COBRA-Slim With or Without Fast Access to TNF Blockade for Remission Induction in Early RA

NCT ID: NCT03649061

Last Updated: 2025-06-19

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

276 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-06-08

Study Completion Date

2022-07-01

Brief Summary

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In the Care in Rheumatoid Arthritis (CareRA) trial (NCT01172639) about 70% of early RA patients are in remission at the 2 year evaluation point independent of the combination scheme used.

Interesting to see is that the 30% of insufficient responders can be identified in an early stage of the treatment course.

The purpose of the present study is to investigate if, for patients with an insufficient response to a COBRA-Slim regimen, accelerated access to a short course of anti-TNF therapy already early after treatment initiation (from w8 until w32) could improve outcomes compared to a more traditional treat to target sequence.

Detailed Description

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Conditions

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Arthritis, Rheumatoid

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Insufficient responders to a COBRA-Slim strategy, defined as not reaching low disease activity based on DAS28 CRP from week 8 until week 32 or not reaching remission based on DAS28 CRP at week 32, will be randomly assigned to one of the two arms.

Randomization will be balanced according to time-point of randomization, baseline (BL) disease activity and Anti-Citrullinated Protein Antibody (ACPA) and Rheumatoid Factor (RF) status to ensure comparability of the treatment groups with respect to these prognostic variables.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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standard COBRA-Slim induction

Leflunomide 10mg PO daily added to the COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)

Group Type ACTIVE_COMPARATOR

Leflunomide 10 milligram (MG)

Intervention Type DRUG

Leflunomide 10mg PO daily added to the COBRA-Slim scheme

COBRA-Slim Bio-induction

Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme (Methotrexate 15 mg PO weekly, Step down scheme of GC: 30-20-12,5-10-7,5-5 mg prednisone PO daily, each for 7 days except for the lowest dose of 5 mg, this will be maintained until w28 and then tapered to 2.5 mg daily for two weeks before stopping completely.)

Group Type EXPERIMENTAL

Etanercept 50 MG/ML

Intervention Type DRUG

Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme

Interventions

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Etanercept 50 MG/ML

Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme

Intervention Type DRUG

Leflunomide 10 milligram (MG)

Leflunomide 10mg PO daily added to the COBRA-Slim scheme

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age 18 years and older
* Diagnosis of RA as defined by the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for early RA
* Early RA defined by a diagnosis made ≤ 1 year ago.
* Use a reliable method of contraception for women of childbearing potential to be evaluated as in daily clinical practice
* Able and willing to give written informed consent and to participate in the study
* Understanding and able to write Dutch or French

Exclusion Criteria

* Previous treatment with:

* Methotrexate (MTX) or leflunomide
* cyclophosphamide, azathioprine or cyclosporine
* sulphasalazine (SSZ) for more than 3 weeks
* hydroxychloroquine for more than 6 weeks
* oral Glucocorticoids (GC) for more than 4 weeks within 4 months before screening
* oral GC at a daily dosage of more than 10 mg prednisone equivalent within 4 weeks before baseline
* oral GC at a daily dosage equal to or less than 10 mg prednisone equivalent within 2 weeks before baseline
* intra-articular GC within 4 weeks before BL
* an investigational drug for the treatment/prevention of RA
* History of chronic heart failure
* History of severe infections or chronic infection
* History of malignant neoplasm within 5 years
* Contra indications for GC
* Contra indications for TNF blocking agents
* Contra indications for MTX or leflunomide
* Psoriatic Arthritis
* Underlying cardiac, pulmonary, metabolic, renal or gastrointestinal conditions, chronic or latent infectious diseases or immune deficiency which in the opinion of the investigator places the patient at an unacceptable risk for participation in the study
* Pregnancy, breastfeeding or no use of a reliable method of contraception for woman of childbearing potential (as in daily clinical practice)
* Alcohol or drug abuse
* Active tuberculosis (TB)
* Latent TB unless adequate prophylactic treatment is given according to local guidelines
* No access to the Belgian Health Insurance system-
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Belgium Health Care Knowledge Centre

OTHER_GOV

Sponsor Role collaborator

P. Verschueren

OTHER

Sponsor Role lead

Responsible Party

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P. Verschueren

Prof. Dr.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Patrick Verschueren, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

