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

Arthritis, Rheumatoid Clinical Trial

— CareRA2020  

Official title:

Effectiveness of a Combination of Methotrexate and a Step Down Glucocorticoid Regimen (COBRA-Slim) for Remission Induction in Patients With Early Rheumatoid Arthritis (RA), With or Without Fast Access to 24 Weeks of Tumor Necrosis Factor (TNF) Blockade in Insufficient Responders, a Randomized, Multicenter, Pragmatic Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03649061
• Other study ID #: KCE-16002
• Secondary ID: 2017-004054-41
• Status: Completed
• Phase: Phase 4
• Start date: June 8, 2018
• Est. completion date: July 1, 2022

Study information

• Verified date: July 2022
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 284
• Est. completion date: July 1, 2022
• Est. primary completion date: July 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Etanercept 50 MG/ML
Etanercept 50mg subcutaneous (SC) weekly added for 24 weeks to COBRA-Slim scheme
• Leflunomide 10 milligram (MG)
Leflunomide 10mg PO daily added to the COBRA-Slim scheme

Locations

Country	Name	City	State
Belgium	OLV Ziekenhuis Aalst	Aalst	Oost Vlaanderen
Belgium	Imelda Ziekenhuis Bonheiden	Bonheiden	Antwerpen
Belgium	AZ Sint Jan Brugge	Brugge	West-Vlaanderen
Belgium	AZ St Lucas Brugge	Brugge	West Vlaanderen
Belgium	CHU Saint Pierre	Brussel
Belgium	Cliniques Universitaire Saint Luc (UCL)	Brussel
Belgium	Hôpital Erasme-ULB	Brussel
Belgium	UZ Brussel	Brussels
Belgium	Reuma centrum Genk	Genk	Limburg
Belgium	Reuma Clinic Genk	Genk	Limburg
Belgium	GHdC Saint Joseph	Gilly	Henegouwen
Belgium	Reuma Instituut Hasselt	Hasselt	Limburg
Belgium	AZ Herentals	Herentals	Antwerpen
Belgium	Regionaal Ziekenhuis Heilig Hart Leuven	Leuven	Vlaams Brabant
Belgium	UZ Leuven	Leuven	Vlaams Brabant
Belgium	CHU Liège	Liège
Belgium	ZNA Jan Palfijn	Merksem	Antwerpen
Belgium	AZ Jan Portaels	Vilvoorde	Vlaams Brabant
Belgium	CHU UCL Namur ASBL Site Godinne	Yvoir	Namur

Sponsors (2)

Lead Sponsor	Collaborator
P. Verschueren	Belgium Health Care Knowledge Centre

Country where clinical trial is conducted

Belgium, 

References & Publications (13)

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 pr — View Citation

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. Revi — View Citation

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 a — View Citation

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. do — View Citation

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. — View Citation

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. — View Citation

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, V — View Citation

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, V — View Citation

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 — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under Curve (AUC) DAS28 C reactive protein (CRP)		over 104 weeks
Secondary	Remission	DAS28 CRP<2.6	at 28 weeks after randomization
Secondary	Remission	DAS28 CRP<2.6	at week 104
Secondary	EULAR response		at 28 weeks after randomization
Secondary	EULAR response		at week 104
Secondary	Health Assessment Questionnaire (HAQ) response	HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.	at 28 weeks after randomization
Secondary	Health Assessment Questionnaire (HAQ) response	HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.	at week 104
Secondary	Radiographic progression		at week 52
Secondary	Radiographic progression		at week 104
Secondary	Analysis of reported (Serious) Adverse Reactions	(Serious) Adverse Reactions will be captured by the investigator using his/her clinical judgement. Number of events will be analysed and described in total and per patient	over 104 weeks