scholarly journals Clinical Response Within 12 Weeks as a Predictor of Future Low Disease Activity in Patients with Early RA: Results from the TEAR Trial

2013 ◽  
Vol 40 (5) ◽  
pp. 572-578 ◽  
Author(s):  
Jeffrey R. Curtis ◽  
Theresa McVie ◽  
Ted R. Mikuls ◽  
Richard J. Reynolds ◽  
Iris Navarro-Millán ◽  
...  

Objective.Rapidly predicting future outcomes based on short-term clinical response would be helpful to optimize rheumatoid arthritis (RA) management in early disease. Our aim was to derive and validate a clinical prediction rule to predict low disease activity (LDA) at 1 year among patients participating in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial escalating RA therapy by adding either etanercept or sulfasalazine + hydroxychloroquine [triple therapy (TT)] after 6 months of methotrexate (MTX) therapy.Methods.Eligible subjects included in the derivation cohort (used for model building, n = 186) were participants with moderate or higher disease activity [Disease Activity Score 28-erythrocyte sedimentation rate (DAS-ESR) > 3.2] despite 24 weeks of MTX monotherapy who added either etanercept or sulfasalazine + hydroxychloroquine. Clinical characteristics measured within the next 12 weeks were used to predict LDA 1 year later using multivariable logistic regression. Validation was performed in the cohort of TEAR patients randomized to initially receive either MTX + etanercept or TT.Results.The derivation cohort yielded 3 prediction models of varying complexity that included age, DAS28 at various timepoints, body mass index, and ESR (area under the receiver-operator characteristic curve up to 0.83). Accuracy of the prediction models ranged between 80% and 95% in both derivation and validation cohorts, depending on the complexity of the model and the cutpoints chosen for response and nonresponse. About 80% of patients could be predicted to be responders or nonresponders at Week 12.Conclusion.Clinical data collected early after starting or escalating disease-modifying antirheumatic drug/biologic treatment could accurately predict LDA at 1 year in patients with early RA. For patients predicted to be nonresponders, treatment could be changed at 12 weeks to optimize outcomes.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 458.1-458
Author(s):  
R. Yokochi ◽  
H. Tamai ◽  
T. Kido ◽  
Y. Yagyu ◽  
D. Waki ◽  
...  

Background:Several previous observational studies have suggested that patients with anti-Ro/SSA antibody-positive rheumatoid arthritis (RA) may respond poorly to treatment, including tumor necrosis factor inhibitors1. However, its influence on methotrexate (MTX) treatment, which is the anchor drug of treat-to-target strategy in RA treatment, remains unclear.Objectives:We compared the clinical response to MTX in both anti-Ro/SSA antibody-positive and -negative patients with MTX-naiive RA and investigated the reasons for the difference in response.Methods:We recruited 210 consecutive patients with RA who were newly started on MTX in this retrospective cohort study. The effect of the presence of anti-Ro/SSA antibodies on achieving low disease activity (LDA) of DAS28-CRP at six months after initiating MTX was investigated by using logistic regression analysis. CDAI, SDAI, concomitant using DMARDs and painkillers, patient’s and evaluator’s VAS, tender joint counts, and swollen joint counts at six months were also compared between the anti-Ro/SSA-positive patients and -negative patients. Missing data were imputed by using multiple imputations before multivariate analysis.Results:32 anti-Ro/SSA antibody-positive patients and 178 anti-Ro/SSA antibody-negative patients were included. The rate of achieving DAS28-LDA at six months was significantly lower in the anti-Ro/SSA antibody-positive patients than those in the anti-Ro/SSA antibody-negative patients (56.2% versus 75.8%, P=0.03). in the logistic regression analysis, the presence of anti-Ro/SSA antibodies was an independent negative predictor for achieving DAS-28-LDA at six months (OR:0.431, 95%CI: 0.190-0.978, P=0.044) (Table1). Anti-Ro/SSA antibody-positive patients had significantly higher patient’s VAS at six months (median [IQR]: 22 [15-41] vs 19 [5-30], P=0.038), and prescribed NSAIDs (37.5% vs 18.0%, P=0.018). CDAI and SDAI after six months were not significantly different between the group.Conclusion:The presence of anti-Ro/SSA antibodies might be one of the predictive factors for the insufficient response to treat to target strategy in RA treatment. Residual pain was suspected as one of the mechanisms contributing to the lesser clinical response of MTX in anti-Ro antibody-positive RA.References:[1]Ran Matsudaira wt al. J Rheumatol 2011;38(11):2346-54Table 1.Logistic regression analysis for the rate of achieving DAS28 low disease activity at six months.Risk factor Odds ratio95%CIP valueAge at onset0.9930.968-1.0180.586Sex (woman)0.6430.300-1.3840.258RF-positive1.9620.853-4.5110.112ACPA-positive0.5520.225-1.3510.192Anti-Ro/SSA antibody-positive0.4310.190-0.9780.044Disclosure of Interests:None declared


2016 ◽  
Vol 83 (6) ◽  
pp. 721-725 ◽  
Author(s):  
Florenzo Iannone ◽  
Giorgio Carlino ◽  
Antonio Marchesoni ◽  
Piercarlo Sarzi-Puttini ◽  
Roberto Gorla ◽  
...  

