Baseline predictors of different types of treatment success in rheumatoid arthritis

2021 ◽  
pp. annrheumdis-2021-220853
Author(s):  
Dafne Capelusnik ◽  
Daniel Aletaha
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Activity Index ◽  
Treatment Success ◽  
Disease Activity Index ◽  
Acute Phase Reactants ◽  
Reactive Protein ◽  
Composite Indices ◽  
Lower Disease Activity

ObjectiveTo perform a comprehensive analysis on predictors of achieving disease activity outcomes by change, response and state measures.MethodsWe used data from three rheumatoid arthritis (RA) trials (one for main analysis, two for validation) to analyse the effect of patient and disease characteristics, core set measure and composite indices on the achievement of different outcomes: response outcomes (% of patients achieving a relative response margin); state outcomes (remission or low disease activity, LDA) and change outcomes (numerical change on metric scales).ResultsWe included patients from the ASPIRE trial (for analysis) and from the ATTRACT and GO-BEFORE trials (for validation). While lower disease activity components at baseline—except acute phase reactants—were associated with achievement of state outcomes (such as LDA by the Simplified Disease Activity Index, SDAI), higher baseline values were associated with change outcomes (such as SDAI absolute change). A multivariate analysis of the identified predictors of state outcomes identified best prediction by a combination of shorter disease duration, male gender and lower disease activity. For prediction of response, no consistently significant predictors were found, again, with exception of C reactive protein, for which higher levels at baseline were associated with better responses.ConclusionPrediction of treatment success is limited in RA. Particularly in early RA, prediction of state targets can be achieved by lower baseline levels of diseases activity. Gender and disease duration may improve the predictability of state targets. In clinical trials, included populations and choice of outcomes can be coordinated to maximise efficiency from these studies.

THU0620-HPR MEASUREMENT OF LOW DISEASE ACTIVITY USING THE CLINICAL DISEASE ACTIVITY INDEX (CDAI) VERSUS THE DISEASE ACTIVITY SCORE 28 (DAS 28): IMPACT OF INFLAMMATION MARKERS ON THE COMPARATIVE EFFECTIVENESS OF BIOLOGICS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 553.1-553
Author(s):  
K. Janke ◽  
K. Biester ◽  
D. Krause ◽  
B. Richter ◽  
C. Schürmann ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Comparative Effectiveness ◽  
Inflammatory Markers ◽  
Activity Index ◽  
Disease Activity Index ◽  
Signs And Symptoms ◽  
Acute Phase Reactants ◽  
Das 28 ◽  
Effectiveness Studies

