Timing and Magnitude of Initial Change in Disease Activity Score 28 Predicts the Likelihood of Achieving Low Disease Activity at 1 Year in Rheumatoid Arthritis Patients Treated with Certolizumab Pegol: A Post-hoc Analysis of the RAPID 1 Trial

Heijde, Desirée van der; Keystone, Edward; Curtis, Jeffrey R.; Landewé, Robert; Schiff, Michael; Khanna, Dinesh; Kvien, Tore K; Ionescu, Lucian; Gervitz, Leon; Davies, O.; Luijtens, K.; Fürst, Daniel E.

doi:10.3899/jrheum.111171

Cited by 66 publications

(36 citation statements)

References 11 publications

(20 reference statements)

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“…Although it is possible that the rapid 4-week response to the combination of DMARDs represents regression to the mean, the continued good response of these patients argues against this. Our data also are consistent with recent studies demonstrating that early good response to combination therapy (in the TEAR and RAPID 1 trials) is associated with a continued good response 21 22. In these studies, rapid response was ascertained 12 weeks after initiation of combination therapy.…”

Section: Discussionsupporting

confidence: 92%

Trajectory of intensive treat-to-target disease modifying drug regimen in an observational study of an early rheumatoid arthritis cohort

et al. 2013

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ObjectivesStudies of early rheumatoid arthritis (RA) cohorts have analysed treatment response and prognostic factors at fixed time points. However, in treat-to-target protocols, therapeutic decision-making is dynamic and responsive to disease activity over time. To determine when a minimal residual disease response target should be expected, our primary objective was to identify the time-dependent therapeutic response to combination disease modifying antirheumatic drugs (DMARDs) for 12 months. Our secondary objective determined factors affecting this response trajectory.DesignObservational cohort.SettingTreat-to-target early RA clinic in Australian tertiary referral hospital.ParticipantsWe enrolled consecutive patients attending an early arthritis clinic with symptom duration less than 12 months, who were diagnosed with RA for the first time between 2004 and 2008. 101 met these eligibility criteria and data were available at baseline through 12 months.Interventionsintensive DMARDs according to a treat-to-target protocol.Primary and secondary outcome measuresWe measured disease activity scores (DAS) at each visit, then analysed therapeutic response and associated factors in a time-dependent fashion over 12 months.ResultsThe median DAS4vESR of 4.46 at baseline decreased 12 weeks later by 24%, while the proportion with DAS4v ≤ 2.6 increased (p<0.01). DAS4v continued to decrease over 52 weeks. DAS4v reduction of at least −0.45 at 4 weeks was predictive of DAS4v at 28 and 52 weeks. Female gender, current smoking, primary education and an interaction between baseline weight and C reactive protein (CRP) negatively impacted DAS4v reduction over 4 and 52 weeks. Time-varying effects of blood pressure, neutrophils, erythrocyte sedimentation rate and CRP also significantly influenced DAS4v over 52 weeks.ConclusionsTime-dependent data suggest that the largest reduction of DAS4v to combination DMARDs occurs in the first month of therapy, and this predicts subsequent response. Variables known to impact long-term treatment response in RA also impacted early DAS4v response to combination DMARDs.

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Section: Discussionsupporting

confidence: 92%

Trajectory of intensive treat-to-target disease modifying drug regimen in an observational study of an early rheumatoid arthritis cohort

et al. 2013

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“…Thus, there was a relatively low proportion of such patients (∼32%) who achieved low disease activity at week 52. Response at earlier time points and higher thresholds for response in order to classify a patient as a predicted responder (>20%) would increase the likelihood of achieving low disease activity in the future, as has been shown in other studies of CZP 21, 22. Also, it is theoretically possible that in order to achieve performance comparable to that of the CDAI, the absolute or relative improvement in the RAPID‐3 score might be different than the published cut points that we tested.…”

Section: Discussionmentioning

confidence: 74%

A Randomized Trial Comparing Disease Activity Measures for the Assessment and Prediction of Response in Rheumatoid Arthritis Patients Initiating Certolizumab Pegol