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110118
Author(s):  
Serena Bugatti ◽  
Ludovico De Stefano ◽  
Antonio Manzo ◽  
Garifallia Sakellariou ◽  
Blerina Xoxi ◽  
...  

Background: The patient global assessment of disease activity (PGA) is the major limiting factor to Boolean remission in patients with established rheumatoid arthritis (RA). Here, we investigated the limiting variables to disease remission in patients with early RA treated with conventional synthetic disease modifying anti-rheumatic drugs, also in relation to autoantibody status. Methods: Data were retrieved from 535 early RA patients (<12 months of symptoms) with an observation period of 6–12 months upon initiation of therapy with methotrexate aimed at the achievement of low disease activity based on the 28-joints disease activity score. Near-remission was defined as any of the four core items of Boolean remission >1 with the remaining three all ⩽1. Reasons for missing Boolean remission and predictors of near-remission subcategories were analyzed in relation to baseline disease variables. Results: After 6 and 12 months, near-remission was two-times more frequent than Boolean remission (25.6% and 26.9% at the two time-points). A 28-swollen joint count (SJC28) >1 was responsible for the majority of near-remission (56.2% and 57.6% at 6 and 12 months, respectively), and PGA > 1 accounted for approximatively 35% of the cases. Autoantibody-positivity independently predicted the risk of missing remission because of SJC28 > 1 [adjusted odds ratio (OR) 95% confidence interval (CI) 2.81 (1.59–4.9) at 6 months and 1.73 (1.01–3.01) at 12 months], whilst autoantibody-negativity was an independent predictor of PGA near-remission [adjusted OR (95% CI) 2.45 (1.25–4.80) at 6 months and 5.71 (2.47–13.2) at 12 months]. Conclusion: In early RA, Boolean remission is more frequently missed because of persistent swollen joints. However, barriers to full-remission vary in relation to the autoantibody status. Autoantibody-positive patients more commonly experience residual swollen joints, whilst PGA more frequently impairs remission in autoantibody-negative patients. Efforts to target full-remission in early RA may thus require different strategies according to autoantibody profile.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 955-956
Author(s):  
J. Pope ◽  
M. Movahedi ◽  
E. Rampakakis ◽  
A. Cesta ◽  
J. Sampalis ◽  
...  

