Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid Arthritis, OSKIRA, fostamatinib
Brief summary
The purpose of the study is to evaluate the improvements in signs and symptoms of rheumatoid arthritis (RA) for fostamatinib compared to placebo or adalimumab in patients who are Disease-Modifying anti-rheumatic drug (DMARD) naïve, DMARD intolerant or have had an inadequate response to DMARDs. The study will last for approximately six months
Detailed description
Sub-study: Full title: Optional Genetic Research Date: 10 September 2010 Version: 1 Objectives: To collect and store, with appropriate consent , DNA samples for future exploratory research into genes/genetic variation that may influence response (ie, absorption, distribution, metabolism and excretion, safety, tolerability and efficacy) to fostamatinib disodium and/or adalimumab; and/or susceptibility to, progression of and prognosis of RA The main study recruitment is complete, and sub study recruitment will continue until the target is reached, estimated to be June 2013 Sub-study: Full title: (Sub-study to OSKIRA-4): A Phase IIB, Multi-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy and Safety of Fostamatinib Disodium Monotherapy Compared with Placebo or Adalimumab Monotherapy in Patients with Active Rheumatoid Arthritis: Magnetic Resonance Imaging Sub-Study Date: 21 March 2011 Version: 1 Primary objective: Assess the efficacy of fostamatinib in reducing joint synovial disease activity as measured by: * Change from baseline to Week 6 (versus placebo) in OMERACT RAMRIS synovitis score.
Interventions
DRUGFostamatinib and placebo injections
Fostamatinib 100mg twice daily and placebo injection once every two weeks
DRUGAdalimumab and placebo of fostamatinib
Adalimumab 40mg injection once every two weeks and placebo to fostamatinib twice daily.
DRUGPlacebo of fostamatinib, fostamatinib, and placebo injections
Placebo injection once every two weeks. Placebo to fostamatinib for six weeks, followed by fostamatinib 100mg twice daily (Group F) / fostamatinib 100mg twice daily then 150mg once daily (Group G).
Sponsors
AstraZeneca
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
* Male or female aged 18 and over * Active rheumatoid arthritis (RA) diagnosed after the age of 16 and diagnosis within 5 years prior to study visit 1 and inadequate response to treatment with a maximum 2 Disease-Modifying anti-rheumatic drug (DMARD) therapies, or diagnosis within 5 years prior to study visit 1 and intolerance to DMARD therapy, or diagnosis within 2 years prior to study visit 1 and no previous use of DMARDs * 4 or more swollen joints and 4 or more tender/painful joints (from 28 joint count) and either Erythrocyte Sedimentation Rate (ESR) blood result of 28mm/h or more, or C-Reactive Protein (CRP) blood result of 10mg/L or more * At least 2 of the following: documented history or current presence of positive rheumatoid factor (blood test), radiographic erosion within 12 months prior to study enrolment, presence of serum anti-cyclic citrullinated peptide antibodies (blood test)
Exclusion criteria
* Females who are pregnant or breast feeding * Poorly controlled hypertension * Liver disease or significant liver function test abnormalities * Certain inflammatory conditions (other than rheumatoid arthritis), connective tissue diseases or chronic pain disorders * Recent or significant cardiovascular disease * Significant active or recent infection including tuberculosis * Previously received treatment with a TNF alpha antagonist (including etanercept, certolizumab, adalimumab, infliximab, golimumab) or anakinra or previous treatment with other biological agent including rituximab, abatacept and tocilizumab * Use of any DMARDs within 6 weeks before first study visit * Severe renal impairment * Neutropenia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo | Baseline and 6 weeks | DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous. |
| DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | Baseline and 24 weeks | DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Achieving ACR20 up to Week 24 | 6 and 24 weeks | ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. |
| Proportion of Patients Achieving ACR50 up to Week 24 | 6 and 24 weeks | ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. |
| Proportion of Patients Achieving ACR70 up to Week 24 | 6 and 24 weeks | ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. |
| ACRn - Comparison Between Fostamatinib and Placebo at Week 6 | Baseline and 6 weeks | ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 6. Treatment difference: difference between fostamatinib and placebo groups. |
| DAS28 EULAR Response at Week 6 | 6 weeks | Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous. |
| HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6 | Baseline and 6 weeks | HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. |
| HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | Baseline and 24 weeks | HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. |
| SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | Baseline and 24 weeks | SF-36: 36-item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Non-responder imputation applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous. |
| SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | Baseline and 24 weeks | SF-36: 36-item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Non-responder imputation applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous. |
| ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24 | Baseline and 24 weeks | ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 24. Treatment difference: difference between fostamatinib and adalimumab groups. |
| DAS28 EULAR Response at Week 24 | 24 weeks | Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous. |
Countries
Bulgaria, Canada, Czechia, Germany, Hungary, Netherlands, Poland, Russia, Slovakia, South Africa, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
452 patients were enrolled into the main study, with 198 patients enrolled into a separate MRI sub-study. Synovitis results for the MRI sub-study were reported later due to study delays and so are presented entirely separately.