Curtis

Churchill²,

Kivitz

et al. 2015

Arthritis & Rheumatology

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ObjectiveThe aim of the Patient/Physician Reported Efficacy Determination In Clinical Practice Trial (PREDICT; ClinicalTrials identifier NCT01255761) was to compare the patient‐reported Routine Assessment of Patient Index Data 3 (RAPID‐3) instrument with the investigator‐based Clinical Disease Activity Index (CDAI) for assessing certolizumab pegol (CZP) treatment response in rheumatoid arthritis patients at 12 weeks and to predict the treatment response at week 52 using the data from week 12 (coprimary end points).MethodsPatients received 400 mg of CZP at weeks 0, 2, and 4 (loading dose), followed by 200 mg every 2 weeks thereafter. Patients were randomized 1:1 to assessment with the RAPID‐3 or the CDAI. Responder classification was performed at week 12; treatment response was defined as a score of ≤6 or a 20% improvement over baseline on the RAPID‐3 or a score of ≤10 or a 20% improvement over baseline on the CDAI. Long‐term treatment success was defined as a Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28‐ESR) of ≤3.2 at week 52. Comparisons were made for the coprimary end points using noninferiority methods. Patients with improvement of <1 on the CDAI score or with no improvement on the RAPID‐3 score at week 12 or patients with high levels of disease activity (CDAI score >22 or RAPID‐3 score >12) at 2 consecutive visits were withdrawn from the study.ResultsPatients had longstanding disease (mean 8.9 years) and high levels of disease activity (mean scores of 6.3 on the DAS28‐ESR, 16.1 on the RAPID‐3, and 40.2 on the CDAI). Previous anti–tumor necrosis factor therapy had failed in 55.5% of them. At week 12, a total of 64.7% (by RAPID‐3) and 76.4% (by CDAI) of the patients were classified as responders (difference of −11.9% [95% confidence interval −18.4%, −5.3%]). At week 52, a total of 31.5% (by RAPID‐3) and 32.3% (by CDAI) of the responders achieved a low level of disease activity on the DAS28‐ESR (difference of −1.3% [95% confidence interval −9.3%, 6.6%]).ConclusionThe CDAI classified more patients as CZP responders at week 12 than did the RAPID‐3. Although these outcome measures were not statistically comparable, the positive predictive value for low disease activity at week 52 was similar. As these tools cover differing domains of therapy response, further evaluation for clinical disease activity assessments and treatment decisions is needed.

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“…Improvement by 3 months refers to the fact that if a minimal change is not achieved, there is only a low likelihood of reaching the treatment target. Thus, a change to a better disease activity state should be seen at 3 months or a relative improvement, pertaining to at least 50% improvement in activity by a composite score, at that point in time, in order to have a considerable chance of reaching the target 31 100 112 113. Of note, adjustment of therapy includes the optimisation of MTX (or other csDMARD) dose or route of administration,4 or intra-articular injections of GC in the presence of one or few residual active joints, and refers to a change of drugs only if these measures have not been successful or are not appropriate.…”

Section: Resultsmentioning

confidence: 99%

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

et al. 2017

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Recent insights in rheumatoid arthritis (RA) necessitated updating the European League Against Rheumatism (EULAR) RA management recommendations. A large international Task Force based decisions on evidence from 3 systematic literature reviews, developing 4 overarching principles and 12 recommendations (vs 3 and 14, respectively, in 2013). The recommendations address conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GC); biological (b) DMARDs (tumour necrosis factor (TNF)-inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, clazakizumab, sarilumab and sirukumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (Janus kinase (Jak) inhibitors tofacitinib, baricitinib). Monotherapy, combination therapy, treatment strategies (treat-to-target) and the targets of sustained clinical remission (as defined by the American College of Rheumatology-(ACR)-EULAR Boolean or index criteria) or low disease activity are discussed. Cost aspects were taken into consideration. As first strategy, the Task Force recommends MTX (rapid escalation to 25 mg/week) plus short-term GC, aiming at >50% improvement within 3 and target attainment within 6 months. If this fails stratification is recommended. Without unfavourable prognostic markers, switching to—or adding—another csDMARDs (plus short-term GC) is suggested. In the presence of unfavourable prognostic markers (autoantibodies, high disease activity, early erosions, failure of 2 csDMARDs), any bDMARD (current practice) or Jak-inhibitor should be added to the csDMARD. If this fails, any other bDMARD or tsDMARD is recommended. If a patient is in sustained remission, bDMARDs can be tapered. For each recommendation, levels of evidence and Task Force agreement are provided, both mostly very high. These recommendations intend informing rheumatologists, patients, national rheumatology societies, hospital officials, social security agencies and regulators about EULAR's most recent consensus on the management of RA, aimed at attaining best outcomes with current therapies.

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Timing and Magnitude of Initial Change in Disease Activity Score 28 Predicts the Likelihood of Achieving Low Disease Activity at 1 Year in Rheumatoid Arthritis Patients Treated with Certolizumab Pegol: A Post-hoc Analysis of the RAPID 1 Trial

Cited by 66 publications

References 11 publications

Trajectory of intensive treat-to-target disease modifying drug regimen in an observational study of an early rheumatoid arthritis cohort

Trajectory of intensive treat-to-target disease modifying drug regimen in an observational study of an early rheumatoid arthritis cohort

A Randomized Trial Comparing Disease Activity Measures for the Assessment and Prediction of Response in Rheumatoid Arthritis Patients Initiating Certolizumab Pegol

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

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