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Imelda Ziekenhuis Bonheiden

Bonheiden, Antwerpen, Belgium

Site Status

AZ Herentals

Herentals, Antwerpen, Belgium

Site Status

ZNA Jan Palfijn

Merksem, Antwerpen, Belgium

Site Status

GHdC Saint Joseph

Gilly, Henegouwen, Belgium

Site Status

Reuma centrum Genk

Genk, Limburg, Belgium

Site Status

Reuma Clinic Genk

Genk, Limburg, Belgium

Site Status

Reuma Instituut Hasselt

Hasselt, Limburg, Belgium

Site Status

CHU UCL Namur ASBL Site Godinne

Yvoir, Namur, Belgium

Site Status

OLV Ziekenhuis Aalst

Aalst, Oost Vlaanderen, Belgium

Site Status

Regionaal Ziekenhuis Heilig Hart Leuven

Leuven, Vlaams Brabant, Belgium

Site Status

UZ Leuven

Leuven, Vlaams Brabant, Belgium

Site Status

AZ Jan Portaels

Vilvoorde, Vlaams Brabant, Belgium

Site Status

AZ St Lucas Brugge

Bruges, West Vlaanderen, Belgium

Site Status

AZ Sint Jan Brugge

Bruges, West-Vlaanderen, Belgium

Site Status

CHU Saint Pierre

Brussels, , Belgium

Site Status

Cliniques Universitaire Saint Luc (UCL)

Brussels, , Belgium

Site Status

Hôpital Erasme-ULB

Brussels, , Belgium

Site Status

UZ Brussel

Brussels, , Belgium

Site Status

CHU Liège

Liège, , Belgium

Site Status

Countries

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Belgium

References

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Van der Elst K, De Cock D, Vecoven E, Arat S, Meyfroidt S, Joly J, Moons P, Verschueren P, Westhovens R, CareRA Study Group. Are illness perception and coping style associated with the delay between symptom onset and the first general practitioner consultation in early rheumatoid arthritis management? An exploratory study within the CareRA trial. Scand J Rheumatol. 2016;45(3):171-8. doi: 10.3109/03009742.2015.1074278. Epub 2015 Sep 23.

Reference Type BACKGROUND
PMID: 26399601 (View on PubMed)

Verschueren P, Esselens G, Westhovens R. Predictors of remission, normalized physical function, and changes in the working situation during follow-up of patients with early rheumatoid arthritis: an observational study. Scand J Rheumatol. 2009 May-Jun;38(3):166-72. doi: 10.1080/03009740802484846.

Reference Type BACKGROUND
PMID: 19169906 (View on PubMed)

Verschueren P, Westhovens R. The use of glucocorticoids in early rheumatoid arthritis. Rheumatology (Oxford). 2018 Aug 1;57(8):1316-1317. doi: 10.1093/rheumatology/kex271. No abstract available.

Reference Type RESULT
PMID: 28968687 (View on PubMed)

Verschueren P, De Cock D, Corluy L, Joos R, Langenaken C, Taelman V, Raeman F, Ravelingien I, Vandevyvere K, Lenaerts J, Geens E, Geusens P, Vanhoof J, Durnez A, Remans J, Vander Cruyssen B, Van Essche E, Sileghem A, De Brabanter G, Joly J, Meyfroidt S, Van der Elst K, Westhovens R. Effectiveness of methotrexate with step-down glucocorticoid remission induction (COBRA Slim) versus other intensive treatment strategies for early rheumatoid arthritis in a treat-to-target approach: 1-year results of CareRA, a randomised pragmatic open-label superiority trial. Ann Rheum Dis. 2017 Mar;76(3):511-520. doi: 10.1136/annrheumdis-2016-209212. Epub 2016 Jul 18.

Reference Type RESULT
PMID: 27432356 (View on PubMed)

De Cock D, Van der Elst K, Meyfroidt S, Verschueren P, Westhovens R. The optimal combination therapy for the treatment of early rheumatoid arthritis. Expert Opin Pharmacother. 2015;16(11):1615-25. doi: 10.1517/14656566.2015.1056735. Epub 2015 Jun 10.

Reference Type RESULT
PMID: 26058860 (View on PubMed)

Verschueren P, De Cock D, Corluy L, Joos R, Langenaken C, Taelman V, Raeman F, Ravelingien I, Vandevyvere K, Lenaerts J, Geens E, Geusens P, Vanhoof J, Durnez A, Remans J, Vander Cruyssen B, Van Essche E, Sileghem A, De Brabanter G, Joly J, Van der Elst K, Meyfroidt S, Westhovens R; CareRA study group. Patients lacking classical poor prognostic markers might also benefit from a step-down glucocorticoid bridging scheme in early rheumatoid arthritis: week 16 results from the randomized multicenter CareRA trial. Arthritis Res Ther. 2015 Apr 9;17(1):97. doi: 10.1186/s13075-015-0611-8.