Pre-assignment details
A total of 173 patients failed screening to the main study.
Participants by arm
| Arm | Count |
|---|---|
| FOSTA 100 MG BID PO Dosing Group A | 54 |
| FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO Dosing Group B | 48 |
| FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO Dosing Group C | 57 |
| ADALIMUMAB 40 MG SC Dosing Group D | 54 |
| PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO Dosing Group F | 27 |
| PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO Dosing Group G | 25 |
| Total | 265 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 7 | 8 | 0 | 2 | 1 |
| Overall Study | Dev. of study specific discont. criteria | 2 | 0 | 0 | 0 | 1 | 1 |
| Overall Study | e.g., change in circumstances | 8 | 3 | 3 | 3 | 4 | 4 |
| Overall Study | Lack of therapeutic response | 1 | 0 | 2 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Not reported | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Severe non-compliance to protocol | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | FOSTA 100 MG BID PO | FOSTA 100 MG BID (4 WKS) THEN 150 MG QD PO | FOSTA 100 MG BID (4 WKS) THEN 100 MG QD PO | ADALIMUMAB 40 MG SC | PLACEBO (6 WKS) THEN FOSTA 100 MG BID PO | PLACEBO (6 WK) THEN FOSTA 100 MG BID (4 WK) THEN 150 MG QD PO | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 50 years STANDARD_DEVIATION 11.5 | 50 years STANDARD_DEVIATION 12.6 | 50 years STANDARD_DEVIATION 11 | 48 years STANDARD_DEVIATION 12.4 | 50 years STANDARD_DEVIATION 12.7 | 53 years STANDARD_DEVIATION 10.8 | 50 years STANDARD_DEVIATION 11.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants | 0 Participants | 6 Participants | 1 Participants | 3 Participants | 1 Participants | 16 Participants |
| Race/Ethnicity, Customized Indian or Pakistani | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 48 Participants | 47 Participants | 48 Participants | 51 Participants | 23 Participants | 23 Participants | 240 Participants |
| Sex: Female, Male Female | 38 Participants | 39 Participants | 48 Participants | 45 Participants | 20 Participants | 20 Participants | 210 Participants |
| Sex: Female, Male Male | 16 Participants | 9 Participants | 9 Participants | 9 Participants | 7 Participants | 5 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 15 / 54 | 30 / 54 | 19 / 57 | 20 / 48 | 13 / 25 | 1 / 25 | 11 / 27 | 3 / 27 |
| serious Total, serious adverse events | 4 / 54 | 5 / 54 | 4 / 57 | 1 / 48 | 0 / 25 | 1 / 25 | 0 / 27 | 0 / 27 |
Outcome results
Primary
DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab
DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
Time frame: Baseline and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | 1.0 Units on a scale | Standard Deviation 1.31 |
| Dosing Group B | DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | 1.1 Units on a scale | Standard Deviation 1.22 |
| Dosing Group C | DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | 1.0 Units on a scale | Standard Deviation 1.25 |
| Dosing Group E | DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | 1.8 Units on a scale | Standard Deviation 1.45 |
| Dosing Group F | DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | 1.1 Units on a scale | Standard Deviation 1.26 |
| Dosing Group G | DAS28-CRP Score - Change From Baseline to Week 24 Compared to Adalimumab | 1.4 Units on a scale | Standard Deviation 1.26 |
Comparison: Change from baseline at Week 24. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.p-value: 0.00580% CI: [-1.04, -0.4]ANCOVA
Comparison: Change from baseline at Week 24. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.p-value: 0.0280% CI: [-0.94, -0.27]ANCOVA
Comparison: Change from baseline at Week 24. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.p-value: 0.00480% CI: [-1.04, -0.4]ANCOVA
Primary
DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo
DAS28-CRP: Disease Activity Score based on a count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (CRP) and the patient's own assessment. Scores can take any positive value with a lower value indicating a better clinical condition. Mean changes from baseline in DAS28-CRP score are shown at each visit and are presented as decreases from baseline (defined as baseline minus post-baseline) with larger changes indicative of a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, QD = once a day, SC = subcutaneous.
