Clinical and epidemiological research period II (withdrawal), mean reductions were sustained throughout period II and remained stable during period III (ﬁgure 3A). For patients who had SC abatacept withdrawn in period II, DAS28 worsened slightly during withdrawal (ﬁgure 3A) and improved following reintroduction of SC abatacept and, by the end of period III (day 253), was comparable to patients maintained on SC abatacept (ﬁgure 3A). Mean DAS28 scores by the end of period III were similar, irrespective of whether or not patients received intravenous abatacept load- ing at reintroduction. High proportions of patients achieved DAS28-deﬁned LDAS and remission by the end of period III, regardless of whether they were withdrawn from SC abatacept (ﬁgure 3B). Patients treated during period II had a mean (SD) HAQ-DI of 1.30 (0.66) at baseline. For patients maintained on SC abata- cept during period II, mean reductions from baseline seen in period I were maintained through periods II and III (ﬁgure 3C). For patients withdrawn from SC abatacept, mean reductions in HAQ-DI seen in period I deteriorated slightly following with- drawal and improved upon reintroduction. Table 2 Immunogenicity summary Impact of immunogenicity on efﬁcacy and safety Based on the seven patients treated with SC placebo who were seropositive (ELISA) at the end of period II, the presence of antibodies did not affect the safety or efﬁcacy of SC abatacept. Following reintroduction, all but one of these patients demon- strated an efﬁcacy response at the end of period III based on DAS28 and/or HAQ-DI. None of these seven patients experi- enced SAEs or severe or drug-related AEs after reintroduction, whether SC abatacept was reintroduced with or without intra- venous abatacept loading. DISCUSSION In clinical practice, patients may experience periods when treat- ment is temporarily withdrawn and reintroduced. Given the risk of increased immunogenicity and the potential impact on safety and efﬁcacy resulting from treatment withdrawal and reintro- duction, evaluating these outcomes is important. The present study showed that, following a response to SC abatacept, 3-month interruption followed by reintroduction End of period II (Withdrawal phase) End of period III (Reintroduction phase)* Period II SC placebo (n=80) Period II SC abatacept† (n=40) Period II SC placebo‡ (n=79) Anti-abatacept, n/N (%) 95% CI Anti-CTLA4-T, n/N (%) 95% CI Total, n/N (%) 95% CI Estimate of difference, % (95% CI) p Value Period II SC abatacept (n=40) 0/37 (0) – 0/38 (0) – 0/38 (0) – 9.59 (0.83 to 18.34) 0.119 *All patients received SC abatacept during period III, with results shown by period II treatment group. †Patients received intravenous placebo loading at the start of period III. ‡Patients received intravenous abatacept or intravenous placebo (1:1 ratio) loading at the start of period III. SC, subcutaneous. 0/38 (0) – 1/38 (2.6) 0.0 to 7.7 1/38 (2.6) 0.0 to 7.7 0.11 (–8.21 to 8.43) – 0/73 (0) – 2/73 (2.7) 0.0 to 6.5 2/73 (2.7) 0.0 to 6.5 Table 3 Safety summary Patients with event (n (%)) AEs Most common AEs* URTI Vaginal infection Nausea Flu UTI Laryngitis Discontinuations due to AEs SAEs Deaths Infections and infestations Serious infections† Malignancies Autoimmune events SC injection site reaction Acute infusional events 42 1/71 (1.4) 0.0 to 4.1 6/73 (8.2) 1.9 to 14.5 7/73 (9.6) 2.8 to 16.3 0 0 0 1 (1.3) 1 (1.3) 0 0 2 (2.5) 0 7 (8.8) 0 0 0 0 0 SC abatacept (n=40) 13 (32.5) SC placebo (n=80) 29 (36.3) 1 (2.5) 2 (5.0) 2 (5.0) 0 1 (2.5) 0 0 0 0 5 (12.5) 0 0 0 0 0 Period I (Introduction phase) Period II (Withdrawal phase) SC abatacept (with intravenous abatacept load) (n=167) 82 (49.1) 12 (7.2) 0 2 (1.2) 5 (3.0) 3 (1.8) 1 (0.6) 1 (0.6) 3 (1.8) 1 (0.6) 42 (25.1) 1 (0.6) 0 0 2 (1.2) 1 (0.6)‡ *AEs reported in ≥5% of patients in any group during any treatment period. †Serious infections is a subset of SAEs. ‡Mild non-serious headache, considered probably related to study drug, was reported following intravenous abatacept loading in period I. AE, adverse event; SAE, serious adverse event; SC, subcutaneous; URTI, upper respiratory tract infection; UTI, urinary tract infection. Period III (Reintroduction phase) Period II SC abatacept (with intravenous placebo load) (n=40) 15 (37.5) 2 (5.0) 0 0 0 3 (7.5) 0 0 0 0 7 (17.5) 0 0 0 0 0 Period II SC placebo Intravenous abatacept load (n=35) 17 (48.6) Intravenous placebo load (n=44) 16 (36.4) 1 (2.9) 0 0 2 (5.7) 0 3 (8.6) 0 0 0 8 (22.9) 0 0 0 0 0 1 (2.3) 0 0 2 (4.5) 1 (2.3) 0 0 1 (2.3) 0 7 (15.9) 0 0 0 0 0 Ann Rheum Dis 2012;71:38–44. doi:10.1136/annrheumdis-2011-200344