Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

August 6, 2025 updated by: University of Nebraska

Treatment of Rheumatoid Arthritis With Disease-modifying Antirheumatic Drugs (DMARDs): Predictors of Response

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 If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator.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.

Study Overview

Status

Recruiting

Conditions

Intervention / 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.

Study Type

Interventional

Enrollment (Estimated)

400

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Principal Investigator:
          • James R O'Dell, MD
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Methotrexate Therapy
Participants will receive methotrexate therapy for rheumatoid arthritis (RA) treatment.
Drug: Methotrexate
Starting dose of Methotrexate of 15 mg once a week plus folic acid 1mg daily.
Other Names:
  • Methotrexate (MTX)
Active Comparator: Abatacept Therapy
Participants will receive abatacept therapy for rheumatoid arthritis (RA) treatment.
Drug: Abatacept
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Orencia
Active Comparator: Adalimumab Therapy
Participants will receive adalimumab therapy for rheumatoid arthritis (RA) treatment.
Drug: Adalimumab
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Humira
Active Comparator: Azathioprine Therapy
Participants will receive azathioprine therapy for rheumatoid arthritis (RA) treatment.
Drug: Azathioprine
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Imuran
Active Comparator: Barcitinib Therapy
Participants will receive barcitinib therapy for rheumatoid arthritis (RA) treatment.
Drug: Baricitinib
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Olimuant
Active Comparator: Certolizumab Therapy
Participants will receive certolizumab therapy for rheumatoid arthritis (RA) treatment.
Drug: Certolizumab
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Cimzia
Active Comparator: Etanercept Therapy
Participants will receive etanercept therapy for rheumatoid arthritis (RA) treatment.
Drug: Etanercept
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Enbrel
Active Comparator: Golimumab Therapy
Participants will receive golimumab therapy for rheumatoid arthritis (RA) treatment.
Drug: Golimumab
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Simponi
Active Comparator: Hydroxycholoroquine Therapy
Participants will receive hydroxychloroquine therapy for rheumatoid arthritis (RA) treatment.
Drug: Hydroxychloroquine
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Plaquenil
Active Comparator: Infliximab Therapy
Participants will receive infliximab therapy for rheumatoid arthritis (RA) treatment.
Drug: Infliximab
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Remicade
Active Comparator: Leflunomide Therapy
Participants will receive leflunomide therapy for rheumatoid arthritis (RA) treatment.
Drug: Leflunomide
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Arava
Active Comparator: Minocycline Therapy
Participants will receive minocycline therapy for rheumatoid arthritis (RA) treatment.
Drug: Minocycline
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Minocin
Active Comparator: Rituximab Therapy
Participants will receive rituximab therapy for rheumatoid arthritis (RA) treatment.
Drug: Rituximab
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Rituxin
Active Comparator: Sarilumab Therapy
Participants will receive sarilumab therapy for rheumatoid arthritis (RA) treatment.
Drug: Sarilumab
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Kevzara
Active Comparator: Sulfasalazine Therapy
Participants will receive sulfasalazine therapy for rheumatoid arthritis (RA) treatment.
Drug: Sulfasalazine
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Azulfidine
Active Comparator: Tofacitinib Therapy
Participants will receive tofacitinib therapy for rheumatoid arthritis (RA) treatment.
Drug: Tofacitinib
Starting dose may be adjusted as needed at investigator's discretion.
Other Names:
  • Xeljanz

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis
Time Frame: 16 weeks
The efficacy of the disease-modifying antirheumatic drugs (DMARD) in the study will be determined using the American College of Rheumatology 50 (ACR50). This is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genetic factors as Predictors of Disease-modifying Antirheumatic Drugs Response
Time Frame: 16 weeks
Based on American College of Rheumatology 50 (ACR50) composite measure after 16 weeks of treatment, the number of participants will be determined that have genetic factors, such as the shared epitope, that demonstrate a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks
Serological Factors as Predictors of Disease-modifying Antirheumatic Drugs Response
Time Frame: 16 weeks
Based on American College of Rheumatology 50 (ACR50) composite measure after 16 weeks of treatment, the number of participants will be determined that have serological factors, such as cyclic citrullinated peptide (CCP) isotypes, that demonstrate a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks
Co-morbid Conditions as Predictors of Disease-modifying Antirheumatic Drugs Response
Time Frame: 16 weeks
Based on American College of Rheumatology 50 (ACR50) composite measure after 16 weeks of treatment, the number of participants will be determined that have co-morbid conditions, such as periodontal disease, that demonstrate a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of five criteria: patient global assessment, physician global assessment, functional ability measure (most often Health Assessment Questionnaire/HAQ), visual analog pain scale and erythrocyte sedimentation rate or C-reactive protein (CRP).
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Nebraska

Investigators

  • Principal Investigator: James R O'Dell, MD, University of Nebraska

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 10, 2007

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

March 1, 2029

Study Registration Dates

First Submitted

January 2, 2014

First Submitted That Met QC Criteria

January 22, 2018

First Posted (Actual)

January 30, 2018

Study Record Updates

Last Update Posted (Actual)

August 8, 2025

Last Update Submitted That Met QC Criteria

August 6, 2025

Last Verified

August 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0439-23-FB

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Data remains stored at UNMC for approved investigators at this site only at this time

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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