Joint Damage
Conditions
Keywords
Gout, Hyperuricemia, Uric Acid, Drug Therapy
Brief summary
This purpose of this study is to assess the effect of febuxostat, once daily (QD), on joint damage in patients with elevated serum urate levels and gout.
Detailed description
Gout is caused by high levels of uric acid in the body, and is associated with a broad range of comorbidities including heart disease, chronic kidney disease and additional risk factors like obesity and high blood pressure. Hyperuricemia, which is defined as an elevation in serum urate levels, develops into gout when urate crystals form from supersaturated body fluids and settle in joints and other organs. Urate-lowering therapy is used to treat hyperuricemia in patients with gout. Current treatments focus on initiating urate-lowering therapy in hyperuricemic gout patients who have experienced multiple acute gout flares within the past year. However, joint damage caused by crystal deposition may occur much earlier than previously considered. Monosodium urate crystals have been found present in the joints of people with hyperuricemia who do not have any symptoms. The presence of monosodium urate crystals would indicate that after the crystals form, they stay within the joint if serum urate levels are not reduced. Lowering uric acid levels and maintaining them may reduce acute gout flare episodes and possibly halt or reduce joint damage in patients with gout. This study will evaluate the effect of febuxostat on joint damage in hyperuricemic patients with early gout. All patients will receive gout flare prophylaxis for the first 6 months of the study. Gout flares may also be treated throughout the study. A variety of imaging techniques are in use to evaluate gout. Plain radiographs (x-rays), Magnetic Resonance Imaging (MRI) and Dual Energy Computed Tomography (DECT) will be utilized in this study. The modified Sharp/Van Der Heijde scoring method (named after Drs. Sharp and Van Der Heijde) for assessment of x-rays has been validated in patients with chronic gout and will be used in this study for evaluating erosion and joint space narrowing. Participants are expected to have 15 visits which will include plain radiographic examinations at 5 visits, 3 Magnetic Resonance Imaging (MRI) examinations and 3 DECT procedures at selected sites.
Interventions
DRUGFebuxostat
Febuxostat capsules
DRUGPlacebo for Febuxostat
Febuxostat placebo-matching capsules
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* The participant, or the participant's legally acceptable representative, signs a written informed consent form/Health Insurance Portability & Accountability Act (HIPAA) Authorization prior to the initiation of any study procedures. * Must have a history or presence of gout defined as having one or more of the following conditions of the American Rheumatism Association (ARA) preliminary criteria for the diagnosis of gout * A tophus proven to contain urate crystals by chemical or polarized light microscopic means and/or * Characteristic urate crystals in the joint fluid and/or * History of at least 6 of the following clinical, laboratory and x-ray phenomena\*: \*More than one flare criteria will be excluded for the purpose of this study if the participant has a history of only a single acute gout flare. * More than one attack of acute arthritis\* * maximum inflammation developed within 1 day * monoarticular arthritis * redness observed over joints * first metatarsophalangeal joint painful or swollen * unilateral first metatarsophalangeal joint attack * unilateral tarsal joint attack * tophus (proven or suspected) * hyperuricemia * asymmetric swelling within a joint on x-ray * sub-cortical cysts without erosions on x-ray * joint fluid culture negative for organisms during attacks * \*More than one flare criteria will be excluded for the purpose of this study if the participant has a history of only a single acute gout flare. * Is male and at least 18 years of age OR; * Female ≥45 years of age and at least 2 years post-menopausal AND has a Follicle Stimulating Hormone (FSH) level ≥40 IU/L OR * Female receiving hormone replacement therapy (HRT) must be ≥55 years of age (FSH level not required). * Has hyperuricemia defined as serum Uric Acid (sUA) level ≥7.0 mg/dL at Screening. * Has a history of ≤2 (1 or 2) flares. In participants with a history of 2 flares, must have had only one flare in any 12 month period. The primary affected joint will be based on the location of the first gout flare which must be located within right or left metatarsophalangeal (MTP), interphalangeal (IP), ankle, metacarpophalangeal (MCP), Proximal Inter-Phalangeal (PIP), or distal inter-phalangeal (DIP) joints prior to Screening. * Is capable of understanding and complying with protocol requirements, including scheduled clinic procedures.
