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Completed

NCT Number: NCT03649061

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

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.

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Key information

Conditions

Arthritis, Rheumatoid Arthritis Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Imelda Ziekenhuis Bonheiden, Bonheiden, Antwerpen, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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-

Treatment and study plan

Etanercept 50 MG/ML

Drug

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

Leflunomide 10 milligram (MG)

Drug

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

Primary outcomes

  1. Area Under Curve (AUC) of Disease Activity Score Based on a 28 Jointcount and C-reactive Protein (DAS28CRP)

    Time frame: baseline, w4, w8, w16, w24, w32, w40, w52, w64, w78, w92 and w104

    Analysis was based on an intention to treat population, which focused on all patients randomized into the study, irrespective if they actually received the randomized treatment. Fifty-five patients were allocated to Standard COBRA-Slim and 55 to COBRA-Slim Bio-induction.

    This measure is an indication of the total disease-activity over time or long-term effectiveness, a higher area under the curve indicates a higher disease activity over time and so a lower effectiveness over the time frame of the trial.

    The scale range for the duration of the trial (104 weeks) is 0.0 to 977.6

    • remission: value below 270.4
    • low disease activity: from 270.4 till 332.8 (included)
    • moderate disease activity: above 332.8 till 530.4
    • high disease activity: above 530.4

Secondary outcomes

  1. Proportion of Insufficient Responders Achieving Remission (DAS28CRP<2.6) 28 Weeks After Randomization (Short Term Efficacy) to Either COBRA-Slim Bio-Induction or Standard COBRA-Slim Induction

    Time frame: From randomization till 28 weeks after randomization.

    Short-time efficacy of disease activity based on a swollen and tender joint count of 28 joints and C-reactive proteine (scale range 0.0 to 9.4; remission: value below 2.6; low disease activity: from 2.6 till 3.2 (included); moderate disease activity: above 3.2 till 5.1; high disease activity: above 5.1).

  2. Proportion of Patients in Remission Defined as DAS28CRP<2.6

    Time frame: at week 104

    Short-time efficacy of disease activity based on a swollen and tender joint count of 28 joints and C-reactive proteine (scale range 0.0 to 9.4; remission: value below 2.6; low disease activity: from 2.6 till 3.2 (included); moderate disease activity: above 3.2 till 5.1; high disease activity: above 5.1).

  3. Proportion of Patients Achieving a EULAR Response

    Time frame: at 28 weeks after randomization

    proportion of patients achieving a EULAR response, based on actual disease activity on a tender/swollen joint count and C-reactive proteine (DAS28-CRP) 28 weeks after randomization and improvement in DAS28-CRP from baseline.

    The EULAR response criteria classify patients as good, moderate or non-responders, using the individual amount of change in the DAS28-CRP and the DAS28-CRP value (low, moderate, or high) reached according to the following tabel:

    DAS28-CRP at endpoint improvement in DAS28-CRP from baseline <=1,2 >0,6 and <= 1,2 <=0,6 <= 3,2 good moderate none >3,2 and <= 5,1 moderate moderate none >5,1 moderate none none Additionally all patients with a good response were also included in the number of participants with at least a moderate response.

  4. Proportion of Patients Achieving a EULAR Response

    Time frame: at week 104

    proportion of patients achieving a EULAR response, based on actual disease activity on a tender/swollen joint count and C-reactive proteine (DAS28-CRP) at week 104 and improvement in DAS28-CRP from baseline.

    The EULAR response criteria classify patients as good, moderate or non-responders, using the individual amount of change in the DAS28-CRP and the DAS28-CRP value (low, moderate, or high) reached according to the following tabel:

    DAS28-CRP at endpoint improvement in DAS28-CRP from baseline <=1,2 >0,6 and <= 1,2 <=0,6 <= 3,2 good moderate none >3,2 and <= 5,1 moderate moderate none >5,1 moderate none none Additionally all patients with a good response were also included in the number of participants with at least a moderate response.

  5. Health Assessment Questionnaire (HAQ) Response

    Time frame: at 28 weeks after randomization

    HAQ measures physical function as reported by the patient, total score range from 0-3 of which higher scores represent worse physical function.

  6. Health Assessment Questionnaire (HAQ) Response

    Time frame: 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.

  7. Radiographic Progression

    Time frame: at week 52

    Radiographic progression at week 52 is scored according to the Sharp-Van der Heijde score (SvdH).

    The SvdH method scores the presence of erosions in 16 joints of hands and wrists (graded from 0 to 5), and in 6 joints of the feet (graded from 0 to 10), and the presence of joint space narrowing in 15 joints of the hands and wrists (graded from 0 to 4) and in 6 joints of the feet (graded from 0 to 4). The maximal range is 280 units for erosion and 168 units for joint space narrowing, summing up to 448 units for the total score.

    The progression is calculated by subtracting the total score at week 52 minus the total score at baseline (ranging from 0 to 448) Higher values in each (sub) scale represents a worse outcome.

  8. Radiographic Progression

    Time frame: at week 104

    Radiographic progression at week 104 is scored according to the Sharp-Van der Heijde score (SvdH).

    The SvdH method scores the presence of erosions in 16 joints of hands and wrists (graded from 0 to 5), and in 6 joints of the feet (graded from 0 to 10), and the presence of joint space narrowing in 15 joints of the hands and wrists (graded from 0 to 4) and in 6 joints of the feet (graded from 0 to 4). The maximal range is 280 units for erosion and 168 units for joint space narrowing, summing up to 448 units for the total score.

    The progression is calculated by subtracting the total score at week 104 minus the total score at baseline (ranging from 0 to 448) Higher values in each (sub) scale represents a worse outcome.

Sponsors and collaborators

Lead sponsor

P. Verschueren

Other

Collaborators

  • Belgium Health Care Knowledge Centre

Registry information

Official study 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

Acronym: CareRA2020

Important dates

Study start
2018
Primary completion
2022
Study completion
2022
First posted
Aug 28, 2018
Registry last updated
Jun 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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