Time frame: Baseline and 6 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo | 1.1 Units on a scale | Standard Deviation 0.92 |
| Dosing Group B | DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo | 1.1 Units on a scale | Standard Deviation 1.01 |
| Dosing Group C | DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo | 0.8 Units on a scale | Standard Deviation 0.96 |
| Dosing Group E | DAS28-CRP Score - Change From Baseline to Week 6 Compared to Placebo | 0.6 Units on a scale | Standard Deviation 1.14 |
Comparison: Change from baseline at Week 6. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.p-value: 0.00690% CI: [0.23, 0.9]ANCOVA
Comparison: Change from baseline at Week 6. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.p-value: 0.02290% CI: [0.14, 0.84]ANCOVA
Comparison: Change from baseline at Week 6. Non-responder imputation applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of parenteral steroids, or for patients with no post baseline data.p-value: 0.2890% CI: [-0.12, 0.56]ANCOVA
Secondary
ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24
ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 24. Treatment difference: difference between fostamatinib and adalimumab groups.
Time frame: Baseline and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle.In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24 | 18.35 Percentage improvement from baseline | Standard Deviation 34.355 |
| Dosing Group B | ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24 | 22.03 Percentage improvement from baseline | Standard Deviation 32.361 |
| Dosing Group C | ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24 | 11.49 Percentage improvement from baseline | Standard Deviation 26.916 |
| Dosing Group E | ACRn - Comparison Between Fostamatinib and Adalimumab at Week 24 | 31.21 Percentage improvement from baseline | Standard Deviation 39.187 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.0390% CI: [-25.01, 0]Van Elteren
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.20790% CI: [-25, 6.96]Van Elteren
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00290% CI: [-30.01, -6.25]Van Elteren
Secondary
ACRn - Comparison Between Fostamatinib and Placebo at Week 6
ACRn: American College of Rheumatology Index of RA improvement, based on smallest percentage improvement in the count of swollen joints (out of 28 joints), count of tender joints (out of 28 joints) or in blood test measures of inflammation (such as CRP) or the physician and patient's own asessment of disease activity, pain and physical function. Scores are reported as a percentage improvement on a scale of -100 to +100, with larger values representing a better clinical outcome. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous. Mean refers to change at Week 6. Treatment difference: difference between fostamatinib and placebo groups.
Time frame: Baseline and 6 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | ACRn - Comparison Between Fostamatinib and Placebo at Week 6 | 16.60 Percentage improvement from baseline | Standard Deviation 30.682 |
| Dosing Group B | ACRn - Comparison Between Fostamatinib and Placebo at Week 6 | 15.07 Percentage improvement from baseline | Standard Deviation 33.334 |
| Dosing Group C | ACRn - Comparison Between Fostamatinib and Placebo at Week 6 | 6.48 Percentage improvement from baseline | Standard Deviation 32.237 |
| Dosing Group E | ACRn - Comparison Between Fostamatinib and Placebo at Week 6 | 15.53 Percentage improvement from baseline | Standard Deviation 43.015 |
| Dosing Group F | ACRn - Comparison Between Fostamatinib and Placebo at Week 6 | -6.49 Percentage improvement from baseline | Standard Deviation 35.159 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: <0.00190% CI: [9.57, 40]Van Elteren
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00690% CI: [7.84, 38.34]Van Elteren
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.23490% CI: [-3.2, 21.68]Van Elteren
Secondary
DAS28 EULAR Response at Week 24
Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous.
