Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study will determine the efficacy, safety, and tolerability of denosumab (AMG 162) in the treatment of Rheumatoid Arthritis (RA).

Official Title
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A Randomized, Double-blind, Placebo-controlled, Multi-dose Phase 2 Study to Determine the Efficacy, Safety and Tolerability of Denosumab in the Treatment of Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: placebo
* Drug: denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA. All subjects will be required to have been taking a stable dose of methotrexate. Active RA at screening defined as greater than or equal to 6 swollen joints. The presence of erosive disease Exclusion Criteria: Received any biologic agent (e.g., Enbrel®, Remicade®, Humira®, Kineret®) or Arava® within 8 weeks before randomization; past use of these agents is allowed. Steroid use greater than 15 mg/day. Scheduled for surgery or joint replacement in the hands, wrists or feet.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Denosumab 180 mg<br>Participants received 180 mg denosumab by subcutaneous injection on Day 1 and at Month 6. | Drug: denosumab<br>* For subcutaneous injection<br>* Other names: AMG 162;|
| Experimental: Denosumab 60 mg<br>Participants received 60 mg denosumab by subcutaneous injection on Day 1 and at Month 6. | Drug: denosumab<br>* For subcutaneous injection<br>* Other names: AMG 162;|
| Placebo Comparator: Placebo<br>Participants received placebo subcutaneous injections on Day 1 and at Month 6. | Drug: placebo<br>* placebo subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Rheumatoid Arthritis Erosion Score Measured From MRI Assessments (RA-MRI ES) at Month 6 | Fifteen sites in each wrist and 10 sites in each hand were assessed by a blinded and independent reader. Each site was scored from 0 to 10 (in accordance with the European League Against Rheumatism [EULAR]-Outcome Measures in Rheumatology Clinical Trials convention), with each unit increment representing 10% incremental loss of the peripheral 1 cm of articular bone. The Erosion Score is a sum of erosion scores from 50 joint sites in both hands/wrists and ranges from 0 (normal, no erosion) to 500 (worst possible erosion). | Baseline, Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 12 | TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst). | Baseline, Month 12 | 
| Change From Baseline in Radiographic Total Modified Sharp Score (TSS) at Month 6 | TSS is the sum of erosion and joint space narrowing scores obtained from radiographs of the hands and feet, assessed by 2 independent readers. The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. The TSS ranged from 0 (normal) to 448 (worst). | Baseline, Month 6 | 
| Change From Baseline in Radiographic Erosion Score at Month 12 | The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. | Baseline, Month 12 | 
| Change From Baseline in Radiographic Erosion Score at Month 6 | The joint erosion score is a summary of erosion severity in 32 joints of the hands and 12 joints in the feet, obtained from radiographs of the hands and feet and assessed by 2 independent readers. Each joint was scored, according to the surface area involved, from 0 (no erosion) to 5 (extensive loss of bone from more than one half of the articulating bone). Because each side of a foot joint was graded on this scale, the maximum erosion score for a foot joint was 10 and the maximal erosion score was 280. | Baseline, Month 6 | 
| Change From Baseline in Radiographic Joint Space Narrowing Score at Month 12 | Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168. | Baseline, Month 12 | 
| Change From Baseline in Radiographic Joint Space Narrowing Score at Month 6 | Joint Space Narrowing (JSN) Score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet obtained from radiographs of the hands and feet and assessed by 2 independent readers. Assessment of JSN for each hand (15 joints per hand) and foot (6 joints per foot), including subluxation, was scored from 0 (normal JSN) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score (indicating worst joint space narrowing) of 168. | Baseline, Month 6 | 
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 1 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((month 1 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 1 | 
