Effect of baseline rheumatoid factor and anticitrullinated peptide antibody serotype on rituximab clinical response: a meta-analysis.
BACKGROUND
Studies examining the relationship between serological status (rheumatoid factor and/or anticitrullinated antibody) and rituximab treatment outcome in rheumatoid arthritis (RA) have been hampered by limited numbers of seronegative patients.


OBJECTIVE
To carry out a meta-analysis of trials from the rituximab RA clinical programme to investigate this relationship further.


METHODS
This was a meta-analysis of four placebo-controlled, phase II or III clinical trials. The efficacy end point in all analyses was change from baseline in Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) at 24 weeks. Assay of serotype and missing data imputation methods were consistent across all studies.


RESULTS
The population analysed comprised 2177 patients (rituximab, n=1416; placebo, n=761). Demographics and baseline disease characteristics were well balanced. When a fixed-effects meta-analysis approach was used, the overall-effect model indicated evidence of additional treatment benefit with rituximab in seropositive patients: reduction in DAS28-ESR at week 24 was on average 0.35 units (95% CI 0.12 to 0.84; n=1394) greater than in seronegative patients; this effect was not seen in placebo patients. Heterogeneity indices indicated significant uncertainty in the overall-effect model (Q=8.8, I=0.77; p=0.03 (χ(2) test)). Baseline Health Assessment Questionnaire score, pain visual analogue scale, swollen joint counts of 28 joints and race were significant contributors to this heterogeneity, with additional analysis indicating that these effects may predominate in early RA (methotrexate-naïve) populations. A dominant effect was seen in patients for whom one or more tumour necrosis factor inhibitors had failed.


CONCLUSIONS
Although the difference was modest, the overall-effect model indicates that seropositive patients respond better to rituximab than seronegative patients.
Newcastle University, Newcastleupon Tyne NE7 7DN, UK. john.isaacs@newcastle.ac.uk
John D
JD
Isaacs
Stanley B
SB
Cohen
Paul
P
Emery
Paul P
PP
Tak
Jianmei
J
Wang
Guiyuan
G
Lei
Sarah
S
Williams
Preeti
P
Lal
Simon J
SJ
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D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D004311:Double-Blind Method; D006801:Humans; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012217:Rheumatoid Factor / Q000097:blood*; D000069283:Rituximab; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D001323:Autoantibodies; D000069283:Rituximab; D012217:Rheumatoid Factor