Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response

Last updated: September 12, 2024
Sponsor: University of Nebraska
Overall Status: Active - Recruiting

Phase

3

Condition

Rheumatoid Arthritis

Joint Injuries

Arthritis And Arthritic Pain

Treatment

Baricitinib

Sarilumab

Hydroxychloroquine

Clinical Study ID

NCT03414502
0439-23-FB
  • Ages > 19
  • All Genders

Study Summary

This is a 16-week, open-label study to identify factors that help predict clinical responses to disease-modifying antirheumatic drugs (DMARD) therapies for rheumatoid arthritis (RA) 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 If a subject becomes intolerant to a DMARD medication the subject will be withdrawn from the study at the discretion of the investigator.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.

Eligibility Criteria

Inclusion

INCLUSION CRITERIA:

  • Diagnosed with rheumatoid arthritis (RA) with 4 of 7 American College ofRheumatolgoy criteria: 1) Morning stiffness for at least 1 hour for at least 6 weeks
  1. Swelling of 3 or more joints for at least 6 weeks. 3) Swelling of wrist,metacarpophalangeal (MCP), or proximal interphalangeal joints for 6 or more weeks 4)Symmetric joint swelling. 5) Hand x-rays with erosions or bony decalcifications. 6)RA nodules 7) Rheumatoid factor (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 dayor equivalent)

  • Able to adhere to study visit schedule: enrollment, 8 wks & 16 wks (+/- 2 wks)

  • Hgb > 9g/dl

  • Platelets >100

  • Creatinine <1.6

  • Aspartate transferase (AST) or alanine aminotransferase (ALT) not over 1.2 x upperlimit

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

Exclusion

EXCLUSION CRITERIA:

  • Pregnant or breastfeeding women

  • Men and women of child bearing potential not willing to practice successful methodof contraception

Study Design

Total Participants: 400
Treatment Group(s): 16
Primary Treatment: Baricitinib
Phase: 3
Study Start date:
December 10, 2007
Estimated Completion Date:
March 31, 2028

Study Description

The purpose of the study is to prospectively gather information on patients with rheumatoid arthritis (RA) and their response to disease-modifying antirheumatic drugs (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 rheumatoid arthritis (RA) participants will be consented for this protocol. 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) in initial analyses involving 54 participants with early RA treated with methotrexate monotherapy in past Rheumatoid Arthritis Investigational Network (RAIN) clinical trials. In the initial analyses, factors showing discriminatory characteristics have included 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. For instance, it has been found that participants 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. 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 participants will be female. Participants will be > 19 years of age (age of majority in Nebraska). 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 participants will not be enrolled in this study. Rheumatoid arthritis occurs in all races. No enrollment restrictions have been based on race or ethnic origin.

Connect with a study center

  • University of Nebraska Medical Center

    Omaha, Nebraska 68198
    United States

    Active - Recruiting

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