A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study

Heimans, L.; Boer, K.V.C. Wevers-de; Visser, Karen; Goekoop, R.J.; Oosterhout, M. van; Harbers, J.B.; Bijkerk, C.; Speyer, I.; Buck, Michelle; Sonnaville, Peter B J de; Grillet, Bernard; Huizinga, T.W.J.; Allaart, Cornelia F

doi:10.1136/annrheumdis-2013-203243

Cited by 104 publications

(87 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Also, in the IMPROVED study, patients who were treated for flares based on DAS28 criteria had similar efficacy outcomes to those who were treated based on nonprotocol‐endorsed criteria, demonstrating that DAS28‐based criteria to detect flares that matter for outcomes are limited 9.…”

Section: Discussionmentioning

confidence: 94%

Evaluation of the Disease Activity Score in Twenty‐Eight Joints–Based Flare Definitions in Rheumatoid Arthritis: Data From a Three‐Year Clinical Trial

Dougados

Huizinga

Choy

et al. 2015

Arthritis Care & Research

View full text Add to dashboard Cite

ObjectiveTo assess the flare rate using published criteria (Disease Activity Score in 28 joints [DAS28‐2] increase between visits of >1.2 or >0.6 if current DAS28 ≥3.2) in patients receiving constant treatment, and to compare published flare criteria to criteria used by study investigators after biologic treatment discontinuation in the ACT‐RAY study.MethodsPatients with rheumatoid arthritis (n = 553) were randomized to add tocilizumab to ongoing methotrexate, or switch to tocilizumab plus placebo. If DAS28 ≤3.2 occurred at week 24, treatment remained constant until week 52; here we assessed the DAS28‐2 flare rate. Between weeks 52 and 104, patients in sustained remission (DAS28 <2.6 at 2 consecutive visits 12 weeks apart) discontinued tocilizumab and were assessed every 4 weeks. Per protocol, flare was defined as a worsening of disease activity that required treatment beyond the permitted therapy based on investigator opinions (investigator flare) and was compared with the DAS28‐2 definition.ResultsAfter tocilizumab discontinuation, DAS28‐2 was sensitive (88–100%), but not specific (57–65%), for detecting investigator flare. Under constant treatment, DAS28‐2 criteria were met in 136 cases per 100 patient‐years despite stable disease activity. Sustained flares were infrequent. Other DAS28‐based criteria led to similar conclusions.ConclusionDAS28‐based flare occurred more often than investigator‐defined flares after biologic agent discontinuation. More stringent criteria may be more appropriate for clinical practice.

show abstract

Section: Discussionmentioning

confidence: 94%

Evaluation of the Disease Activity Score in Twenty‐Eight Joints–Based Flare Definitions in Rheumatoid Arthritis: Data From a Three‐Year Clinical Trial

Dougados

Huizinga

Choy

et al. 2015

Arthritis Care & Research

View full text Add to dashboard Cite

show abstract

“…Our analysis showed that the effect of a TNF inhibitor plus methotrexate was significantly superior to combination DMARD treatment during the first 6 months, but this difference almost disappeared after 12 months, and especially after 18/24 months (no outcomes differed). Furthermore, in 3 studies using an initial course of steroids (3,4,14,15), there was no difference between the 2 treatment principles at any time (Figures 2-5 and Supplementary Figures 1-3, available in the online version of this article at http://onlinelibrary.wiley. com/doi/10.1002/acr.22618/abstract).…”

Section: Discussionmentioning

confidence: 99%

“…Concerning outcomes, only 1 study presented ESRs (14), 1 study presented CRP levels (11), and 3 studies presented joint swelling scores (10,14,16). Consequently, these outcomes, which we defined in the protocol, were not summarized in the present analysis.…”

mentioning

confidence: 99%

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

Graudal

Hubeck-Graudal

Faurschou

et al. 2015

Arthritis Care & Research

View full text Add to dashboard Cite

Objective. The costs of biologic treatment per patient with rheumatoid arthritis (RA) are approximately 100 times the costs of treatment with a combination of conventional disease-modifying antirheumatic drugs (DMARDs). Despite this, biologic agents have not been proven superior. We compared the effects of combination DMARD therapies with and without biologic agents as therapy for patients with RA. Methods. Eight randomized controlled trials published in 10 articles were selected from a systematic literature search of 1,674 identified studies and integrated in a meta-analysis. These trials compared combinations of DMARDs versus a tumor necrosis factor (TNF) inhibitor plus methotrexate. Two reviewers independently entered data into standardized extraction forms. The combined effect measures were compared by means of the inverse variance method (continuous data) and the Mantel-Haenszel method (dichotomous data) using a random-effects model. Results. The primary outcome, radiographic progression score, did not differ between the combination DMARD group and the TNF inhibitor group, neither during the second year (20.09 units [20.61, 0.44]) of treatment or during the first 2 years (0.66 units [20.12, 1.43]). There were significant differences in the radiographic progression score, the American College of Rheumatology criteria for 50% improvement (ACR50), and the ACR70 response criteria at 6 months in favor of TNF inhibitor treatment, but these differences were not present in patients treated with an initial steroid course and disappeared at 24 months, irrespective of the use of steroids. Conclusion. The difference between DMARD combination treatments, including or excluding TNF inhibitors, is small. Due to the enormous cost differences, RA guidelines should recommend combination DMARD treatment before initiation of TNF inhibitors.

show abstract

“…In this randomised study with a blinded outcome assessment (disease activity score and radiographic damage score), the GC arm showed a higher rate of improvement at week 28 than with SSZ alone (72 versus [58] and COBRA-light [59]) helped build on the idea that there was a ''window of opportunity'' in early RA and that tight control the Aging Clin Exp Res (2016) 28: 1-16 5 inflammation or ''treating-to-target'' (i.e. remission or minimal disease activity) resulted in better long-term outcomes.…”

Section: Gc Therapeutic Strategies In Ramentioning

confidence: 99%

Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

et al. 2016

View full text Add to dashboard Cite

Purpose This consensus review article considers the question of whether glucocorticoid (GC) therapy is still relevant in the treatment of rheumatic diseases, with a particular focus on rheumatoid arthritis (RA), and whether its side effects can be adequately managed. Recent basic and clinical research on the molecular, cellular and clinical effects of GCs have considerably advanced our knowledge in this field. An overview of the subject seems appropriate.

show abstract

A two-step treatment strategy trial in patients with early arthritis aimed at achieving remission: the IMPROVED study

Cited by 104 publications

References 27 publications

Evaluation of the Disease Activity Score in Twenty‐Eight Joints–Based Flare Definitions in Rheumatoid Arthritis: Data From a Three‐Year Clinical Trial

Evaluation of the Disease Activity Score in Twenty‐Eight Joints–Based Flare Definitions in Rheumatoid Arthritis: Data From a Three‐Year Clinical Trial

Combination Therapy With and Without Tumor Necrosis Factor Inhibitors in Rheumatoid Arthritis: A Meta‐Analysis of Randomized Trials

Balancing benefits and risks of glucocorticoids in rheumatic diseases and other inflammatory joint disorders: new insights from emerging data. An expert consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)

Contact Info

Product

Resources

About