Background:Biologics for the treatment of rheumatoid arthritis (RA) have different modes of action to target auto-inflammatory processes causing the signs and symptoms of the disease. Different biologics may thus have different effects on inflammatory markers. For instance, previous studies have shown that the interleukin-6-inhibitor tocilizumab (TOC) decreases the level of acute phase reactants (APRs) [1]. Such direct effects on inflammatory markers may lead to an overestimation of clinical response if disease activity is measured via scores including inflammatory markers, such as the Disease Activity Score 28 (DAS 28). The detected changes in disease activity may not adequately reflect the clinical improvement of signs and symptoms.Objectives:In our study, we compared biologics with each other using two different disease activity scores: the DAS 28 including APRs and the clinical disease activity index (CDAI) excluding APRs. The aim of this study was to assess whether the use of the two different scores affects comparative effectiveness studies on biologics for the treatment of RA.Methods:We compared results on the comparative effectiveness of biologics using the corresponding thresholds for low disease activity (LDA) for the DAS 28 (< 3.2) and the CDAI (≤ 10). We performed two separate network meta-analyses (NMAs) after a thorough step-by-step evaluation of the similarity, homogeneity and consistency assumptions of the patient populations and the study data.Our study formed part of a systematic review (including NMAs) that was largely based on clinical study reports and re-analyses of LDA using individual patient data provided by sponsors for studies conducted up to 2017. Thus, the analyses include hitherto unknown data on LDA analysed by means of the CDAI, especially data from older studies. An extensive comparison of DAS 28 and CDAI in different patient populations was possible.Results:For all analysed patient populations, comparisons of TOC versus other biologics yielded remarkable results: advantages for TOC were found in NMAs using the DAS 28, which were not confirmed in NMAs using the CDAI. For methotrexate (MTX)-naïve patients, using the DAS 28, TOC showed a greater benefit than abatacept (ABA), certolizumab pegol (CZP), and etanercept (ETA), which was not confirmed by the CDAI. In contrast, TOC showed less benefit than adalimumab (ADA) and ETA. For patients after MTX failure and using the DAS 28, TOC showed a greater benefit than ABA, ADA, anakinra (ANA), ETA, golimumab (GOL), and infliximab (INF). With the exception of ANA, these advantages were not confirmed by the CDAI. Similar differences between DAS 28 and CDAI were shown in patients treated with biologics in monotherapy or after failure of biologics.Conclusion:In comparative effectiveness studies of biologics, the assessment of LDA using the DAS 28 instead of the CDAI leads to a consistent overestimation of the benefit of TOC in all patient populations, regardless of pre-treatment or combined therapy with MTX. The inclusion of APRs in disease activity scores may thus introduce bias. A score excluding inflammatory markers should therefore be used to ensure valid results.References:[1]Smolen JS, Aletaha D. Interleukin-6 receptor inhibition with tocilizumab and attainment of disease remission in rheumatoid arthritis: the role of acute-phase reactants. Arthritis Rheum 2011; 63(1): 43-52.Disclosure of Interests:Kirsten Janke: None declared, Katharina Biester: None declared, Dietmar Krause Grant/research support from: Pfizer and AbbVie (Abbott), Bernd Richter: None declared, Christoph Schürmann: None declared, Katharina Hirsch: None declared, Beate Wieseler: None declared

scholarly journals Effect of disease duration and prior disease-modifying antirheumatic drug use on treatment outcomes in patients with rheumatoid arthritis

2019 ◽  
Vol 78 (12) ◽  
pp. 1609-1615 ◽  
Author(s):  
Daniel Aletaha ◽  
Jen-fue Maa ◽  
Su Chen ◽  
Sung-Hwan Park ◽  
Dave Nicholls ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Duration ◽  
Activity Index ◽  
Health Assessment ◽  
Disease Activity Index ◽  
Response To Therapy ◽  
Joint Disease ◽  
Adalimumab Therapy ◽  
Disease Modifying

ObjectivesTo determine if disease duration and number of prior disease-modifying antirheumatic drugs (DMARDs) affect response to therapy in patients with established rheumatoid arthritis (RA).MethodsAssociations between disease duration or number of prior DMARDs and response to therapy were assessed using data from two randomised controlled trials in patients with established RA (mean duration, 11 years) receiving adalimumab+methotrexate. Response to therapy was assessed at week 24 using disease activity outcomes, including 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)), Simplified Disease Activity Index (SDAI) and Health Assessment Questionnaire Disability Index (HAQ-DI), and proportions of patients with 20%/50%/70% improvement in American College of Rheumatology (ACR) responses.ResultsIn the larger study (N=207), a greater number of prior DMARDs (>2 vs 0–1) was associated with smaller improvements in DAS28(CRP) (–1.8 vs –2.2), SDAI (–22.1 vs –26.9) and HAQ-DI (–0.43 vs –0.64) from baseline to week 24. RA duration of >10 years versus <1 year was associated with higher HAQ-DI scores (1.1 vs 0.7) at week 24, but results on DAS28(CRP) and SDAI were mixed. A greater number of prior DMARDs and longer RA duration were associated with lower ACR response rates at week 24. Data from the second trial (N=67) generally confirmed these findings.ConclusionsNumber of prior DMARDs and disease duration affect responses to therapy in patients with established RA. Furthermore, number of prior DMARDs, regardless of disease duration, has a limiting effect on the potential response to adalimumab therapy.

