Background We previously reported results of the 24-week phase IIb ADDRESS II study of atacicept, which demonstrated clinical response in patients with autoantibody-positive SLE, particularly those with high disease activity (HDA; SLEDAI 2K ≥10 at screening).

Objectives This extension study of ADDRESS II evaluated safety and disease activity in patients with SLE given continued atacicept treatment to week 48 (NCT01972568).

Methods Atacicept was given as weekly subcutaneous injection to completers of ADDRESS II on average for an additional ≥24 weeks (i.e. ≥48 weeks total from Day 1 of ADDRESS II). Patients already receiving atacicept continued on the same dose (75 mg or 150 mg); those receiving placebo (PBO) switched to atacicept 150 mg (PBO/150 mg).

Results Of 262 patients completing ADDRESS II, 253 (95%) entered the extension (PBO/150 mg n=83; 75 mg n=82; 150 mg n=88). Demographics were balanced between groups, and most patients were female (91.3%) and white (70%). All three treatment groups had similar rates of treatment-emergent adverse events (TEAEs), TEAEs leading to treatment discontinuation, serious TEAEs, and serious/severe infection (Table 1). Two deaths occurred in the 150 mg arm, considered unrelated to treatment (reported events of stroke and abdominal pain with hematemesis). In the ITT population (n=253), SLE responder index (SRI)-4 rates were maintained between weeks 24 and 48 in the original atacicept groups (75 mg 56.9 vs 55.9%; 150 mg 53.8 vs 56.7%) and moderately increased in the PBO/150 mg group (44.0 vs 48.0%). This improvement was greater for SRI-6 in the HDA subpopulation (PBO/150 mg 28.8% at week 24 vs 42.3% at week 48; 75 mg 41.8 vs 54.5%; 150 mg 54.9 vs 60.8%; Figure 1). The proportion of HDA patients achieving SLEDAI scores ≤2 was also maintained in the atacicept groups (75 mg 20.0 vs 21.8%; 150 mg 37.3 vs 39.2%) and increased in the PBO/150 mg group (13.5 vs 19.2%). In the ITT and HDA populations, most flares occurred before week 24, with reduced risk of severe (BILAG A) and moderate/severe (BILAG A/2B) flares afterwards. Some increase in complement C3 and C4, and decrease in anti-dsDNA antibodies occurred after week 24. Serum IgG decreased moderately, without severe hypogammaglobulinemia (IgG <3 g/L) in any patients.

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Conclusions There were no new safety signals with atacicept between week 24 and 48, and clinical responses achieved during the first 24 weeks were maintained.

Acknowledgements The study was sponsored by EMD Serono Research & Development Institute Inc., USA (a business of Merck KGaA, Germany). Medical writing support was provided by Bioscript Science, UK, and funded by Merck KGaA, Germany.

Disclosure of Interest D. Wallace Consultant for: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, D. Isenberg Consultant for: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, S. Wax Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, A. Kao Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, P. Chang Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, P. Fraser Employee of: EMD Serono Research & Development Institute, Inc. (a business of Merck KGaA, Darmstadt, Germany), Billerica, MA, USA, J. Merrill Consultant for: Anthera Pharmaceuticals, Lilly, EMD Serono, GlaxoSmithKline and Biogen