCIATED TO BIOLOGICAL THERAPY / SYNTHETIC FAME OPTIMIZATION IN A COHORT OF PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASES TREATED BY OBJECTIVES.

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5354 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1865.2-1866

Author(s):

P. Castro ◽

A. Onteniente

Keyword(s):

Decision Making ◽

Disease Activity ◽

Rheumatic Diseases ◽

Cost Savings ◽

Treatment Costs ◽

Clinical Activity ◽

Inflammatory Rheumatic Diseases ◽

Therapeutic Decision ◽

Real Cost ◽

Therapeutic Decision Making

Background:Therapeutic decision-making for biologic-therapies/ synthetic FAME (BT/SD) dose optimization, should be based on optimal disease activity results according to a treatment strategy by objectives. The goal of BT optimization is to guarantee long-term effectiveness and safety, maximising economic savingsObjectives:To evaluate BT optimization patterns in patients with rheumatic diseases (RD) and associated economic savings.Methods:An observational and prospective study, which included a cohort of patients with rheumatoid arthritis (RA), spondyloarthropathies (SA) and psoriatic arthritis (PsA) treated with BT from January 2014 to December 2019. BT optimization, achieved by reducing or prolonging the interval at least one dose, was indicated when patients have more than 6 months of treatment and are in clinical remission (DAS28 <2.6 for RA and PsA, and BASDAI<2 for SA) or minimal clinical activity (DAS28<3.2 for RA and PsA, and BASDAI<4 for SA).Variables were described as frequencies and means. Diagnosis, BT (abatacept, adalimumab, apremilast, baricitinib, certolizumab, etanercept, golimumab, ixekizumab, secukinumab, tocilizumab, tofacitinib, and ustekinumab), dose regimens, total treatment duration, time on BT optimization (TO) and treatment costs were collected.Cost savings were calculated per patient by comparing optimization treatment costs to conventional treatment and globally by comparing real cost to theoretical conventional doses cost.Results:A total of 260 patients were included in the study. Switching were observed in 32.7%. From all patients, 53% were candidates for BT optimization (according to diagnosis: 60.9% with RA, followed by 52.2% with SA and 43.4% with PsA)A 40% of patients with BT optimization were treated with adalimumab and etanercept being also the most common BT used in RD treatmentBT optimization allowed a pharmaceutical saving of€ 177,539.40per year against the use of conventional therapy, resulting in a reduction of the total cost of€1,065,236.40in the last 6 years. The saving per patient / year was € 707.63 for RA; € 850,40 for SA and of €493,21 for the PsA.Conclusion:Therapeutic decision-making based on validated disease activity scales has allowed the BT optimization in approximately 53% of patients with RD.BT optimization allowed a pharmaceutical saving of € 177,539.40 per year being higher in the SA (€ 850.40) followed by the RA (€ 707.63) and finally the PsA (€ 493.21)The BT optimization allows to reduce costs maintaining the effectiveness and safety.Disclosure of Interests:None declared

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OP0143 IMPACT OF ADALIMUMAB VERSUS NON-BIOLOGIC THERAPY ON DISEASE ACTIVITY AND PATIENT-REPORTED OUTCOMES IN ANKYLOSING SPONDYLITIS OVER 24 MONTHS – RESULTS OF THE COMPLETE-AS CANADIAN OBSERVATIONAL STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2608 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 84.2-85

Author(s):

L. Bessette ◽

A. Chow ◽

V. Pavlova ◽

M. C. Laliberté ◽

M. Khraishi

Keyword(s):