Reference Type RESULT
PMID: 25889222 (View on PubMed)

Meyfroidt S, Van der Elst K, De Cock D, Joly J, Westhovens R, Hulscher M, Verschueren P. Patient experiences with intensive combination-treatment strategies with glucocorticoids for early rheumatoid arthritis. Patient Educ Couns. 2015 Mar;98(3):384-90. doi: 10.1016/j.pec.2014.11.011. Epub 2014 Nov 20.

Reference Type RESULT
PMID: 25483574 (View on PubMed)

Verschueren P, De Cock D, Corluy L, Joos R, Langenaken C, Taelman V, Raeman F, Ravelingien I, Vandevyvere K, Lenaerts J, Geens E, Geusens P, Vanhoof J, Durnez A, Remans J, Vander Cruyssen B, Van Essche E, Sileghem A, De Brabanter G, Joly J, Meyfroidt S, Van der Elst K, Westhovens R. Methotrexate in combination with other DMARDs is not superior to methotrexate alone for remission induction with moderate-to-high-dose glucocorticoid bridging in early rheumatoid arthritis after 16 weeks of treatment: the CareRA trial. Ann Rheum Dis. 2015 Jan;74(1):27-34. doi: 10.1136/annrheumdis-2014-205489. Epub 2014 Oct 30.

Reference Type RESULT
PMID: 25359382 (View on PubMed)

Meyfroidt S, van Hulst L, De Cock D, Van der Elst K, Joly J, Westhovens R, Hulscher M, Verschueren P. Factors influencing the prescription of intensive combination treatment strategies for early rheumatoid arthritis. Scand J Rheumatol. 2014;43(4):265-72. doi: 10.3109/03009742.2013.863382. Epub 2014 Feb 24.

Reference Type RESULT
PMID: 24559216 (View on PubMed)

Westhovens R, Verschueren P. Rheumatoid arthritis: defining remission in patients with RA in clinical practice. Nat Rev Rheumatol. 2012 Aug;8(8):445-7. doi: 10.1038/nrrheum.2012.111. Epub 2012 Jul 3. No abstract available.

Reference Type RESULT
PMID: 22751567 (View on PubMed)

Verschueren P, Westhovens R. Optimal care for early RA patients: the challenge of translating scientific data into clinical practice. Rheumatology (Oxford). 2011 Jul;50(7):1194-200. doi: 10.1093/rheumatology/ker131. Epub 2011 Mar 30.

Reference Type RESULT
PMID: 21454307 (View on PubMed)

Durez P, Malghem J, Nzeusseu Toukap A, Depresseux G, Lauwerys BR, Westhovens R, Luyten FP, Corluy L, Houssiau FA, Verschueren P. Treatment of early rheumatoid arthritis: a randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone. Arthritis Rheum. 2007 Dec;56(12):3919-27. doi: 10.1002/art.23055.

Reference Type RESULT
PMID: 18050189 (View on PubMed)

Boers M, Verhoeven AC, Markusse HM, van de Laar MA, Westhovens R, van Denderen JC, van Zeben D, Dijkmans BA, Peeters AJ, Jacobs P, van den Brink HR, Schouten HJ, van der Heijde DM, Boonen A, van der Linden S. Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis. Lancet. 1997 Aug 2;350(9074):309-18. doi: 10.1016/S0140-6736(97)01300-7.

Reference Type RESULT
PMID: 9251634 (View on PubMed)

Bertrand D, Joly J, Neerinckx B, Durez P, Lenaerts J, Joos R, Thevissen K, Zwaenepoel T, Vanhoof J, Di Romana S, Taelman V, Van Essche E, Corluy L, Ribbens C, Vanden Berghe M, Devinck M, Ajeganova S, Durnez A, Boutsen Y, Margaux J, Peene I, Van Offel J, Doumen M, Pazmino S, De Meyst E, Kulyk M, Creten N, Westhovens R, Verschueren P; CareRA2020 Study group. Effectiveness of methotrexate and bridging glucocorticoids with or without early introduction of a 6-month course of etanercept in early RA: results of the 2-year, pragmatic, randomised CareRA2020 trial. RMD Open. 2024 Aug 7;10(3):e004535. doi: 10.1136/rmdopen-2024-004535.

Reference Type DERIVED
PMID: 39117445 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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2017-004054-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

KCE-16002

Identifier Type: -

Identifier Source: org_study_id

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