Clinical trial NCT03414502: Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response
Official title: Treatment of Rheumatoid Arthritis With Disease-modifying Antirheumatic Drugs (DMARDs): Predictors of Response
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Rheumatoid Arthritis
Keywords: Methotrexate
DMARD
Lead sponsor: University of Nebraska
Sponsor class: OTHER
First posted: 2018-01-30
Enrollment: 400
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator.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

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.

Eligibility 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

Primary outcomes:
measure: Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis
timeFrame: 16 weeks
Secondary outcomes:
measure: Genetic factors as Predictors of Disease-modifying Antirheumatic Drugs Response
timeFrame: 16 weeks
measure: Serological Factors as Predictors of Disease-modifying Antirheumatic Drugs Response
timeFrame: 16 weeks
measure: Co-morbid Conditions as Predictors of Disease-modifying Antirheumatic Drugs Response
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
Study officials:
affiliation: University of Nebraska
name: James R O'Dell, MD
role: PRINCIPAL_INVESTIGATOR
References: