Should We Redefine Treatment Targets in Rheumatoid Arthritis? Low Disease Activity Is Sufficiently Strict for Patients Who Are Anticitrullinated Protein Antibody-negative

2013 ◽  
Vol 40 (8) ◽  
pp. 1268-1274 ◽  
Author(s):  
Yvonne M.R. de Punder ◽  
Jos Hendrikx ◽  
Alfons A. den Broeder ◽  
Elia Valls Pascual ◽  
Piet L. van Riel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Joint Damage ◽  
Activity Level ◽  
Lower Probability ◽  
Treatment Target ◽  
Low Disease Activity ◽  
Treatment Targets ◽  
Damage Progression ◽  
Ratingen Score

Objective.Clinical remission currently is the treatment target for all patients with rheumatoid arthritis (RA). At the same level of inflammation, the prognosis regarding joint damage is believed to be different for anticitrullinated protein antibody (ACPA)-negative and ACPA-positive patients. Our objective was to show the difference in prognosis at similar disease activity levels, and to illustrate how this could be translated to differentiation of treatment targets.Methods.Data were used from the Nijmegen Early RA Cohort. The relation between the time-averaged disease activity level (by Disease Activity Score; DAS) and joint damage progression over 3 years was analyzed, separately for ACPA-negative and ACPA-positive patients. Joint damage was assessed as change in Ratingen score, and dichotomized as occurrence of erosions in joints that were unaffected at baseline. Linear and logistic multivariable regression models were used.Results.The regression coefficient of DAS on change in Ratingen score was 3.9 (p < 0.001) for ACPA-negative and 4.7 (p < 0.001) for ACPA-positive patients, showing less joint damage progression at the same disease activity level in ACPA-negative patients. This difference became greater with increasing disease activity. The probability for erosions in joints unaffected at baseline was 0.35 in ACPA-negative patients when time-averaged DAS was < 2.4 versus 0.80 in ACPA-positive patients.Conclusion.At the same level of inflammation, ACPA-negative patients have less joint damage and lower probability for damage in newly affected joints than ACPA-positive patients. Low disease activity might be a sufficiently strict treatment target for ACPA-negative patients to prevent progression of joint damage.

Personalizing Treatment Targets in Rheumatoid Arthritis by Using a Simple Prediction Model

2015 ◽  
Vol 42 (3) ◽  
pp. 398-404 ◽  
Author(s):  
Yvonne M.R. de Punder ◽  
Tim L.Th.A. Jansen ◽  
Annelies E. van Ede ◽  
Alfons A. den Broeder ◽  
Piet L.C.M. van Riel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Disease Activity ◽  
Joint Damage ◽  
Baseline Risk ◽  
Individual Treatment ◽  
Logistic Regression Models ◽  
Treatment Targets ◽  
Damage Progression ◽  
High Erythrocyte Sedimentation Rate

Objective.To develop a personalized treatment target approach in patients with rheumatoid arthritis (RA) based on baseline risk factors for joint damage progression in combination with disease activity over time.Methods.Data were used from the Nijmegen early RA cohort. Presence or absence of anticyclic citrullinated peptide antibodies (anti-CCP), high erythrocyte sedimentation rate, and erosions were translated into 4 risk profiles: 0, 1, 2, and 3. Joint damage progression was assessed with the Ratingen score, and disease activity with the original Disease Activity Score (DAS) over 3 years. The probability for joint damage progression was calculated for each risk profile and each DAS category using logistic regression models. The probabilities were translated into personalized disease activity treatment targets.Results.More risk factors at baseline as well as a higher DAS level resulted in a higher probability for joint damage progression in a dose-dependent way. Low DAS corresponded with a probability of 0.0, 0.08, 0.20, and 0.58 in patients with 0, 1, 2, and 3 risk factors, respectively. Moderate DAS corresponded with a probability of 0.06 in patients with 0 risk factors and 0.35 with 1 risk factor. High DAS resulted in a probability of 0.50 with no risk factors present at baseline.Conclusion.Presence of anti-CCP, acute-phase response, and erosions at baseline can be used to set individual treatment targets in RA. In patients without these risk factors, a moderate DAS as a target is sufficient, while for patients with all 3 risk factors, a low DAS is not strict enough to limit the risk for joint damage.

