Table 4. Summary of AEs and AESI for year 1 and years 1 + 2 (ITT population; N=292).
| Number of patients (%) | ||||||
| Year 1 (on-treatment*) | Year 1+2 (on-study†) | |||||
| BEL/PBO(n=72) | BEL/RTX(n=144) | BEL/ST‡(n=76) | BEL/PBO(n=72) | BEL/RTX(n=144) | BEL/ST‡(n=76) | |
| AEs, n (%) | ||||||
| Any event | 63 (87.5) | 127 (88.2) | 62 (81.6) | 63 (87.5) | 132 (91.7) | 64 (84.2) |
| AEs by SOC occurring in ≥5% of patients in any treatment group | ||||||
| Infections and infestations | 41 (56.9) | 85 (59.0) | 43 (56.6) | 44 (61.1) | 100 (69.4) | 46 (60.5) |
| Musculoskeletal and connective tissue disorders | 18 (25.0) | 38 (26.4) | 21 (27.6) | 21 (29.2) | 49 (34.0) | 24 (31.6) |
| Gastrointestinal disorders | 20 (27.8) | 42 (29.2) | 12 (15.8) | 21 (29.2) | 51 (35.4) | 18 (23.7) |
| Nervous system disorders | 17 (23.6) | 40 (27.8) | 14 (18.4) | 21 (29.2) | 48 (33.3) | 17 (22.4) |
| General disorders and administration site conditions | 18 (25.0) | 32 (22.2) | 16 (21.1) | 22 (30.6) | 40 (27.8) | 18 (23.7) |
| Skin and subcutaneous tissue disorders | 7 (9.7) | 31 (21.5) | 7 (9.2) | 12 (16.7) | 39 (27.1) | 9 (11.8) |
| Respiratory, thoracic and mediastinal disorders | 10 (13.9) | 21 (14.6) | 4 (5.3) | 10 (13.9) | 25 (17.4) | 9 (11.8) |
| Psychiatric disorders | 12 (16.7) | 20 (13.9) | 4 (5.3) | 12 (16.7) | 25 (17.4) | 6 (7.9) |
| Injury, poisoning and procedural complications | 8 (11.1) | 17 (11.8) | 6 (7.9) | 10 (13.9) | 23 (16.0) | 9 (11.8) |
| Blood and lymphatic system disorders | 5 (6.9) | 17 (11.8) | 8 (10.5) | 6 (8.3) | 22 (15.3) | 9 (11.8) |
| Vascular disorders | 5 (6.9) | 16 (11.1) | 6 (7.9) | 7 (9.7) | 20 (13.9) | 7 (9.2) |
| Eye disorders | 6 (8.3) | 11 (7.6) | 1 (1.3) | 6 (8.3) | 19 (13.2) | 3 (3.9) |
| Investigations | 7 (9.7) | 9 (6.3) | 4 (5.3) | 7 (9.7) | 13 (9.0) | 5 (6.6) |
| Reproductive system and breast disorders | 3 (4.2) | 9 (6.3) | 2 (2.6) | 5 (6.9) | 14 (9.7) | 3 (3.9) |
| Renal and urinary disorders | 3 (4.2) | 3 (2.1) | 6 (7.9) | 4 (5.6) | 6 (4.2) | 7 (9.2) |
| Cardiac disorders | 2 (2.8) | 6 (4.2) | 3 (3.9) | 2 (2.8) | 6 (4.2) | 5 (6.6) |
| Ear and labyrinth disorders | 0 (0.0) | 6 (4.2) | 0 (0.0) | 1 (1.4) | 8 (5.6) | 1 (1.3) |
| Metabolism and nutrition disorders | 4 (5.6) | 2 (1.4) | 2 (2.6) | 4 (5.6) | 3 (2.1) | 3 (3.9) |
| AE related to BEL | 24 (33.3) | 47 (32.6) | 23 (30.3) | 25 (34.7) | 52 (36.1) | 29 (38.2) |
| AE related to RTX | 12 (16.7) | 46 (31.9) | 0 (0.0) | 12 (16.7) | 46 (31.9) | 0 (0.0) |
| AE resulting in discontinuation and/or withdrawal | ||||||
| AE resulting in BEL discontinuation | 5 (6.9) | 13 (9.0) | 3 (3.9) | 7 (9.7) | 14 (9.7) | 4 (5.3) |
| AE resulting in RTX discontinuation | 0 (0.0) | 7 (4.9) | 0 (0.0) | 0 (0.0) | 7 (4.9) | 0 (0.0) |
| AE resulting in study withdrawal | 2 (2.8) | 4 (2.8) | 1 (1.3) | 3 (4.2) | 6 (4.2) | 1 (1.3) |
| Serious AEs | 8 (11.1) | 25 (17.4) | 10 (13.2) | 10 (13.9) | 32 (22.2) | 15 (19.7) |
| Serious AEs by SOC occurring in ≥2% of patients in any treatment group | ||||||
| Infections and infestations | 2 (2.8) | 8 (5.6) | 1 (1.3) | 2 (2.8) | 13 (9.0) | 4 (5.3) |
| Blood and lymphatic system disorders | 1 (1.4) | 3 (2.1) | 2 (2.6) | 1 (1.4) | 4 (2.8) | 2 (2.6) |
| Cardiac disorders | 2 (2.8) | 0 (0.0) | 2 (2.6) | 2 (2.8) | 0 (0.0) | 3 (3.9) |
| Musculoskeletal and connective tissue disorders | 0 (0.0) | 4 (2.8) | 0 (0.0) | 1 (1.4) | 4 (2.8) | 1 (1.3) |
| Vascular disorders | 1 (1.4) | 3 (2.1) | 0 (0.0) | 1 (1.4) | 3 (2.1) | 0 (0.0) |