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 6 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to month 6 calculated using ((month 6 value - baseline value) / baseline value ) x 100. Least squares means are based on a repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, month 6 | 
| Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 12 | 
| Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 1 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 1 | 
| Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 6 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 6 | 
| Percent Change From Baseline in Femoral Neck Bone Mineral Density at Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 12 | 
| Percent Change From Baseline in Total Hip Bone Mineral Density at Month 1 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 1 calculated using ((Month 1 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 1 | 
| Percent Change From Baseline in Total Hip Bone Mineral Density at Month 6 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 6 calculated using ((Month 6 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 6 | 
| Percent Change From Baseline in Total Hip Bone Mineral Density at Month 12 | Bone Mineral Density Assessed by Dual Energy X-Ray Absorptiometry. Percent change from baseline to Month 12 calculated using ((Month 12 value - baseline value) / baseline value ) x 100. Least squares means based on repeated measures model adjusting for treatment, visit, baseline value, and strata (4 strata from the combination of baseline use of steroid and previous use of biologic). | Baseline, Month 12 | 
| Percent Change From Baseline in Serum Collagen C-Telopeptide (CTX) at Month 3 | Percent change from baseline to Month 3 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 3 | 
| Percent Change From Baseline in Serum CTX at Month 6 | Percent change from baseline to Month 6 in serum Collagen C-Telopeptide (CTX) Type I calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 6 | 
| Percent Change From Baseline in Serum CTX at Month 12 | Percent change from Baseline to Month 12 in serum C-Telopeptide (CTX) Type I calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 12 | 
| Percent Change From Baseline in Procollagen 1 N-terminal Peptide (P1NP) at Month 3 | Percent change from baseline to Month 3 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 3 | 
| Percent Change From Baseline in P1NP at Month 6 | Percent change from baseline to Month 6 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 6 | 
| Percent Change From Baseline in P1NP at Month 12 | Percent change from baseline to Month 12 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 12 | 
| Percent Change From Baseline in Urine Type II Collagen C-telopeptide (C-Tx) /Creatinine at Month 3 | Percent change from baseline to Month 3 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 3 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 3 | 
| Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 6 | Percent change from baseline to Month 6 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 6 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 6 | 
| Percent Change From Baseline in Urine Type II C-Tx /Creatinine at Month 12 | Percent change from baseline to Month 12 in urine Type II collagen C-Telopeptide (CTX)/Creatinine calculated using ((Month 12 value - Baseline value) / Baseline value ) x 100. | Baseline, Month 12 | 
| Number of Participants With Anti-Denosumab Binding Antibodies | Serum from participants was tested for antibodies to denosumab by immuoassay at months 1, 3, 6 and 12. The number of participants with anti-denosumab antibodies at any assessment is reported. | Assessed at Baseline and at Months 1, 3, 6 and 12. | 
| Number of Participants With Anti-Denosumab Binding Antibody and Neutralizing Antibody | Serum from participants testing positive for anti-denosumab binding antibodies was tested in a cell-based bioassay for neutralizing activity against denosumab. | Baseline to Month 12 | 
| Change From Baseline in Albumin at Month 1 | Laboratory Chemistry Albumin | Baseline, month 1 | 
| Change From Baseline in Albumin at Month 3 | Laboratory chemistry albumin | Baseline, month 3 | 
