Treatment of Rheumatoid Arthritis With Disease-modifying Antirheumatic Drugs (DMARDs): Predictors of Response
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 400
- 试验地点
- 2
- 主要终点
- Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis
研究概览
简要总结
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 If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator.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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Pregnant or breastfeeding women
- •Men and women of child bearing potential unwilling to practice effective method of contraception
研究组 & 干预措施
Golimumab Therapy
Participants will receive golimumab therapy for rheumatoid arthritis (RA) treatment.
干预措施: Golimumab (Drug)
Hydroxycholoroquine Therapy
Participants will receive hydroxychloroquine therapy for rheumatoid arthritis (RA) treatment.
干预措施: Hydroxychloroquine (Drug)
Infliximab Therapy
Participants will receive infliximab therapy for rheumatoid arthritis (RA) treatment.
干预措施: Infliximab (Drug)
Abatacept Therapy
Participants will receive abatacept therapy for rheumatoid arthritis (RA) treatment.
干预措施: Abatacept (Drug)
Leflunomide Therapy
Participants will receive leflunomide therapy for rheumatoid arthritis (RA) treatment.
干预措施: Leflunomide (Drug)
Rituximab Therapy
Participants will receive rituximab therapy for rheumatoid arthritis (RA) treatment.
干预措施: Rituximab (Drug)
Sarilumab Therapy
Participants will receive sarilumab therapy for rheumatoid arthritis (RA) treatment.
干预措施: Sarilumab (Drug)
Sulfasalazine Therapy
Participants will receive sulfasalazine therapy for rheumatoid arthritis (RA) treatment.
干预措施: Sulfasalazine (Drug)
Tofacitinib Therapy
Participants will receive tofacitinib therapy for rheumatoid arthritis (RA) treatment.
干预措施: Tofacitinib (Drug)
Minocycline Therapy
Participants will receive minocycline therapy for rheumatoid arthritis (RA) treatment.
干预措施: Minocycline (Drug)
Etanercept Therapy
Participants will receive etanercept therapy for rheumatoid arthritis (RA) treatment.
干预措施: Etanercept (Drug)
Methotrexate Therapy
Participants will receive methotrexate therapy for rheumatoid arthritis (RA) treatment.
干预措施: Methotrexate (Drug)
Adalimumab Therapy
Participants will receive adalimumab therapy for rheumatoid arthritis (RA) treatment.
干预措施: Adalimumab (Drug)
Azathioprine Therapy
Participants will receive azathioprine therapy for rheumatoid arthritis (RA) treatment.
干预措施: Azathioprine (Drug)
Barcitinib Therapy
Participants will receive barcitinib therapy for rheumatoid arthritis (RA) treatment.
干预措施: Baricitinib (Drug)
Certolizumab Therapy
Participants will receive certolizumab therapy for rheumatoid arthritis (RA) treatment.
干预措施: Certolizumab (Drug)
结局指标
主要结局
Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis
时间窗: 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).
次要结局
- Genetic factors as Predictors of Disease-modifying Antirheumatic Drugs Response(16 weeks)
- Serological Factors as Predictors of Disease-modifying Antirheumatic Drugs Response(16 weeks)
- Co-morbid Conditions as Predictors of Disease-modifying Antirheumatic Drugs Response(16 weeks)