| Injury, poisoning and procedural complications | 1 (1.4) | 0 (0.0) | 2 (2.6) | 1 (1.4) | 0 (0.0) | 2 (2.6) |
| Nervous system disorders | 0 (0.0) | 1 (0.7) | 2 (2.6) | 0 (0.0) | 1 (0.7) | 2 (2.6) |
| Severe AEs | 9 (12.5) | 20 (13.9) | 10 (13.2) | 10 (13.9) | 28 (19.4) | 12 (15.8) |
| AEs of special interest | ||||||
| All malignancies§ ¶ | 0 (0.0) | 0 (0.0) | 1 (1.3) | 1 (1.4) | 1 (0.7) | 1 (1.3) |
| Postinjection systemic reactions | 7 (9.7) | 16 (11.1) | 3 (3.9) | 7 (9.7) | 19 (13.2) | 4 (5.3) |
| All infections of special interest§ | 4 (5.6) | 6 (4.2) | 1 (1.3) | 5 (6.9) | 12 (8.3) | 5 (6.6) |
| Serious infections of special interest§ ** | 0 (0.0) | 1 (0.7) | 0 (0.0) | 0 (0.0) | 1 (0.7) | 0 (0.0) |
| Opportunistic infections†† | 1 (1.4) | 2 (1.4) | 0 (0.0) | 1 (1.4) | 2 (1.4) | 0 (0.0) |
| Active tuberculosis§ | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| All herpes zoster§ | 2 (2.8) | 5 (3.5) | 1 (1.3) | 2 (2.8) | 6 (4.2) | 1 (1.3) |
| Non-opportunistic herpes zoster†† | 2 (2.8) | 3 (2.1) | 1 (1.3) | 2 (2.8) | 4 (2.8) | 1 (1.3) |
| Opportunistic herpes zoster†† ‡‡ | 0 (0.0) | 2 (1.4) | 0 (0.0) | 0 (0.0) | 2 (1.4) | 0 (0.0) |
| Recurrent herpes zoster†† | 0 (0.0) | 2 (1.4) | 0 (0.0) | 0 (0.0) | 2 (1.4) | 0 (0.0) |
| Sepsis§ | 0 (0.0) | 1 (0.7) | 0 (0.0) | 0 (0.0) | 1 (0.7) | 0 (0.0) |
| Depression (inc. mood disorders and anxiety)/suicide/self-injury | 9 (12.5) | 13 (9.0) | 4 (5.3) | 9 (12.5) | 16 (11.1) | 5 (6.6) |
| Serious depression | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (0.7) | 0 (0.0) |
| Serious suicide/self-injury | 1 (1.4) | 1 (0.7) | 0 (0.0) | 1 (1.4) | 1 (0.7) | 1 (1.3) |
| Suicidal behaviour | 1 (1.4) | 1 (0.7) | 0 (0.0) | 1 (1.4) | 1 (0.7) | 1 (1.3) |
| Deaths | 0 (0.0) | 1 (0.7)§§ | 0 (0.0) | 1 (1.4)¶¶ | 2 (1.4)*** | 0 (0.0) |
Note: patients were counted only once in each row and column for which they have any AE meeting the criterion.
On treatment was defined as from first dose of belimumab to the latter of: last dose of belimumab+28 days or last dose of rituximab+28 days.
On study was defined as from the first dose of belimumab until the date of study completion or study withdrawal (including lost to follow-up and death).
ST included corticosteroids, antimalarials, immunosuppressants, and NSAIDs.
Per Custom MedDRA query (version 24.0).
Year 1: malignancy (stage 0 cervix carcinoma) reported in 1 patient in the BEL/ST group; year 1 + 2: malignant neoplasm (solid tumour) reported in 1 patient in each treatment group.
Opportunistic infections, herpes zoster, tuberculosis and sepsis.
Per sponsor adjudication.
Defined as non-recurrent or non-disseminated.
One death while off-treatment but on-study was reported in BEL/RTX group 94 days after the first dose of study treatment and 65 days after the most recent dose of study treatment in a patient with severe pneumonia.
The fatal SAE of cholangiocarcinoma started on study but the death occurred after the patient was withdrawn from the study. This patient also experienced another fatal SAE of septic shock that started while patient was not on study.
The fatal SAEs of pneumonia and sudden death occurred on study.
AE, adverse event; AESI, adverse events of special interest; BEL, belimumab; HZ, herpes zoster; ITT, intention-to-treat; NSAIDs, non-steroidal anti-inflammatory drugs; PBO, placebo; RTX, rituximab; SAE, serious adverse event; SC, subcutaneous; SOC, system organ class; ST, standard therapy