| Change From Baseline in Albumin at Month 6 | Laboratory chemistry albumin | Baseline, month 6 | 
| Change From Baseline in Albumin at Month 12 | Laboratory chemistry albumin | Baseline, month 12 | 
| Change From Baseline in Alkaline Phosphatase at Month 1 | Laboratory chemistry alkaline phoshatatse | Baseline, month 1 | 
| Change From Baseline in Alkaline Phosphatase at Month 3 | Laboratory chemisrty alkaline phosphatase | baseline, month 3 | 
| Change From Baseline in Alkaline Phosphatase at Month 6 | Laboratory chemistry alkaline phosphatase | baseline, month 6 | 
| Change From Baseline in Alkaline Phosphatase at Month 12 | Laboratory chemistry alkaline phosphatase | baseine, month 12 | 
| Change From Baseline in Bicarbonate at Month 1 | Laboratory chemistry bicarbonate | baseline, month 1 | 
| Change From Baseline in Bicarbonate at Month 3 | Laboratory chemistry bicarbonate | baseline, month 3 | 
| Change From Baseline in Bicarbonate at Month 6 | Laboratory chemistry bicarbonate | Baseline, month 6 | 
| Change From Baseline in Bicarbonate at Month 12 | Laboratory chemistry bicarbonate | Baseline, Month 12 | 
| Change From Baseline in Total Bilirubin at Month 1 | Laboratory chemistry total bilirubin | baseline, month 1 | 
| Change From Baseline in Total Bilirubin at Month 3 | Laboratory chemistry total bilirubin | Baseline, month 3 | 
| Change From Baseline in Total Bilirubin at Month 6 | Laboratory chemistry total bilirubin | Baseline, month 6 | 
| Change From Baseline in Total Bilirubin at Month 12 | Laboratory chemistry total bilirubin | Baseline, month 12 | 
| Change From Baseline in Blood Urea Nitrogen at Month 1 | Laboratory chemistry blood urea nitrogen | Baseline, month 1 | 
| Change From Baseline in Blood Urea Nitrogen at Month 3 | Laboratory chemistry blood urea nitrogen | Baseline, month 3 | 
| Change From Baseline in Blood Urea Nitrogen at Month 6 | Laboratory chemistry blood urea nitrogen | Baseline, month 6 | 
| Change From Baseline in Blood Urea Nitrogen at Month 12 | Laboratory chemistry blood urea nitrogen | baseline, month 12 | 
| Change From Baseline in Calcium at Month 1 | Laboratory chemistry calcium | baseline. month 1 | 
| Change From Baseline in Calcium at Month 3 | Laboratory chemistry calcium | Baseline, month 3 | 
| Change From Baseline in Calcium at Month 6 | Laboratory chemistry calcium | baseline, month 6 | 
| Change From Baseline in Calcium at Month 12 | Laboratory chemistry calcium | Baseline, month 12 | 
| Change From Baseline in Calcium (Corrected) at Month 1 | Laboratory chemistry albumin-adjusted calcium | Baseline, month 1 | 
| Change From Baseline in Calcium (Corrected) at Month 3 | Laboratory chemistry albumin-adjusted calcium | baseline, month 3 | 
| Change From Baseline in Calcium (Corrected) at Month 6 | Laboratory chemistry albumin-adjusted calcium | Baseline, Month 6 | 
| Change From Baseline in Calcium (Corrected) at Month 12 | Laboratory chemistry albumin-adjusted calcium | Baselien, Month 12 | 
| Change From Baseline in Chloride at Month 1 | Laboratory chemistry chloride | baseline, month 1 | 
| Change From Baseline in Chloride at Month 3 | Laboratory chemistry chloride | Baseline, month 3 | 
| Change From Baseline in Chloride at Month 6 | Laboratory chemistry chloride | Baseline, month 6 | 
| Change From Baseline in Chloride at Month 12 | Laboratory chemistry chloride | Baseline, month 12 | 
| Change From Baseline in Creatinine at Month 1 | Laboratory chemistry creatinine | Baseline, month 1 | 
| Change From Baseline in Creatinine at Month 3 | Laboratory chemistry creatinine | Baseline, month 3 | 
| Change From Baseline in Creatinine at Month 6 | Laboratory chemistry creatinine | Baseline, month 6 | 
| Change From Baseline in Creatinine at Month 12 | Laboratory chemistry creatinine | Baseline, month 12 | 
| Change From Baseline in Gamma-Glutamyl Transferase at Month 1 | Laboratory chemistry gamma-glutamyl transferase | Baseline, month 1 | 
| Change From Baseline in Gamma-Glutamyl Transferase at Month 3 | Laboratory chemistry gamma-glutamyl transferase | Baseline, month 3 | 
| Change From Baseline in Gamma-Glutamyl Transferase at Month 6 | Laboratory chemistry gamma-glutamyl transferase | Baseline, month 6 | 
| Change From Baseline in Gamma-Glutamyl Transferase at Month 12 | Laboratory chemistry gamma-glutamyl transferase | Baseline, month 12 | 
