Summary of the safety profile The safety of belimumab in patients with SLE has been evaluated in three pre- registration placebo-controlled intravenous studies and one subsequent regional placebo-controlled intravenous study, one placebo-controlled subcutaneous study, and two post-marketing placebo-controlled intravenous studies; the safety in patients with active lupus nephritis has been evaluated in one placebo-controlled intravenous study.
The data presented in the table below reflect exposure in 674 patients with SLE from the three pre-registration clinical studies and 470 patients in the subsequent placebo- controlled study administered Benlysta intravenously (10 mg/kg body weight over a 1-hour period on Days 0, 14, 28, and then every 28 days for up to 52 weeks), and 556 patients with SLE exposed to 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 body weight 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 medicinal products, anti-malarials, non-steroidal anti-inflammatory medicinal products.
Adverse reactions were reported in 84 % of Benlysta-treated patients and 87 % of placebo-treated patients. The most frequently reported adverse reaction (≥ 5 % of patients with SLE treated with Benlysta plus standard of care and at a rate ≥ 1 % greater than placebo) was nasopharyngitis.
The proportion of patients who discontinued treatment due to adverse reactions was 7 % for Benlysta-treated patients and 8 % for placebo-treated patients. The most frequently reported adverse reactions (> 5 % of patients with active lupus nephritis treated with Benlysta plus standard of care) were upper respiratory tract infection, urinary tract infection, and herpes zoster.
9 % for placebo-treated patients. 4). Tabulated list of adverse reactions Adverse reactions are listed below by MedDRA system organ class and by frequency.
The frequency categories used are:
Very common ≥ 1/10 Common ≥ 1/100 to < 1/10 Uncommon ≥ 1/1000 to < 1/100 Rare ≥ 1/10 000 to < 1/1000 Not known cannot be estimated from the available data. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
The frequency given is the highest seen with either formulation. g. 4 ‘Infections’ for further information. 2 ‘Hypersensitivity reactions’ covers a group of terms, including anaphylaxis, and can manifest as a range of symptoms including hypotension, angioedema, urticaria or other rash, pruritus, and dyspnoea.
‘Infusion or injection-related systemic reactions’ covers a group of terms and can manifest as a range of symptoms including bradycardia, myalgia, headache, rash, urticaria, pyrexia, hypotension, hypertension, dizziness, and arthralgia.
Due to overlap in signs and symptoms, it is not possible to distinguish between hypersensitivity reactions and infusion or injection-related systemic reactions in all cases. 3 Applies to subcutaneous formulation only. Description of selected adverse reactions Data presented below are pooled from the three pre-registration intravenous clinical studies (10 mg/kg body weight intravenous dose only) and the subcutaneous clinical study.
‘Infections’ and ‘Psychiatric disorders’ also include data from a post-marketing study.
Infusion or injection-related systemic reactions and hypersensitivity:
Infusion or injection-related systemic reactions and hypersensitivity were generally observed on the day of administration, but acute hypersensitivity reactions may also occur several days after dosing. Patients with a history of multiple drug allergies or significant hypersensitivity reactions may be at increased risk.
3 %, respectively, requiring permanent treatment discontinuation. The incidence of post-injection systemic reactions and hypersensitivity reactions occurring within 3 days of subcutaneous administration was 7 % in the group receiving Benlysta and 9 % in the group receiving placebo.
Clinically significant hypersensitivity reactions associated with Benlysta administered subcutaneously and requiring permanent treatment […]