Exclusion criteria
* Previously on urate-lowering therapy (allopurinol, febuxostat or probenecid). * Has secondary hyperuricemia (eg due to myeloproliferative disorder or organ transplant). * Has a history of xanthinuria. * Has a known hypersensitivity to any component of the febuxostat formulation. * Has rheumatoid arthritis. * Has active peptic ulcer disease. * Has a history of cancer, except basal cell carcinoma of the skin, which has not been in remission for at least 5 years prior to the first dose of study medication. * Has experienced either a myocardial infarction (MI) or stroke within 90 days prior to the Screening visit. * Has alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) values greater than 2.0 the upper limit of normal during the Screening period. * Has a significant medical condition and/or conditions that would interfere with the treatment, safety or compliance with the protocol at the discretion of the Investigator. * Has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse with 5 years prior to the Screening visit. Participant consumes \>14 alcoholic beverages/week. * Has received any investigational medicinal product within 30 days prior to the Screening visit. In addition, the participant has been previously randomized into this study and received at least one dose of double blind study drug treatment. * Has an estimated Glomerular filtration rate (eGFR) \<60 mL/min calculated using the Modification of Diet in Renal Disease (MDRD) formula by the Central Laboratory. * Has a serum creatinine at Screening greater than 2.0 mg/dL. * Has a known history of infection with hepatitis B, hepatitis C or human immunodeficiency virus. * Is a study site employee, or is an immediate family member (ie, spouse, parent, child, and sibling) of a study site employee involved in conduct of this study. * Is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent form is available. * Is required to take excluded medications. * Magnetic Resolution Imaging: * Has a known hypersensitivity to gadolinium * Has history of severe asthma * Has an electronically, magnetically or mechanically activated implanted device * Has any object that could present a potential hazard or interfere with MRI interpretation secondary to the artifact (i.e. metallic foreign bodies) * Has a significant medical condition considered by the Investigator (or radiologist) to interfere with the participant's ability to receive gadolinium (eg Sickle cell anemia).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint | Baseline and Month 24 | The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of this single joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst). Individual erosion scores were summed to a maximum erosion score of 5 for joints in the hands and 10 for joints in the feet. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs | Baseline and Month 24 | Radiographs (X-rays) of 40 joints in the hands and 12 joints in the feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) for a total erosion score range of 0 to 320. Joint space narrowing (JSN) was assessed using a 5-point scale where 0=normal (best) to 4=absence of joint space, presumptive evidence of ankyloses, or complete luxation (worst) for a total JSN score range of 0 to 208. The Erosion Score and the JSN Score were combined for a total possible score of 0 to 528. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement. |
| Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs | Baseline and Month 24 | Radiographs (X-rays) of 40 joints in the hands and 12 joints in the feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) for a total erosion score range of 0 to 320. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement. |
| Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Baseline and Month 24 | The single affected joint was defined as the joint with the history of the first acute gout flare. Magnetic Resonance Imaging (MRI) was evaluated using the Rheumatoid Arthritis MRI Score (RAMRIS). Bone erosion in the proximal and distal location were each assessed in the affected joint using an 11-point scale where 0=no erosion (best) to 10=91-100% bone eroded (worst) for a bone erosion score range of 0 to 20. Bone marrow edema in the proximal and distal location were each assessed using a 4-point scale where 0=no edema (best) to 3=67-100% edema (worst) for a bone marrow edema (BME) score range of 0 to 6. Synovitis was assessed in the affected joint using a 4-point scale where 0=normal (best) to 3=severe (worst). Higher scores indicated more joint damage. A negative change from Baseline indicated improvement. |
| Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint | Baseline and Month 24 | The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of the single affected joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) and Joint space narrowing (JSN) was assessed using a 5-point scale where 0=normal (best) to 4=absence of joint space, presumptive evidence of ankyloses, or complete luxation (worst). The Erosion Score and the JSN Score were summed for the Total Score. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 65 investigative sites in the United States from 10 March 2010 to 3 September 2013.