FRI0076 Low Disease Activity or DAS-Remission as Treatment Target in Early Rheumatoid Arthritis Patients

2016 ◽  
Vol 75 (Suppl 2) ◽  
pp. 454.1-454
Author(s):  
G. Akdemir ◽  
I.M. Markusse ◽  
A.A. Schouffoer ◽  
P.B. de Sonnaville ◽  
B.A. Grillet ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Early Rheumatoid Arthritis ◽  
Treatment Target ◽  
Low Disease Activity

scholarly journals A Multibiomarker Disease Activity Score for Rheumatoid Arthritis Predicts Radiographic Joint Damage in the BeSt Study

2014 ◽  
Vol 41 (11) ◽  
pp. 2114-2119 ◽  
Author(s):  
Iris M. Markusse ◽  
Linda Dirven ◽  
Marianne van den Broek ◽  
Casper Bijkerk ◽  
K. Huub Han ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Radiographic Progression ◽  
Joint Damage ◽  
Activity Score ◽  
Serum Samples ◽  
Radiographic Damage ◽  
Damage Progression ◽  
Increased Risk

Objective.To determine whether a multibiomarker disease activity (MBDA) score predicts radiographic damage progression in the subsequent year in patients with early rheumatoid arthritis.Methods.There were 180 serum samples available in the BeSt study (trial numbers NTR262, NTR 265): 91 at baseline (84 with radiographs available) and 89 at 1-year followup (81 with radiographs available). Radiographs were assessed using the Sharp/van der Heijde Score (SvdH). Twelve serum biomarkers were measured to determine MBDA scores using a validated algorithm. Receiver-operating curves and Poisson regression analyses were performed, with Disease Activity Score (DAS) and MBDA score as independent variables, and radiographic progression as dependent variable.Results.At baseline, MBDA scores discriminated more between patients who developed radiographic progression (increase in SvdH ≥ 5 points) and patients who did not [area under the curve (AUC) 0.767, 95% CI 0.639–0.896] than did DAS (AUC 0.521, 95% CI 0.358–0.684). At 1 year, MBDA score had an AUC of 0.691 (95% CI 0.453–0.929) and DAS had an AUC of 0.649 (95% CI 0.417–0.880). Adjusted for anticitrullinated protein antibody status and DAS, higher MBDA scores were associated with an increased risk for SvdH progression [relative risk (RR) 1.039, 95% CI 1.018–1.059 for baseline MBDA score; 1.037, 95% CI 1.009–1.065 for Year 1 MBDA score]. Categorized high MBDA scores were also correlated with SvdH progression (RR for high MBDA score at baseline 3.7; low or moderate MBDA score as reference). At 1 year, high MBDA score gave a RR of 4.6 compared to low MBDA score.Conclusion.MBDA scores predict radiographic damage progression at baseline and during disease course.

scholarly journals A systematic review of guidelines for managing rheumatoid arthritis

2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Aneela Mian ◽  
Fowzia Ibrahim ◽  
David L. Scott
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Treatment Target ◽  
Low Disease Activity ◽  
Disease Modifying Drugs ◽  
Early Ra ◽  
Core Dataset ◽  
Moderate Disease ◽  
Conventional Dmards ◽  
Current Guidelines

