Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

NCT03414502 | Recruiting Phase 3 FDA Drug

• 1 other identifier: 0439-23-FB
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

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 If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator.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

Conditions

Rheumatoid Arthritis

Keywords

Methotrexate; DMARD

Outcome Measures

Primary Outcomes (1)

• Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis

  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 Outcomes (3)

• Genetic factors as Predictors of Disease-modifying Antirheumatic Drugs Response

  16 weeks

• Serological Factors as Predictors of Disease-modifying Antirheumatic Drugs Response

  16 weeks

• Co-morbid Conditions as Predictors of Disease-modifying Antirheumatic Drugs Response

  16 weeks

Study Arms (16)

Methotrexate Therapy

ACTIVE COMPARATOR

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

Drug: Methotrexate

Abatacept Therapy

ACTIVE COMPARATOR

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

Drug: Abatacept

Adalimumab Therapy

ACTIVE COMPARATOR

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

Drug: Adalimumab

Azathioprine Therapy

ACTIVE COMPARATOR

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

Drug: Azathioprine

Barcitinib Therapy

ACTIVE COMPARATOR

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

Drug: Baricitinib

Certolizumab Therapy

ACTIVE COMPARATOR

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

Drug: Certolizumab

Etanercept Therapy

ACTIVE COMPARATOR

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

Drug: Etanercept

Golimumab Therapy

ACTIVE COMPARATOR

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

Drug: Golimumab

Hydroxycholoroquine Therapy

ACTIVE COMPARATOR

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

Drug: Hydroxychloroquine

Infliximab Therapy

ACTIVE COMPARATOR

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

Drug: Infliximab

Leflunomide Therapy

ACTIVE COMPARATOR

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

Drug: Leflunomide

Minocycline Therapy

ACTIVE COMPARATOR

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

Drug: Minocycline

Rituximab Therapy

ACTIVE COMPARATOR

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

Drug: Rituximab

Sarilumab Therapy

ACTIVE COMPARATOR

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

Drug: Sarilumab

Sulfasalazine Therapy

ACTIVE COMPARATOR

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

Drug: Sulfasalazine

Tofacitinib Therapy

ACTIVE COMPARATOR

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

Drug: Tofacitinib

Interventions

Methotrexate DRUG

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

Also known as: Methotrexate (MTX)

Methotrexate Therapy

Abatacept DRUG

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

Also known as: Orencia

Abatacept Therapy

Adalimumab DRUG

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

Also known as: Humira

Adalimumab Therapy

Azathioprine DRUG

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

Also known as: Imuran

Azathioprine Therapy

Baricitinib DRUG

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

Also known as: Olimuant

Barcitinib Therapy

Certolizumab DRUG

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

Also known as: Cimzia

Certolizumab Therapy

Etanercept DRUG

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

Also known as: Enbrel

Etanercept Therapy

Golimumab DRUG

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

Also known as: Simponi

Golimumab Therapy

Hydroxychloroquine DRUG

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

Also known as: Plaquenil

Hydroxycholoroquine Therapy

Infliximab DRUG

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

Also known as: Remicade

Infliximab Therapy

Leflunomide DRUG

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

Also known as: Arava

Leflunomide Therapy

Minocycline DRUG

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

Also known as: Minocin

Minocycline Therapy

Rituximab DRUG

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

Also known as: Rituxin

Rituximab Therapy

Sarilumab DRUG

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

Also known as: Kevzara

Sarilumab Therapy

Sulfasalazine DRUG

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

Also known as: Azulfidine

Sulfasalazine Therapy

Tofacitinib DRUG

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

Also known as: Xeljanz

Tofacitinib Therapy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Methotrexate; Abatacept; Adalimumab; Azathioprine; baricitinib; Certolizumab Pegol; Etanercept; golimumab; Hydroxychloroquine; Infliximab; Leflunomide; Minocycline; Rituximab; sarilumab; Sulfasalazine; tofacitinib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Immunoconjugates; Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Immunoproteins; Thionucleosides; Sulfur Compounds; Organic Chemicals; Mercaptopurine; Purines; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Immunoglobulin Fc Fragments; Immunoglobulin Constant Regions; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Chloroquine; Aminoquinolines; Quinolines; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Sulfonamides; Amides; Sulfones

Study Officials

• James R O'Dell, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aimee B Schreiner, MS

CONTACT

402-559-4873; aischreiner@unmc.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2014
• First Posted: January 30, 2018
• Study Start: December 10, 2007
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)