Methotrexate-Inadequate Response Study

Phase 3

Completed

Conditions: Rheumatoid Arthritis (RA)

Interventions: Drug: Intravenous (IV) Abatacept
Drug: Subcutaneous (SC) Abatacept

Registration Number: NCT00559585

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: The purpose of this study is to determine whether a weekly subcutaneous dose of abatacept yields clinical efficacy comparable to that of monthly intravenous doses of abatacept in participants with rheumatoid arthritis and an inadequate response to current methotrexate therapy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2492

Inclusion Criteria

Subjects who are considered methotrexate inadequate responders
10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)

Exclusion Criteria

Subjects who failed one or multiple anti-tumor necrosis factor (TNF) therapies
Subjects who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematous)
Subjects with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)
Subjects with severe chronic or recurrent bacterial infections
Subjects who have received treatment with rituximab

An Anti-TNF Failure Sub-study was initiated (recruited separately from Main study) using the same treatment as the Main study in order to assess the immunogenicity and safety in the Anti-TNF Failure population. The Sub-study terminated due to low recruitment and participants were permitted to roll into the LT Open Label Period.

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous (IV) Abatacept	Intravenous (IV) Abatacept	Participants received IV abatacept infusions on Days 1, 15, 29, and every 28 days, thereafter. A double-dummy design was used to protect the blind, thus, participants also received SC injections of placebo (SC Placebo).
Subcutaneous (SC) Abatacept	Subcutaneous (SC) Abatacept	Participants received 125 mg weekly SC abatacept injections (with an intravenous \[IV\] abatacept loading dose on Day 1, based on weight). A double-dummy design was used to protect the blind, thus, participants also received IV injections of placebo (IV Placebo) with the exception that on Day 1 a loading dose of IV abatacept replaced the IV Placebo treatment.

Primary Outcome Measures

Name	Time	Method
Double-blind Period: Number of Participants Achieving American College of Rheumatology (ACR) 20 Response at Day 169	Day 169	The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein).
Anti-TNF Failure Sub-Study Double Blind Period : Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Response in Anti-TNF Failure Population	Days 85, and 169 and postvisits on Days 28, 56, and 85	Serum samples from all treated adult participants with active rheumatoid arthritis who were from the Anti-TNF failure population were screened for the presence of drug-specific antibodies using Enzyme Linked Immunoabsorbant Assay (ELISA). The number of participants who had the presence of anti-abatacept antibodies or anti-CTLA-4 antibodies present in their serum are summarized.