Abstract Background We systematically reviewed current guidelines for managing rheumatoid arthritis (RA) to evaluate their range and nature, assess variations in their recommendations and highlight divergence in their perspectives. Methods We searched Medline and Embase databases using the terms ‘clinical practice guidelines’ and ‘rheumatoid arthritis’ from January 2000 to January 2017 together with publications of national and international bodies. We included guidelines providing recommendations on general RA management spanning a range of treatments and published in English. We undertook narrative assessments due to the heterogeneity of the guidelines. Results We identified 529 articles; 22 met our inclusion criteria. They were primarily developed by rheumatologists with variable involvement of patient and other experts. Three dealt with early RA, one established RA and 18 all patients. Most guidelines recommend regular assessments based on the Outcome Measures in Rheumatology core dataset; 18 recommended the disease activity score for 28 joints. Twenty recommended targeting remission; 16 suggested low disease activity as alternative. All guidelines recommend treating active RA; 13 made recommendations for moderate disease. The 21 guidelines considering early RA all recommended starting disease modifying drugs (DMARDs) as soon as possible; methotrexate was recommended for most patients. Nineteen recommended combination DMARDs when patients failed to respond fully to monotherapy and biologics were not necessarily indicated. Twenty made recommendations about biologics invariably suggesting their use after failing conventional DMARDs, particularly methotrexate. Most did not make specific recommendations about using one class of biologics preferentially. Eight recommended tapering biologics when patients achieved sustained good responses. Conclusions Five general principles transcend most guidelines: DMARDs should be started as soon as possible after the diagnosis; methotrexate is the best initial treatment; disease activity should be regularly monitored; give biologics to patients with persistently active disease who have already received methotrexate; remission or low disease activity are the preferred treatment target.

scholarly journals AB0216 LONG-TERM RESULTS OF T2T THERAPY INITIATED AT THE ONSET OF RHEUMATOID ARTHRITIS (DATA FROM OREL REGISTRY)

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1134.2-1134
Author(s):  
V. Rybakova ◽  
A. Avdeeva ◽  
Y. Olyunin ◽  
E. Nasonov
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Long Term Results ◽  
Treatment Target ◽  
Low Disease Activity ◽  
Synthetic Dmards ◽  
Real Clinical Practice

Background:Current guidelines for the treatment of rheumatoid arthritis (RA) recommend early administration of methotrexate (MTX) and addition of a biologic if MTX monotherapy does not provide remission or low activity of the disease. Efficacy of this strategy in real clinical practice was assessed using data from the Russian RA registry OREL.Objectives:To analyze long-term results of intensive treatment initiated at RA onset in real clinical practice.Methods:141 RA patients with disease duration less than 3 years (29 men, 112 women) were included. 112 were positive for rheumatoid factor and 119 – for anti-cyclic citrullinated peptide antibody. Subcutaneous MTX was initiated at 10-15 mg per week with further dose escalation up to 20-30 mg per week. Therapy was adjusted every 3 months. If MTX monotherapy did not allow to achieve treatment target of remission or low disease activity, biologics were added.Results:Median DAS 28 at baseline was 5,31 [4,79; 6,14]. Initiation of treatment resulted in steady decrease of disease activity (p<0.05, table1). After 1 year of follow-up 33.8% of patients received MTX monotherapy, 33.8% – MTX in combination with tumor necrosis factor alpha inhibitors, 22.0% – MTX +abatacept, 0.55% – MTX+ tocilizumab, 0.47% – MTX + rituximab. Low disease activity was achieved in 16.3% patients, and remission - in 45.8%. After 6 years median age of patients was 58 [49; 66] years, disease duration – 84 [79; 89] months, low disease activity was documented in 21.3%, and remission – in 7.8% of cases (fig. 1). 7% of patients were able to maintain remission without any treatment. Biologics were discontinued in 15 patients after achieving remission or low disease activity, and synthetic DMARDs – in 5 patients having remission.Conclusion:Intensive therapy initiated at RA onset demonstrates high effectiveness, allowing 61.5% of patients to achieve low disease activity or remission within 12 months, and to maintain these results after 6 years of treatment in 29.2%. Adherence to this strategy allowed to discontinue biologics in 15 patients and synthetic DMARDs in 5 patients after achieving treatment target.Figure 1.Changes of the disease activity during follow-upTable 1.Changes of the main inflammatory activity measures, Me [25th; 75th percentile]Parametres012 months6 yearsDAS285,31 [4,79; 6,14]2,85 [2; 3,90] *4,008 [3,4; 4,59] *SDAI28,27 [18,79; 40,73]5,67 [2; 11,98] *15,06 [9,32; 21] *CDAI25 [17; 36]5 [1,7; 11] *15 [9; 21] *ESR (mm/hr)32 [19; 50]16 [8; 30] *16 [10; 25] *CRP (mg/l)26,55 [6,4; 45,30]3,85 [1,5; 11,3]*2,2 [0,9; 4,9] ** p<0.05 in all cases.Disclosure of Interests:None declared