scholarly journals Predictor of the Simplified Disease Activity Index 50 (SDAI 50) at Month 3 of bDMARD Treatment in Patients with Long-Established Rheumatoid Arthritis

2017 ◽  
Vol 11 (1) ◽  
pp. 106-112 ◽  
Author(s):  
Yusuke Miwa ◽  
Mayu Saito ◽  
Hidekazu Furuya ◽  
Ryo Yanai ◽  
Tsuyoshi Kasama
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Odds Ratio ◽  
Disease Duration ◽  
Activity Index ◽  
Short Form ◽  
Disease Activity Index ◽  
Smoking History ◽  
Tender Joint Count ◽  
Tender Joint

Objectives:The Simplified Disease Activity Index (SDAI) 50 has good agreement with European League Against Rheumatism (EULAR) response measures for early Rheumatoid Arthritis (RA). There have been reports on early RA, but not on long-established RA. In this study, we analysed the relationships between various baseline factors and SDAI 50 after three months of treatment with biological disease-modifying antirheumatic drugs (bDMARDs) to determine the prognostic factors for long-established RA.Methods:Subjects were 260 RA patients who had been treated with bDMARDs for 3 months. The following characteristics were investigated: Patient backgrounds, the erythrocyte sedimentation rate (ESR), C-reactive protein and serum matrix metalloproteinase-3 levels, SDAI scores, and health assessment questionnaire disability index and short form-36 scores. As a primary outcome index, the SDAI response was defined as a 50% reduction in the SDAI score between baseline and 3 months (SDAI 50).Results:Baseline values of disease duration (odds ratio: 0.942, 95% CI: 0.902-0.984), smoking history (odds ratio: 2.272, 1.064-4.850), 28-tender joint count (odds ratio: 0.899, 0.827-0.977), evaluator's global assessment (odds ratio: 1.029, 1.012-1.047) and ESR (odds ratio: 1.015, 1.001-1.030) were determined to be significant factors based on logistic regression analysis.Conclusion:Our study demonstrated that RA patients with shorter disease duration, no smoking, and higher RA disease activity are more likely to achieve SDAI 50 through bDMARD treatment.

Carotid Plaque Characteristics and Disease Activity in Rheumatoid Arthritis

2013 ◽  
Vol 40 (4) ◽  
pp. 359-368 ◽  
Author(s):  
Anne G. Semb ◽  
Silvia Rollefstad ◽  
Sella A. Provan ◽  
Tore K. Kvien ◽  
Einar Stranden ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Analysis Of Covariance ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
Different Levels ◽  
Index Disease ◽  
Active Disease

Objective.Carotid plaques (CP) are predictive of acute coronary syndrome in patients with rheumatoid arthritis (RA), suggesting that atherosclerotic plaques in these patients are vulnerable. The objective of our study was to characterize vulnerability of CP in patients with RA compared to a control population, and between RA patients with different levels of disease activity.Methods.Ultrasound examination of carotid arteries was performed in 152 patients with RA and 89 controls. CP echolucency was evaluated by the Gray-Scale Median (GSM) technique. Lower GSM values indicate higher vulnerability of plaques. CP characteristics were compared between RA patients with active disease and in remission, and between patients and controls. All analyses were performed with adjustment for confounding factors (sex, age, smoking, and blood pressure). Poisson regression analysis was used for count data, mixed modeling for GSM and area per plaque, and analysis of covariance for minimum GSM value per patient.Results.Patients with RA more frequently had CP (median 2, range 0, 4) compared with controls (median 1, range 0, 3; p < 0.001), after adjustment for age and sex. Patients with active RA disease according to the Clinical Disease Activity Index (CDAI) had lower median GSM (p = 0.03), minimum GSM (p = 0.03), and a larger CP area (although the latter finding was not significant; p = 0.27), compared with patients with RA in remission. These findings were not confirmed for other disease measures (Simplified Disease Activity Index, Disease Activity Score-28, C-reactive protein, erythrocyte sedimentation rate).Conclusion.Patients with RA had more CP compared with controls and patients in CDAI remission, and controls had more stable CP than patients with active disease; these findings point to the importance of achieving remission in RA.

scholarly journals Definition of Treatment Targets in Rheumatoid Arthritis: Is It Time for Reappraisal?

