RESULTS Patient disposition and baseline demographics A total of 157/167 patients (94.0%) completed period I (Introduction); 120 (71.9%) qualiﬁed for period II (ﬁgure 2). In period II (Withdrawal), 40 and 80 patients were treated with SC abatacept and SC placebo, respectively. Forty and 79 patients entered period III (Reintroduction), with 40 and 77 completing period III. For patients who were treated during period II, baseline dis- ease characteristics were consistent with mild-to-moderate active inﬂammatory disease and were similar between treat- ment groups (table 1). All patients had received prior MTX treat- ment and >90% had not received biological agents. In period I, 49.7% of patients received corticosteroids (oral and/or injectable); the mean (SD) oral dose was 3.1 (3.8) mg. Five patients (3.0%) received symptomatic treatment with high-dose corticosteroids in period I (oral (≥40 mg/day), intramuscular or intravenous). In period II, 57.5% of patients treated with SC abatacept and 55.0% of those given SC pla- cebo received corticosteroids (mean (SD) oral doses 4.2 (5.0) vs 3.8 (4.6) mg). One patient (1.3%) in the SC placebo group received high-dose corticosteroids. During period III, 55.0% of patients treated with SC abatacept and 54.4% of those given SC placebo received corticosteroids (mean (SD) oral doses 3.6 (4.4) vs 3.4 (4.1) mg). One patient (2.5%) in the SC abatacept group received high-dose corticosteroids. During the course of the trial no patient received high-dose corticosteroids for ≥28 days. Immunogenicity End of period II (Withdrawal) The immunogenicity rate (ELISA) at the end of period II (day 169) was low with a positive response in 0% (0/38) and 9.6% (7/73) of patients in the SC abatacept and SC placebo groups, Table 1 Demographic and clinical characteristics at baseline* for patients treated in period II (Withdrawal phase) SC abatacept (n=40) SC placebo (n=80) Age (years) Weight (kg) Weight category, n (%) <60 kg 60–100 kg >100 kg Gender (% female) Race (% Caucasian) Disease duration (years) Tender joints Swollen joints Disease activity, DAS28 (CRP) HAQ-DI RF positive (%) CRP level (mg/dl) Prior antirheumatic drug, n (%) Systemic corticosteroids Methotrexate Cyclophosphamide Leﬂunomide Etanercept Inﬂiximab Adalimumab 48.9 (14.2) 67.9 (15.8) 14 (35.0) 25 (62.5) 1 (2.5) 85.0 95.0 7.4 (7.7) 13.6 (7.7) 10.5 (5.4) 4.8 (0.8) 1.4 (0.7) 85.0 1.27 (1.76) 24 (60) 40 (100) 0 (0) 0 (0) 1 (2.5) 0 (0) 2 (5.0) 49.1 (12.8) 68.9 (14.7) 19 (23.8) 60 (75.0) 1 (1.3) 83.8 93.8 6.2 (5.8) 14.6 (9.2) 10.6 (5.4) 4.8 (0.8) 1.3 (0.7) 86.1 1.23 (1.54) 41 (51.3) 80 (100) 1 (1.3) 2 (2.5) 2 (2.5) 4 (5.0) 2 (2.5) Data are mean (SD) unless otherwise stated. *Baseline is the start of period I. CRP, C reactive protein; DAS28, Disease Activity Score 28; HAQ-DI, Health Assessment Questionnaire-Disability Index; RF, rheumatoid factor; SC, subcutaneous. Ann Rheum Dis 2012;71:38–44. doi:10.1136/annrheumdis-2011-200344 Clinical and epidemiological research respectively (estimate of difference 9.59 (95% CI 0.83 to 18.34), p=0.119; table 2). Of the 7/73 patients with a positive response in the SC placebo group at the end of period II, one patient was positive for anti-abatacept antibodies and six for anti-CTLA4-T antibodies. Period III (Reintroduction) Of the seven patients who were positive for antibodies at the end of period II, three patients remained positive after drug reintro- duction; one was negative by the end of period III, one (period II SC placebo group) had persistent antibodies throughout period III and one had persistent positivity at all post-treatment assess- ments following discontinuation. At the last visit of period III (day 253), 1/38 patients treated with SC abatacept during period II and 2/73 patients treated with SC placebo during period II had positive responses (table 2). For two of these patients (one from each period II treatment group), antibodies were detected only at this assessment. Immunogenicity following reintroduction of SC abatacept for patients randomised to SC placebo in period II was simi- lar regardless of whether they received intravenous abatacept or intravenous placebo loading at the start of the reintroduc- tion period (0/32 and 2/41 (both anti-CTLA4-T), respectively, at day 253; estimate of difference 4.88% (95% CI –4.50% to 14.25%)). Immunogenicity by ECL Immunogenicity assessed by this secondary assay was consis- tent with the ELISA observations (data not shown). Safety Overall, 49.1% of patients experienced an AE during period I. The frequency of AEs remained consistent during periods II and III and was similar between groups (table 3). The majority of AEs were mild or moderate. Throughout the study, SAEs were reported in six patients: three in period I (cholelithiasis, extreme fatigue, cellulitis and pulmonary embolism), two in period II (osteoarthritis of the right hip, and rectal ﬁssure, laceration, pel- vic fracture (motorcycle accident)) and one in period III (severe back pain, urinary retention and benign prostatic hypertrophy). The patient with pulmonary embolism died as a result of the event; all other SAEs resolved. The frequency of infection was similar between groups in periods II and III (table 3). The most common infections (occur- ring in ≥5% of patients) were vaginal infection during period II and urinary tract infection, upper respiratory tract infection, laryngitis and ﬂu during period III. Only two infections were severe (cellulitis and gastroenteritis salmonella), both of which occurred in period I. The cellulitis event was considered a seri- ous infection and led to discontinuation. Reactions at the SC injection site were rare and mild (table 3), with only two events reported (haematoma and pruritus in period I); no injection site reactions were reported upon drug reintroduction. Four patients (2.4%) in period I experienced hypertension of mild or moderate intensity within 24 hours of SC injection. One further moderate case was reported in period II in a patient withdrawn from SC abatacept. No anaphylactic reactions were reported. Clinical efﬁcacy For patients treated in period II, mean (SD) DAS28 at baseline (day 1) was 4.80 (0.83). At the end of period I signiﬁcant reduc- tions from baseline in DAS28 were observed (ﬁgure 3A). For patients who continued to receive SC abatacept throughout 41