BENLYSTA: a guideline-recommended biologic for lupus and lupus nephritis

Recommended by ACR, EULAR, and KDIGO1-3

ACR Guidelines for lupus nephritis

EULAR Recommendations

KDIGO Guidelines

BENLYSTA: a guideline-recommended biologic for lupus and lupus nephritis

Recommended by ACR, EULAR, and KDIGO1-3

ACR Guidelines for lupus nephritis

EULAR Recommendations

KDIGO Guidelines

Select ACR Guidelines summary for lupus nephritis1

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 therapy

ACR conditionally recommends a triple immunosuppressive regimen consisting of pulse IV glucocorticoids (GCs) 250–1000 mg methylprednisolone daily x 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)
Icon: Inflammation in multiple organ systems

Extra-renal manifestations: lupus disease activity

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

These are selected guidelines, not the complete ACR guidelines. Full guidelines for lupus and lupus nephritis are pending release by ACR.

Adapted from the summary of the 2024 American College of Rheumatology Guidelines for Lupus Nephritis. 

* Recommended preferentially when significant extra-renal manifestations present.

† Recommended preferentially when proteinuria ≥3.0 g.

ACR = American College of Rheumatology; EULAR = European Alliance of Associations for Rheumatology; IV = intravenous; KDIGO = Kidney Disease Improving Global Outcomes.

Select treatment approach from the 2024 ACR Guidelines summary for lupus nephritis1,4

For the treatment of active, newly diagnosed, or flaring Class III/IV ± V lupus nephritis

Recommended approach from the 2024 ACR guidelines for lupus nephritis
Recommended approach from the 2024 ACR guidelines for lupus nephritis

‡ Discuss adjunctive treatments with systemic anticoagulation with nephrology for patients with LN and significant risk factors for thrombosis (e.g., low serum albumin in context of severe proteinuria).

§ Mycophenolic analogs (including MMF and MPA).

‖ Recommended preferentially when significant extrarenal manifestations present.

¶ Recommended preferentially when proteinuria ≥3.0 g.

** Substitute MPAA once low-dose CYC cycle is completed.

 

Goal: complete renal response (CRR)

  • Within 6–12 months, reduction in proteinuria to ≤0.5 g/g, and
  • Stabilization or improvement in kidney function (±20% baseline)

Duration of therapy: at least 3–5 years after achievement of CRR.

Glucocorticoids pulse/oral taper: pulse IV glucocorticoids (250–1000 mg methylprednisolone daily x 1–3 days) followed by oral glucocorticoids ≤0.5 mg/kg/day (maximum dose 40 mg/day) and taper to a target dose of ≤ 5mg/day by 6 months.

Low dose CYC: as per ELNT protocol, 500 mg IV CYC every 2 weeks for 6 doses.4

Dual therapy: glucocorticoid pulse/oral taper plus one immunosuppressive agent, usually MPAA or low-dose CYC.

These are selected guidelines, not the complete ACR guidelines. Full guidelines for lupus and lupus nephritis are pending release by ACR.

Adapted from the summary of the 2024 American College of Rheumatology Guidelines for Lupus Nephritis.

HCQ = hydroxychloroquine; LN = lupus nephritis; MMF = mycophenolate mofetil; MPA = mycophenolic acid; RAAS-I = renin-angiotensin-aldosterone system inhibitors.

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Summary of select 2023 EULAR recommendations2

Icon: Inflammation in multiple organ systems

Lupus

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

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

Steroids

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

Icon: Renal

Lupus nephritis

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

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

 
Icon: checkmark

BENLYSTA was acknowledged to have more than 10 years of real-life clinical experience2

EULAR recommendations in lupus nephritis2:

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.

Treatment of lupus nephritis

Chart of EULAR recommendations in lupus nephritis
Chart of EULAR recommendations in lupus nephritis

Used with permission from Fanouriakis A, et al. Ann Rheum Dis. 2024;83(1):15-29. © BMJ.

* In addition to general protective measures outlined in treatment of non-renal SLE treatment figure.

† Belimumab should always be given in combination with MMF or low-dose CYC as initial therapy, and with MMF or AZA as maintenance therapy.

‡ CNIs should be given in combination with MMF.

§ Particularly recommended in the presence of poor prognostic factors: reduced eGFR, histological presence of cellular crescents or fibrinoid necrosis, or severe interstitial inflammation.

¶ Extension of high-dose CYC to subsequent phase refers to severe lupus nephritis cases, in which bimonthly or quarterly CYC pulses may be given following 6 monthly pulses.

** In relapsing/refractory disease, especially after failure to CYC-based regimens.

ACEi = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; eGFR = estimated glomerular filtration rate; MP = methylprednisolone; SGLT2i = sodium glucose cotransporter-2 inhibitor; TAC = tacrolimus; UPr = urine protein; VOC = voclosporin.

Select overarching principles from the 2023 EULAR recommendations for lupus2

Select overarching principles from the EULAR 2023 lupus
recommendations
Select overarching principles from the EULAR 2023 lupus
recommendations

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Recommended approach for initial therapy of active Class III/IV lupus nephritis3

Graph of recommended approach for initial therapy of active Class III/IV lupus nephritis

These are only select guideline recommendations, not the complete KDIGO guidelines.

Caution is warranted when CNIs are used in patients with significantly impaired kidney function, in view of increased susceptibility for severe consequences due to CNI nephrotoxicity. The eGFR and SCr levels stated in the figure were patient selection criteria adopted in the respective clinical trials.

b.i.d. = twice daily; p.o. = oral; q2wk = every 2 weeks; q4wk = every 4 weeks; SCr = serum creatinine.

Icon: Patients

Choose BENLYSTA after HCQ* for patients with lupus.

* As part of standard therapy.

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BENLYSTA for Lupus

BENLYSTA improved key clinical outcomes for appropriate patients.

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BENLYSTA for lupus nephritis

BENLYSTA improved key clinical outcomes for appropriate patients.

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