Ankylosing Spondylitis ◽

Observational Study ◽

Disease Activity ◽

Patient Reported Outcomes ◽

Disease Burden ◽

Therapeutic Response ◽

Morning Stiffness ◽

Research Support ◽

Patient Reported ◽

Response Thresholds

Background:COMPLETE-AS was an observational study among Canadian biologic-naïve adults with active ankylosing spondylitis (AS) treated with either adalimumab or subsequent non-biologic disease-modifying anti-rheumatic drugs and/or non-steroidal anti-inflammatory drugs (nbDMARD/NSAID) after having switched from initial treatment with a preceding nbDMARD and/or NSAID due to lack of response or intolerance, as per treating physician judgement.Objectives:To assess the impact of adalimumab on disease activity and patient-reported outcomes among adalimumab- vs. nbDMARD/NSAID-treated patients over 24 months.Methods:Patients were enrolled between July 2011 and December 2017 and followed for up to 24 months. Treatment was per routine care and all analyses were perfomed using the intent-to-treat (ITT) approach. Between-group differences for change in patient-reported disease activity (BASDAI), morning stiffness (minutes/day), functional limitation (BASFI), quality of life (QoL: SF-12), depression (BDI-II), and work productivity (WLQ) were assessed with repeated measures models for overall treatment effect; baseline-adjusted estimates (least square means [LSM]) for each visit were produced. Achievement of, and time to the following endpoints were assessed: 50% improvement from baseline in BASDAI (BASDAI50); minimum clinically important improvements (MCIIs) in BASDAI (Δ≥1.1); BASFI (Δ≥0.6); SF-12 physical component score (PCS; Δ≥4.4) and mental component score (MCS; Δ≥3.1); and low disease activity for BASDAI (<4) and BASFI (<3.8).Results:A total of 452 adalimumab-treated patients and 187 nbDMARD/NSAID-treated patients were enrolled in the study and included in the analyses. At baseline, mean (SD) BASDAI [6.4 (1.8) vs. 5.0 (1.8); p<0.001] and BASFI [5.5 (2.4) vs. 3.7 (2.4)] were however significantly (p<0.001) higher among adalimumab-treated patients compared to nbDMARD/NSAID-treated patients, respectively.Over 24 months, adalimumab-treated patients had significantly lower overall BASDAI scores compared to nbDMARD/NSAID-treated patients [estimate (95% CI): -0.7 (-1.2, -0.3); p=0.007]. BASFI scores were also significantly lower among adalimumab-treated patients over the course of the study [estimate (95% CI): -0.4 (-0.8, 0.0); p=0.013]. Both groups had statistically comparable outcomes for morning stiffness, BDI-II, WLQ, and SF-12.Adalimumab-treated patients were also at significantly higher odds of achieving therapeutic response thresholds, including BASDAI50 [OR (95% CI): 1.7 (1.2-2.3)], BASDAI<4 [1.8 (1.2-2.7)], MCII for BASDAI [1.9 (13.-2.9)], and MCII for BASFI [1.6 (1.1-1.2)]. Time to achievement of each threshold was significantly shorter among adalimumab-treated patients for BASDAI50 [HR (95% CI): 1.8 (1.1-2.8)], BASDAI<4 [1.7 (1.6-3.6)], and MCII for BASDAI [1.5 (1.0-2.3)]. Time to achievement of MCII for BASFI was not statistically different between groups; for BASFI<3.8 and MCII for both SF-12 PCS and MCS, both odds of, and time to achievement, were also statistically comparable.At month 24, baseline-adjusted BASDAI and BASFI was comparable (p>0.05): LSM (95%CI) 3.5 (3.3, 3.8) vs. 3.6 (3.2-4.0), and 2.9 (2.6-3.1) vs. 3.3 (2.9-3.7), respectively, for adalimumab-treated vs. nbDMARD/NSAID-treated patients.Conclusion:Among Canadian patients with active AS, adalimumab-treated patients reported a greater overall reduction in disease burden related to both self-reported disease activity and functional capacity compared to nbDMARD/NSAID-treated patients, along with higher odds and shorter time to achieving therapeutic response thresholds. Despite the overall beneficial effects observed with adalimumab, residual disease burden, however, is observed for Canadian AS patients even after 24 months of treatment.Acknowledgements:The authors wish to acknowledge JSS Medical Research for their contribution to the statistical analysis, medical writing, and editorial support during the preparation of this abstract. AbbVie provided funding to JSS Medical Research for this work.Disclosure of Interests:Louis Bessette Speakers bureau: Speaker for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Lilly, Novartis, Gilead, Sandoz, Fresenius Kabi, Consultant of: Consultant for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Celgene, Lilly, Novartis, Gilead, Sandoz, Samsung Bioepis, Fresenius Kabi, Grant/research support from: Investigator for Amgen, BMS, Janssen, UCB, AbbVie, Pfizer, Merck, Celgene, Sanofi, Lilly, Novartis, Gilead, Andrew Chow Speakers bureau: Speaker for AbbVie, BMS, Janssen, Pfizer, Consultant of: Consultant for AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Grant/research support from: Investigator for AbbVie, Amgen, BMS, Celgene, Janssen, Lilly, Merck, Novartis, Pfizer, Roche, Viktoria Pavlova Speakers bureau: Speaker for Amgen, Abbvie, BMS, Jenssen, Lilly, Merk, Novartis, Roche, UCB, and Pfizer, Consultant of: Consultant for Amgen, Abbvie, BMS, Jenssen, Lilly, Merk, Novartis, Roche, UCB, and Pfizer, Grant/research support from: Investigator for Janssen, UCB, Abbvie, and Pfizer; and received research grants from UCB, Marie-Claude Laliberté Employee of: Employee of AbbVie, Majed Khraishi Speakers bureau: Speaker for AbbVie, Consultant of: Consultant for AbbVie, Grant/research support from: Principal Investigator for AbbVie

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High-Frequency Ultrasound to Assess Activity in Connective Tissue Panniculitis

Journal of Clinical Medicine ◽

10.3390/jcm10194516 ◽

2021 ◽

Vol 10 (19) ◽

pp. 4516

Author(s):

Priscila Giavedoni ◽

Sebastian Podlipnik ◽

Irene Fuertes de Vega ◽

Pilar Iranzo ◽

José Manuel Mascaró

Keyword(s):

Decision Making ◽

Connective Tissue ◽

Disease Activity ◽

High Frequency ◽

Therapeutic Decision ◽

High Frequency Ultrasound ◽

Therapeutic Decisions ◽

Therapeutic Decision Making ◽

Frequency Ultrasound

Determining disease activity from clinical signs in patients with connective tissue panniculitis (CTP) is often challenging but is essential for therapeutic decision making, which largely relies on immunosuppressant treatment. High-frequency ultrasound (HFUS) may be useful in supporting such decisions by accurately determining CTP activity. This study aimed to investigate the accuracy of HFUS in identifying signs of CTP activity or inactivity and assess its usefulness in therapeutic decision making. A prospective cohort study of consecutive patients with biopsy-proven CTP receiving HFUS was conducted in a tertiary university hospital (2016–2020). HFUS was performed at inclusion and at each 3- or 6-month follow-up visit, depending on disease activity. Twenty-three patients with CTP were included, and 134 HFUSs were performed. In 59.7% (80) of the evaluations, the clinical presentation did not show whether CTP was active or not. In these cases, HFUS showed activity in 38.7% (31) and inactivity in 61.3% (49). In 71.25% (57) of the visits, HFUS was the determinant for therapeutic decisions. Further follow-up showed consistent clinical and HFUS responses in all unclear cases after treatment modification. HFUS appears to be a useful adjunct to the clinical examination for CTP to assess activity and make therapeutic decisions.

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