2021 ◽  
pp. jrheum.210050
Author(s):  
Ricardo J.O. Ferreira ◽  
Robert B.M. Landewé ◽  
José A.P. da Silva
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Current Issue ◽  
Activity Index ◽  
Disease Activity Index ◽  
Clinical Disease ◽  
Moderate Correlation ◽  
Composite Indices ◽  
Definition Of ◽  
Routine Assessment

In the current issue of The Journal of Rheumatology, Kremer and colleagues1 compare the Clinical Disease Activity Index (CDAI) with a slightly modified Corrona Routine Assessment of Patient Index Data 3 (cRAPID3) in terms of correlation and disease activity categorization, using 2 large US registries of patients with rheumatoid arthritis (RA). Overall, a low concordance between these 2 composite indices (κ = 0.29) was found in terms of disease activity categories, despite a moderate correlation between their numerical global scores (rs = 0.58 and 0.72, for the BRASS and CORRONA registries, respectively).

scholarly journals Clinical Advantage of Attaining Index-Based Remission Criteria prior to Composite Remission in Treating Rheumatoid Arthritis

2021 ◽  
Author(s):  
Ichiro Yoshii ◽  
Tatsumi Chijiwa ◽  
Naoya Sawada
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Disease Activity Score ◽  
Activity Index ◽  
Disease Activity Index ◽  
Reactive Protein ◽  
Remission Criteria ◽  
Clinical Advantage ◽  
Rate Of Failure ◽  
Activity Indices

Background and objectives: The clinical advantage of targeting index-based remission criteria (IR) prior to Boolean remission (BR) was evaluated retrospectively. Materials and Methods: A total of 578 patients with rheumatoid arthritis (RA), who were treated for more than three years, were recruited. Patients who were treated to targeted IR and composite measure remission criteria such as BR from the first consultation were divided according to the turn of attaining BR and IR: IB-R, a group that matched IR at the same time BR is attained or earlier; BI-F, a group that attained BR followed by IR or failed; IR-BF, a group that could not attain BR despite attaining IR; Both-F, a group that failed to attain either BR or IR. Background factors were statistically compared among groups. The BR rate in patients who attained IR (BRR) and the rate of failure to attain IR in patients who failed to attain BR (BFR) were statistically evaluated. Results: Groups made of 225, 231, and 482 in IB-R; 160, 154, and 8 in BI-F; 18, 18, and 75 in IR-BF; and 175, 175, and 13 in Both-F when indexing the clinical disease activity index (CDAI), simplified disease activity index (SDAI), and 28-joints disease activity score with C-reactive protein (DAS28-CRP), respectively. Disease activity indices&rsquo; scores after BR demonstrated significantly higher in the BI-F group than in the IB-R group. BRR was 92.6%, 92.8%, and 86.5%, while BFR was 71.3%, 71.3%, and 13.8% when indexing CDAI, SDAI, and DAS28-CRP, respectively. Conclusions: Targeting CDAI and SDAI remission prior to BR contributes to a stable clinical course.

Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab

2020 ◽  
Vol 79 (7) ◽  
pp. 874-882
Author(s):  
Inbal Haya Shafran ◽  
Farideh Alasti ◽  
Josef S Smolen ◽  
Daniel Aletaha
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Inflammatory Responses ◽  
Activity Index ◽  
Disease Activity Index ◽  
Positive Association ◽  
C Reactive Protein ◽  
Therapeutic Success ◽  
Reactive Protein ◽  
Early Ra

