Calprotectin as a marker of inflammation in patients with early rheumatoid arthritis

2017 ◽  
Vol 76 (12) ◽  
pp. 2031-2037 ◽  
Author(s):  
Maria Karolina Jonsson ◽  
Nina Paulshus Sundlisæter ◽  
Hilde Haugedal Nordal ◽  
Hilde Berner Hammer ◽  
Anna-Birgitte Aga ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Radiographic Progression ◽  
Activity Index ◽  
Inflammatory Marker ◽  
Target Therapy ◽  
Power Doppler ◽  
Treat To Target ◽  
Symptom Duration

ObjectivesCalprotectin is an inflammatory marker of interest in rheumatoid arthritis (RA). We evaluated whether the level of calprotectin was associated with disease activity, and if it was predictive of treatment response and radiographic progression in patients with early RA.MethodsPlasma from disease-modifying antirheumatic drug (DMARD)-naïve patients with RA fulfilling 2010 American College of Rheumatology/European League Against Rheumatism classification criteria with symptom duration <2 years was analysed for calprotectin at baseline, and after 1, 3 and 12 months. All patients received treat-to-target therapy, as part of a randomised controlled strategy trial (ARCTIC). The association between calprotectin, erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) and measures of disease activity were assessed by correlations. We used likelihood ratios and logistic regression models to assess the predictive value of the baseline inflammatory markers for treatment response and radiographic damage.Results215 patients were included: 61% female, 82% anti-citrullinated peptide antibody positive, mean (SD) age 50.9 (13.7) years and median (25, 75 percentile) symptom duration 5.8 (2.8, 10.5) months. Calprotectin was significantly correlated with Clinical Disease Activity Index (r=0.32), ESR (r=0.50) and ultrasonography power Doppler (r=0.42) before treatment onset. After 12 months of treatment, calprotectin, but not ESR and CRP, was significantly correlated with power Doppler (r=0.27). Baseline levels of calprotectin, ESR and CRP were not predictive of treatment response, but high levels of calprotectin were associated with radiographic progression in multivariate models.ConclusionsCalprotectin was correlated with inflammation assessed by ultrasound before and during DMARD treatment, and was also associated with radiographic progression. The data support that calprotectin may be of interest as an inflammatory marker when assessing disease activity in different stages of RA.Trial registration numberNCT01205854; Post-results.

scholarly journals Clinical and ultrasound remission after 6 months of treat-to-target therapy in early rheumatoid arthritis: associations to future good radiographic and physical outcomes

2018 ◽  
Vol 77 (10) ◽  
pp. 1421-1425 ◽  
Author(s):  
Nina Paulshus Sundlisæter ◽  
Anna-Birgitte Aga ◽  
Inge Christoffer Olsen ◽  
Hilde Berner Hammer ◽  
Till Uhlig ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Radiographic Progression ◽  
Activity Index ◽  
Power Doppler ◽  
Disease Activity Index ◽  
Treat To Target ◽  
Good Outcome ◽  
Grey Scale

ObjectiveTo explore associations between remission, based on clinical and ultrasound definitions, and future good radiographic and physical outcome in early rheumatoid arthritis (RA).MethodsNewly diagnosed patients with RA followed a treat-to-target strategy incorporating ultrasound information in the Aiming for Remission in rheumatoid arthritis: a randomised trial examining the benefit of ultrasound in a Clinical TIght Control regimen (ARCTIC) trial. We defined 6-month remission according to Disease Activity Score, Disease Activity Score in 28 joints-erythrocyte sedimentation rate, American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean criteria, Simplified Disease Activity Index, Clinical Disease Activity Index and two ultrasound definitions (no power Doppler signal, grey scale score ≤2). Two outcomes were defined: no radiographic progression and good outcome (no radiographic progression+physical function≥general population median), both sustained 12–24 months. We calculated the ORs of these outcomes for the remission definitions.ResultsOf 103 patients, 42%–82% reached remission at 6 months, dependent on definition. Seventy-one per cent of patients had no radiographic progression and 37% had good outcome. An association between 6-month remission and no radiographic progression was observed for ACR/EULAR Boolean remission (44 joints, OR 3.2, 95% CI 1.2 to 8.4), ultrasound power Doppler (OR 3.6, 95% CI 1.3 to 10.0) and grey scale remission (OR 3.2, 95% CI 1.2 to 8.0). All clinical, but not ultrasound remission criteria were associated with achievement of a good outcome.ConclusionsOur data support ACR/EULAR Boolean remission based on 44 joints as the preferred treatment target in early RA. Absence of ultrasound inflammation was associated with no radiographic progression.Trial registration numberNCT01205854; Post-results.