| Change From Baseline in Glucose at Month 1 | Laboratory chemistry glucose | Baseline, month 1 | 
| Change From Baseline in Glucose at Month 3 | Laboratory chemistry glucose | Baseline, month 3 | 
| Change From Baseline in Glucose at Month 6 | Laboratory chemistry glucose | Baseline, month 6 | 
| Change From Baseline in Glucose at Month 12 | Laboratory chemistry glucose | baseline, month 12 | 
| Change From Baseline in Potassium at Month 1 | Laboratory chemistry potassium | Baseline, month 1 | 
| Change From Baseline in Potassium at Month 3 | Laboratory chemistry potassium | Baseline, month 3 | 
| Change From Baseline in Potassium at Month 6 | Laboratory chemistry potassium | Baseline, month 6 | 
| Change From Baseline in Potassium at Month 12 | Laboratory chemistry potassium | Baseline, month 12 | 
| Change From Baseline in Magnesium at Month 1 | Laboratory chemistry magnesium | Baseline, month 1 | 
| Change From Baseline in Magnesium at Month 3 | Laboratory chemistry magnesium | Baseline, month 3 | 
| Change From Baseline in Magnesium at Month 6 | Laboratory chemistry magnesium | Baseline, month 6 | 
| Change From Baseline in Magnesium at Month 12 | Laboratory chemistry magnesium | Baseline, month 12 | 
| Change From Baseline in Sodium at Month 1 | Laboratory chemistry sodium | Baseline, month 1 | 
| Change From Baseline in Sodium at Month 3 | Change From Baseline in Sodium at Month 3 | Baseline, Month 3 | 
| Change From Baseline in Sodium at Month 6 | Laboratory chemistry sodium | Baseline, month 6 | 
| Change From Baseline in Sodium at Month 12 | Laboratory chemistry sodium | Baseline, month 12 | 
| Change From Baseline in Phosphorus at Month 1 | Laboratory chemistry phosphorus | Baseline, month 1 | 
| Change From Baseline in Phosphorus at Month 3 | Laboratory chemistry phosphorus | Baseline, month 3 | 
| Change From Baseline in Phosphorus at Month 6 | Laboratory chemistry phosphorus | Baseline, month 6 | 
| Change From Baseline in Phosphorus at Month 12 | Change From Baseline in Phosphorus at Month 12 | Baseline, month 12 | 
| Change From Baseline in Total Protein at Month 1 | Laboratory chemistry total protein | Baseline, month 1 | 
| Change From Baseline in Total Protein at Month 3 | Laboratory chemistry total protein | Baseline, month 3 | 
| Change From Baseline in Total Protein at Month 6 | Laboratory chemistry total protein | Baseline, month 6 | 
| Change From Baseline in Total Protein at Month 12 | Laboratory chemistry total protein | Baseline, month 12 | 
| Change From Baseline in Aspartate Amino Transferase at Month 1 | Laboratory chemistry aspartate amino transferase | Baseline, month 1 | 
| Change From Baseline in Aspartate Amino Transferase at Month 3 | Laboratory chemistry aspartate amino transferase | Baseline, month 3 | 
| Change From Baseline in Aspartate Amino Transferase | Laboratory chemistry aspartate amino transferase | Baseline, month 6 | 
| Change From Baseline in Aspartate Amino Transferase at Month 12 | Laboratory chemistry aspartate amino transferase | Baseline, month 12 | 
| Change From Baseline in Alanine Amino Transferase at Month 1 | Laboratory chemistry alanine amino transferase | Baseline, month 1 | 
| Change From Baseline in Alanine Amino Transferase at Month 3 | Laboratory Chemistry alanine amino transferase | Baseline, month 3 | 
| Change From Baseline in Alanine Amino Transferase at Month 6 | Laboratory chemistry alanine amino transferase | Baseline, month 6 | 
| Change From Baseline in Alanine Amino Transferase at Month 12 | Laboratory chemistry alanine amino transferase | Baseline, month 12 | 
| Change From Baseline in Basophils at Month 1 | Laboratory hematology basophils | baseline, month 1 | 
| Change From Baseline in Basophils at Month 3 | Laboratory hematology basophils | Baseline, month 3 | 
| Change From Baseline in Basophils at Month 6 | Laboratory hematology basophils | Baseline, month 6 | 
| Change From Baseline in Basophils at Month 12 | Laboratory hematology basophils | Baseline, month 12 | 
| Change From Baseline in Eosinophils at Month 1 | Laboratory hematology eosinophils | Baseline, month 1 | 
| Change From Baseline in Eosinophils at Month 3 | Laboratory hematology eosinophils | Baseline, month 3 | 
| Change From Baseline in Eosinophils at Month 6 | Laboratory hematology eosinophils | Baseline, month 6 | 
