Evaluation of Effectiveness of Two Dosing Regimens of Fostamatinib Compared to Placebo in Patients With Rheumatoid Arthritis (RA) Who Are Taking Disease Modifying Anti-rheumatic Drug (DMARD) But Not Responding.

ACRn - Comparison Between Fostamatinib and Placebo 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 or patient's own assessments 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. BID = twice daily, CI = confidence interval, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, PO = orally, QD = once a day. Mean refers to change at Week 24.

Time frame: Baseline and 24 weeks

Proportion of Patients Achieving DAS28-CRP <2.6 at Week 12, Comparison Between Fostamatinib and 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. A DAS28-CRP score of \<2.6 is indicative of remission of RA symptoms. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.

Time frame: 12 weeks

Proportion of Patients Achieving DAS28-CRP <2.6 at Week 24, Comparison Between Fostamatinib and 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. A DAS28-CRP score of \<2.6 is indicative of remission of RA symptoms. BID = twice daily, CRP = C-reactive protein, DMARD = Disease-modifying anti-rheumatic drug, OR=odds ratio, PO = orally, QD=once a day.

Time frame: 24 weeks

Proportion of Patients Achieving 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. 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.

Time frame: 24 weeks

HAQ-DI Response - Comparison of the Change(>=0.22) From Baseline Between Fostamatinib and Placebo at Week 24

HAQ-DI: Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is then 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. The HAQ-DI response is a reduction from baseline in HAQ-DI score greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day.

Time frame: Baseline and 24 weeks

Change From Baseline to Week 24 in mTSS, Comparison Between Fostamatinib and Placebo

mTSS: modified total sharp score, a measure of structural progression based upon X-rays. Hand and foot joints are scored for erosions and joint space narrowing and the results summed to give a value between 0 and 448. A higher value represents more serious progression of the disease. After disregarding ineligible records, patients with 2 or more non-missing values have had missing data imputed via linear extrapolation/interpolation methods. Patients with only 1 result were excluded from the analysis. ANCOVA = analysis of covariance, BID = twice daily, IP = investigational product, QD = once a day.

Time frame: Baseline and 24 weeks

SF-36 - Comparison of the Change in PCS From Baseline Between Fostamatinib and Placebo at Week 24

SF-36: 36-item Short Form Health Survey, a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0-100. Physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50+/- 10. Higher scores represent a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once a day.

Time frame: Baseline and 24 weeks

SF-36 - Comparison of the Change in MCS From Baseline Between Fostamatinib and Placebo at Week 24

SF-36: 36-item Short Form Health Survey, a measure of health related quality of life. Scores for 8 sub-domains (Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Function, Role-Emotional and Mental Health) are derived and normalised to a scale of 0-100. Physical and mental component scores (PCS and MCS) are derived by multiplying each of these 8 scores by a constant, summing them and standardising against a population with mean of 50+/- 10. Higher scores represent a better quality of life. Mean changes from baseline score are presented as increases from baseline (defined as post-baseline minus baseline); larger changes indicate a better clinical condition. ANCOVA = analysis of covariance, BID = twice daily, DMARD = disease modifying antirheumatic drugs, PO = orally, QD = once a day.

Time frame: Baseline and 24 weeks