Citation

Sheikh SZ, Scheinberg MA, Wei JCC, Tegzova D, Stohl W, de Toledo RA, Mucenic T, Banfi MRA, Maksimowicz-McKinnon K, Abud-Mendoza C, Navarra S, Garcia M, Garcia-De La Torre I, Ros JO, Levy RA, Bass DL, Terrés JR, Punwaney R, Harris J, Nami A, Pierce A, Thorneloe KS, Ji B, Roth DA. Lancet Rheumatol. 2021; 3(2): e122-e130.

Copyright

(Copyright © 2021, Elsevier Publishing)

DOI

10.1016/S2665-9913(20)30355-6

PMID

unavailable

Abstract

BACKGROUND: Belimumab is approved for the treatment of active systemic lupus erythematosus (SLE). Although clinical trials showed a favourable benefit-risk profile, numerical differences in the incidence of mortality and adverse events of special interest (AESIs) have been reported. We assessed the frequency of these events in patients with SLE receiving belimumab or placebo plus standard therapy.

METHODS: BASE was a double-blind, randomised, placebo-controlled, phase 4 trial done in 33 countries. Adults with active SLE were randomly assigned (1:1) to receive intravenous belimumab (10 mg/kg) or placebo, plus standard therapy, for 48 weeks. The primary endpoints were incidences of all-cause mortality and AESIs during the on-treatment period (first-to-last study drug dose + 28 days). Safety analyses were done in the as-treated population (patients grouped by actual treatment received >50% of the time). This study was registered with ClinicalTrials.gov (NCT01705977).

FINDINGS: Between Nov 27, 2012, and July 28, 2017, we randomly assigned 4018 patients. The as-treated population included 2002 patients in the belimumab group versus 2001 in the placebo group. Ten (0·50%) patients in the belimumab group died versus eight (0·40%) in the placebo group (difference 0·10%, 95% CI −0·31 to 0·51). Incidences were similar in the belimumab and placebo groups for serious infections (75 [3·75%] of 2002 vs 82 [4·10%] of 2001; difference −0·35%, 95% CI −1·55 to 0·85), opportunistic infections and other infections of interest (36 [1·80%] vs 50 [2·50%]; −0·70%, −1·60 to 0·20), non-melanoma skin cancers (4 [0·20%] vs 3 [0·15%]; 0·05%, −0·21 to 0·31) and other malignancies (5 [0·25%] vs 5 [0·25%]; 0·00%, −0·31 to 0·31). A higher proportion of patients in the belimumab group than in the placebo group had infusion and hypersensitivity reactions (8 [0·40%] vs 2 [0·10%]; 0·30%, −0·01 to 0·61), serious depression (7 [0·35%] vs 1 [0·05%]; 0·30%, 0·02 to 0·58), treatment-emergent suicidality (28 [1·42%] of 1972 patients vs 23 [1·16%] of 1986; 0·26%, −0·44 to 0·96), and sponsor-adjudicated serious suicide or self-injury (15 [0·75%] of 1972 patients vs 5 [0·25%] of 1986; post hoc difference 0·50%, 0·06 to 0·94).

INTERPRETATION: In line with previously published data, incidences of all-cause mortality and AESIs were similar in patients given belimumab and placebo, except for serious infusion or hypersensitivity reactions, serious depression, treatment-emergent suicidality, and sponsor-adjudicated serious suicide or self-injury events. Funding: GSK. © 2021 Elsevier Ltd

Language: en

Keywords

adolescent; adult; human; suicide; child; female; male; injury; aged; incidence; depression; randomized controlled trial; suicidal behavior; disease severity; kidney disease; major clinical study; mental disease; controlled study; automutilation; priority journal; double blind procedure; drug safety; placebo; drug fatality; multicenter study; corticosteroid; respiratory tract disease; systemic lupus erythematosus; neurologic disease; side effect; infection; heart disease; immunopathology; hematologic disease; gastrointestinal disease; musculoskeletal disease; vascular disease; thorax disease; antimalarial agent; neoplasm; drug hypersensitivity; Article; skin disease; treatment duration; post hoc analysis; immunomodulating agent; connective tissue disease; genital system disease; infestation; mediastinum disease; urinary tract disease; opportunistic infection; prednisone; lymphatic system disease; hepatobiliary disease; phase 4 clinical trial; adverse drug reaction; breast disease; cyst; belimumab; autoantibody; non melanoma skin cancer; infusion related reaction; mortality rate; malignant neoplasm; all cause mortality; polyp