Pre-assignment details
Participants with a diagnosis of gout were enrolled equally in 1 of 2 treatment groups, once a day placebo or febuxostat 40 mg or 80 mg based on serum urate levels.
Participants by arm
| Arm | Count |
|---|---|
| Febuxostat 40 mg or 80 mg Febuxostat 40 mg or 80 mg (based on serum urate levels at Day 14), capsules, orally, once daily for up to 24 Months. | 157 |
| Placebo Febuxostat placebo-matching capsules, orally, once daily for up to 24 Months. | 157 |
| Total | 314 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 6 |
| Overall Study | Lost to Follow-up | 23 | 23 |
| Overall Study | Major Protocol Deviation | 2 | 0 |
| Overall Study | Other | 9 | 2 |
| Overall Study | Voluntary Withdrawal | 20 | 36 |
Baseline characteristics
| Characteristic | Febuxostat 40 mg or 80 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 12.36 | 50.1 years STANDARD_DEVIATION 11.72 | 50.8 years STANDARD_DEVIATION 12.04 |
| Age, Customized 45 to <65 years | 85 participants | 99 participants | 184 participants |
| Age, Customized <45 years | 49 participants | 42 participants | 91 participants |
| Age, Customized ≥65 years | 23 participants | 16 participants | 39 participants |
| Alcohol History Current Drinker | 103 participants | 106 participants | 209 participants |
| Alcohol History Ex-Drinker | 17 participants | 16 participants | 33 participants |
| Alcohol History Never Drank | 37 participants | 35 participants | 72 participants |
| BMI Categories <25 kg/m^2 | 11 participants | 11 participants | 22 participants |
| BMI Categories 25 to <30 kg/m^2 | 37 participants | 46 participants | 83 participants |
| BMI Categories ≥30 kg/m^2 | 109 participants | 100 participants | 209 participants |
| Body Mass Index (BMI) | 33.1 kg/m^2 STANDARD_DEVIATION 6.4 | 32.3 kg/m^2 STANDARD_DEVIATION 6.23 | 32.7 kg/m^2 STANDARD_DEVIATION 6.32 |
| Height | 176.3 cm STANDARD_DEVIATION 9.22 | 176.5 cm STANDARD_DEVIATION 8.36 | 176.4 cm STANDARD_DEVIATION 8.79 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 8 participants | 10 participants | 18 participants |
| Race/Ethnicity, Customized Black or African American | 25 participants | 24 participants | 49 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 26 participants | 36 participants | 62 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 131 participants | 121 participants | 252 participants |
| Race/Ethnicity, Customized Other | 3 participants | 2 participants | 5 participants |
| Race/Ethnicity, Customized White | 119 participants | 121 participants | 240 participants |
| Region of Enrollment United States | 157 participants | 157 participants | 314 participants |
| Renal History (Modification of Diet in Renal Disease [MDRD]) Mildly Impaired MDRD | 105 participants | 115 participants | 220 participants |
| Renal History (Modification of Diet in Renal Disease [MDRD]) Moderately Impaired MDRD | 3 participants | 2 participants | 5 participants |
| Renal History (Modification of Diet in Renal Disease [MDRD]) Normal MDRD | 49 participants | 40 participants | 89 participants |
| Sex: Female, Male Female | 14 Participants | 12 Participants | 26 Participants |
| Sex: Female, Male Male | 143 Participants | 145 Participants | 288 Participants |
| Smoking History Current Smoker | 32 participants | 25 participants | 57 participants |
| Smoking History Ex-Smoker | 41 participants | 38 participants | 79 participants |
| Smoking History Never Smoked | 84 participants | 94 participants | 178 participants |
| Weight | 102.8 kg STANDARD_DEVIATION 20.88 | 100.7 kg STANDARD_DEVIATION 21.2 | 101.7 kg STANDARD_DEVIATION 21.04 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 73 / 157 | 67 / 157 |
| serious Total, serious adverse events | 13 / 157 | 11 / 157 |
Outcome results
Primary
Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint
The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of this single joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst). Individual erosion scores were summed to a maximum erosion score of 5 for joints in the hands and 10 for joints in the feet. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.