scholarly journals Fatigue in patients with early rheumatoid arthritis undergoing treat-to-target therapy: predictors and response to treatment

2021 ◽  
pp. annrheumdis-2021-220750
Author(s):  
Karen Holten ◽  
Nina Paulshus Sundlisater ◽  
Siri Lillegraven ◽  
Joseph Sexton ◽  
Lena Bugge Nordberg ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Target Therapy ◽  
Randomised Trial ◽  
Power Doppler ◽  
Disease Onset ◽  
Treat To Target ◽  
Symptom Duration ◽  
Tight Control ◽  
Early Ra

ObjectivesFatigue is a frequent symptom in rheumatoid arthritis (RA) and has high impact on quality of life. We explored associations between disease activity and fatigue in patients with early RA during the initial 24 months of modern treat-to-target therapy and predictors of fatigue after 24 months of follow-up.MethodsData were obtained from the treat-to-target, tight control Aiming for Remission in Rheumatoid Arthritis: a Randomised Trial Examining the Benefit of Ultrasound in a Clinical Tight Control Regime (ARCTIC) trial. Fatigue was measured on a visual analogue scale (VAS) from 0 to 100 mm and defined as clinically relevant if VAS was ≥20 mm. Baseline predictors of fatigue at 24 months were analysed by multivariable logistic regression.Results205 patients with fatigue data at baseline and 24 months were included. Median (25th, 75th percentiles) symptom duration was 5.4 months (2.8, 10.4), fatigue VAS 37.0 mm (13.0, 62.0) and mean Disease Activity Score (DAS) 3.4 (SD 1.1) at baseline. Prevalence of fatigue declined from 69% at baseline to 38% at 24 months. Fewer swollen joints (OR 0.92, 95% CI 0.87 to 0.98, p=0.006), lower power Doppler ultrasound score (OR 0.95, 95% CI 0.90 to 0.99, p=0.027) and higher patient global assessment (PGA) (OR 1.03, 95% CI 1.01 to 1.04, p<0.001) increased the risk of clinically relevant fatigue at 24 months. Not achieving remission at 6 months was associated with a higher risk of reporting fatigue at 24 months.ConclusionsFatigue in patients with early RA was prevalent at disease onset, with a rapid and sustained reduction during treatment. Low objective disease activity and high PGA at baseline were predictors of clinically relevant fatigue at 24 months.

Musculoskeletal ultrasound using superb microvascular imaging documents treatment response to biosimilar infliximab in rheumatoid arthritis

2021 ◽  
Vol 14 (2) ◽  
pp. e239112
Author(s):  
Julian Alejandro Santos ◽  
Cherica Afurong Tee ◽  
Romelito Jose Galvan Galsim ◽  
Michael Lucas Tee
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Activity Index ◽  
Power Doppler ◽  
Musculoskeletal Ultrasound ◽  
Joint Effusion ◽  
Das 28 ◽  
Superb Microvascular Imaging ◽  
Microvascular Imaging

A 60-year-old woman with rheumatoid arthritis consulted for acute flare. She had elevated disease activity score 28 - erythrocyte sedimentation rate (DAS 28-ESR) of 6.88 and clinical disease activity index (CDAI) of 32. Her 12-joint ultrasound revealed widespread joint effusion. Synovial vascularity scores measured through superb microvascular imaging (SMI) and power Doppler were universally increased. We documented her treatment response 2 weeks after she received a single dose of biosimilar infliximab using clinical and sonographic data. Her DAS 28-ESR and CDAI scores decreased to 4.21 and 7.0, respectively. Reduction in synovial vascularity scores was demonstrated using SMI. While there was near total resolution in joint effusion and tenosynovitis, SMI was able to demonstrate synovial vascularity in joints with no clinical swelling nor tenderness. Musculoskeletal ultrasound and superb microvascular imaging are useful adjuncts in evaluating synovitis in rheumatoid arthritis and documenting treatment response through documentation of synovial vascularity, effusion and tenosynovitis.

