GSK Benlysta (beliumumab) Monograph – 2025 Edition

Published: September 29, 2025

Benlysta (belimumab) was originally approved by the U.S. Food and Drug Administration (FDA) in March 2011 for the treatment of lupus. Since then, the approval has expanded to include not only active systemic lupus erythematosus and active lupus nephritis in adults, but also pediatric patients five years and older with those forms of lupus.

In June 2025, the FDA approved the 200 mg/mL autoinjector of Benlysta for patients five years and older with active lupus nephritis who are receiving standard therapy. Previously, in May 2024, the autoinjector was approved for the same age demographic for active systemic lupus erythematosus.

Benlysta is a B-lymphocyte stimulator-specific inhibitor, currently available as an intravenous infusion or subcutaneous injection.

Medication Overview:

Brand Name: Benlysta
Generic Name: belimumab
Treatment for: Active systemic lupus erythematosus / Active lupus nephritis
Manufacturer(s): GSK
Initial FDA Approval: March 2011

Benlysta Indications Overview

Indicated Condition	Indication	Age	Initial Approval
Active Systemic Lupus Erythematosus	BENLYSTA is indicated for patients aged ≥5 with active systemic lupus erythematosus (SLE) or active lupus nephritis who are receiving standard therapy. BENLYSTA is not recommended in patients with severe active central nervous system lupus.	5 and older	March 2011
Active Lupus Nephritis	BENLYSTA is indicated for patients aged ≥5 with active systemic lupus erythematosus (SLE) or active lupus nephritis who are receiving standard therapy. BENLYSTA is not recommended in patients with severe active central nervous system lupus.	5 and older	December 2020

Warnings and Precautions:

Serious Infections: Serious and sometimes fatal infections have been reported and occurred more frequently with Benlysta. Use caution in patients with severe or chronic infections, and consider interrupting therapy in patients with a new infection.

Progressive Multifocal Leukoencephalopathy (PML): Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported. If PML is suspected, immunosuppressant therapy, including Benlysta, must be suspended until PML is excluded. If confirmed, stop immunosuppressant therapy, including Benlysta.

Hypersensitivity Reactions (Including Anaphylaxis): Acute hypersensitivity reactions, including anaphylaxis and death, and infusion-related reactions have been reported. Generally, reactions occurred within hours of the infusion but may occur later, including in patients who have previously tolerated Benlysta. Non-acute hypersensitivity reactions (eg, rash, nausea, fatigue, myalgia, headache, and facial edema) typically occurred up to a week after infusion. Monitor patients during and after treatment and be prepared to manage anaphylaxis and infusion-related reactions. Be aware of the risk of hypersensitivity reactions, which may present as infusion-related reactions. Discontinue immediately in the event of a serious reaction. With intravenous administration, if an infusion reaction develops, slow or interrupt the infusion.

Depression and Suicidality: Depression and suicidality were reported in patients receiving Benlysta. Before adding Benlysta, assess patients’ risk of depression and suicide and monitor them during treatment. Instruct patients/caregivers to contact their HCP if they experience new/worsening depression, suicidal thoughts/behavior, or other mood changes.

Malignancy: There is an increased risk of malignancies with the use of immunosuppressants. The impact of Benlysta on the development of malignancies is unknown.

Immunization: Live vaccines should not be given for 30 days before or concurrently with Benlysta as clinical safety has not been established.

Use With Biologic Therapies: Available data do not support the safety and efficacy of concomitant use of Benlysta with rituximab in patients with SLE. An increased incidence of serious infections and post-injection systemic reactions in patients receiving Benlysta concomitantly with rituximab compared to patients receiving Benlysta alone has been observed. The safety and efficacy of Benlysta concomitantly with other biologic therapies, including B-cell-targeted therapies, have not been established. Caution should be exercised if Benlysta is administered in combination with other biologic therapies.

Dosage and Administration:

Benlysta Autoinjector Dosing

For active lupus:

Pediatric patients ≥5 years weighing 15 kg to <40 kg: 200 mg once every two weeks.
Adult and pediatric (≥5 years weighing ≥40 kg) patients: 200 mg once per week.

For active lupus nephritis:

Pediatric patients ≥5 years weighing 15 kg to <40 kg: 200 mg once per week for four doses; then 200 mg one every two weeks.
Adult and pediatric (≥5 years weighing ≥40 kg) patients: 2 x 200 mg once per week for four doses; then 200 mg once per week.

Benlysta IV Dosing

Recommended IV dosing in patients five years and older with active lupus or active lupus nephritis:

Benlysta IV is administered as a one-hour infusion. 10 mg/kg is administered every two weeks for the first three doses and every four weeks thereafter.

Contraindications:

Previous anaphylaxis with Benlysta.

Drug Interactions:

Formal drug interaction studies have not been performed with Benlysta. In clinical trials, Benlysta was administered concomitantly with other drugs, including corticosteroids, antimalarials, immunomodulatory and immunosuppressive agents (including azathioprine, cyclophosphamide, methotrexate, and mycophenolate), angiotensin pathway antihypertensives, HMG-CoA reductase inhibitors (statins), and/or non-steroidal anti-inflammatory drugs (NSAIDs) without evidence of a clinically meaningful effect of these concomitant medications on belimumab pharmacokinetics. The effect of belimumab on the pharmacokinetics of other drugs has not been evaluated.

Adverse Reactions:

Common adverse reactions (≥5%): nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous administration).

Examples of Belimumab in Guidelines

Screening, Treatment, and Management of Lupus Nephritis
American College of Rheumatology (ACR), September 2025

“In people with active, new onset, or flare of Class III/IV (with or without concomitant Class V) LN: We conditionally recommend therapy with a triple immunosuppressive regimen consisting of pulse intravenous glucocorticoids (250–1000 mg methylprednisolone daily × 1–3 days) followed by oral glucocorticoid (≤0.5 mg/kg/day, maximum dose 40 mg/day) taper, plus: Mycophenolic acid analogs (including mycophenolate mofetil, or MMF, and mycophenolic acid, or MPA) (MPAA) –or MPAA plus calcineurin inhibitor therapies (cyclosporine, tacrolimus, voclosporin) (CNI) –or Euro-Lupus Nephritis Trial (ELNT) low-dose cyclophosphamide (CYC) plus belimumab (MPAA substituted for CYC after CYC course is complete).”
Summary
Full Text

Management of Systemic Lupus Erythematosus
European League Against Rheumatism (EULAR), October 2023

“In patients not responding to hydroxychloroquine (alone or in combination with glucocorticoids) or patients unable to reduce glucocorticoids below doses acceptable for chronic use, addition of immunomodulating/immunosuppressive agents (eg, methotrexate (1b/B), azathioprine (2b/C) or mycophenolate (2a/B)) and/or biological agents (eg, belimumab (1a/A) or anifrolumab (1a/A)) should be considered.”
Summary
Full Text

Please note: This article is current as of September 27, 2025. Consult our clinical guidelines library or drug information tool to ensure you always have the most up-to-date information.