Latest EULAR recommendations in SLE and lupus nephritis

The new European Alliance of Associations for Rheumatology (EULAR) recommendations for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have adopted a more proactive treatment approach that focuses on early use of biologics to enable faster steroid tapering and preservation of renal function, as well as to minimize the risk of flares and organ damage progression. At European Congress of Rheumatology 2023 (EULAR 2023), Dr Dimitrios Boumpas, Chair of the EULAR Task Force on SLE, presented key changes in the new guidelines and discussed the established efficacy and safety of belimumab, a biologic indicated for SLE and LN.

Why update the EULAR recommendations?
The new recommendations were developed to include new treatment strategies with more ambitious goals and to streamline and simplify the recommendations for easier dissemination. They were developed by a task force comprising experts from Europe, North America, Asia and Australia. [Boumpas DT, EULAR 2023]

The overarching principles that guide these recommendations deal with the need for multidisciplinary, individualized management of SLE; monitoring of disease activity and organ damage; pharmacologic and nonpharmacologic interventions; and early SLE diagnosis and prompt treatment to prevent flares and organ damage, improve prognosis and enhance quality of life.

GCs as bridging therapy Only

The new recommendation for GC maintenance dose is ≤5 mg/day (prednisone equivalent), as compared with 7.5 mg/day in the previous iteration. [Ann Rheum Dis 2019;78:736-745]

“This recommendation pertains to both new-onset and relapsing disease,” noted Boumpas. “We now use GCs in lupus as a bridging therapy only, for short, limited periods of time. We should shy away from chronic use of GCs for >3 months, and for this we need GC-sparing strategies.”

GC-sparing strategies


Disease-modifying antirheumatic drugs (DMARDs) or biologics are recommended as GC-sparing agents. [Boumpas DT, EULAR 2023]

“To allow more flexibility for physicians and patients, it is not necessary to use DMARDs or immunosuppressive drugs first, if you prefer biologics,” pointed out Boumpas. “We are becoming more liberal with the use of biologics because new data confirm the efficacy of belimumab and anifrolumab.” [Rheumatol Ther 2022;9:975-991; Ann Rheum Dis 2023;82:639-645]

Belimumab as an add-on therapy for all LN patients


Emerging clinical trial data demonstrate that combination therapy with belimumab may help preserve long-term kidney function in LN patients. A post hoc analysis of BLISS-LN, a 2-year, randomized, double-blind controlled trial, found that belimumab reduced the risk of LN flare by 55 percent vs placebo (hazard ratio [HR], 0.45; 95 percent confidence interval [CI], 0.28–0.72; p=0.0008) in patients with active LN. Furthermore, belimumab-treated patients had a lower risk of a 30 percent or 40 percent decline in estimated glomerular filtration rate (eGFR) (p<0.05) and a lower annual rate of eGFR decline between weeks 24 and 104 (p=0.04 for on-study population). [Kidney Int 2022;101:403-413]

“Unlike the 2019 recommendations, there is no more distinction between class III/IV and class V LN,” emphasized Boumpas. “Belimumab and CNIs should be considered in all patients as add-on therapy from the beginning, because LN is associated with significant morbidity, and it is hard to predict who is more likely to benefit [from add-on therapy] at the beginning.”

“The decision of whether to use belimumab or voclosporin is a question of gentle vs forceful power and collateral damage,” he continued.“Voclosporin works rapidly, but we worry about side effects. Belimumab is gentle and demonstrates sustained response, reduces GC use, prevents flares and decreases organ damage. Neither belimumab nor voclosporin is effective in class V [LN], yet flare reduction may justify belimumab use.”

After initial therapy and renal response, subsequent therapy for ≥3 years is recommended. Patients initially treated with belimumab should continue to receive it during this maintenance phase.

Belimumab as a disease modifier in lupus
A poster and an abstract presented at EULAR 2023 reported the disease modification potential of SLE and LN treatments at 1 year, 2–5 years and >5 years based on evidence from published literature. Disease-modification was defined as minimizing disease activity with the fewest treatment-associated toxicities and slowing or preventing organ damage progression (or, in the case of LN, progression to end-stage kidney disease). Classification of available SLE treatments as disease-modifying would assist in treatment comparison and treatment decision-making. [Ann Rheum Dis 2023;82:907-908; Askanase AD, EULAR 2023, abstract POS1153; Ann Rheum Dis 2023;82:1463-1464; Askanase AD, EULAR 2023, abstract AB0531; Lupus Sci Med 2022;9:e000634]

SLE outcome measures included reduction in disease activity, reduction/prevention of severe flares, reduction in steroid/immunosuppressant use, improvement/no worsening in multiple organ domains, and no delayed progression (beyond 5 years). Among 14 SLE treatments evaluated, belimumab was the only agent that met all disease modification criteria at all time points. (Table 1) [Askanase AD, EULAR 2023, abstract POS1153]

Outcomes compared across LN treatments included improvement in urine protein/creatinine ratio, minimization of eGFR decline, reduction/prevention of renal flares, reduction in steroid/immunosuppressant use, and no delayed progression (beyond 5 years). Belimumab met more criteria across the three time points than any other biologics. (Table 2) [Askanase AD, EULAR 2023, abstract AB0531]

Long-term safety of belimumab
Belimumab’s long-term safety was evaluated in a post-hoc analysis of pooled data from three open-label extension studies (LBSL02 LTE, BLISS-76 LTE [US patients only] and BLISS-52 + BLISS-76 LTE [excluding US patients in BLISS-76]), where a total of 1,299 adult patients with SLE received ≥1 dose of belimumab every 28 days plus standard therapy. [Ann Rheum Dis 2023;82:1454-1455; Askanase AD, EULAR 2023, abstract AB0519]

Over >11 years of exposure to belimumab, 1,267 patients (97.5 percent) had ≥1 adverse event (AE). The incidence of most AEs decreased year on year and no new safety concerns were observed. Furthermore, 525 patients (40.4 percent) had ≥1 serious AE and 139 patients (10.7 percent) experienced ≥1 AE resulting in study drug discontinuation, although the incidence of each remained stable over time.

Summary
The 2023 EULAR recommendations suggest GCs as bridging therapy only. Early use of biologics, such as belimumab, enables faster steroid tapering and achievement of remission or low disease activity, while minimizing the risk of flares and organ damage progression. With more than a decade of robust clinical data, belimumab is recognized as an effective disease modifier in SLE and LN, with a well-established safety profile.