Administering belimumab along with antimalarial agents enhances its protection against renal flares in patients with systemic lupus erythematosus (SLE), according to study results published in Rheumatology (Oxford).
Researchers performed a post-hoc analysis using data from 4 phase 4 randomized controlled trials of belimumab (BLISS-52, BLISS-76, BLISS-SC, and BLISS NEA; ClinicalTrials.gov Identifiers: NCT00424476, NCT00410384, NCT01484496, and NCT01345253, respectively).
In total, 3225 participants with active SLE were assigned to receive intravenous (IV) belimumab 1 mg/kg (N=559), IV belimumab 10 mg/kg (N=1033), subcutaneous belimumab 200 mg (N=556), or placebo (N=1077).
If the baseline value was less than 0.2 g/day, the flare was defined as an increase to more than 1 g/day. If the baseline value was between 0.2 and 1.0 g/day, the flare was defined as an increase to more than 2 g/day. If the baseline value was more than 1 g/day, the flare was defined as an increase to more than twice that of the baseline value. If the level of serum creatinine increased by 20% or reached 0.3 mg/dL and was accompanied by proteinuria, hematuria, or red blood cell (RBC) casts, or a new case of hematuria of glomerular origin and accompanied by proteinuria or RBC casts.
Cox proportional hazards regression models were used to evaluate the risk for renal flares. The analysis was adjusted for factors including age, sex, ethnicity, renal history, baseline proteinuria, kidney function, and the use of immunosuppressants and glucocorticoids.
A total of 54.6% of patients had current or previous kidney involvement at baseline, as per the British Isles Lupus Assessment Group scale (renal BILAG A-D). After a median of 197 days, 192 patients (6.0%) qexperienced a renal flare with belimumab and antimalarial treatment.
According to multivariable Cox regression analysis, the use of antimalarials resulted in a decreased risk for renal flares (hazard ratio [HR], 0.66; 95% CI, 0.55-0.78; P <.001).
Patients who received IV belimumab at a dose of 1 mg/kg or 10 mg/kg vs those who received placebo had a lower risk for renal flares (HR, 0.42; 95% CI, 0.22-0.79; P =.007 and HR, 0.62; 95% CI, 0.41-0.92; P =.018, respectively). However, those who received subcutaneous belimumab 200 mg vs placebo did not have a significantly lower risk for renal flares.
The subgroup analysis that accounted for patients whose renal function was rated as BILAG A-D at baseline demonstrated that the use of AMA (adjusted HR, 0.67; 95% CI, 0.49-0.92; P =.013) and IV belimumab 1 mg/kg (HR, 0.45; 95%CI, 0.24-0.87; P =.017) corresponded to lower risk for renal flares.
Overall, belimumab plus antimalarials demonstrated the ability to reduce the risk for renal flares in people with active SLE.
Limitations of the study were the generalizability of the findings as the majority of patients had moderate to high disease activity, as well as the post hoc design, which may have restricted the statistical power.
Researchers concluded, “Our findings also corroborated the beneficial effects of [antimalarials] against the development of renal flares, and support its use in all [patients with] SLE, irrespective of activity state or organ involvement, unless contraindicated.”
Disclosure: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Gomez A, Jägerback S, Sjöwall C, et al. Belimumab and antimalarials combined against renal flares in patients treated for extra-renal systemic lupus erythematosus: results from 4 phase III clinical trials. Rheumatology (Oxford). Published online May 25, 2023. doi:10.1093/rheumatology/kead253