Time frame: Baseline and Month 24
Population: Full Analysis Set included all randomized participants who received at least one dose of study medication. Participants were analyzed according to the treatment group to which they actually received. Participants with data available for analysis and missing values at Month 24 imputed using linear extrapolation are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint | Baseline | 0.16 score on a scale | Standard Deviation 0.444 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint | Change from Baseline at Month 24 | 0.01 score on a scale | Standard Deviation 0.33 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint | Baseline | 0.11 score on a scale | Standard Deviation 0.438 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Score of the Single Affected Joint | Change from Baseline at Month 24 | 0.01 score on a scale | Standard Deviation 0.248 |
Comparison: Change from Baseline at Month 24p-value: 0.472Ranked Analysis of Covariance (ANCOVA)
Secondary
Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs
Radiographs (X-rays) of 40 joints in the hands and 12 joints in the feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) for a total erosion score range of 0 to 320. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.
Time frame: Baseline and Month 24
Population: Full Analysis Set included all randomized participants who received at least one dose of study medication. Participants were analyzed according to the treatment group to which they actually received. Participants with data available at Baseline and Month 24 are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs | Baseline | 0.36 score on a scale | Standard Deviation 1.16 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs | Change from Baseline at Month 24 (n=78,74) | 0.17 score on a scale | Standard Deviation 1.709 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs | Baseline | 0.17 score on a scale | Standard Deviation 0.473 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Erosion Scores From Full Hands and Feet Radiographs | Change from Baseline at Month 24 (n=78,74) | 0.11 score on a scale | Standard Deviation 0.969 |
Comparison: Change from Baseline at Month 24p-value: 0.389Ranked ANCOVA
Secondary
Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint
The single affected joint was defined as the joint with the history of the first acute gout flare. Radiographs (X-rays) of the single affected joint in the hands or feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) and Joint space narrowing (JSN) was assessed using a 5-point scale where 0=normal (best) to 4=absence of joint space, presumptive evidence of ankyloses, or complete luxation (worst). The Erosion Score and the JSN Score were summed for the Total Score. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.
Time frame: Baseline and Month 24
Population: Full Analysis Set included all randomized participants who received at least one dose of study medication. Participants were analyzed according to the treatment group to which they actually received. Participants with data available at Baseline and Month 24 are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint | Baseline | 0.85 score on a scale | Standard Deviation 1.057 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint | Change from Baseline at Month 24(n=81,76) | 0.00 score on a scale | Standard Deviation 0.602 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint | Baseline | 0.77 score on a scale | Standard Deviation 1.022 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Score of the Single Affected Joint | Change from Baseline at Month 24(n=81,76) | 0.05 score on a scale | Standard Deviation 0.361 |
Comparison: Change from Baseline at Month 24p-value: 0.122Ranked ANCOVA
Secondary
Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs
Radiographs (X-rays) of 40 joints in the hands and 12 joints in the feet were evaluated using the modified Sharp/van der Heijde method. Each erosion was assessed using a 4-point scale where 0=no erosions (best) to 3=large erosion passing the mid-line (worst) for a total erosion score range of 0 to 320. Joint space narrowing (JSN) was assessed using a 5-point scale where 0=normal (best) to 4=absence of joint space, presumptive evidence of ankyloses, or complete luxation (worst) for a total JSN score range of 0 to 208. The Erosion Score and the JSN Score were combined for a total possible score of 0 to 528. Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.
