Treatment Guidelines

BENLYSTA is the only biologic recommended by all major guidelines for early* treatment of both SLE and LN1-5

Recommended by ACR, EULAR, and KDIGO1-5

*When HCQ alone isn't enough in SLE, and as part of initial treatment in lupus nephritis.

LUPUS RECOMMENDATIONS & GUIDELINES
LUPUS NEPHRITIS RECOMMENDATIONS & GUIDELINES

Add BENLYSTA early after hydroxychloroquine* in patients with lupus

See how leading guidelines position BENLYSTA

* As part of standard therapy. 

ACR = American College of Rheumatology; EULAR = European Alliance of Associations for Rheumatology; KDIGO = Kidney Disease: Improving Global Outcomes; LN = lupus nephritis; SLE = systemic lupus erythematosus. 

Recommendations and guidelines for lupus 

Select 2025 ACR guidelines for lupus1

Implement guidelines to optimize lupus care across patient needs 

The 2025 ACR guidelines emphasize early, individualized treatment of lupus to control disease activity and minimize glucocorticoid exposure.1

The ACR guidelines include early introduction of biologics such as BENLYSTA.1

ACR recommends1: 

  • Universal use of hydroxychloroquine 
  • Minimizing glucocorticoid exposure 
  • Early introduction of conventional and/or biologic
  • immunosuppressive therapies

The 2025 ACR guidelines conditionally recommend tapering immunosuppressives after 3–5 years in stable patients.1 

The 2025 ACR guidelines endorse early consideration of conventional or biologic immunosuppressive therapies such as BENLYSTA when lupus disease activity in organ systems is refractory to initial therapy.1 

Select recommendations from the 2025 ACR guidelines for lupus: from disease monitoring to comprehensive treatment strategies

Treatment goals and medication guidance1

 

  • Aim for optimal control: achieving remission or low disease activity to improve long-term outcomes 
  • Glucocorticoids: use lowest dose for the shortest duration; minimize glucocorticoid-related toxicity by early introduction of immunosuppressive therapies 
  • Immunosuppressive therapy: conditionally taper after 3–5 years in patients with stable disease who have achieved sustained remission or low disease activity 
  • Organ damage monitoring: conditionally recommended to assess organ damage (SDI) annually in patients with SLE  

Individualized, shared decision-making is essential to respecting patient values and preferences in lupus treatment.1

    Adapted from the 2025 American College of Rheumatology guidelines for systemic lupus erythematosus. 

    SEE THE FULL 2025 ACR GUIDELINES FOR LUPUS

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    Ready to see how these recommendations extend to lupus nephritis? 

    JUMP TO THE ACR GUIDELINES FOR LUPUS NEPHRITIS

    Summary of select 2023 EULAR recommendations for lupus2

    Lupus 

    Consider adding biologics, such as BENLYSTA (belimumab) or anifrolumab, after HCQ: 

    • If not responding to HCQ (alone or in combination with GC) 
    • Or if unable to taper steroids below doses acceptable for chronic use 

    Steroids 

    Maintenance steroid dose should be ≤5 mg/day and, when possible, withdrawn. 

    These are only select recommendations, not the complete EULAR recommendations. 
     
    GC = glucocorticoid; HCQ = hydroxychloroquine. 

    Supported by more than 10 years of real-life clinical experience with BENLYSTA in SLE as recognized by EULAR2 

    Select overarching principles from the 2023 EULAR recommendations for lupus2

    Lupus requires multidisciplinary, individualized management with patient education and shared decision-making, taking into consideration the costs to patient and society. 

    Lupus disease activity should be assessed at each clinic visit (the frequency depending on physician's discretion), with evaluation of organ damage (at least annually), using validated instruments. 

    Non-pharmacological interventions, including sun protection, smoking cessation, a healthy, balanced diet, regular exercise, and measures to promote bone health are important to improve long-term outcomes.  


    Selected pharmacological interventions directed by: 

     

    • Patient characteristics and preferences 
    • Comorbidities 
    • Type and severity of organ involvement 
    • Risk for progressive organ damage 
    • Treatment-related harms 

    To prevent flares and organ damage, improve prognosis, and enhance quality of life, the following are essential: 

     

    • Early lupus diagnosis (including serological assessment) 
    • Regular screening for organ involvement (especially nephritis) 
    • Prompt initiation of treatment aiming at remission (or low disease activity if this is not possible)
    •  Strict adherence to treatment 

      SEE THE FULL 2023 EULAR RECOMMENDATIONS

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      Looking for EULAR recommendations on lupus nephritis? 

      JUMP TO RECOMMENDATIONS ON LUPUS NEPHRITIS

      Use BENLYSTA early as part of initial therapy in patients with lupus nephritis 

      See where BENLYSTA fits in expert recommendations 

      Recommendations and guidelines for lupus nephritis

      2024 ACR guidelines for lupus nephritis3 

      BENLYSTA has been recommended as part of first-line therapy

      In patients with active, newly diagnosed, or flaring Class III/IV ± V lupus nephritis:

      First-line triple therapy3

      ACR conditionally recommends a triple immunosuppressive regimen consisting of pulse IV glucocorticoids (GCs) 250–1000 mg methylprednisolone daily for 1–3 days, followed by oral GC ≤0.5 mg/kg/day (maximum dose 40 mg/day) with taper to a target dose of ≤5 mg/day by 6 months plus: 

      • Mycophenolic acid analogs (MPAA) plus BENLYSTA,* or 
      • MPAA plus a calcineurin inhibitor (CNI),† or 
      • Euro-Lupus Nephritis Trial (ELNT) low-dose cyclophosphamide (CYC) plus BENLYSTA (MPAA substituted for CYC after CYC course complete) 

      Extra-renal manifestations: lupus disease activity3 

      With moderate to severe extra-renal manifestations, ACR conditionally recommends a triple immunosuppressive regimen that contains BENLYSTA. 