scholarly journals Comparing the disease course of patients with seronegative and seropositive rheumatoid arthritis fulfilling the 2010 ACR/EULAR classification criteria in a treat-to-target setting: 2-year data from the ARCTIC trial

RMD Open ◽  
2018 ◽  
Vol 4 (2) ◽  
pp. e000752 ◽  
Author(s):  
Lena Bugge Nordberg ◽  
Siri Lillegraven ◽  
Anna-Birgitte Aga ◽  
Joseph Sexton ◽  
Inge Christoffer Olsen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Response ◽  
Radiographic Progression ◽  
Classification Criteria ◽  
Inflammatory Activity ◽  
The Arctic ◽  
Treat To Target ◽  
Disease Course ◽  
Remission Rates

ObjectivesRecent studies suggest that implementation of the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for rheumatoid arthritis (RA) leads to higher inflammatory activity in seronegative compared with seropositive patients at time of diagnosis. Our aim was to compare the disease course in seronegative and seropositive patients classified according to the 2010 criteria.MethodsDMARD-naïve patients with RA fulfilling the 2010 criteria were included in the treat-to-target ARCTIC trial and followed for 24 months. We stratified patients as seropositive (rheumatoid factor (RF)+, anticitrullinated protein antibodies (ACPA)+ or both) or seronegative (RF– and ACPA–) and compared disease activity, radiographic progression, treatment response and remission rates across groups.Results230 patients were included with mean (SD) age 51.4 (13.7) years, and 61% were female. 34 patients (15%) were seronegative. At 24  months, disease activity measures, radiographic progression and remission rates were similar between groups, despite more inflammatory activity in seronegative patients at baseline. Treatment response was slower in seronegative compared with seropositive patients. The groups received similar treatment.ConclusionOur findings suggest that among patients with RA classified according to the 2010 ACR/EULAR criteria, seronegative patients respond well to modern treatment strategies. However, treatment response was somewhat slower in seronegative patients and radiographic progression was similar in seronegative and seropositive patients. Our results indicate that seronegative RA is not a mild form of the disease and requires intensive treat-to-target therapy similar to treatment of seropositive RA.

scholarly journals Do Poor Prognostic Factors in Rheumatoid Arthritis Affect Treatment Choices and Outcomes? Analysis of a US Rheumatoid Arthritis Registry

2018 ◽  
Vol 45 (10) ◽  
pp. 1353-1360 ◽  
Author(s):  
Evo Alemao ◽  
Heather J. Litman ◽  
Sean E. Connolly ◽  
Sheila Kelly ◽  
Winnie Hua ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Prognostic Factors ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Activity Index ◽  
Functional Limitation ◽  
Disease Activity Index ◽  
Treat To Target ◽  
Work Status ◽  
Logistic Regression Models

Objective.To characterize patients with rheumatoid arthritis (RA) by number of poor prognostic factors (PPF: functional limitation, extraarticular disease, seropositivity, erosions) and evaluate treatment acceleration, clinical outcomes, and work status over 12 months by number of PPF.Methods.Using the Corrona RA registry (January 2005–December 2015), biologic-naive patients with diagnosed RA having 12-month (± 3 mos) followup were identified and categorized by PPF (0–1, 2, ≥ 3). Changes in medication, Clinical Disease Activity Index (CDAI), and work status (baseline–12 mos) were evaluated using linear and logistic regression models.Results.There were 3458 patients who met the selection criteria: 1489 (43.1%), 1214 (35.1%), and 755 (21.8%) had 0–1, 2, or ≥ 3 PPF, respectively. At baseline, patients with ≥ 3 PPF were older, and had longer RA duration and higher CDAI versus those with 0–1 PPF. In 0–1, 2, and ≥ 3 PPF groups, respectively, 20.9%, 23.2%, and 26.5% of patients received ≥ 1 biologic (p = 0.011). Biologic/targeted synthetic disease-modifying antirheumatic drug (tsDMARD) use was similar in patients with/without PPF (p = 0.57). After adjusting for baseline CDAI, mean (standard error) change in CDAI was −4.95 (0.24), −4.53 (0.27), and −2.52 (0.34) for 0–1, 2, and ≥ 3 PPF groups, respectively. More patients were working at baseline but not at 12-month followup in 2 (13.9%) and ≥ 3 (12.5%) versus 0–1 (7.3%) PPF group.Conclusion.Despite high disease activity and worse clinical outcomes, number of PPF did not significantly predict biologic/tsDMARD use. This may warrant reconsideration of the importance of PPF in treat-to-target approaches.

