Biologic Tested to Prevent Lupus Flares

October 14, 2015

Lower doses of the fusion protein atacicept do not prevent flares in patients with moderate-to-severe systemic lupus erythematosus, study shows

Lower doses of the fusion protein atacicept do not prevent flares in patients with moderate-to-severe systemic lupus erythematosus (SLE), according to a new prospective trial. Higher doses appear to be effective, but may be deadly. Unlike patients with other rheumatic diseases, those with systemic lupus erythematosus have yet to benefit from revolutionary biologic drugs. Strategies to target B cells have led to some, but limited, success.[[{"type":"media","view_mode":"media_crop","fid":"42432","attributes":{"alt":"©lculig/Shutterstock.com","class":"media-image media-image-right","id":"media_crop_9992727788630","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4592","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":" ","typeof":"foaf:Image"}}]] Atacicept is a fusion protein that blocks B-lymphocyte stimulator and a proliferation-inducing ligand, which are increased in patients with systemic lupus erythematosus. Researchers led by David Isenberg, MD, of the University College London in London, conducted a 52-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter trial to determine the efficacy and safety of atacicept in the prevention of flares in systemic lupus erythematosus. The study randomized 461 systemic lupus erythematosus patients to receive either 75 mg or 150 mg doses of atacicept or placebo. The patients had recently had a lupus flare that was controlled by a relatively short course of glucocorticoids. Enrollment in the 150 mg atacicept arm was discontinued prematurely due to two deaths from pneumonias complicated by pulmonary hemorrhage. When treatment was discontinued, 62 of 144 patients on the higher dose had completed treatment; 27 other patients had already been withdrawn for various reasons. For 55 other patients, the treatment was stopped early as a safety precaution. A total of 111 patients in the placebo group and 112 patients in the 75 mg atacicept group completed treatment. There was no difference in flare rates or time to first flare between these two groups. A post hoc analysis suggested that patients treated with 150 mg atacicept had a beneficial effect in flare rates and time to first flare compared to placebo. Both atacicept doses were associated with reductions in total immunoglobulin levels and anti-dsDNA antibodies, and increases in complement (C3 and C4) levels. Most treatment-emergent adverse events were mild or moderate. The researchers pointed out that other trials of B-cell inhibitors have led to deaths in active treatment arms. Also, in a dose-escalating Phase Ib study in mild/moderate non-renal lupus, atacicept reduced B-cells and immunoglobulin levels without significant adverse events. “The overall similarity in adverse events between the three arms of the study, including serious events, is reassuring and consistent with previous studies of atacicept in rheumatoid arthritis, although the rate of total infections and serious infections was slightly higher with atacicept 150 mg,” they stated.  They suggest that underlying disease, steroid therapy and delays in diagnosis and treatment may have contributed to the deaths in the study. 

 

References:

Isenberg D, Gordon C, et al. "Efficacy and safety of atacicept for prevention of flares in patients with moderate-to-severe systemic lupus erythematosus (SLE): 52-week data (APRIL-SLE randomised trial),"Annals of Rheumatic Diseases. Published Online First 20 June 2014. (http://dx.doi.org/10.1136/annrheumdis-2013-05067).