      BENLYSTA is preferred over CNIs in select patient subgroups3:

      BENLYSTA is conditionally recommended over CNIs for patients with:

      • eGFR ≤45 
      • Blood pressure >165/105
      •  Significant chronicity on kidney biopsy 

       

      In these subgroups of patients, ACR recommends BENLYSTA over a CNI regimen because of potential CNI-associated nephrotoxicity and hypertension.  

      Therapy should be maintained for at least 3–5 years after achievement of complete renal response (CRR) to help sustain remission.  

       

      Complete renal response (CRR): within 6–12 months of starting therapy (may take >12 months):

      • Reduction in proteinuria <0.5 g/g (50 mg/mmol) (24-hour collection or urine protein/creatinine ratio); AND
      • Stabilization or improvement in kidney function (+20% baseline, ie, at least 80% of baseline)

      These are selected guidelines, not the complete ACR guidelines.  

      * Recommended preferentially when significant extra-renal manifestations present.

      † Recommended preferentially when proteinuria ≥3.0 g.

      eGFR = estimated glomerular filtration rate.

        SEE THE FULL 2024 ACR LN GUIDELINES

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        Clinical trial data for BENLYSTA contributed to its inclusion in recommended triple therapy regimens for lupus nephritis 

        DIVE DEEPER INTO THE DATA

        EULAR recommendations in lupus nephritis5 

        According to EULAR, changes in the treatment landscape have inspired discussions on a “paradigm shift” in the treatment of lupus nephritis, moving from the traditional “induction-maintenance” regimen to the early use of combination therapies.

        Consider the  addition of BENLYSTA or CNIs  at the beginning of treatment  for ALL patients with active proliferative lupus nephritis.5  

        Following renal response, continue treatment for at least 3 years.5 

          SEE THE FULL 2023 EULAR RECOMMENDATIONS

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          2024 KDIGO guidelines summary4

          KDIGO guidelines recommend that patients with active Class III or IV lupus nephritis, with or without a membranous component, be treated initially with glucocorticoids plus one of the following4: 

           

          • Mycophenolic acid analogs (MPAA) (1B); or 
          • Low-dose IV cyclophosphamide (CYC) (1B); or 
          • BENLYSTA  and either MPAA or low-dose IV CYC (1B); or 
          • MPAA and a calcineurin inhibitor (CNI) when kidney function is not severely impaired (1B) 

          Patients treated with triple immunosuppressive regimens that include BENLYSTA (belimumab) or a CNI, in addition to standard maintenance immunosuppression, can be continued for 2–3 years.4 

          A triple immunosuppressive regimen of BENLYSTA with glucocorticoids and either MPAA or reduced-dose cyclophosphamide may be preferred in patients with repeated kidney flares or at high risk of progression to kidney failure due to severe chronic kidney disease.4 

            SEE THE FULL 2024 KDIGO GUIDELINES

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            Choose BENLYSTA after HCQ* in lupus and as part of initial therapy in lupus nephritis

            * As part of standard therapy. 

            Learn more

            BENLYSTA for lupus 

            BENLYSTA improved key clinical outcomes for appropriate patients.

            SEE EFFICACY DATA

            BENLYSTA for lupus nephritis 

            BENLYSTA improved key clinical outcomes for appropriate patients. 

            SEE LN EFFICACY DATA

            Indication & Safety Info

            Indication

            Important Safety Information

            Indication

            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.

            Important Safety Information

            CONTRAINDICATION

            Previous anaphylaxis with BENLYSTA.

            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.

             

            ADVERSE REACTIONS

            The most common serious adverse reactions in adult SLE clinical trials were serious infections; some were fatal. The most common adverse reactions (≥5%) were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous injection).

             

            Adverse reactions reported in clinical trials with SLE pediatric patients (≥5 years) and adult patients with lupus nephritis were consistent with those observed in adult SLE trials.

             

            USE IN SPECIFIC POPULATIONS

            Pregnancy: There are insufficient data in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. After a risk/benefit assessment, if prevention is warranted, women of childbearing potential should use contraception during treatment and for ≥4 months after the final treatment.

             

            Pregnancy Registry: HCPs are encouraged to refer patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/benlysta-belimumab/.

             

            Please see full Prescribing Information and Medication Guide for BENLYSTA.

            To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249, or
            FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

            References

            1. Sammaritano LR, Askanase A, Bermas BL, et al. 2025 American College of Rheumatology (ACR) guideline for the treatment of systemic lupus erythematosus. Arthritis Care Res (Hoboken). Published online November 3, 2025. doi:10.1002/acr.25690 

            2. Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83(1):15-29. 

            3. Sammaritano LR, Askanase A, Bermas BL, et al. 2024 American College of Rheumatology (ACR) guideline for the screening, treatment, and management of lupus nephritis. Arthritis Rheumatol. 2025;1115-1135. 

            4. Kidney Disease: Improving Global Outcomes. KDIGO 2024 clinical practice guideline for the management of lupus nephritis. Kidney Int. 2024;105(1S):S1-S69. 

            5. Fanouriakis A, Kostopoulou M, Andersen J, et al. EULAR recommendations for the management of systemic lupus erythematosus with kidney involvement: 2025 update. Ann Rheum Dis. 2026;85(1):75-90. 

            6. Houssiau FA, Vasconcelos C, D’Cruz D, et al. Immunosuppressive therapy in lupus nephritis: the Euro-Lupus Nephritis Trial, a randomized trial of low-dose versus high-dose intravenous cyclophosphamide. Arthritis Rheumatol. 2002;46(8):2121-2131.