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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 If a participant becomes intolerant of a DMARD medication, the participant will be withdrawn at the discretion of the investigator.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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Methotrexate Therapy | Active Comparator | Participants will receive methotrexate therapy for rheumatoid arthritis (RA) treatment. |
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| Abatacept Therapy | Active Comparator | Participants will receive abatacept therapy for rheumatoid arthritis (RA) treatment. |
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| Adalimumab Therapy | Active Comparator | Participants will receive adalimumab therapy for rheumatoid arthritis (RA) treatment. |
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| Azathioprine Therapy | Active Comparator | Participants will receive azathioprine therapy for rheumatoid arthritis (RA) treatment. |
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| Barcitinib Therapy | Active Comparator | Participants will receive barcitinib therapy for rheumatoid arthritis (RA) treatment. |
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| Certolizumab Therapy | Active Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methotrexate | Drug | Starting dose of Methotrexate of 15 mg once a week plus folic acid 1mg daily. |
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| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Disease-modifying Antirheumatic Drugs Therapy for Rheumatoid Arthritis | 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). | 16 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Genetic factors as Predictors of Disease-modifying Antirheumatic Drugs Response | 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). |
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INCLUSION CRITERIA:
Diagnosed rheumatoid arthritis (RA) with 4 of 7 American College of Rheumatology criteria
>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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Aimee B Schreiner, MS | Contact | 402-559-4873 | aischreiner@unmc.edu |
| Name | Affiliation | Role |
|---|---|---|
| James R O'Dell, MD | University of Nebraska | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Nebraska Medical Center | Recruiting | Omaha | Nebraska | 68198 | United States |
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Participants will receive certolizumab therapy for rheumatoid arthritis (RA) treatment.
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| Etanercept Therapy | Active Comparator | Participants will receive etanercept therapy for rheumatoid arthritis (RA) treatment. |
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| Golimumab Therapy | Active Comparator | Participants will receive golimumab therapy for rheumatoid arthritis (RA) treatment. |
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| Hydroxycholoroquine Therapy | Active Comparator | Participants will receive hydroxychloroquine therapy for rheumatoid arthritis (RA) treatment. |
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| Infliximab Therapy | Active Comparator | Participants will receive infliximab therapy for rheumatoid arthritis (RA) treatment. |
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| Leflunomide Therapy | Active Comparator | Participants will receive leflunomide therapy for rheumatoid arthritis (RA) treatment. |
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| Minocycline Therapy | Active Comparator | Participants will receive minocycline therapy for rheumatoid arthritis (RA) treatment. |
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| Rituximab Therapy | Active Comparator | Participants will receive rituximab therapy for rheumatoid arthritis (RA) treatment. |
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| Sarilumab Therapy | Active Comparator | Participants will receive sarilumab therapy for rheumatoid arthritis (RA) treatment. |
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| Sulfasalazine Therapy | Active Comparator | Participants will receive sulfasalazine therapy for rheumatoid arthritis (RA) treatment. |
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| Tofacitinib Therapy | Active Comparator | Participants will receive tofacitinib therapy for rheumatoid arthritis (RA) treatment. |
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| Abatacept | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Adalimumab | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Azathioprine | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Baricitinib | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Certolizumab | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Etanercept | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Golimumab | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Hydroxychloroquine | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Infliximab | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Leflunomide | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Minocycline | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Rituximab | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Sarilumab | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Sulfasalazine | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| Tofacitinib | Drug | Starting dose may be adjusted as needed at investigator's discretion. |
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| 16 weeks |
| Serological Factors as Predictors of Disease-modifying Antirheumatic Drugs Response | 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). | 16 weeks |
| Co-morbid Conditions as Predictors of Disease-modifying Antirheumatic Drugs Response | 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). | 16 weeks |
| ID | Term |
|---|---|
| D001172 | Arthritis, Rheumatoid |
| ID | Term |
|---|---|
| D001168 | Arthritis |
| D007592 | Joint Diseases |
| D009140 | Musculoskeletal Diseases |
| D012216 | Rheumatic Diseases |
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D008727 | Methotrexate |
| D000069594 | Abatacept |
| D000068879 | Adalimumab |
| D001379 | Azathioprine |
| C000596027 | baricitinib |
| D000068582 | Certolizumab Pegol |
| D000068800 | Etanercept |
| C529000 | golimumab |
| D006886 | Hydroxychloroquine |
| D000069285 | Infliximab |
| D000077339 | Leflunomide |
| D008911 | Minocycline |
| D000069283 | Rituximab |
| C000592401 | sarilumab |
| D012460 | Sulfasalazine |
| C479163 | tofacitinib |
| ID | Term |
|---|---|
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D018796 | Immunoconjugates |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D012712 | Serum Globulins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D005916 | Globulins |
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D007162 | Immunoproteins |
| D013872 | Thionucleosides |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D015122 | Mercaptopurine |
| D011687 | Purines |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D011092 | Polyethylene Glycols |
| D011108 | Polymers |
| D046911 | Macromolecular Substances |
| D007140 | Immunoglobulin Fab Fragments |
| D007128 | Immunoglobulin Fragments |
| D010446 | Peptide Fragments |
| D010455 | Peptides |
| D007141 | Immunoglobulin Fc Fragments |
| D007127 | Immunoglobulin Constant Regions |
| D018124 | Receptors, Tumor Necrosis Factor |
| D018121 | Receptors, Cytokine |
| D011971 | Receptors, Immunologic |
| D011956 | Receptors, Cell Surface |
| D008565 | Membrane Proteins |
| D002738 | Chloroquine |
| D000634 | Aminoquinolines |
| D011804 | Quinolines |
| D007555 | Isoxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D013450 | Sulfones |
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