Figure 3 Clinical efﬁcacy. (A) Mean change in DAS28 (CRP) over time by period II (Withdrawal phase) treatment group. (B) Proportion of patients achieving LDAS and DAS28-deﬁned remission by period II (Withdrawal phase) treatment group. (C) Mean change in HAQ-DI score over time by period II (Withdrawal phase) treatment group. Data are as-observed for all patients who received ≥1 dose of study drug during period II. Error bars represent 95% CI. CRP, C reactive protein; DAS28, Disease Activity Score 28; HAQ-DI, Health Assessment Questionnaire- Disability Index; LDAS, low disease activity state; SC, subcutaneous. of treatment was well tolerated without a signiﬁcant impact on immunogenicity. Following withdrawal of SC abata- cept, immunogenicity was observed in approximately 10% of patients, with only one showing persistent seropositivity. The increase in immunogenicity for patients withdrawn from treatment was not signiﬁcantly different from that of patients Ann Rheum Dis 2012;71:38–44. doi:10.1136/annrheumdis-2011-200344 Clinical and epidemiological research kept on treatment. After reintroduction of abatacept, <3% of patients demonstrated immunogenicity with only one case of persistent seropositivity. Immunogenicity was low regardless of whether intravenous abatacept or intravenous placebo was administered at reintroduction. Immunogenicity also appeared to have little effect on safety and efﬁcacy, as shown in patients in whom treatment was withdrawn and subsequently reintro- duced. Importantly, these data also demonstrate that immu- nogenicity with SC abatacept is consistent with intravenous administration.1 11 The low immunogenicity rates observed with SC abatacept mirror those observed in other SC abatacept studies. In a phase II study9 assessing weight-tiered versus ﬁxed SC dosing over 4 months, only one of 51 patients demonstrated immunogenicity. This was transient and the patient was seronegative at study completion. Results from subsequent phase III studies have dem- onstrated low rates of immunogenicity. In a 4-month OL phase III study of SC abatacept with or without MTX, only four cases of transient immunogenicity were observed.10 Immunogenicity observed with SC abatacept9 10 is at the lower end of that seen with other biological agents. Immunogenicity rates of between 17% (21 patients) and 20% (46 patients) over 28 weeks have been seen with SC adalimumab,13 14 immunogenicity rates of approximately 6% (12 patients) over 24 weeks have been reported with SC etanercept15 and rates of 44% (33 patients) over 24 weeks have been found with intravenous inﬂiximab.6 The safety of SC abatacept was consistent across periods dur- ing this study. Importantly, in patients in whom SC abatacept was withdrawn and reintroduced, the frequency of AEs did not increase and no unexpected events occurred compared with those who received continuous treatment. The incidence of infection with SC abatacept was consistent with intravenous administra- tion, with the majority of events mild or moderate.16 17 There were no reports of autoimmune events or malignancies. The inci- dence of injection site reactions was low and all events were mild- to-moderate in intensity. Previous studies with SC abatacept have also reported a low incidence of injection site reactions,18 with fewer events seen with increasing treatment exposure.19 Patients who received continuous SC abatacept treatment had improvements in disease activity and physical function that were maintained over time, supporting the ﬁndings in patients with active RA who received SC abatacept with or without background MTX.19 Patients who withdrew SC abatacept treat- ment for 12 weeks experienced increased disease activity and slight worsening of physical function. Upon reintroduction, improvements in disease activity were noted within 1 month of re-initiation and, by the end of period III, disease activity was comparable with patients who received continuous SC abatacept. Similarly, physical function improved upon reintro- duction of SC abatacept. These ﬁndings suggest that temporary short-term withdrawal of treatment has a minimal impact on sustained efﬁcacy improvements seen in patients who respond to treatment. These are important ﬁndings, and provide some conﬁdence for clinicians that interruption of SC abatacept treat- ment for up to 3 months is safe and well tolerated with a limited impact on efﬁcacy. Certain limitations of the study design should be considered. All patients received background immunosuppressive therapy with MTX, and caution should be used when extrapolating these conclusions to patients on monotherapy. However, a previous study determined that treatment with abatacept alone resulted in comparable immunogenicity to abatacept plus MTX, suggest- ing that the impact of background MTX on immunogenicity with SC abatacept is minimal.10 Patients were also permitted rescue 43