Time frame: 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Dosing Group A | DAS28 EULAR Response at Week 24 | Moderate response | 29.6 Percentage of responders | — |
| Dosing Group A | DAS28 EULAR Response at Week 24 | No response | 51.9 Percentage of responders | 1.46 |
| Dosing Group A | DAS28 EULAR Response at Week 24 | Good response | 18.5 Percentage of responders | — |
| Dosing Group B | DAS28 EULAR Response at Week 24 | Moderate response | 39.6 Percentage of responders | — |
| Dosing Group B | DAS28 EULAR Response at Week 24 | No response | 41.7 Percentage of responders | 1.34 |
| Dosing Group B | DAS28 EULAR Response at Week 24 | Good response | 18.8 Percentage of responders | — |
| Dosing Group C | DAS28 EULAR Response at Week 24 | Moderate response | 29.8 Percentage of responders | — |
| Dosing Group C | DAS28 EULAR Response at Week 24 | No response | 52.6 Percentage of responders | 1.3 |
| Dosing Group C | DAS28 EULAR Response at Week 24 | Good response | 17.5 Percentage of responders | — |
| Dosing Group E | DAS28 EULAR Response at Week 24 | Moderate response | 27.8 Percentage of responders | — |
| Dosing Group E | DAS28 EULAR Response at Week 24 | No response | 31.5 Percentage of responders | 1.58 |
| Dosing Group E | DAS28 EULAR Response at Week 24 | Good response | 40.7 Percentage of responders | — |
| Dosing Group F | DAS28 EULAR Response at Week 24 | Moderate response | 33.3 Percentage of responders | — |
| Dosing Group F | DAS28 EULAR Response at Week 24 | No response | 55.6 Percentage of responders | 1.33 |
| Dosing Group F | DAS28 EULAR Response at Week 24 | Good response | 11.1 Percentage of responders | — |
| Dosing Group G | DAS28 EULAR Response at Week 24 | No response | 40.0 Percentage of responders | 1.48 |
| Dosing Group G | DAS28 EULAR Response at Week 24 | Good response | 24.0 Percentage of responders | — |
| Dosing Group G | DAS28 EULAR Response at Week 24 | Moderate response | 36.0 Percentage of responders | — |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00790% CI: [0.2, 0.68]Proportional odds model
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.05190% CI: [0.26, 0.89]Proportional odds model
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00490% CI: [0.2, 0.65]Proportional odds model
Secondary
DAS28 EULAR Response at Week 6
Change in DAS28 was derived for each post baseline scheduled assessment and categorised using the European League Against Rheumatism (EULAR) response criteria. Non-responder imputation has been applied by carrying the baseline observation forward. bid = twice daily, DAS28 = Disease Activity Score based on a 28-joint count, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, qd = once a day, SC = subcutaneous.
Time frame: 6 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.