BackgroundRheumatoid arthritis (RA) is characterised by clinical joint swelling and elevation of acute phase reactant levels, typically measured by the C-reactive protein (CRP). Clinical and inflammatory responses are usually concordant, except for inhibition of IL-6, which often disproportionally reduces the CRP due to direct inhibition of its hepatic production. We investigated whether pre-treatment CRP is a useful marker that can guide a preferential treatment choice towards IL-6 inhibition.MethodsData of 1126 treatment courses with tocilizumab (TCZ; early RA), 250 courses of rituximab (RTX; established RA) and 249 courses of methotrexate (MTX; established RA) were analysed. We compared clinical disease activity index (CDAI) values and change along 24 weeks’ follow-up to CRP values at baseline or its early change. We validated the results using data from a separate TCZ trial in early RA.ResultsCRP levels in the TCZ group on average dropped by 74% within 4 weeks. Patients who attained CDAI remission at 24 weeks on TCZ had the highest baseline CRP levels while patients in high disease activity had the lowest; this association was reverse in the RTX and MTX groups. TCZ patients who achieved remission at 24 weeks showed the largest reductions of CRP levels by week 4 compared with those reaching higher disease activity states. Early CRP non-response was indicative of a risk of not achieving clinical treatment goals (p=0.038).ConclusionBaseline CRP appears to have a positive association with reaching the therapeutic target on TCZ treatment, but is a negative predictor for RTX and MTX. Patients on TCZ without an early CRP response have a lower chance of achieving remission. CRP and its early course may inform, to some extent, the estimation of potential therapeutic success in patients with RA.

Incidence and Predictors of Biological Antirheumatic Drug Discontinuation Attempts among Patients with Rheumatoid Arthritis in Remission: A CORRONA and NinJa Collaborative Cohort Study

2015 ◽  
Vol 42 (12) ◽  
pp. 2238-2246 ◽  
Author(s):  
Kazuki Yoshida ◽  
Helga Radner ◽  
Maria D. Mjaavatten ◽  
Jeffrey D. Greenberg ◽  
Arthur Kavanaugh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Cox Regression ◽  
Activity Index ◽  
Disease Activity Index ◽  
Frailty Models ◽  
National Database ◽  
Drug Discontinuation ◽  
The Us ◽  
Lower Disease Activity

Objective.We conducted a longitudinal observational study of biological disease-modifying antirheumatic drugs (bDMARD) to describe the proportions of patients with rheumatoid arthritis in remission who discontinued these agents, and to assess the potential predictors of the decision to discontinue.Methods.We used data from the US COnsortium of Rheumatology Researchers Of North America (CORRONA) and the Japanese National Database of Rheumatic Diseases by iR-net in Japan (NinJa) registries, and ran parallel analyses. Patients treated with bDMARD who experienced remission (defined by the Clinical Disease Activity Index ≤ 2.8) were included. The outcome of interest was the occurrence of bDMARD discontinuation while in remission. The predictors of discontinuation were assessed in the Cox regression models. Frailty models were also used to examine the effects of individual physicians in the discontinuation decision.Results.The numbers of eligible patients who were initially in remission were 6263 in the CORRONA and 744 in the NinJa. Among these patients, 10.0% of patients in CORRONA and 11.8% of patients in NinJa discontinued bDMARD while in remission over 5 years, whereas many of the remaining patients lost remission before discontinuing bDMARD. Shorter disease duration was associated with higher rates of discontinuation in both cohorts. In CORRONA, methotrexate use and lower disease activity were also associated with discontinuation. In frailty models, physician random effects were significant in both cohorts.Conclusion.Among patients who initially experienced remission while receiving bDMARD, around 10% remained in remission and then discontinued bDMARD in both registries. Several factors were associated with more frequent discontinuation while in remission. Physician preference likely is also an important correlate of bDMARD discontinuation, indicating the need for standardization of practice.

scholarly journals Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study

2021 ◽  
pp. annrheumdis-2021-219876
Author(s):  
Evgeniy Nasonov ◽  
Saeed Fatenejad ◽  
Eugen Feist ◽  
Mariana Ivanova ◽  
Elena Korneva ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Activity Index ◽  
Disease Activity Index ◽  
Phase Iii ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.

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