scholarly journals Comparison between low disease activity or DAS remission as treatment target in patients with early active rheumatoid arthritis

RMD Open ◽  
2018 ◽  
Vol 4 (1) ◽  
pp. e000649 ◽  
Author(s):  
Gülşah Akdemir ◽  
Iris M Markusse ◽  
Sytske Anne Bergstra ◽  
Robbert J Goekoop ◽  
Esmeralda T Molenaar ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Active Rheumatoid Arthritis ◽  
Treatment Target ◽  
Low Disease Activity

scholarly journals Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction

2011 ◽  
Vol 71 (5) ◽  
pp. 687-693 ◽  
Author(s):  
Josef S Smolen ◽  
José C Martinez Avila ◽  
Daniel Aletaha
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Structural Damage ◽  
Activity Index ◽  
Joint Damage ◽  
Disease Activity Index ◽  
High Disease Activity ◽  
X Ray ◽  
Damage Progression ◽  
Spearman Test

BackgroundTreatment with tumour necrosis factor inhibitors (TNF-i) plus methotrexate (MTX), but not MTX monotherapy alone, inhibits joint damage progression even at higher levels of disease activity. Such disassociation of disease activity and structural damage has not been shown for biological agents other than TNF-i.ObjectivesTo evaluate whether interleukin 6 (IL-6) inhibition with tocilizumab (TCZ) interferes with joint destruction beyond its effects on disease activity.MethodsA random 90% sample of data from the (The Tocilizumab Safety and the Prevention of Structural Joint Damage Study) LITHEtrial on active rheumatoid arthritis (RA) despite MTX was used, which compared addition of placebo (n=117) with addition of TCZ (n=414) every 4 weeks. Baseline and 1-year values of clinical and serological variables were correlated with changes to 1 year of the total Genant-modified Sharp score (TGSS) using a Spearman test, and the progression of TGSS, erosion and joint space narrowing (JSN) scores in groups with low and high disease activity were compared for placebo and TCZ (Kruskal–Wallis).ResultsBaseline variables were similar among the groups. Change of TGSS was lower in patients receiving TCZ than placebo (TCZ: 0.29±0.96; placebo: 0.90±1.92; p=0.0007). In patients receiving placebo, the correlation with TGSS change was significant for baseline scores of the simplified disease activity index (SDAI; r=0.18, p=0.047) and swollen joint count 28 (r=0.22, p=0.019), with similar trends for C-reactive protein. Similar correlations were seen for SDAI, clinical disease activity index, disease activity score 28 at 1 year with x-ray change during that year (r=0.26–0.28, p=0.002–0.006). In contrast, none of the baseline or 1-year variables showed significant correlation with x-ray changes in patients receiving TCZ+MTX, suggesting a disassociation of the link between disease activity and damage by TCZ. Finally, for patients in remission or with low disease activity, progression of TGSS, erosion and JSN was similar among treatment groups (TGSS: placebo, 0.4±1.1; TCZ, 0.2±0.7; p=NS), while for patients with moderate or high disease activity placebo-treated patients progression was significantly greater (TGSS: 1.2±2.2 vs 0.4±1.2; p=0.0009).ConclusionsIL-6 inhibition with TCZ plus MTX retards joint damage progression independently of its impact on disease activity. Similar effects have hitherto been reported only for TNF-i. This indicates that the effects of IL-6 inhibition on progression of joint damage in RA are among the most profound currently attainable.

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