scholarly journals Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis

2020 ◽  
pp. annrheumdis-2020-218412
Author(s):  
Roy M Fleischmann ◽  
Ricardo Blanco ◽  
Stephen Hall ◽  
Glen T D Thomson ◽  
Filip E Van den Bosch ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Kinase Inhibitor ◽  
Activity Index ◽  
Disease Activity Index ◽  
Initial Therapy ◽  
Janus Kinase ◽  
Treat To Target ◽  
Efficacy And Safety ◽  
Insufficient Response

ObjectivesTo evaluate efficacy and safety of immediate switch from upadacitinib to adalimumab, or vice versa, in patients with rheumatoid arthritis with non-response or incomplete-response to the initial therapy.MethodsSELECT-COMPARE randomised patients to upadacitinib 15 mg once daily (n=651), placebo (n=651) or adalimumab 40 mg every other week (n=327). A treat-to-target study design was implemented, with blinded rescue occurring prior to week 26 for patients who did not achieve at least 20% improvement in both tender and swollen joint counts (‘non-responders’) and at week 26 based on Clinical Disease Activity Index (CDAI) >10 (‘incomplete-responders’) without washout.ResultsA total of 39% (252/651) and 49% (159/327) of patients originally randomised to upadacitinib and adalimumab were rescued to the alternate therapy. In both switch groups (adalimumab to upadacitinib and vice versa) and in non-responders and incomplete-responders, improvements in disease activity were observed at 3 and 6 months following rescue. CDAI low disease activity was achieved by 36% and 47% of non-responders and 45% and 58% of incomplete-responders switched to adalimumab and upadacitinib, respectively, 6 months following switch. Overall, approximately 5% of rescued patients experienced worsening in disease activity at 6 months postswitch. The frequency of adverse events was similar between switch groups.ConclusionsThese observations support a treat-to-target strategy, in which patients who fail to respond initially (or do not achieve sufficient response) are switched to a therapy with an alternate mechanism of action and experience improved outcomes. No new safety findings were observed despite immediate switch without washout.

scholarly journals Effect of Glucocorticoids on the Clinical and Radiographic Efficacy of Tofacitinib in Patients with Rheumatoid Arthritis: A Posthoc Analysis of Data from 6 Phase III Studies

2017 ◽  
Vol 45 (2) ◽  
pp. 177-187 ◽  
Author(s):  
Christina Charles-Schoeman ◽  
Désirée van der Heijde ◽  
Gerd R. Burmester ◽  
Peter Nash ◽  
Cristiano A.F. Zerbini ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Radiographic Progression ◽  
Activity Index ◽  
Disease Activity Index ◽  
Response Rates ◽  
Phase Iii ◽  
Inadequate Response ◽  
Link Type ◽  
Phase Iii Studies

Objective.Tofacitinib has been investigated for the treatment of rheumatoid arthritis (RA) in phase III studies in which concomitant glucocorticoids (GC) were allowed. We analyzed the effect of GC use on efficacy outcomes in patients with RA receiving tofacitinib and/or methotrexate (MTX) or conventional synthetic disease-modifying antirheumatic drugs (csDMARD) in these studies.Methods.Our posthoc analysis included data from 6 phase III studies (NCT01039688; NCT00814307; NCT00847613; NCT00853385; NCT00856544; NCT00960440). MTX-naive patients or patients with inadequate response to csDMARD or biological DMARD received tofacitinib 5 or 10 mg twice daily alone or with csDMARD, with or without concomitant GC. Patients receiving GC (≤ 10 mg/day prednisone or equivalent) before enrollment maintained a stable dose throughout. Endpoints included the American College of Rheumatology (ACR) 20/50/70 response rates, rates of Clinical Disease Activity Index (CDAI)-defined low disease activity (LDA; CDAI ≤ 10) and remission (CDAI ≤ 2.8), and changes from baseline in CDAI, 28-joint count Disease Activity Score (DAS28-4)–erythrocyte sedimentation rate (ESR), Health Assessment Questionnaire–Disability Index (HAQ-DI), pain visual analog scale (VAS), and modified total Sharp score.Results.Of 3200 tofacitinib-treated patients, 1258 (39.3%) received tofacitinib monotherapy and 1942 (60.7%) received tofacitinib plus csDMARD; 1767 (55.2%) received concomitant GC. ACR20/50/70 response rates, rates of CDAI LDA and remission, and improvements in CDAI, DAS28-4-ESR, HAQ-DI, and pain VAS with tofacitinib were generally similar with or without GC in monotherapy and combination therapy studies. GC use did not appear to affect radiographic progression in tofacitinib-treated MTX-naive patients. MTX plus GC appeared to inhibit radiographic progression to a numerically greater degree than MTX alone.Conclusion.Concomitant use of GC with tofacitinib did not appear to affect clinical or radiographic efficacy. MTX plus GC showed a trend to inhibit radiographic progression to a greater degree than MTX alone.

