腎臟科 紀竣議 醫師臺大醫院雲林分院 National Taiwan University Hospital, Yunlin BranchSponsored by GSK. The speaker has received honoraria from GSK for speaking engagements and is not an employee of GSK. GSK does not recommend any use outside the approved package inserts; refer to the TFDA-approved prescribing information. This talk cites guideline positions (ACR 2024 / EULAR 2025 / KDIGO 2024) that differ from the TFDA indications and NHI reimbursement criteria — some uses described are off-label in Taiwan. Content reviewed 2026-09-05; regulatory checks are dated on the relevant slides. Verify current TFDA/NHI rules and local formulary. Educational content remains subject to local medical/legal/regulatory review.
2026
Outline
大綱
016 min
Where LN stands in 2026Outcomes, targets, and three guidelines: ACR 2024 · EULAR 2025 · KDIGO 2024
026 min
The kidney biopsyIndications, classification, activity/chronicity, repeat biopsy, adequacy
Belimumab in practiceBLISS-LN, East Asian subgroup, Japan LOOPS registry, safety, dosing, 健保給付條件
058 min
Case sharing兩例在雲林分院接受 belimumab 的 LN 病人與追蹤結果
Outline40 min + Q & A
Section 01
Where LN Stands in 2026
疾病規模、現有治療的天花板、治療目標 — 以及三份指引指向同一個方向
01 · Where LN stands
Lupus Nephritis: Scale of the Problem
40–60%of patients with SLE develop kidney involvement; estimates vary by cohort and follow-up
10–30%of LN progress to kidney failure over long-term follow-up; risk varies by cohort and treatment era
12 moproteinuria <0.8 g/day — the single best predictor of good 7-year kidney outcome; months 3–12 carry the trajectory
—Kidney involvement can be the first manifestation of SLE, and may be clinically silent — screen even when symptoms are limited.
—Many Asian cohorts report more proliferative disease and worse renal outcomes; avoid treating this as a universal individual-level prediction.
Almaani S, et al. Clin J Am Soc Nephrol 2017;12(5):825–35 · Anders HJ, et al. Nat Rev Dis Primers 2020;6:7 · Dall'Era M, et al. Arthritis Rheumatol 2015;67(5):1305–1304
01 · Where LN stands
The Unmet Need Behind Standard of Care
—In AURORA 1, the control regimen had CRR below 25% at week 52; the voclosporin regimen reached about 41%.
—Relapse after remission remains common and each flare adds chronic damage.
—Cumulative glucocorticoid exposure drives infection, bone loss and metabolic damage.
—Delay between clinical suspicion and definitive therapy is still measured in months.
Trial comparison, not a universal dual-versus-triple response rate; endpoint was CRR at week 52.
Rovin BH, et al. Lancet 2021;397:2070–80 (AURORA 1)05
01 · Where LN stands
Treatment Targets and Milestones
MONTH 3≥25% drop in proteinuriaComplement and anti-dsDNA trends are supportive monitoring, not formal EULAR response thresholds
MONTH 6≥50% drop in proteinuriaPrednisone ≤5 mg/day — ACR target · EULAR 2025 ≤5 mg/d by 4–6 mo
MONTH 12Proteinuria <0.7 g/gStable or improving eGFR
YEAR 3+Sustained complete responseThen discuss withdrawal individually
Missing or plateauing at a milestone prompts reassessment — adherence, dose, pathology, alternative diagnoses and complications — not automatic escalation.
COMMON GROUND — AND WHERE THEY PARTBiopsy early, combine when appropriate, taper steroids, treat long. The live disagreement: how many agents to start with — and how fast new data should change that.
WHAT 2018 CHANGEDThe A / C / A+C suffixes and the IV-S / IV-G split were retired. A modern report states the class plus the activity and chronicity indices — the next slide.若報告仍寫 IV-G(A) 為舊格式，可請病理科補 AI / CI 指數。
ISN/RPS 2003, revised 2018 — Bajema IM, et al. Kidney Int 2018;93(4):789–9611
CHRONICITY · 0–12Global/segmental glomerulosclerosis, fibrous crescents, tubular atrophy, interstitial fibrosisHigher chronicity predicts poorer prognosis and limits reversibility. EULAR 2025 lists high chronicity and tubulointerstitial lesions as adverse factors, but active lesions can coexist and remain treatable — CI alone is not a treatment cutoff.
Treat the active component and protect the remaining kidney — integrate AI, CI, eGFR trajectory, treatment risk and patient goals. No universal CI threshold replaces that assessment.