Background:Previous studies have shown that early diagnosis and treatment of rheumatoid arthritis (RA) is important for achieving comprehensive disease control and have identified established disease as an independent predictor of worse clinical outcomes. However, it is not clear whether these differences are driven by patient-reported or objective outcome measures.Objectives:The aim of this analysis was to compare the time to achieving low disease activity (LDA) and remission based on both objective and patient-reported outcomes in people with early vs. established RA followed in routine clinical care.Methods:RA patients enrolled in the Ontario Best Practices Research Initiative (OBRI) registry that were not in a low disease state at baseline based on the CDAI, SJC28, PtGA, pain and fatigue criteria below, and had at least six months of follow-up, were included in the analysis. LDA was defined as CDAI≤10, SJC28≤2, TJC28≤2, PtGA≤2cm, pain≤2cm, fatigue≤2cm, and MDGA≤2cm; remission was defined as CDAI≤2.8, SJC28≤1, TJC28≤1, PtGA≤1cm, pain≤1cm, fatigue≤1cm, and MDGA≤1cm. Between group (early vs. established) differences in time to first LDA/remission were assessed with Kaplan-Meier survival analysis and the log-rank test.Results:A total of 986 patients were included, 347 (35%) with early RA and 639 (65%) with established RA. At baseline, patients with early RA were significantly younger (55.8 vs. 58.3 years) and were less likely to have a comorbidity (94.5% vs. 97.5%) or an erosion (26.7% vs. 62.6%), be RF-positive (65.6% vs. 74.2%), use bDMARDs (7.5% vs. 26.6%), and be non-smokers (38.9% vs. 47.3%).Time to achieving LDA based on CDAI (HR [95%CI]: (1.23 [1.07,1.43]), SJC28 (1.32 [1.15,1.51]), TJC28 (1.18 [1.02,1.36]), MDGA (1.28 [1.10,1.49]), PtGA (1.23 [1.05,1.44]), and pain (1.29 [1.09,1.52]) were significantly shorter in early RA compared to established RA. Similarly, time to achieving remission based on CDAI (HR [95%CI]: (1.50 [1.22,1.84]), SJC28 (1.35 [1.17,1.55]), MDGA (1.25 [1.06,1.47]), PtGA (1.22 [1.02,1.47]), and pain (1.37 [1.14,1.65]) were significantly shorter in early RA. However, no differences were observed in time to remission based on TJC28 (1.12 [0.96,1.31]) and either LDA or remission based on fatigue (LDA (1.10 [0.94,1.30]); remission (1.09 [0.92,1.31]).Adjustment for age, gender, presence of comorbidities, and baseline scores did not alter the results.Conclusion:Time to achieving low disease state or remission based on various objective and patient-reported measures is significantly shorter in early compared to established RA with the exception of fatigue.Disclosure of Interests:Janet Pope Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly & Company, Merck, Roche, Seattle Genetics, UCB, Consultant of: AbbVie, Actelion, Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eicos Sciences, Eli Lilly & Company, Emerald, Gilead Sciences, Inc., Janssen, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi, UCB, Speakers bureau: UCB, Mohammad Movahedi Consultant of: Allergan, Emmanouil Rampakakis: None declared, Angela Cesta: None declared, John Sampalis: None declared, Claire Bombardier Grant/research support from: Dr Bombardier reports sources of funding for Ontario Best Practice Research Initiative Research grants from Abbvie, Janssen, Amgen, Medexus, Merck, Pfizer, and Novartis outside of the submitted work. Consulting Agreements: Abbvie, Covance, Janssen, Merck, Pfizer, Sanofi and Novartis outside of the submitted work. Advisory Board Membership: Hospira, Sandoz, Merck, Pfizer and Novartis outside of the submitted work.


2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Aneela Mian ◽  
Fowzia Ibrahim ◽  
David L. Scott

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.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 581.3-581
Author(s):  
N. Iwamoto ◽  
T. Suzuki ◽  
A. Okada ◽  
K. Fujikawa ◽  
T. Aramaki ◽  
...  

Background:Tofacitinib is a non-selective first-generation JAK inhibitor and baricitinib was approved for the treatment of Rheumatoid arthritis several years after approve of tofacitinib. Randomized controlled trials have shown good treatment response for RA in these two drugs. However, the evaluation of these two drugs in real-world setting have been rarely reported, moreover, until now, no published data of a direct comparison among JAK inhibitors in RA have been available.Objectives:To compare the efficacy and safety of the JAK inhibitors tofacitinib and baricitinib in patients with rheumatoid arthritis (RA) by using propensity score matching in a real-world setting.Methods:A total of 242 patients with RA who were treated with tofacitinib (n=161) or baricitinib (n=81) were enrolled. To avoid confounding, we performed propensity score matching based on multiple baseline characteristic variables, and then 80 baricitinib-treated patients and 57 tofacitinib-treated patients were extracted for the direct comparison. A mixed effect model with a repeated measures analysis of variance (ANOVA) was performed to ascertain whether there were significant differences in clinical efficacy between the two treatment groups during the treatment period.Finally, We evaluated the predictive factor of clinical responses by performing univariate and multivariable logistic regression analyses.Results:The mean delta disease activity scores (DAS)28-ESR from baseline to 6 months were −1.60 (tofacitinib) and −1.46 (baricitinib). The remission rate defined by the DAS28-ESR at 24 weeks were 21.1% (tofacitinib) and 25.0% (baricitinib). There was no significant difference in the clinical response between the baricitinib-treated and tofacitinib-treated groups. Although there was no significant difference, the concomitant use of methotrexate (MTX) showed better clinical efficacy in the cases of baricitinib treatment as compared with in the case of tofacitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response differed. The concomitant use of oral steroid was independently associated with the achievement of DAS-low disease activity in both groups, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used and the DAS28-ESR at the time of initiation were associated with DAS-low disease activity.Conclusion:This study indicate that tofacitinib and baricitinib had comparable efficacies and safety profiles in a real-world setting. However, the influence of clinical characteristics on the treatment response differed between these two drugs. Direct comparison between two JAK inhibitors provide useful information to optimal use of JAK inhibitors in real-world settings.Disclosure of Interests:None declared


2015 ◽  
Vol 42 (4) ◽  
pp. 599-607 ◽  
Author(s):  
Tsutomu Takeuchi ◽  
Nobuyuki Miyasaka ◽  
Takashi Inui ◽  
Toshiro Yano ◽  
Toru Yoshinari ◽  
...  

