Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

Study Purpose

This is a 16-week, open-label study to identify factors that help predict clinical responses to DMARD therapies for RA (Rheumatoid Arthritis) patients. All patients will receive a starting dose of DMARD medication(s) which may be adjusted by the investigator as needed. If a subject becomes intolerant to a DMARD medication the subject will be withdrawn from the study at the discretion of the investigator. Visits (prior to week 16) where withdrawal is determined to be necessary will be considered end of study. End of study data (week 16) as well as study serum will be collected. (Serum only collected on those subjects who have consented to the addendum Serum and DNA of this study). A portion of the blood collected at baseline, week 8 and week 16 with the addendum portion of the study is for future research and will be utilized attempting to look to detect the generation of superoxide radicals. The radicals have been shown to be associated with inflammation and may correlate with the progression of RA. If this is true, then treatment with RA 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:

- Diag.

with RA with 4 of 7 ACR criteria: 1) Morning stiffness for at least 1 hr. and at least 6 wks 2) Swelling of 3 or more joints for at least 6 wks. 3) Swelling of wrist, MCP, or proximal interphalangeal joints for 6 or more wks 4) Symmetric joint swelling. 5) Hand x-rays with erosions or bony decalcifications. 6) RA nodules 7) RF positive.

- >19 yrs old at time of diagnosis of RA.

- Current active disease with at least1 swollen joint.

- Starting new DMARD medication(s) please circle: 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 per day or equivalent) - Able to adhere to study visit schedule: enrollment, 8 wks & 16 wks (+/- 2 wks) - Hgb > 9g/dl.

- WBC > 3.5.

- Neutrophils > 1.0.

- Platelets >100.

- Creatinine <1.6.

- AST or ALT not over 1.2 x upper limit.

- Albumin: up to 1.0 g/dL less than lower limit of normal.

EXCLUSION CRITERIA:

- Pregnant or breastfeeding women.

- Men and women of child bearing potential not willing to practice successful 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

The purpose of the study is to gather, in a prospective manner, information on patients with rheumatoid arthritis and their response to DMARD therapy. Specific aims of this study are: A. To evaluate the efficacy of DMARD therapy as defined by attaining ACR 50 response after 16 weeks of therapy. B. To identify predictors of DMARD response in patients with RA.

- Does the presence of certain genetic factors such as the shared epitope predict DMARD response.

- Does the presence of serological factors (e.g. ccp (cyclic citrullinated peptide) isotypes) predict DMARD response.

- Does evidence of co-morbid conditions (e.g. periodontal disease) predict DMARD response.

A maximum of 400 RA patients will be consented for this protocol. Subject accrual for protocol v1.0 included UNMC (University of Nebraska Medical Center) and the RAIN (Rheumatoid Arthritis Investigational Network) sites. Subject accrual for protocol v2.0 will be derived exclusively from UNMC. Investigators have examined the discriminatory characteristics of several clinical and biologic parameters in predicting treatment response (at least 50% improvement based on ACR criteria) in initial analyses involving 54 participants with early RA treated with methotrexate monotherapy in past RAIN clinical trials. In the initial analyses, factors showing discriminatory characteristics have included rheumatoid factor (RF) isotypes (particularly IgA (Immunoglobulin A) and IgM (Immunoglobulin M), matrix metalloproteinase (MMP)-3, HLA-DRB1 (human leukocyte antigen-DR isotope) shared epitope (SE)-containing alleles, C-reactive protein, and interleukin (IL)-1. For instance, we have found that subjects with low serum concentrations of RF-IgM (< 27 IU/ml) are more likely to be non-responders than those with higher (> 27 IU/ml) serum concentrations (79% vs.#46; 43%). Males and females will participate in this protocol. As RA is approximately three times more common in females, it is anticipated that a higher percentage of the study subjects will be female. Subjects will be > 19 years of age. This age range was chosen because the age of majority in Nebraska is 19. RA diagnosed before the age of 19 may not have the same disease characteristics as defined by the American College of Rheumatology (ACR) criterion for RA. Pediatric subjects will not be enrolled in this study. Rheumatoid arthritis occurs in all races. No enrollment restrictions have been based on race or ethnic origin.

Arms & Interventions

Arms

Active Comparator: Methotrexate Therapy

Subjects will receive methotrexate therapy for RA treatment.

Active Comparator: Abatacept Therapy

Subjects will receive abatacept therapy for RA treatment.

Active Comparator: Adalimumab Therapy

Subjects will receive adalimumab therapy for RA treatment.

Active Comparator: Azathioprine Therapy

Subjects will receive azathioprine therapy for RA treatment.

Active Comparator: Barcitinib Therapy

Subjects will receive barcitinib therapy for RA treatment.

Active Comparator: Certolizumab Therapy

Subjects will receive certolizumab therapy for RA treatment.

Active Comparator: Etanercept Therapy

Subjects will receive etanercept therapy for RA treatment.

Active Comparator: Golimumab Therapy

Subjects will receive golimumab therapy for RA treatment.

Active Comparator: Hydroxycholoroquine Therapy

Subjects will receive hydroxychloroquine therapy for RA treatment.

Active Comparator: Infliximab Therapy

Subjects will receive infliximab therapy for RA treatment.

Active Comparator: Leflunomide Therapy

Subjects will receive leflunomide therapy for RA treatment.

Active Comparator: Minocycline Therapy

Subjects will receive minocycline therapy for RA treatment.

Active Comparator: Rituximab Therapy

Subjects will receive rituximab therapy for RA treatment.

Active Comparator: Sarilumab Therapy

Subjects will receive sarilumab therapy for RA treatment.

Active Comparator: Sulfasalazine Therapy

Subjects will receive sulfasalazine therapy for RA treatment.

Active Comparator: Tofacitinib Therapy

Subjects will receive tofacitinib therapy for RA treatment.