Bajema IM, et al. Kidney Int 2018;93:789–96 · KDIGO 202412
02 · Kidney biopsy
The Biopsy Is a Repeatable Measurement
WHY CLINICAL RESPONSE IS NOT ENOUGH
—Clinical and histologic response diverge in both directions — proteinuria can persist after inflammation resolves, or fall while it persists. That is the reason to look again.
—Residual proteinuria with a scarred biopsy → RAAS/SGLT2i, not more immunosuppression.
—Anti-CD20 programmes now report histologic endpoints — emerging, not standard.
WHEN TO REPEAT IT
Suspected flareRising proteinuria, new haematuria, or falling eGFR after remission
Non-response≥6 months of therapy with ongoing or worsening kidney findings
Before withdrawalNot routine — only if it would change a high-stakes tapering decision
ACR 2024 · conditional; not mandatory in every flare
IMPLICATIONA repeat biopsy answers what no laboratory panel can: active disease, or scar?
—MPAA-based regimens are generally preferred over CYC-based regimens when suitable and tolerated.
—For patients already started on dual therapy: reassess response, adherence, dose, pathology and toxicity before considering a third agent; timing is individualised.
—EULAR recommends combinations, especially for poor prognosis, with dual regimens as alternatives.
Significant extra-renal diseaseMPAA + belimumabACR conditional — systemic activity and flare control
Proteinuria ≥3 g/g with preserved eGFRMPAA + CNIACR conditional — proteinuria reduction; assess kidney function
Rapidly progressive disease / extensive crescentsConsider IV CYC 0.5–0.75 g/m² monthly; 6–7 pulsesEULAR 2025 Rec 5 (1a/A) — high risk of kidney failure
Inadequate response by 6–12 monthsDual → triple; if on triple, switch regimen or add anti-CD20ACR escalation pathway, simplified — verify adherence and dosing first
Refractory after two coursesAlternative listed triple · add anti-CD20 · trial referralACR refractory pathway — MPAA + belimumab + CNI is listed; belimumab + CNI is not an initial combo
Initial regimens include GC. ACR also lists ELNT low-dose CYC + belimumab (500 mg IV q2w ×6); this is distinct from high-dose CYC. EULAR also lists obinutuzumab + MMF (1b/A).
PROTEINURIA ≥1 g/gTriple therapy: pulse steroid, taper, MPAA + CNICNI adds a direct antiproteinuric effect on the podocyte.
PROTEINURIA <1 g/gGlucocorticoid and/or a single agentMPAA, AZA or CNI, with full non-immunologic kidney protection.
—Mixed class IV+V follows the proliferative pathway — treat the proliferative component.
—Discuss thrombosis prevention with nephrology when nephrotic-range proteinuria and low albumin create significant risk; thresholds are risk-based, not an automatic prescription.
ACR 2024 (Arthritis Rheumatol 2025;77(9):1115–35) — pure class V17
03 · Treatment trends
Glucocorticoid Minimization
INDUCTION250–1000 mgIV methylprednisolone for 1–3 days; pulse dose follows disease severity and local protocol
ORAL START≤0.5 mg/kg/dayMaximum 40 mg/day in the ACR framework, then a structured taper
BY MONTH 6≤5 mg/dayACR 2024 conditional target; EULAR 2025 says by 4–6 months. Withdrawal is individualised and should not destabilise renal disease
Steroid-sparing is a major treatment goal, but tapering must remain tied to renal response and flare risk.
Phase 3 REGENCY, class III/IV (incl. mixed V) LN, N=271.
—First B-cell-depleting agent with a positive phase 3 result in LN — rituximab (LUNAR, 2012) was negative; the U.S. FDA label was expanded in October 2025 for adults with active LN, supported by phase 2 NOBILITY and phase 3 REGENCY.
—ACR 2024 predates REGENCY — anti-CD20 is positioned for inadequate response or refractory disease, without these data.
—EULAR 2025 names obinutuzumab alongside belimumab and rituximab as a biologic option.
MycophenolateTeratogenic. Effective contraception during treatment and ≥6 weeks after stopping (women); men counselled per current PI (some PI recommend 90 days); switch well before conception.
CyclophosphamideGonadotoxic. Discuss fertility preservation before the first dose; GnRH agonist co-treatment may reduce ovarian toxicity.
ACEi / ARBSwitch to a pregnancy-compatible agent before conception; avoid once pregnant.
Voclosporin BelimumabHuman pregnancy data remain limited; review the current PI before conception.
Tacrolimus · AZA HydroxychloroquineThe pregnancy-compatible backbone — the regimen you convert to, and the reason AZA still has a role.