| Arm | Measure | Group | Value (NUMBER) | Dispersion |
|---|---|---|---|---|
| Dosing Group A | DAS28 EULAR Response at Week 6 | No response | 37.0 Percentage of responders | 1.46 |
| Dosing Group A | DAS28 EULAR Response at Week 6 | Good response | 9.3 Percentage of responders | — |
| Dosing Group A | DAS28 EULAR Response at Week 6 | Moderate response | 53.7 Percentage of responders | — |
| Dosing Group B | DAS28 EULAR Response at Week 6 | Moderate response | 47.9 Percentage of responders | — |
| Dosing Group B | DAS28 EULAR Response at Week 6 | No response | 33.3 Percentage of responders | 1.34 |
| Dosing Group B | DAS28 EULAR Response at Week 6 | Good response | 18.8 Percentage of responders | — |
| Dosing Group C | DAS28 EULAR Response at Week 6 | Moderate response | 35.1 Percentage of responders | — |
| Dosing Group C | DAS28 EULAR Response at Week 6 | No response | 57.9 Percentage of responders | 1.3 |
| Dosing Group C | DAS28 EULAR Response at Week 6 | Good response | 7.0 Percentage of responders | — |
| Dosing Group E | DAS28 EULAR Response at Week 6 | No response | 40.7 Percentage of responders | 1.58 |
| Dosing Group E | DAS28 EULAR Response at Week 6 | Good response | 20.4 Percentage of responders | — |
| Dosing Group E | DAS28 EULAR Response at Week 6 | Moderate response | 38.9 Percentage of responders | — |
| Dosing Group F | DAS28 EULAR Response at Week 6 | Moderate response | 25.0 Percentage of responders | — |
| Dosing Group F | DAS28 EULAR Response at Week 6 | No response | 67.3 Percentage of responders | 1.33 |
| Dosing Group F | DAS28 EULAR Response at Week 6 | Good response | 7.7 Percentage of responders | — |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00590% CI: [1.59, 5.86]Proportional odds model
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: <0.00190% CI: [2.1, 8.05]Proportional odds model
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.33590% CI: [0.76, 2.83]Proportional odds model
Secondary
HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24
HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time frame: Baseline and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | 0.3 Units on a scale | Standard Deviation 0.57 |
| Dosing Group B | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | 0.4 Units on a scale | Standard Deviation 0.56 |
| Dosing Group C | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | 0.2 Units on a scale | Standard Deviation 0.45 |
| Dosing Group E | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | 0.5 Units on a scale | Standard Deviation 0.53 |
| Dosing Group F | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | 0.3 Units on a scale | Standard Deviation 0.47 |
| Dosing Group G | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Adalimumab at Week 24 | 0.1 Units on a scale | Standard Deviation 0.35 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.04390% CI: [-0.36, -0.04]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.15890% CI: [-0.31, 0.02]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00190% CI: [-0.47, -0.16]ANCOVA
Secondary
HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6
HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygiene, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. Non-responder imputation has been applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time frame: Baseline and 6 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6 | 0.3 Units on a scale | Standard Deviation 0.35 |
| Dosing Group B | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6 | 0.3 Units on a scale | Standard Deviation 0.54 |
| Dosing Group C | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6 | 0.2 Units on a scale | Standard Deviation 0.43 |
| Dosing Group E | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6 | 0.3 Units on a scale | Standard Deviation 0.45 |
| Dosing Group F | HAQ-DI - Comparison of the Change From Baseline Between Fostamatinib and Placebo at Week 6 | 0.1 Units on a scale | Standard Deviation 0.52 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00790% CI: [0.09, 0.38]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.01690% CI: [0.07, 0.37]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.09490% CI: [0, 0.29]ANCOVA
Secondary
Proportion of Patients Achieving ACR20 up to Week 24
ACR20: American College of Rheumatology 20% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time frame: 6 and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6 and with adalimumab (not placebo) at Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dosing Group A | Proportion of Patients Achieving ACR20 up to Week 24 | Week 6 | 48.1 Percentage of responders |