Secondary Outcome Measures

Name	Time	Method
Double-blind Period: Mean Baseline Health Assessment Questionnaire Disability Index (HAQ-DI) for Participants With Assessments at Day 169	Day 169	The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered.
Double-blind Period: Number of Participants Achieving Clinically Meaningful HAQ-DI Response at Day 169	Day 169	The disability section of the full HAQ-DI includes 20 questions to assess physical functions in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip and common activities. The questions are evaluated on a 4-point scale: 0=without any difficulty, 1= with some difficulty, 2= with much difficulty, and 3=unable to do. Higher scores=greater dysfunction. A disability index was calculated by summing the worst scores in each domain and dividing by the number of domains answered. Clinically meaningful HAQ-DI response=an improvement of at least 0.3 units from baseline in HAQ-DI.
Double-blind Period: Minimum Observed Serum Concentration of Abatacept	Days 57, 85, 113, 120, 127, 134, 141, and 169
Double-blind Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Day 169	Day 169	The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures.
Double-blind Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation	Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug
Double-blind Period: Number of Participants With AEs of Special Interest	Day 1 up to 56 days post last dose in short- term period or first dose in the long -term period, whichever occurs first.	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections,serious infections,and opportunistic infections; autoimmune disorders; malignancies; acute infusional AEs (prespecified AEs occurring within 1 hr of start of infusion), peri-infusional AEs (prespecified AEs occurring within 24 hrs of the start of infusion), system injection reactions, and local injection site reactions
Double-blind Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements	Day 1 through end of short-term period (Day 169)	Vital sign measurements were performed for participants before and after infusion/subcutaneous injection of study medication at each visit and included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.
Double-blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept	Dosing interval between Days 113 and 141 (TAU=28 days)
Double-blind Period: Adjusted Mean Change From Baseline to Day 169 in HAQ-DI	Baseline to Day 169	The HAQ-DI includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI ranges from 0 to a maximum overall score of 3.0.
Anti-TNF Failure Sub-study Double-blind Period: Number of Participants With SAEs, AEs Leading to Discontinuation or Who Died	Day 1 to 56 days after last dose in short-term or first dose in the long-term, whichever occurs first.	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Double-blind Period: Number of Participants With Hematology Laboratory Test Results Meeting the Criteria for Marked Abnormality	Day 1 through end of short-term period (Day 169)	ULN=upper limit of normal; LLN=lower limit of normal; BL= baseline. Marked abnormality criteria: Hemoglobin: \>3 g/dL decrease from BL; hematocrit: \<0.75\BL; erythrocytes: \<0.75\BL; platelets: \<0.67\LLN/\>1.5\ULN, or if BL\<LLN, use \<0.5\BL and \<100,000 mm\^3; leukocytes: \<0.75\LLN/\>1.25\ULN, or if BL\<LLN use \<0.8\BL or \>ULN, or if BL\>ULN, use \>1.2\BL or \<LLN; neutrophils+bands: \<1.0\10\^3 c/uL; eosinophils: \>0.750\10\^3 c/uL; basophils: \>400 mm\^3; monocytes: \>2000 mm\^3; lymphocytes: \<0.750\10\^3 c/uL/\>7.50\*10\^3 c/uL.
Anti-TNF Failure Sub-study Double-blind Period: Minimum Observed Serum Concentration (Cmin) of Abatacept	Days 57, 85, 113, 120, 127, 134, 141, and 169 (ST Period)	Serum concentrations of abatacept were analyzed using a validated ELISA. Steady-state trough observed concentration in serum (Cminss) was measured in μg/mL. Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169.
Double-blind Period: Maximum Observed Serum Concentration of Abatacept	End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous
Anti-TNF Failure Sub-study Double Blind Period: Area Under The Curve In A Dose Interval (AUC TAU) of Abatacept	Dosing Interval between Days 113 and 141 (TAU=28 days)	Serum concentrations of abatacept were analyzed using a validated ELISA. AUC(TAU) was measured as μg\*h/mL. Samples for AUC (TAU) were obtained on Days 113, 120, 127, 134, and 141.