TIMING
—Conceive only from sustained remission — most guidance asks for ≥6 months of quiescent disease and stable kidney function.
—Continue hydroxychloroquine throughout — fewer flares; congenital-heart-block evidence is conditional, strongest for recurrent-risk pregnancies.
—Start low-dose aspirin in early pregnancy according to obstetric guidance, commonly by 12–16 weeks, for pre-eclampsia risk.
—Plan the switch at the visit where you start therapy — not at the visit where she tells you she is pregnant.
ACR Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases (2020) · EULAR 202524
Section 04
Belimumab in Practice
BLISS-LN、亞洲與日本真實世界資料、長期安全性證據，以及台灣健保實務
04 · Belimumab
BLISS-LN: Design and Results
DESIGN
Population448 adults; biopsy-proven active class III, IV or V LN
RegimenBelimumab 10 mg/kg IV or placebo + standard therapy (MMF, or CYC→AZA)
Duration104 weeks — among the longest randomised LN trials at publication
Primary · PERRUPCR ≤0.7 g/g · eGFR ≥60 or ≥80% of pre-flare value · no rescue therapy
Secondary · CRRUPCR <0.5 g/g · eGFR ≥90 or ≥90% of pre-flare value · no rescue therapy
RESULTS AT WEEK 104
Primary efficacy renal response
Belimumab + SoC
43%
Placebo + SoC
32%
Complete renal response
Belimumab + SoC
30%
Placebo + SoC
20%
HR 0.51Time to kidney-related event or death Separate secondary endpoint; 95% CI 0.34–0.77, p=0.001. Not a comparison with other biologics.
—Higher baseline proteinuria, creatinine and hypertension were associated with lower response probability — hypothesis-generating, not proof of benefit.
—86.7% of patients in PERR at month 6 maintained response — selected responder subgroup, not ITT.
—Anti-Sm positivity and early 6-month response predicted durable PERR at 12 and 24 months.
HOW TO WEIGH THESE SIGNALS
Post-hoc and registryUncontrolled, responder-enriched, cohort-specific endpoints — hypothesis-generating, not a treatment-effect estimate.
Where they agreeLower baseline proteinuria, preserved kidney function and an early 6-month response track with durable PERR — the case for adding earlier rather than later.
—Higher than BLISS-LN East Asia: week 52 CRR 70.0% and PERR 83.3%.
—Steroid-sparing: PSL down to 4.2 mg/d (vs 6.7 mg; p < 0.001); fewer AEs (40% vs 69%).
—A real-world cohort, not an RCT — supportive for early induction add-on.
JAPAN LOOPS · 52-WEEK OUTCOMES (BEL+SoC vs SoC)
ENDPOINTBEL + SoC (n=30)SoC ALONE (n=32)
CRR · week 5270.0% (21/30)34.4% (p=0.006)
PERR · week 5283.3% (25/30)50.0% (p=0.007)
BEL Retention90.0% (27/30)—
Mean PSL · week 524.2 mg/day6.7 mg (p<0.001)
Higher response than BLISS-LN East Asia (W52 PERR 62%, W104 CRR 35%) reflects earlier add-on (≤6 wk, shorter disease duration) and 90% retention.
Sakai H, et al. Rheumatology 2025;64(4):1930–1939 · Multicentre Japanese registry29
04 · Belimumab
Belimumab Safety Evidence Map
2009–2011Phase II (N=449); BLISS-52/-76 (N=1,684 combined)
2017–2021BLISS-SC (N=836) and BASE phase 4 RCT (N=4,003 as-treated)
2020PLUTO paediatric trial (N=93)
2020–2022 →BLISS-LN (N=448) and EMBRACE (N=503), then real-world exposure
Consistent profileSafety findings in LN and paediatric populations were consistent with the known adult SLE profile; injection site reactions were added with the SC formulation.
What to monitorFollow the current TFDA PI: serious infection; infusion/hypersensitivity reactions; depression or suicidality. Do not combine belimumab with other B-cell-targeting biologics — concurrent safety and efficacy are not established.
Evidence map: BLISS-52/-76 · BLISS-SC · BASE · EMBRACE · BLISS-LN · PLUTO — refer to TFDA-approved prescribing information30
04 · Belimumab
IV Dosing for Lupus Nephritis
DAY 010 mg/kgFirst infusion
DAY 1410 mg/kgSecond infusion
DAY 2810 mg/kgThird infusion
THEN EVERY 4 WEEKSMaintenanceAlongside standard therapy
—Supplied as 120-mg and 400-mg lyophilized powder single-dose vials for IV use; reconstitute and dilute according to the current TFDA PI.