| Dosing Group A | Proportion of Patients Achieving ACR20 up to Week 24 | Week 24 | 40.7 Percentage of responders |
| Dosing Group B | Proportion of Patients Achieving ACR20 up to Week 24 | Week 6 | 47.9 Percentage of responders |
| Dosing Group B | Proportion of Patients Achieving ACR20 up to Week 24 | Week 24 | 56.3 Percentage of responders |
| Dosing Group C | Proportion of Patients Achieving ACR20 up to Week 24 | Week 6 | 38.6 Percentage of responders |
| Dosing Group C | Proportion of Patients Achieving ACR20 up to Week 24 | Week 24 | 35.1 Percentage of responders |
| Dosing Group E | Proportion of Patients Achieving ACR20 up to Week 24 | Week 6 | 53.7 Percentage of responders |
| Dosing Group E | Proportion of Patients Achieving ACR20 up to Week 24 | Week 24 | 59.3 Percentage of responders |
| Dosing Group F | Proportion of Patients Achieving ACR20 up to Week 24 | Week 6 | 19.2 Percentage of responders |
| Dosing Group F | Proportion of Patients Achieving ACR20 up to Week 24 | Week 24 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR20 up to Week 24 | Week 6 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR20 up to Week 24 | Week 24 | 44.4 Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR20 up to Week 24 | Week 6 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR20 up to Week 24 | Week 24 | 44.0 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: <0.00190% CI: [0.17, 0.4]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: <0.00190% CI: [0.18, 0.43]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00790% CI: [0.07, 0.31]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.04990% CI: [-0.3, -0.03]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.80390% CI: [-0.16, 0.12]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00390% CI: [-0.37, -0.1]Mantel Haenszel
Secondary
Proportion of Patients Achieving ACR50 up to Week 24
ACR50: American College of Rheumatology 50% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time frame: 6 and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6 and with adalimumab (not placebo) at Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dosing Group A | Proportion of Patients Achieving ACR50 up to Week 24 | Week 6 | 13.0 Percentage of responders |
| Dosing Group A | Proportion of Patients Achieving ACR50 up to Week 24 | Week 24 | 20.4 Percentage of responders |
| Dosing Group B | Proportion of Patients Achieving ACR50 up to Week 24 | Week 6 | 12.5 Percentage of responders |
| Dosing Group B | Proportion of Patients Achieving ACR50 up to Week 24 | Week 24 | 18.8 Percentage of responders |
| Dosing Group C | Proportion of Patients Achieving ACR50 up to Week 24 | Week 6 | 7.0 Percentage of responders |
| Dosing Group C | Proportion of Patients Achieving ACR50 up to Week 24 | Week 24 | 12.3 Percentage of responders |
| Dosing Group E | Proportion of Patients Achieving ACR50 up to Week 24 | Week 6 | 25.9 Percentage of responders |
| Dosing Group E | Proportion of Patients Achieving ACR50 up to Week 24 | Week 24 | 31.5 Percentage of responders |
| Dosing Group F | Proportion of Patients Achieving ACR50 up to Week 24 | Week 6 | 3.8 Percentage of responders |
| Dosing Group F | Proportion of Patients Achieving ACR50 up to Week 24 | Week 24 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR50 up to Week 24 | Week 6 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR50 up to Week 24 | Week 24 | 22.2 Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR50 up to Week 24 | Week 6 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR50 up to Week 24 | Week 24 | 24.0 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.05990% CI: [0.01, 0.18]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.07190% CI: [0.01, 0.17]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.75890% CI: [-0.05, 0.07]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.11490% CI: [-0.24, 0]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.07890% CI: [-0.26, -0.01]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00390% CI: [-0.32, -0.09]Mantel Haenszel
Secondary
Proportion of Patients Achieving ACR70 up to Week 24
ACR70: American College of Rheumatology 70% response criteria, based on count of swollen and tender joints (out of 28 joints), blood test measures of inflammation (such as CRP) and the physician and patient's own assessments of disease activity, pain and physical function. Non-responder imputation has been applied by carrying the baseline observation forward. BID = twice daily, CRP = C-reactive protein, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, n/a = not applicable, PO = orally, qd = once a day, SC = subcutaneous.