Double-blind Period: Time-matched Median Percent Change From Baseline in Levels of Serum C-reactive Protein Over the Short-term Period	Baseline to Days 15, 29, 57, 85, 113, 141, and 169	C-reactive protein is an acute phase reactant protein that is a clinical marker for rheumatoid arthritis. Time-matched median percent change from baseline= (time-matched baseline value - Post-baseline value)/time-matched baseline value\*100, where the time-matched baseline value represents the median baseline value for only that cohort of participants with measurements available at that visit.
Double-blind Period: Number of Participants With Liver Function Laboratory Test Results Meeting the Criteria for Marked Abnormality	Day 1 through end of short-term period (Day 169)	Marked abnormality criteria: Alkaline phosphatase (ALP): \>2\ULN, or if BL\>ULN, use \>3\BL; aspartate aminotransferase (AST): \>3\ULN, or if BL\>ULN, use \>4\BL; alanine aminotransferase (ALT): \>3\ULN, or if BL\>ULN, use \>4\BL; G-glutamyl transferase (GGT): \>2\* ULN, or if BL\>ULN, use \>3\BL; bilirubin: \>2\ ULN, or if BL\>ULN, use \>4\BL; blood urea nitrogen: \>2\ BL; creatinine: \>1.5\*BL
Double-blind Period: Number of Participants With Electrolyte Laboratory Test Results Meeting the Criteria for Marked Abnormality	Day 1 through end of short-term period (Day 169)	Marked abnormality criteria: Sodium: \<0.95\LLN/\>1.05\ULN, or if BL\<LLN, use \<0.95\* BL or \>ULN, or if BL\>ULN, use\>1.05\* BL or \<LLN; potassium: \<0.9\* LLN/\>1.1\ULN, or if BL\<LLN then use \<0.9\ BL or \>ULN, or if BL\>ULN, use\>1.1\* BL or \<LLN; chlorine: \<0.9\LLN/\>1.1\ ULN, or if BL\<LLN, use \<0.9\BL or \>ULN, or if BL\>ULN, use\>1.1\BL or \<LLN; calcium: \<0.8\* LLN/\>1.2\* ULN, or if BL\<LLN, use \<0.75\BL or \>ULN, or if BL\>ULN, use\>1.25\ BL or \<LLN; phosphorous: \<0.75\* LLN/\>1.25\ULN, or if BL\<LLN, use 0.67\BL or \>ULN, or if BL\>ULN, use\>1.33\* BL or \<LLN
Anti-TNF Failure Substudy Double Blind Period: Geometric Mean Maximum Observed Serum Concentration of Abatacept	End of infusion on Days 1 and 113 for IV infusion and in the dosing interval of Days 113 to 120 for subcutaneous	Serum concentrations of abatacept were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Samples were obtained on Days 57, 85, 113, 120, 127, 134, 141, and 169. Cmax was measured in micrograms per milliliter (μg/mL).
Double-blind Period: Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunoabsorbant Assay (ELISA)	Days 85, and 169 and postvisits on Days 28, 56, and 85	Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept (anti-ABA) or anti-CTLA4 antibody (anti-CTLA4).
Double-blind Period: Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay Among the First 10% of Participants Randomized	Days 85, and 169 and postvisits on Days 28, 56, and 85	An electrochemiluminescence immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; abatacept molecule). Ig and/or Junction (JNCT) category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a postbaseline titer higher than Baseline, or any postbaseline positivity if Baseline value was missing. Trt=treatment.
Double-blind Period: Number of Participants Seroconverting by Day 169 According to Status (Negative or Positive) at Baseline	Baseline to Day 169	Rheumatoid factor (RF) is an autoantibody (antibody directed against an organism's own tissues) most relevant in rheumatoid arthritis. It is an antibody against the Fc portion of Immunoglobulin (Ig)G, which is itself an antibody. RF and IgG join to form immune complexes which contribute to the disease process.
Open-Label LT Period: Number of Participants Achieving ACR 20 Response at Days 169, 729, 1261, and 1821	Days 169, 729, 1261, 1821	The ACR 20 definition of improvement is a 20% improvement from baseline in the number of tender and swollen joints, and a 20% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein).
