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

Phase 4

Completed

• Conditions: Arthritis, Rheumatoid
• Interventions: Drug: Etanercept 50 MG/ML; Drug: Leflunomide 10 milligram (MG)

• Registration Number: NCT03649061
• Lead Sponsor: P. Verschueren

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-08
• Study First Submitted: 2018-07-30
• Study First Submitted QC: 2018-08-23
• Study First Posted: 2018-08-28
• Status Verified: 2022-07
• Primary Completion: 2022-07-01
• Study Completion: 2022-07-01
• Last Update Submitted: 2022-07-04
• Last Update Posted: 2022-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 284

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-

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
COBRA-Slim Bio-induction	Etanercept 50 MG/ML	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.)
standard COBRA-Slim induction	Leflunomide 10 milligram (MG)	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.)

Primary Outcome Measures

Name	Time	Method
Area Under Curve (AUC) DAS28 C reactive protein (CRP)	over 104 weeks

Secondary Outcome Measures

Name	Time	Method
Remission	at week 104	DAS28 CRP\<2.6
EULAR response	at week 104
Health Assessment Questionnaire (HAQ) response	at week 104	HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.
Radiographic progression	at week 104
Analysis of reported (Serious) Adverse Reactions	over 104 weeks	(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

Trial Locations

Locations (19)

UZ Leuven; 🇧🇪 Leuven, Vlaams Brabant, Belgium

CHU Liège; 🇧🇪 Liège, Belgium

CHU Saint Pierre; 🇧🇪 Brussel, Belgium

Cliniques Universitaire Saint Luc (UCL); 🇧🇪 Brussel, Belgium

Hôpital Erasme-ULB; 🇧🇪 Brussel, Belgium

AZ Herentals; 🇧🇪 Herentals, Antwerpen, Belgium

Imelda Ziekenhuis Bonheiden; 🇧🇪 Bonheiden, Antwerpen, Belgium

GHdC Saint Joseph; 🇧🇪 Gilly, Henegouwen, Belgium

ZNA Jan Palfijn; 🇧🇪 Merksem, Antwerpen, Belgium

Reuma centrum Genk; 🇧🇪 Genk, Limburg, Belgium

Reuma Instituut Hasselt; 🇧🇪 Hasselt, Limburg, Belgium

OLV Ziekenhuis Aalst; 🇧🇪 Aalst, Oost Vlaanderen, Belgium

Reuma Clinic Genk; 🇧🇪 Genk, Limburg, Belgium

CHU UCL Namur ASBL Site Godinne; 🇧🇪 Yvoir, Namur, Belgium

Regionaal Ziekenhuis Heilig Hart Leuven; 🇧🇪 Leuven, Vlaams Brabant, Belgium

AZ St Lucas Brugge; 🇧🇪 Brugge, West Vlaanderen, Belgium

AZ Jan Portaels; 🇧🇪 Vilvoorde, Vlaams Brabant, Belgium

AZ Sint Jan Brugge; 🇧🇪 Brugge, West-Vlaanderen, Belgium

UZ Brussel; 🇧🇪 Brussels, Belgium