Time frame: 6 and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with placebo (not adalimumab) at Week 6 and with adalimumab (not placebo) at Week 24.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Dosing Group A | Proportion of Patients Achieving ACR70 up to Week 24 | Week 6 | 1.9 Percentage of responders |
| Dosing Group A | Proportion of Patients Achieving ACR70 up to Week 24 | Week 24 | 9.3 Percentage of responders |
| Dosing Group B | Proportion of Patients Achieving ACR70 up to Week 24 | Week 6 | 4.2 Percentage of responders |
| Dosing Group B | Proportion of Patients Achieving ACR70 up to Week 24 | Week 24 | 10.4 Percentage of responders |
| Dosing Group C | Proportion of Patients Achieving ACR70 up to Week 24 | Week 6 | 1.8 Percentage of responders |
| Dosing Group C | Proportion of Patients Achieving ACR70 up to Week 24 | Week 24 | 3.5 Percentage of responders |
| Dosing Group E | Proportion of Patients Achieving ACR70 up to Week 24 | Week 6 | 7.4 Percentage of responders |
| Dosing Group E | Proportion of Patients Achieving ACR70 up to Week 24 | Week 24 | 20.4 Percentage of responders |
| Dosing Group F | Proportion of Patients Achieving ACR70 up to Week 24 | Week 6 | 3.8 Percentage of responders |
| Dosing Group F | Proportion of Patients Achieving ACR70 up to Week 24 | Week 24 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR70 up to Week 24 | Week 6 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR70 up to Week 24 | Week 24 | 7.4 Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR70 up to Week 24 | Week 6 | NA Percentage of responders |
| Dosing Group G | Proportion of Patients Achieving ACR70 up to Week 24 | Week 24 | 4.0 Percentage of responders |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.4690% CI: [-0.07, 0.03]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.90390% CI: [-0.05, 0.06]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.17290% CI: [-0.08, 0.01]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.08290% CI: [-0.21, -0.01]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.09290% CI: [-0.21, 0]Mantel Haenszel
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.00290% CI: [-0.27, -0.08]Mantel Haenszel
Secondary
SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24
SF-36: 36-item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Non-responder imputation applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous.
Time frame: Baseline and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 3 Units on a scale | Standard Deviation 9.3 |
| Dosing Group B | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 3 Units on a scale | Standard Deviation 11.5 |
| Dosing Group C | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 2 Units on a scale | Standard Deviation 10 |
| Dosing Group E | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 4 Units on a scale | Standard Deviation 9.8 |
| Dosing Group F | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 3 Units on a scale | Standard Deviation 5.9 |
| Dosing Group G | SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 0 Units on a scale | Standard Deviation 10.1 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.56890% CI: [-3.95, 1.92]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.36890% CI: [-4.69, 1.38]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.1690% CI: [-5.38, 0.43]ANCOVA
Secondary
SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24
SF-36: 36-item Short Form Health Survey, a measure of health-related QoL. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional & Mental Health) are derived & normalised to a scale of 0-100. Physical & Mental Component Scores (PCS & MCS) are derived by multiplying each of these 8 scores by a constant, summing them & standardising against a population with mean of 50, standard deviation of 10. Higher scores represent a better QoL. Mean changes from baseline score are presented at each visit as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. Non-responder imputation applied by carrying the baseline observation forward. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, IR = inadequate response, LS = least squares, PO = orally, QD = once a day, QoL = quality of life, SC = subcutaneous.
Time frame: Baseline and 24 weeks
Population: The full analysis set includes those patients who received at least 1 dose of investigational product. Patients were analysed by randomised treatment in accordance with the intention to treat principle. In line with the study objectives, fostamatinib was compared with adalimumab (not placebo) at Week 24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dosing Group A | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 4 Units on a scale | Standard Deviation 7.3 |
| Dosing Group B | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 5 Units on a scale | Standard Deviation 7.2 |
| Dosing Group C | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 4 Units on a scale | Standard Deviation 7.4 |
| Dosing Group E | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 7 Units on a scale | Standard Deviation 8.4 |
| Dosing Group F | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 4 Units on a scale | Standard Deviation 8.7 |
| Dosing Group G | SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Adalimumab at Week 24 | 3 Units on a scale | Standard Deviation 5 |
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.0590% CI: [-5.08, -0.45]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.3690% CI: [-3.73, 1.06]ANCOVA
Comparison: Non-responder imputation has been applied following premature withdrawal, or any DMARD initiation, or for 8 weeks following receipt of any parenteral steroids, or for patients with no post baseline data.p-value: 0.03290% CI: [-5.29, -0.7]ANCOVA