Open-Label LT Period: Number of Participants Achieving ACR 50 and ACR 70 Responses at Days 169, 729, 1261, 1821	Days 169, 729, 1261, 1821	The ACR 50 definition of improvement is a 50% improvement from baseline in the number of tender and swollen joint counts, and a 50% improvement from baseline in 3 of the remaining 5 core set measures: participant global assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, participant assessment of physical function and acute phase reactant value (C-reactive protein). ACR 70 is defined similarly with 70% improvements from baseline for tender and swollen joint counts and 3 out of 5 core measures.
Open-Label LT Period: Mean Change From Baseline in Disease Activity Score in 28 Joints (DAS28) Using C-reactive Protein (CRP) at Days 169, 729, 1261, 1821	Days 169, 729, 1261, 1821	The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from "very good" to "very bad"). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6. A clinically significant response= decrease in DAS28 score of \>1.2 from baseline.
Open-Label LT Period: Number of Participants Achieving DAS 28 Low Disease Activity (LDA) at Days 169, 729, 1261, 1821	Days 169, 729, 1261, 1821	The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from "very good" to "very bad"). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6.
Open-Label LT Period: Number of Participants Achieving DAS 28 Remission at Days 169, 729, 1261, 1821	Days 169, 729, 1261, 1821	The DAS28 index measures disease activity in rheumatoid arthritis and is a composite derived from the number of swollen/tender joints, laboratory tests of inflammation (C-reactive protein measured in mg/L), and participant assessment of global health (by marking a visual analog scale 100 mm line from "very good" to "very bad"). A higher DAS28 score indicates worse control of disease. High disease activity is \> 5.1, low disease activity is \< 3.2 and remission is \< 2.6.
Open-Label LT Period: Number of Participants With Clinically Significant Laboratory Abnormalities	End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)	Laboratory assessments were performed in the LT period at 12-week intervals and at a yearly visit and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Abnormalities were determined to be clinically significant by the investigator.
Open-Label LT Period: Number of Participants With HAQ-DI Response at Days 169, 729, 1261, 1821	Days 169, 729, 1261, 1821	The disability section of the full HAQ includes 20 questions to assess physical function in 8 domains: dressing, arising, eating, walking, hygiene, reach, grip, and common activities. The domain questions are evaluated on a 4-point scale: 0=without any difficulty, 1=with some difficulty, 2=with much difficulty, 3=unable to do. HAQ-DI=sum of worst scores in each domain divided by the number of domains answered. HAQ-DI overall score ranges from a minimum of 0 to a maximum of 3.0. HAQ response was defined as an improvement (reduction) from baseline (Day 1) of at least 0.3 units in the HAQ score.
Open-Label LT Period: Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, or AEs Leading to Discontinuation	End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)	AE=any new untoward medical event or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. Treatment-related SAE=possibly, probably, or certainly related to study drug
Open-Label LT Period: Number of Participants With AEs of Special Interest	End of ST Period (Day 169) to last dose plus 85 days, up to 5 years (September 2014)	AE=any new untoward medical occurrence or worsening of a preexisting medical condition that does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs: all infections, serious infections, and opportunistic infections; autoimmune disorders; malignancies; system injection reactions, and local injection site reactions.
Open-Label LT Period: Number of Participants With Clinically Significant Abnormalities in Vital Sign Measurements	End of ST Period (Day 169) to last dose plus 7 days, up to 5 years (September 2014)	Vital sign assessments were performed in the LT period at 12-week intervals and at a yearly visit (at 16-week intervals) and, for participants who withdrew from the study prematurely, 7 days after the last dose of SC abatacept. Vital signs included seated systolic blood pressure, seated diastolic blood pressure, temperature, and heart rate. Abnormalities were determined to be clinically significant by the investigator.