| Change From Baseline in Eosinophils at Month 12 | Laboratory hematology eosinophils | Baseline, month 12 | 
| Change From Baseline in Hematocrit at Month 1 | Laboratory hematology hematocrit | Baseline, month 1 | 
| Change From Baseline in Hematocrit at Month 3 | Laboratory hematology hematocrit | Baseline, month 3 | 
| Change From Baseline in Hematocrit at Month 6 | Laboratory hematology hematocrit | Baseline, month 6 | 
| Change From Baseline in Hematocrit at Month 12 | Laboratory hematology hematocrit | Baseline, month 12 | 
| Change From Baseline in Hemoglobin at Month 1 | Laboratory hematology hemoglobin | Baseline, month 1 | 
| Change From Baseline in Hemoglobin at Month 3 | Laboratory hematology hemoglobin | Baseline, month 3 | 
| Change From Baseline in Hemoglobin at Month 6 | Laboratory hematology hemoglobin | Baseline, month 6 | 
| Change From Baseline in Hemoglobin at Month 12 | Laboratory hematology hemoglobin | Baseline, month 12 | 
| Change From Baseline in Lymphocytes at Month 1 | Laboratory hematology lymphocytes | Baseline, month 1 | 
| Change From Baseline in Lymphocytes at Month 3 | Laboratory hematology lymphocytes | Baseline, month 3 | 
| Change From Baseline in Lymphocytes at Month 6 | Laboratory hematology lymphocytes | Baseline, month 6 | 
| Change From Baseline in Lymphocytes at Month 12 | Laboratory hematology lymphocytes | Baseline, month 12 | 
| Change From Baseline in Monocytes at Month 1 | Laboratory hematology monocytes | Baseline, month 1 | 
| Change From Baseline in Monocytes at Month 3 | Laboratory hematology monocytes | Baseline, month 3 | 
| Change From Baseline in Monocytes at Month 6 | Laboratory hematology monocytes | Baseline, month 6 | 
| Change From Baseline in Monocytes at Month 12 | Laboratory hematology monocytes | Baseline, month 12 | 
| Change From Baseline in Total Neutrophils at Month 1 | Laboratory hematology total neutrophils | Baseline, month 1 | 
| Change From Baseline in Total Neutrophils at Month 3 | Laboratory hematology total neutrophils | Baseline, month 3 | 
| Change From Baseline in Total Neutrophils at Month 6 | Laboratory hematology total neutrophils | Baseline, month 6 | 
| Change From Baseline in Total Neutrophils at Month 12 | Laboratory hematology total neutrophils | Baseline, month 12 | 
| Change From Baseline in Platelets at Month 1 | Laboratory hematology platelets | Baseline, month 1 | 
| Change From Baseline in Platelets at Month 3 | Laboratory hematology platelets | Baseline, month 3 | 
| Change From Baseline in Platelets at Month 6 | Laboratory hematology platelets | Baseline, month 6 | 
| Change From Baseline in Platelets at Month 12 | Laboratory hematology platelets | Baseline, month 12 | 
| Change From Baseline in Red Blood Cells at Month 1 | Laboratory hematology red blood cells | Baseline, month 1 | 
| Change From Baseline in Red Blood Cells at Month 3 | Laboratory hematology red blood cells | Baseline, month 3 | 
| Change From Baseline in Red Blood Cells at Month 6 | Laboratory hematology red blood cells | Baseline, month 6 | 
| Change From Baseline in Red Blood Cells at Month 12 | Laboratory hematology red blood cells | Baseline, month 12 | 
| Change From Baseline in White Blood Cells at Month 1 | Laboratory hematology white blood cells | Baseline, month 1 | 
| Change From Baseline in White Blood Cells at Month 3 | Laboratpry hematology white blood cells | Baseline, month 3 | 
| Change From Baseline in White Blood Cells at Month 6 | Laboratory hematology white blood cells | Baseline, month 6 | 
| Change From Baseline in White Blood Cells at Month 12 | Laboratory hematology white blood cells | Baseline, month 12 | 
| Number of Participants With Laboratory Common Terminology Criteria for Adverse Events (CTCAE) Grade Greater or Equal to 3 | Participants with laboratory toxicity of grade 3 or 4, graded according to the Common Terminology Criteria for Adverse Events, version 3.0, on the following general guideline: Grade 1 - Mild AE; Grade 2 - Moderate AE; Grade 3 - Severe AE; Grade 4 - Life-threatening or disabling AE; Grade 5 - Death related to AE. | Month 1, month 3, month 6, month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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arthritis, joint pain, Methotrexate