Benlysta Adverse Reactions

Adults: The safety of BENLYSTA in patients with SLE has been evaluated in three pre-registration placebo-controlled intravenous studies, one placebo-controlled subcutaneous study, and one post-marketing placebo-controlled intravenous study; the safety in patients with active lupus nephritis has been evaluated in one placebo-controlled intravenous study.
The data described as follows reflect exposure in 674 patients with SLE administered to BENLYSTA intravenously (10 mg/kg over a 1-hour period on Days 0, 14, 28, and then every 28 days up to 52 weeks), and 556 patients with SLE administered BENLYSTA subcutaneously (200 mg once weekly up to 52 weeks). The safety data presented include data beyond Week 52 in some patients with SLE. The data reflect additional exposure in 224 patients with active lupus nephritis who received BENLYSTA intravenously (10 mg/kg for up to 104 weeks). Data from post-marketing reports are also included.
The majority of patients were also receiving one or more of the following concomitant treatments for SLE: corticosteroids, immunomodulatory agents, anti-malarials, non-steroidal anti-inflammatory drugs. Adverse reactions are listed as follows by MedDRA body system organ class and by frequency. The frequency categories used are: Very common ≥1 in 10, Common ≥1 in 100 and <1 in 10, Uncommon ≥1 in 1,000 and <1 in 100. (See Table 5.)

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Hypersensitivity reactions: Clinically significant hypersensitivity reactions associated with BENLYSTA and requiring permanent treatment discontinuation were reported in 0.4% of patients. These reactions were generally observed on the day of the infusion, and patients with a history of multiple drug allergies or significant hypersensitivity reactions may be at increased risk. Delay in the onset of acute hypersensitivity reactions for several hours after the infusion, and recurrence of clinically significant reactions after initial resolution of symptoms following appropriate treatment, have been observed. Delayed-type, non-acute hypersensitivity reactions have also been observed and included symptoms such as rash, nausea, fatigue, myalgia, headache, and facial oedema.
Infections: In the intravenous SLE pre-registration clinical studies, the overall incidence of infections was 70% in the group receiving belimumab and 67% in the group receiving placebo. Infections occurring in at least 3% of patients receiving belimumab and at least 1% more frequently than patients receiving placebo were nasopharyngitis, bronchitis, pharyngitis, cystitis, and gastroenteritis viral. Serious infections occurred in 5% of patients receiving either belimumab or placebo; serious opportunistic infections accounted for <1% and 0% of these, respectively. Some infections were severe or fatal.
In the randomised (1:1), double-blind, placebo-controlled, 52-week, post-marketing SLE safety study (BEL115467) which assessed mortality and specific adverse events in adults, serious infections occurred in 3.7% of patients receiving BENLYSTA 10 mg/kg intravenously and in 4.1% of patients receiving placebo. Fatal infections occurred in 0.45% (9/2002) of patients receiving BENLYSTA and in 0.15% (3/2001) of patients receiving placebo, while the incidence of all-cause mortality was 0.50% (10/2002) in patients receiving belimumab and 0.40% (8/2001) in patients receiving placebo.
In the lupus nephritis study, patients were receiving a background of standard therapy (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions) and the overall incidence of infections was 82% in patients receiving BENLYSTA compared with 76% in patients receiving placebo. Serious infections occurred in 13.8% of patients receiving BENLYSTA and in 17.0% of patients receiving placebo. Fatal infections occurred in 0.9% (2/224) of patients receiving BENLYSTA and in 0.9% (2/224) of patients receiving placebo.
Psychiatric disorders: In the pre-registration SLE intravenous clinical studies, serious psychiatric events were reported in 1.2% (8/674) of patients receiving BENLYSTA 10 mg/kg and 0.4% (3/675) of patients receiving placebo. Serious depression was reported in 0.6% (4/674) of patients receiving BENLYSTA 10 mg/kg and 0.3% (2/675) of patients receiving placebo. One suicide was reported in a patient receiving BENLYSTA 10 mg/kg (and one was reported in a patient receiving BENLYSTA 1 mg/kg); there were no reports in patients receiving placebo.
In the large post-marketing SLE study, serious psychiatric events were reported in 1.0% (20/2002) of patients receiving BENLYSTA and 0.3% (6/2001) of patients receiving placebo. Serious depression was reported in 0.3% (7/2002) of patients receiving BENLYSTA and <0.1% (1/2001) receiving placebo. The overall incidence of serious suicidal ideation or behaviour or self-injury without suicidal intent was 0.7% (15/2002) in the BENLYSTA group and 0.2% (5/2001) in the placebo group. On the Columbia-Suicide Severity Rating Scale (C-SSRS), 2.4% (48/1974) of patients receiving BENLYSTA reported suicidal ideation or behaviour compared with 2.0% (39/1988) of patients receiving placebo. No suicide was reported in either group.
The SLE intravenous studies did not exclude patients with a history of psychiatric disorders.
In the subcutaneous SLE clinical study, which excluded patients with a history of psychiatric disorders, serious psychiatric events were reported in 0.2% (1/556) of patients receiving BENLYSTA and in no patients receiving placebo. There were no serious depression-related events or suicides reported in either group. On the C-SSRS, 1.3% (7/554) of patients receiving BENLYSTA reported suicidal ideation or behaviour and 0.7% (2/277) of patients receiving placebo.