[FRI0256] AUTOANTIBODY-POSITIVE RHEUMATOID ARTHRITIS (RA) PATIENTS (PTS) HAVE ENHANCED CLINICAL RESPONSE TO RITUXIMAB (RTX) WHEN COMPARED WITH SERONEGATIVE PATIENTS
J.D. Isaacs1, E. Olech2, P.P. Tak3, A. Deodhar4, E. Keystone5, P. Emery6, D. Yocum7, E. Hessey8, S. Read8. 1Musculoskeletal Research Group, ICM, Newcastle University, Newcastle Upon Tyne, United Kingdom; 2Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, United States; 3Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands; 4Rheumatology, Oregon Health & Science University, Portland, United States; 5Rheumatology, University of Toronto, Toronto, Canada; 6Rheumatology, Leeds General Infirmary, Leeds, United Kingdom; 7Immunology, Genentech Inc, South San Francisco, United States; 8Clinical Sciences, Roche Products Ltd, Welwyn Garden City, United Kingdom
Background: Previous studies of RTX in pts with RA and an inadequate response to TNF inhibitors have suggested that seropositivity for either rheumatoid factor (RF) or anti-cyclic citrullinated peptide (aCCP) is associated with improved clinical benefit versus seronegative pts .
Objectives: To examine whether seropositivity (RF and/or aCCP) enriches clinical responses to RTX versus pts seronegative for both autoantibodies in a population of RA pts with an inadequate response to DMARDs.
Methods: A pooled cohort from 2 Phase III studies [2,3]) was analyzed, including pts with active RA where RTX was added to existing methotrexate. RTX was given by IV infusion on days 1 and 15 at doses of 2 x 500 mg or 2 x 1000 mg. From Wk 24 further courses of RTX were permitted according to individual study criteria. Serological status for RF (positive: >20 IU/ml) and aCCP (positive: >5 U/ml, Diastat™, AxisShield) were determined at baseline. Pts positive for either or both RF/aCCP were compared with those who were seronegative for both. Clinical outcomes at Wks 24 and 48 included ACR and EULAR responses, change from baseline in DAS28, low disease (DAS28<3.2) and remission (DAS28≤2.6). Associations of serotype with clinical outcomes were assessed by logistic regression analysis or by analysis of variance as appropriate.
Results: A total of 670 pts were included (554 [82.6%] seropositive, 116 seronegative). While significant benefit was previously shown in all pts [2,3] at 24 wks, seropositivity was significantly associated with an increased probability of pts achieving ACR20, 50 and EULAR responses versus seronegative pts (Table). Seropositive pts also had significantly greater falls in DAS28. These findings were replicated at Wk 48 where seropositivity also significantly increased the probability of achieving ACR70. At Wk 48 odds ratios (95% CI) for seropositive pts achieving ACR 20, 50 and 70 were 2.23 (1.38–3.58), 2.72 (1.58–4.70) and 3.3 (1.40–7.82) respectively, versus seronegative pts.
|Week 24||Week 48|
|ACR Responses (n)||514||106||506||101|
|ACR20 (%)||62.3*||50.9||71. 1*||51.5|
|EULAR Outcomes (n)||507||105||496||101|
|EULAR Response (%)||74.8*||62.9||84.3*||72.3|
|Mean change DAS28||-1.97**||-1.50||-2.48***||-1.72|
|DAS28 Categories (n)||510||105||499||101|
|Low Disease (%)||16.9||10.5||26.5*||12.9|
|DAS28 Remission (%)||10.6||4.8||13.2||5.9|