Objective.To investigate the probability of clinical remission (REM) or low disease activity (LDA) after 1 year of infliximab (IFX) therapy based on disease activity at 3 months in patients with rheumatoid arthritis (RA).Methods.Methotrexate-refractory patients with RA received 3 mg/kg of IFX at weeks 0, 2, and 6, followed by 3 mg/kg, 6 mg/kg, or 10 mg/kg every 8 weeks from Week 14 (W14) to Week 46. Correlation of disease activity at W14 with disease activity at W54 and probability of REM/LDA at W54 were analyzed in each dosing group.Results.Disease activities at W14 were significantly correlated with both disease activity at W54 and probability of REM/LDA at W54 in patients continuing 3 mg/kg as well as in those receiving 6 mg/kg or 10 mg/kg therapy from W14. Results showed that, if approximate REM or LDA had not been achieved by W14, > 50% of patients continuing 3 mg/kg therapy would not be able to achieve REM or LDA at W54. However, even in patients with high or moderate disease activity at W14, dose escalation to 6 mg/kg or 10 mg/kg enabled many to achieve REM/LDA.Conclusion.Disease activity at W14 in standard-dose IFX therapy enabled the prediction of longterm clinical response at continued standard dose, as well as subsequent escalated-dose regimens. Disease activity at W14 was hypothesized to be an important index for IFX treatment strategy.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1016.2-1017
Author(s):  
F. R. Spinelli ◽  
M. S. Chimenti ◽  
M. Vadacca ◽  
C. Iannuccelli ◽  
P. Conigliaro ◽  
...  

Background:Gender medicine aims at describing how diseases differ between men and women in terms of epidemiology, clinical feature, therapeutic approach, treatment response and prognosis, psychological and social impact. Rheumatoid Arthritis (RA) affects women 2-3 times more than men. Female gender seems to be independently associated to a more refractory disease and a worst response to conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs) and biological DMARDs. Male patients achieve remission more often than females probably due to the higher number of tender joints reported by the latter.Objectives:In the light of the effect of Janus kinases inhibitors (JAKi) on pain, the objective of the study was to investigate whether gender might affect the achievement of remission or low disease activity in RA patients treated with baricitinib and tofacitinib.Methods:We performed a multicentric, prospective study on consecutive patients starting one of the two available JAKi: baricitinib and tofacitinib. Demographic and clinical data were recorded in a dedicate database and included: gender, age, disease duration, serological status (Rheumatoid Factor – RF; anti-citrullinated peptide antibodies, ACPA) number of previous csDMARDs and bDMARDs, number of tender joints (TJ) and swollen joints (SJ), C reactive protein (CRP); patient global assessment (PGA) and pain were recorded on a 0-100 mm visual-analogue scale (VAS). Disease activity score (DAS) 28 was calculated at baseline and at two follow-up visits (after 3-4 months and after 6-8 months). Data were expressed as mean±standard deviation or median (interquartile range) according to variables’ distribution. Continuous variables were compared by Mann Whitney test while dichotomous ones by Chi-squared test; p value < 0.05 were considered statistically significant.Results:We enrolled 182 RA patients (149 F:33 M) with similar age (F 58±12 vs M 60±10) and disease duration (F 143±101 vs M 147±105 months). Females and males were previously treated with the same number of csDMARDs [2(2)] but female have previously received numerically more bDMARDs [2(3) vs 1(2)]. At the 3 timepoints females and males showed similar number of TJ, SJ, similar values of CRP, PGA and pain. We did not observe any difference in percentage of males and females achieving remission or low disease activity according to gender (figure 1A) nor in terms of reduction of TJ, SJ and PGA; only pain decreased significantly more in male than in female patients at both timepoints (figure 1B).Conclusion:In RA patients treated with JAK inhibitors, even if the effect of JAKi on pain seems to be more relevant in male than in female, gender seems not to influence the overall clinical response, allowing men and women the same probability of reaching the therapeutic targetReferences:Disclosure of Interests:Francesca Romana Spinelli Grant/research support from: Pfizer, Speakers bureau: Lilly, BMS, Celgene, Maria Sole Chimenti: None declared, Marta Vadacca: None declared, Cristina Iannuccelli: None declared, Paola Conigliaro: None declared, Silvia Laura Bosello: None declared, Fulvia Ceccarelli: None declared, Cristina Garufi: None declared, Giulia Raffone: None declared, Paola Di Noi: None declared, Dario Bruno: None declared, Antonella Afeltra: None declared, Roberto Perricone: None declared, fabrizio conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB


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