Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

Study Purpose

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 If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator.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

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	19 Years and Over
Gender	All

More Inclusion & Exclusion 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT03414502
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	University of Nebraska
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	James R O'Dell, MD
Principal Investigator Affiliation	University of Nebraska
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Rheumatoid Arthritis

Additional Details

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.

Arms & Interventions

Arms

Active Comparator: Methotrexate Therapy

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

Active Comparator: Abatacept Therapy

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

Active Comparator: Adalimumab Therapy

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

Active Comparator: Azathioprine Therapy

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

Active Comparator: Barcitinib Therapy

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

Active Comparator: Certolizumab Therapy

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

Active Comparator: Etanercept Therapy

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

Active Comparator: Golimumab Therapy

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

Active Comparator: Hydroxycholoroquine Therapy

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

Active Comparator: Infliximab Therapy

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

Active Comparator: Leflunomide Therapy

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

Active Comparator: Minocycline Therapy

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

Active Comparator: Rituximab Therapy

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

Active Comparator: Sarilumab Therapy

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

Active Comparator: Sulfasalazine Therapy

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

Active Comparator: Tofacitinib Therapy

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