Treatment of Rheumatoid Arthritis With DMARDs: Predictors of Response
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT03414502
- Lead Sponsor
- University of Nebraska
- 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 If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator.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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Methotrexate Therapy Methotrexate Participants will receive methotrexate therapy for rheumatoid arthritis (RA) treatment. Abatacept Therapy Abatacept Participants will receive abatacept therapy for rheumatoid arthritis (RA) treatment. Adalimumab Therapy Adalimumab Participants will receive adalimumab therapy for rheumatoid arthritis (RA) treatment. Azathioprine Therapy Azathioprine Participants will receive azathioprine therapy for rheumatoid arthritis (RA) treatment. Barcitinib Therapy Baricitinib Participants will receive barcitinib therapy for rheumatoid arthritis (RA) treatment. Certolizumab Therapy Certolizumab Participants will receive certolizumab therapy for rheumatoid arthritis (RA) treatment. Etanercept Therapy Etanercept Participants will receive etanercept therapy for rheumatoid arthritis (RA) treatment. Golimumab Therapy Golimumab Participants will receive golimumab therapy for rheumatoid arthritis (RA) treatment. Hydroxycholoroquine Therapy Hydroxychloroquine Participants will receive hydroxychloroquine therapy for rheumatoid arthritis (RA) treatment. Infliximab Therapy Infliximab Participants will receive infliximab therapy for rheumatoid arthritis (RA) treatment. Leflunomide Therapy Leflunomide Participants will receive leflunomide therapy for rheumatoid arthritis (RA) treatment. Minocycline Therapy Minocycline Participants will receive minocycline therapy for rheumatoid arthritis (RA) treatment. Rituximab Therapy Rituximab Participants will receive rituximab therapy for rheumatoid arthritis (RA) treatment. Sarilumab Therapy Sarilumab Participants will receive sarilumab therapy for rheumatoid arthritis (RA) treatment. Sulfasalazine Therapy Sulfasalazine Participants will receive sulfasalazine therapy for rheumatoid arthritis (RA) treatment. Tofacitinib Therapy Tofacitinib Participants will receive tofacitinib therapy for rheumatoid arthritis (RA) treatment.
- Primary Outcome Measures
Name Time Method Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis 16 weeks 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).
- Secondary Outcome Measures
Name Time Method Genetic factors as Predictors of Disease-modifying Antirheumatic Drugs Response 16 weeks Based on American College of Rheumatology 50 (ACR50) composite measure after 16 weeks of treatment, the number of participants will be determined that have genetic factors, such as the shared epitope, that demonstrate a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of 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).
Serological Factors as Predictors of Disease-modifying Antirheumatic Drugs Response 16 weeks Based on American College of Rheumatology 50 (ACR50) composite measure after 16 weeks of treatment, the number of participants will be determined that have serological factors, such as cyclic citrullinated peptide (CCP) isotypes, that demonstrate a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of 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).
Co-morbid Conditions as Predictors of Disease-modifying Antirheumatic Drugs Response 16 weeks Based on American College of Rheumatology 50 (ACR50) composite measure after 16 weeks of treatment, the number of participants will be determined that have co-morbid conditions, such as periodontal disease, that demonstrate a 50% improvement in the number of tender and swollen joints, and a 50% improvement in three of 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).
Trial Locations
- Locations (1)
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States