Systematic Review Protocol

Two investigators (K.Y.Q and J.X.R) independently reviewed the title and abstract of studies related to fostamatinib for the treatment of RA and selected RCTs. Published or unpublished RCTs were searched in databases without language restriction. All selected studies were read in detail and those that met the inclusion criteria were selected for final analysis. All trials had the following conditions ( Table 1 ):

PICOS criteria for inclusion and exclusion of studies.

PICOS, patients, intervention, comparator, outcomes, study design; RCTs, Randomized clinical trials; qd, once per day. ACR20/50/70, American College of Rheumatology response criteria of 20, 50, 70 percentage; ACRn, American College of Rheumatology index of RA improvement; DAS28-CRP, Disease activity score based on a count of swollen and tender joints (out of 28 joints), C-reactive protein (blood test measures of inflammation) and the patient’s own assessment; SF-36, 36-item short form health survey, evaluation of the indicators of a healthy quality of life; PCS, Physical component scores, a scale of 0 to 100; MCS, Mental component scores, a scale of 0 to 100; HAQ-DI ≥ 0.22, HAQ—disability index response that compares change (≥0.22) from baseline.

Patients: any race, older than 18 years, and diagnosed with inadequate response to MTX or DMARDs for RA.

Interventions: use of fostamatinib in multiple dosages as therapy, with an intervention duration of at least 6 weeks.

Comparison: A) multiple doses of fostamatinib compared to placebo at 24 weeks. B) 100 mg twice per day (bid) for 4 weeks followed by 150 mg once per day (qd) compared to 100 mg bid.

Outcomes: the following indicators were reported from the studies: a) American College of Rheumatology response criteria of 20, 50, 70 percentage (ACR20/50/70); b) American College of Rheumatology index of RA improvement (ACRn); c) Disease activity score based on a count of swollen and tender joints (out of 28 joints), C-reactive protein (blood test measures of inflammation) and the patient’s own assessment (DAS28-CRP). DAS28-CRP < 2.6 or DAS28-CRP ≤ 3.2, DAS28-CRP by using European League Against Rheumatism (EULAR) response; d) SF-36, which is a 36-item short form health survey, evaluation of the indicators of a healthy quality of life. PCS: Physical component scores, a scale of 0 to 100. MCS: Mental component scores, a scale of 0 to 100. A higher score can represent a better quality of life; e) HAQ-DI ≥ 0.22: HAQ - disability index response which compares change (≥0.22) from baseline; and f) serious adverse events (SAEs) and other AEs. Exclusion criteria included non-randomized trials, animals, healthy volunteers, case reports, or conference abstract.