scholarly journals Association of Angiogenic and Inflammatory Markers with Power Doppler Ultrasound Vascularity Grade and DAS28-CRP in Early Rheumatoid Arthritis: A Comparative Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sanchaita Misra ◽  
Sumantro Mondal ◽  
Sudipta Chatterjee ◽  
Aharna Guin ◽  
Pradyot Sinhamahapatra ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Power Doppler ◽  
Significant Rise ◽  
High Disease Activity ◽  
Power Doppler Ultrasonography ◽  
Early Ra ◽  
Grade 3

Objective. Upregulation of various proinflammatory and angiogenic mediators orchestrates the typical pathological synovial alterations in rheumatoid arthritis (RA). DAS28-CRP is commonly used for assessment of RA disease activity and power Doppler ultrasonography (PDUS) is an important modality for assessing synovial vascularity. This study was intended to look for the association of various inflammatory and angiogenic mediators, with respect to different PDUS vascularity grades and disease activity status, in early RA patients. Methods. 50 early RA patients (<6 months disease duration) with either moderate or high disease activity and 30 healthy controls were included in this study. RA patients were subcategorized based on PDUS vascularity grading of wrist joints. Serum levels of proinflammatory cytokines [tumor necrosis factor-α (TNF- α); interleukin-6(IL-6)] and angiogenic markers [angiopoietin-1 and 2 (Ang-1 and Ang-2); vascular endothelial growth factor (VEGF) ] were measured and compared among different patient subgroups. Results. Among 50 patients, 22 and 28 patients had moderate and high DAS28-CRP score, respectively. Patients with grade 3 PDUS score, even with moderate DAS value, showed a significant rise in Ang-1 (p<0.02), VEGF (p<0.008), Ang-2 (p <0.001), and TNF-α (p<0.005) level compared to grade 2 PDUS patients with high DAS values. Conclusion. Higher serum level of angiogenic and inflammatory markers was noted among patients with moderate disease activity but with advanced PDUS vascularity (grade 3) in comparison to high disease activity group with less severe PDUS vascularity (grade 2). PDUS vascularity grading better reflects some markers of angiogenesis and inflammation, than composite disease activity index.

scholarly journals Is treat-to-target really working in rheumatoid arthritis? a longitudinal analysis of a cohort of patients treated in daily practice (RA BIODAM)

2020 ◽  
Vol 79 (4) ◽  
pp. 453-459 ◽  
Author(s):  
Sofia Ramiro ◽  
Robert BM Landewé ◽  
Désirée van der Heijde ◽  
Alexandre Sepriano ◽  
Oliver FitzGerald ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Clinical Practice ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Index ◽  
Disease Activity Index ◽  
Daily Clinical Practice ◽  
Joint Disease ◽  
Activity Score ◽  
Treat To Target

ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definitions. The association between T2T and remission was tested in generalised estimating equations models.ResultsIn total 4356 visits of 571 patients (mean (SD) age: 56 (13) years, 78% female) were included. Appropriate application of T2T was found in 59% of the visits. T2T (vs no T2T) did not yield a higher likelihood of DAS44 remission 3 months later (OR (95% CI): 1.03 (0.92 to 1.16)), but sustained T2T resulted in an increased likelihood of achieving DAS44 remission (OR: 1.19 (1.03 to 1.39)). Similar results were seen with DAS28-ESR remission. For more stringent definitions (CDAI, SDAI and ACR/EULAR Boolean remission), T2T was consistently positively associated with remission (OR range: 1.16 to 1.29), and sustained T2T had a more pronounced effect on remission (OR range: 1.49 to 1.52).ConclusionIn daily clinical practice, the correct application of a T2T-strategy (especially sustained T2T) in patients with RA leads to higher rates of remission.

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