—Do not give as IV push or bolus; vials are for IV use only, not subcutaneous. Infuse over ~1 hr with monitoring; premedication per local PI.
—Schedule all three loading infusions when treatment is approved. For a missed dose, follow the current PI and local protocol; do not double the next dose.
TFDA PI / local protocol · verify current label before prescribing31
—Five glomeruli after two days of pulse steroids — “focal” may reflect sampling, not biology.
—Subepithelial deposits suggest possible class V overlap; classification limited by sample adequacy.
—Nephrotic course + positive serology call for multidisciplinary review, not an assumed class.
Low threshold to repeat the biopsy if the course diverges.
De-identified case35
05 · Case 1
Case 1: Four Years of UPCR
Case 1 UPCR (g/g) by date
Date
UPCR (g/g)
2022/06
1.92
2022/07
4.28
2022/08
4.11
2022/09
2.77
2022/10
1.06
2022/11
1.00
2022/12
1.50
2023/01
1.62
2023/02
1.39
2023/04
0.85
2023/06
0.67
2023/06
0.74
2023/08
0.75
2023/10
0.59
2023/12
0.51
2024/04
0.23
2024/06
0.21
2024/08
0.13
2024/11
0.46
2025/05
0.23
2025/06
0.20
2025/08
0.16
2025/11
0.16
2026/01
1.38
2026/03
0.25
2026/04
1.10
2026/05
0.25
2026/08
0.42
UPCR (g/g) · TIME TO SCALENephrotic at presentation — peak 4.28 (2022/07). CYC + AZA then held a 1.0–1.6 plateau for four months.
2023/03 · BELIMUMAB ADDEDAdded on that plateau (UPCR 1.39). Individual dose D0 / D14 / D28 then Q4W; prednisolone to 1 tablet, AZA halved.
FIRST COURSEAt 0.5 by 2023/12 (0.51), nadir 0.13 (2024/08). Stopped 2025/03 in CRR after 24 funded months.
2026/011.38Renal flare 10 months after stopping — UPCR had held at 0.16–0.23 until then
2026/030.25After immunosuppressant adjustment
2026/041.10Rises again — belimumab reapplied, approved as quickly as the first time
2026/05 → 080.25 → 0.42Second course under way
De-identified case · temporal association only; concurrent CYC/AZA/steroid changes confound attribution36
05 · Case 2
Case 2: Class IV + V, a Slower Response
Case 2 UPCR (g/g) by date
Date
UPCR (g/g)
2023/02
5.07
2023/03
5.67
2023/04
1.35
2023/06
0.47
2023/08
1.24
2023/08
0.94
2023/10
0.81
2023/12
1.46
2024/02
1.71
2024/03
1.12
2024/05
0.96
2024/07
1.13
2024/08
1.89
2024/09
1.55
2024/11
3.42
2024/11
1.93
2025/02
1.00
2025/05
1.03
2025/07
0.70
2025/11
1.49
2026/04
0.73
2026/08
0.46
UPCR (g/g) · TIME TO SCALEWoman, now 28. ANA 1:1280, dsDNA (+), C3/C4 63.7/8.2; biopsy class IV + V. Peak 5.67 (2023/03).
2024/02 · BELIMUMAB ADDEDMMF 1.5 g reached 0.47 once (2023/06) then lost it; the decision was taken at UPCR 1.46 (2023/12). COVID-19 and UTI in 2024; MMF (poor GI tolerance)→AZA.
2024/11 · THE 3.42 SPIKEMeasured during an upper respiratory infection and back to 1.93 two weeks later — an intercurrent illness, not a treatment failure.
2026/02RENEWEDTwo funded years complete — reapplied and granted, treatment continues
2026/04 → 080.73 → 0.46First value under 0.5 g/g since 2023/06
VERSUS CASE 130 vs 13 monthsTime on belimumab to a UPCR under 0.5 g/g — same drug, class IV + V is the slower course
De-identified case · temporal association only37
Take home
Take Home Messages
01Biopsy early, and repeat when the course does not match the report.Class, activity and chronicity guide intensity — NHI reimbursement starts from the report.
02Manage to milestones, not to visits.EULAR: −25% @3 mo, −50% @6 mo, <0.7 g/g @12 mo. ACR: prednisone ≤5 mg/day by month 6.
03Combine early — belimumab is one conditional ACR option.BLISS-LN beat standard therapy alone, including kidney events. KDIGO still allows dual first-line — gap narrowing, not closed.