Trial Locations

Locations (70): Rheumatic Disease Clinical Research Center, Llc
🇺🇸
Houston, Texas, United States
Accurate Clinical Research
🇺🇸
Houston, Texas, United States
Cincinnati Rheumatic Disease Study Group
🇺🇸
Cincinnati, Ohio, United States
Valerius Medical Group &Research Ctr. Of Greater Long Beach
🇺🇸
Long Beach, California, United States
Coastal Clinical Research, Inc
🇺🇸
Mobile, Alabama, United States
Catalina Pointe Clinical Research, Inc.
🇺🇸
Tucson, Arizona, United States
Talbert Medical Group
🇺🇸
Huntington Beach, California, United States
Allergy & Rheumatology Medical Clinic, Inc.
🇺🇸
La Jolla, California, United States
Arthritis Assoicates Of Mississippi
🇺🇸
Jackson, Mississippi, United States
Allergy And Arthritis Associates
🇺🇸
Dover, New Jersey, United States
Acme Research, Llc
🇺🇸
Orangeburg, South Carolina, United States
St. Joseph'S Mercy Clinic
🇺🇸
Hot Springs, Arkansas, United States
Advanced Arthritis Care & Research
🇺🇸
Scottsdale, Arizona, United States
The Arthritis Group, Pc
🇺🇸
Memphis, Tennessee, United States
Physician Research Collaboration, Llc
🇺🇸
Lincoln, Nebraska, United States
St. Thomas Hospital Tower East
🇺🇸
Nashville, Tennessee, United States
Rheumatology Associates, Pc
🇺🇸
Birmingham, Alabama, United States
San Diego Arthritis Medical Clinic
🇺🇸
San Diego, California, United States
Arthritis Assoc And Osteo Ctr Of Col Sprgs
🇺🇸
Colorado Springs, Colorado, United States
Arthritis Center Of The Rockies, Pc
🇺🇸
Loveland, Colorado, United States
Guadagnoli, Germano
🇺🇸
Bridgeport, Connecticut, United States
Joao Nascimento
🇺🇸
Bridgeport, Connecticut, United States
Clinical Research Center Of Ct/Ny
🇺🇸
Danbury, Connecticut, United States
Arthritis And Rheumatic Disease Specialties
🇺🇸
Aventura, Florida, United States
The Arthritis Center
🇺🇸
Springfield, Illinois, United States
Sarasota Arthritis Research Center
🇺🇸
Sarasota, Florida, United States
Arthritis & Rheumatology Of Georgia,Pc
🇺🇸
Atlanta, Georgia, United States
Boise Rheumatology/ Intermountain Research Center, Inc
🇺🇸
Boise, Idaho, United States
Coeur D'Alene Arthrit Clin
🇺🇸
Coeur D Alene, Idaho, United States
Quincy Medical Group
🇺🇸
Quincy, Illinois, United States
Rockford Orthopedic Associates, Ltd.
🇺🇸
Rockford, Illinois, United States
Kansas City Internal Medicine
🇺🇸
Lee'S Summit, Missouri, United States
Albuquerque Clinical Trials, Inc.
🇺🇸
Albuquerque, New Mexico, United States
Albuquerque Rehabilitation & Rheumatology Pc
🇺🇸
Albuquerque, New Mexico, United States
The Center For Rheumatology, Llp
🇺🇸
Albany, New York, United States
Southern Tier Arthritis & Rheumatism
🇺🇸
Olean, New York, United States
Arthritis Health Associates
🇺🇸
Syracuse, New York, United States
Asheville Rheumatology & Osteoporosis Research Asso P. A.
🇺🇸
Asheville, North Carolina, United States
Rheumatology
🇺🇸
Durham, North Carolina, United States
The Arthritis Clinic & Carolina Bone & Joint
🇺🇸
Charlotte, North Carolina, United States
Physicians East, Pa
🇺🇸
Greenville, North Carolina, United States
Carolina Pharmaceutical Research
🇺🇸
Statesville, North Carolina, United States
Carolina Arthritis Associates
🇺🇸
Wilmington, North Carolina, United States
Oklahoma Center For Arthritis Therapy And Research
🇺🇸
Tulsa, Oklahoma, United States
Healthcare Research Consultants
🇺🇸
Tulsa, Oklahoma, United States
Pro Research
🇺🇸
Eugene, Oregon, United States
Portland Rheumatology Clinic, Llc
🇺🇸
Lake Oswego, Oregon, United States
East Penn Rheumatology Associates
🇺🇸
Bethlehem, Pennsylvania, United States
Rheumatology Associates
🇺🇸
Providence, Rhode Island, United States
Columbia Arthritis Center
🇺🇸
Columbia, South Carolina, United States
Carolina Health Specialists
🇺🇸
Myrtle Beach, South Carolina, United States
Arthritis Clinic
🇺🇸
Jackson, Tennessee, United States
Rheumatology Consultants Pllc
🇺🇸
Knoxville, Tennessee, United States
Walter F. Chase
🇺🇸
Austin, Texas, United States
Texas Research Center
🇺🇸
Sugarland, Texas, United States
Arthritis Clinic Of Northern Virginia, P.C.
🇺🇸
Arlington, Virginia, United States
South Puget Sound Clinincal Research Center
🇺🇸
Olympia, Washington, United States
Tacoma Center For Arthritis Research Ps
🇺🇸
Tacoma, Washington, United States
Local Institution
🇬🇧
Newcastle Upon Tyne, Tyne And Wear, United Kingdom
Health Research Of Oklahoma
🇺🇸
Oklahoma City, Oklahoma, United States
Boulder Medical Center
🇺🇸
Boulder, Colorado, United States
Denver Arthritis Clinic
🇺🇸
Denver, Colorado, United States
Center For Arthritis & Rheumatic Diseases, Pc
🇺🇸
Chesapeake, Virginia, United States
Arthritis & Osteoporosis Treatment Center, Pa
🇺🇸
Orange Park, Florida, United States
Shores Rheumatology, P. C.
🇺🇸
St. Clair Shores, Michigan, United States
Clinical Pharmacology Study Group
🇺🇸
Worcester, Massachusetts, United States
Rheumatology Associates Of Central Florida
🇺🇸
Orlando, Florida, United States
Low Country Rheumatology, Pa
🇺🇸
Charleston, South Carolina, United States
Stanford University School Of Medicine
🇺🇸
Palo Alto, California, United States
Klein And Associates, M.D., Pa
🇺🇸
Cumberland, Maryland, United States

Methotrexate-Inadequate Response Study

Recruitment & Eligibility

Study & Design

Trial Locations

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