Time frame: Baseline and Month 24
Population: Full Analysis Set included all randomized participants who received at least one dose of study medication. Participants were analyzed according to the treatment group to which they actually received. Participants with data available at Baseline and Month 24 are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs | Baseline | 4.98 score on a scale | Standard Deviation 9.707 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs | Change from Baseline at Month 24 (n=78,74) | 0.31 score on a scale | Standard Deviation 2.447 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs | Baseline | 4.56 score on a scale | Standard Deviation 8.631 |
| Placebo | Mean Change From Baseline to Month 24 in the Modified Sharp/Van Der Heijde Total Scores From Full Hands and Feet Radiographs | Change from Baseline at Month 24 (n=78,74) | 0.29 score on a scale | Standard Deviation 1.746 |
Comparison: Change from Baseline at Month 24p-value: 0.548Ranked ANCOVA
Secondary
Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint
The single affected joint was defined as the joint with the history of the first acute gout flare. Magnetic Resonance Imaging (MRI) was evaluated using the Rheumatoid Arthritis MRI Score (RAMRIS). Bone erosion in the proximal and distal location were each assessed in the affected joint using an 11-point scale where 0=no erosion (best) to 10=91-100% bone eroded (worst) for a bone erosion score range of 0 to 20. Bone marrow edema in the proximal and distal location were each assessed using a 4-point scale where 0=no edema (best) to 3=67-100% edema (worst) for a bone marrow edema (BME) score range of 0 to 6. Synovitis was assessed in the affected joint using a 4-point scale where 0=normal (best) to 3=severe (worst). Higher scores indicated more joint damage. A negative change from Baseline indicated improvement.
Time frame: Baseline and Month 24
Population: Full Analysis Set included all randomized participants who received at least one dose of study medication. Participants were analyzed according to the treatment group to which they actually received. Participants with data available at Baseline and Month 24 are included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Synovitis:Baseline (BL)(n=82,76) | 1.29 score on a scale | Standard Deviation 0.782 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Synovitis:Change from Baseline (n=75,67) | -0.43 score on a scale | Standard Deviation 0.713 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Erosion (Distal+Proximal):Change from BL(n=79,69) | -0.01 score on a scale | Standard Deviation 0.702 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Erosion (Distal+Proximal):Baseline (n=84,77) | 1.63 score on a scale | Standard Deviation 0.935 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Edema (Distal+Proximal):Baseline (BL) (n=81,75) | 0.73 score on a scale | Standard Deviation 1.022 |
| Febuxostat 40 mg or 80 mg | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Edema (Distal+Proximal):Change from BL(n=77,66) | -0.36 score on a scale | Standard Deviation 0.916 |
| Placebo | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Edema (Distal+Proximal):Baseline (BL) (n=81,75) | 0.51 score on a scale | Standard Deviation 0.919 |
| Placebo | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Synovitis:Baseline (BL)(n=82,76) | 1.09 score on a scale | Standard Deviation 0.687 |
| Placebo | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Erosion (Distal+Proximal):Baseline (n=84,77) | 1.48 score on a scale | Standard Deviation 0.916 |
| Placebo | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Edema (Distal+Proximal):Change from BL(n=77,66) | -0.10 score on a scale | Standard Deviation 0.962 |
| Placebo | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Erosion (Distal+Proximal):Change from BL(n=79,69) | 0.04 score on a scale | Standard Deviation 0.475 |
| Placebo | Mean Change From Baseline to Month 24 in the Rheumatoid Arthritis MRI Scoring System (RAMRIS) Score of the Single Affected Joint | Synovitis:Change from Baseline (n=75,67) | -0.07 score on a scale | Standard Deviation 0.531 |
Comparison: Synovitis: Change from Baseline at Month 24p-value: <0.001Ranked ANCOVA
Comparison: Erosion(Distal+Proximal): Change from Baseline at Month 24p-value: 0.634Ranked ANCOVA
Comparison: Edema(Distal+Proximal): Change from Baseline at Month 24p-value: 0.307Ranked ANCOVA