THU0090 Safety and efficacy of atacicept in combination with rituximab in patients with rheumatoid arthritis: Results from the atacicept for reduction of signs and symptoms in rheumatoid arthritis trial (III)
Authors: R.F. van Vollenhoven, S. Wax, S. Copt, P.P. Tak
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Atacicept neutralizes the B cell maturation/survival factors BLyS and APRIL and has been investigated in autoimmune diseases. <h3>Objectives</h3> This Phase II, randomized, double-blind, placebo-controlled, multicenter trial assessed safety and efficacy of atacicept in combination with rituximab, in patients with rheumatoid arthritis (RA). <h3>Methods</h3> Patients with active RA (DAS28 &gt;3.2) who had received previous rituximab treatment and were candidates for rituximab retreatment were included. Two rituximab infusions (Wks 1 and 3) were given followed by randomization at Wk 7 to atacicept 150 mg or placebo, given subcutaneously once-weekly (2:1 ratio) for 25 weeks. Patients were followed up for 32 weeks off treatment. Primary endpoints were nature, incidence, severity of AEs (particularly infections); proportion of patients developing IgG levels &lt;3 g/L; laboratory safety parameters; immunization status. Secondary endpoints included effect on peripheral blood B cells; biomarkers; composite measures of disease activity. <h3>Results</h3> Of 28 patients given rituximab, 18 were randomized to atacicept, 9 to placebo; 1 patient dropped out after the first rituximab infusion due to an AE (cough). Most patients (94.4% atacicept, 100% placebo) experienced ≥1 AE. SAEs were experienced by 1 patient on atacicept (transient ischemic attack [TIA], drug hypersensitivity) and 2 on placebo (TIA, ruptured cerebral aneurysm) during treatment and by 6 (33.3%) atacicept-treated patients during follow up. AEs led to discontinuation in 4 (22.2%) atacicept-treated patients (hypersensitivity reactions, pruritis, diarrhea/gastritis) vs. 1 (11.1%) placebo-treated patient (ruptured cerebral aneurysm). Infection rates were similar in both groups (12 patients [66.7%] on atacicept; 6 patients [66.7%] on placebo). No infection-related SAEs occurred during treatment and rates were similar between groups during follow up. Hypersensitivity-related events were more common in atacicept-treated patients. Three patients (16.6%) on atacicept withdrew from the study due to hypersensitivity-related events compared with 0 (0%) on placebo. Atacicept reduced total IgG by 35.6% (SD ±15%) at Wk 32, with gradual recovery during follow up (-10% at Wk 64); no patient had IgG &lt;3 g/L. Atacicept reduced immunization titers at Wk 32 (median reduction ≤34%); median values returned to baseline by Wk 48. Decreases in rheumatoid factor (RF), including IgG-RF, IgA-RF and IgM-RF, were ∼60–65%. Atacicept treatment was not associated with subsequent delay in B cell recovery during follow-up. At Wk 32, ACR-CRP20, ACR-CRP50 and ACR-CRP70 response rates were 33.3%, 11.1% and 5.6% respectively in the atacicept group vs. 22.2%, 11.1% and 0% in the placebo group. Hematologic, biochemical, vital signs and ECG assessments revealed no safety concerns. <h3>Conclusions</h3> In this exploratory trial, addition of atacicept to rituximab was associated with an increased risk of events that could be hypersensitivity-related. There was no increase in the clinical response rate. <h3>Disclosure of Interest</h3> R. van Vollenhoven Grant/Research support from: Abbott Laboratories; GlaxoSmithKline; MSD; Merck Serono S.A.; Pfizer Inc.; Roche Pharmaceuticals; UCB Pharma, Consultant for: Abbott Laboratories; GlaxoSmithKline; MSD; Merck Serono S.A.; Pfizer Inc.; Roche Pharmaceuticals; UCB Pharma, S. Wax Employee of: EMD Serono Inc., S. Copt Employee of: Merck Serono S.A., P. Tak Shareholder of: Arthrogen B.V., Consultant for: Genentech; Roche Pharmaceuticals; Merck Serono S.A., Employee of: GlaxoSmithKline