Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

NCT ID: NCT03414502

Last Updated: 2025-08-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 400 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-10
• Study Completion Date: 2029-03-31

Brief Summary

Rheumatoid arthritis (RA) is a common disease with approximately 1% prevalence. RA is also a chronic, progressive disease with no cure. Current treatment goals are to minimize pain, limit joint damage, and prevent loss of function. Drugs used to treat RA include non-steroidal anti-inflammatory drugs (NSAIDS), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs), including biologics. Methotrexate (MTX) is the DMARD of choice in the treatment of RA, because it has been shown to be both well-tolerated and effective in achieving clinical response and slowing radiographic progression of disease. However, this drug alone results in remissions in only a small subset of patients and reliable predictors of DMARD response have yet to be identified.

This study is open-label of 16-weeks duration to identify factors that help predict clinical responses to disease-modifying antirheumatic drugs (DMARD) therapies for rheumatoid arthritis (RA) participants. All participants will receive a starting dose of DMARD medication(s) which may be adjusted by the investigator as needed. If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator. Necessary withdrawals prior to week 16 visits will be considered end of study. Otherwise, end of study data as well as study serum will be collected at week 16. A portion of the blood collected at baseline, week 8 and week 16 for the optional addendum portion of the study is for future research and will be utilized attempting to look to detect the generation of superoxide radicals. These radicals have been shown to be associated with inflammation and may correlate with the progression of RA, which if confirmed, should decrease the levels of these radicals signaling response to treatment.

Detailed Description

Rheumatoid arthritis (RA) is a common disease with approximately 1% prevalence. RA is also a chronic, progressive disease with no cure. Current treatment goals are to minimize pain, limit joint damage, and prevent loss of function. Drugs used to treat RA include non-steroidal anti-inflammatory drugs (NSAIDS), glucocorticoids, and disease-modifying anti-rheumatic drugs (DMARDs), including biologics. Methotrexate (MTX) is the DMARD of choice in the treatment of RA, because it has been shown to be both well-tolerated and effective in achieving clinical response and slowing radiographic progression of disease. However, this drug alone results in remissions in only a small subset of patients and reliable predictors of DMARD response have yet to be identified.

Investigators have examined the discriminatory characteristics of several clinical and biologic parameters in predicting treatment response (at least 50% improvement based on American College of Rheumatology criteria), including rheumatoid factor (RF) isotypes (particularly Immunoglobulin A (IgA) and Immunoglobulin M (IgM), matrix metalloproteinase (MMP)-3, human leukocyte antigen-DR isotope (HLA-DRB1) shared epitope (SE)-containing alleles, C-reactive protein, and interleukin (IL)-1.

The purpose of the study is to prospectively gather information on participants with rheumatoid arthritis (RA) and their response to disease-modifying antirheumatic drugs (DMARD) therapy. Specifically, to evaluate the efficacy of DMARD therapy as defined by attaining American College of Rheumatology 50 (ACR50) response after 16 weeks of therapy and to identify predictors of DMARD response, such as genetic factors, serological factors or co-morbid conditions. A maximum of 400 rheumatoid arthritis (RA) participants will be enrolled in this 16-week, open-label study. Adult males and females will be enrolled, but RA is approximately three times more common in females.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Methotrexate Therapy

Participants will receive methotrexate therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

Starting dose of Methotrexate of 15 mg once a week plus folic acid 1mg daily.

Abatacept Therapy

Participants will receive abatacept therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Abatacept

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Adalimumab Therapy

Participants will receive adalimumab therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Adalimumab

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Azathioprine Therapy

Participants will receive azathioprine therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Azathioprine

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Barcitinib Therapy

Participants will receive barcitinib therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Baricitinib

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Certolizumab Therapy

Participants will receive certolizumab therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Certolizumab

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Etanercept Therapy

Participants will receive etanercept therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Etanercept

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Golimumab Therapy

Participants will receive golimumab therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Golimumab

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Hydroxycholoroquine Therapy

Participants will receive hydroxychloroquine therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Infliximab Therapy

Participants will receive infliximab therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Infliximab

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Leflunomide Therapy

Participants will receive leflunomide therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Leflunomide

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Minocycline Therapy

Participants will receive minocycline therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Minocycline

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Rituximab Therapy

Participants will receive rituximab therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Rituximab

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Sarilumab Therapy

Participants will receive sarilumab therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Sarilumab

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Sulfasalazine Therapy

Participants will receive sulfasalazine therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Sulfasalazine

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Tofacitinib Therapy

Participants will receive tofacitinib therapy for rheumatoid arthritis (RA) treatment.

Group Type: ACTIVE_COMPARATOR

Tofacitinib

Intervention Type: DRUG

Starting dose may be adjusted as needed at investigator's discretion.

Interventions

Methotrexate

Starting dose of Methotrexate of 15 mg once a week plus folic acid 1mg daily.

Intervention Type: DRUG

Abatacept

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Adalimumab

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Azathioprine

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Baricitinib

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Certolizumab

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Etanercept

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Golimumab

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Hydroxychloroquine

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Infliximab

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Leflunomide

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Minocycline

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Rituximab

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Sarilumab

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Sulfasalazine

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Tofacitinib

Starting dose may be adjusted as needed at investigator's discretion.

Intervention Type: DRUG

Other Intervention Names

Methotrexate (MTX); Orencia; Humira; Imuran; Olimuant; Cimzia; Enbrel; Simponi; Plaquenil; Remicade; Arava; Minocin; Rituxin; Kevzara; Azulfidine; Xeljanz

Eligibility Criteria

Inclusion Criteria

• Diagnosed rheumatoid arthritis (RA) with 4 of 7 American College of Rheumatology criteria

• Morning stiffness for at least 1 hour for at least 6 weeks
• Swelling of 3 or more joints for at least 6 weeks
• Swelling of wrist, metacarpophalangeal (MCP), or proximal interphalangeal joints for 6 or more weeks
• Symmetric joint swelling
• Hand x-rays with erosions or bony decalcifications
• RA nodules
• Rheumatoid factor (RF) positive
• >19 yrs old at RA diagnosis
• Active disease with at least 1 swollen joint
• Starting new DMARD medication(s) (abatacept, adalimumab, azathioprine, barcitinib, certolizumab, etanercept, golimumab, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, rituximab, sarilumab, sulfasalazine, tofacitinib)
• If on other DMARDS, must be on stable dose for ≥ 6 wks
• If on glucocorticoids, must be on stable dose for 2 wks (< 10mg of Prednisone/day or equivalent)
• Able to adhere to study visit schedule: enrollment (8 wks & 16 wks +/- 2 wks)
• Hemoglobin (Hgb) > 9g/dl
• Platelets >100
• Creatinine <1.6
• Aspartate transferase (AST) or alanine aminotransferase (ALT) at or below 1.2 x upper limit
• Albumin up to 1.0 g/dL below lower limit of normal

Exclusion Criteria

• Pregnant or breastfeeding women
• Men and women of child bearing potential unwilling to practice effective method of contraception

• Minimum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

James R O'Dell, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Aimee B Schreiner, MS

Role: CONTACT

aischreiner@unmc.edu

402-559-4873

Facility Contacts

Aimee B Schreiner, MS

Role: primary

aischreiner@unmc.edu

402-559-7288

Bridget E Kramer, RN

Role: backup

bridget.kramer@unmc.edu

402-559-7288

Other Identifiers

0439-23-FB

Identifier Type: -

Identifier Source: org_study_id