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

P. Verschueren276 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

276

Conditions

Arthritis, Rheumatoid

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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-

Locations (19)

Imelda Ziekenhuis Bonheiden

Bonheiden, Antwerpen, Belgium

AZ Herentals

Herentals, Antwerpen, Belgium

ZNA Jan Palfijn

Merksem, Antwerpen, Belgium

GHdC Saint Joseph

Gilly, Henegouwen, Belgium

Reuma centrum Genk

Genk, Limburg, Belgium

Reuma Clinic Genk

Genk, Limburg, Belgium

Reuma Instituut Hasselt

Hasselt, Limburg, Belgium

CHU UCL Namur ASBL Site Godinne

Yvoir, Namur, Belgium

OLV Ziekenhuis Aalst

Aalst, Oost Vlaanderen, Belgium

Regionaal Ziekenhuis Heilig Hart Leuven

Leuven, Vlaams Brabant, Belgium

...and 9 more locations

Outcomes

Primary Outcomes

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

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

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

Secondary Outcomes

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

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).

Time frame: From randomization till 28 weeks after randomization.

Proportion of Patients in Remission Defined as DAS28CRP<2.6

Time frame: at week 104

Proportion of Patients Achieving a EULAR Response

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.

Time frame: at 28 weeks after randomization

Proportion of Patients Achieving a EULAR Response

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.

Time frame: at week 104

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.

Time frame: at 28 weeks after randomization

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.

Time frame: at week 104

Radiographic Progression

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.

Time frame: at week 52

Radiographic Progression

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.

Time frame: at week 104