ADDRESS II supports further investigation of atacicept in SLE
medwireNews: Treatment with the B cell inhibitor atacicept may be beneficial for certain subpopulations of patients with systemic lupus erythematosus (SLE), phase IIb trial results suggest.
The ADDRESS II investigators, led by Joan Merrill (University of Oklahoma Health Sciences Center, Oklahoma City, USA), randomly assigned adult patients with active, autoantibody-positive SLE to receive weekly subcutaneous atacicept at a dose of 75 or 150 mg, or matched placebo, for 24 weeks.
At week 24, 57.8% of 102 patients in the 75 mg group, 53.8% of 104 patients in the 150 mg group, and 44.0% of 100 patients given placebo achieved an SLE responder index (SRI)-4) response – a composite endpoint including a reduction in Systemic Lupus Erythematosus Disease Activity Index-2000 score of at least 4 points; an increase in Physician’s Global Assessment of less than 10%; no new organ with severe disease; no more than one new organ with moderate disease; and no clinically significant use of non-permitted treatments.
Although SRI-4 response rates were numerically higher among patients treated with atacicept versus placebo, these differences did not reach statistical significance, meaning that the primary endpoint was not met and all other analyses were considered exploratory, report the researchers in Arthritis & Rheumatology.
However, they remark that “there was robust discrimination between atacicept and placebo” in prespecified subgroup analyses. For example, patients with serologically active disease who were treated with atacicept 75 mg or 150 mg were significantly more likely to achieve an SRI-4 response than placebo-treated patients, with corresponding rates of 62.1% and 61.5% versus 24.1%.
Similarly, SRI-4 response rates were significantly higher for patients in the atacicept 75 mg or 150 mg versus placebo groups among patients with high disease activity (HDA; 60.0 and 62.7 vs 42.3%) and among those with HDA and serologically active disease (64.0 and 65.0 vs 25.0%).
“These findings are consistent with subgroup analyses of blisibimod and belimumab studies that demonstrate increased treatment effect in patients with HDA,” and “suggest that when the target population is patients with HDA, there is a greater likelihood of discriminating an effective treatment from placebo,” say the authors.
They note that the safety profile of atacicept in the ADDRESS II trial was “acceptable,” with no overall increase in serious adverse events (AEs) among patients receiving active treatment. Serious treatment-emergent AEs were reported in 5.8% of patients in the 75 mg group, 8.8% of those in the 150 mg group, and 12.0% of placebo-treated patients. The most frequently occurring AEs of any grade were injection site reactions and pain, urinary and upper respiratory tract infections, and diarrhea.
Taken together, these findings “support further clinical evaluation of atacicept in SLE,” conclude Merrill and colleagues.
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