Factors influencing the choice of non-biologic versus biologic immunosuppressive therapy in systemic lupus erythematosus

Abstract

In systemic lupus erythematosus (SLE), treatment decisions are guided by clinical judgment based on disease manifestations and safety profiles rather than standardized protocols, particularly for extra-renal involvement. In this study of 356 SLE patients, 190 receiving non-biologic immunosuppressants and 166 receiving biologics, we investigated the association of clinical phenotypes with treatment initiation and the impact of damage (SLICC-DI), comorbidities, and hospitalization history on these choices. Dominant clinical phenotypes were defined qualitatively using BILAG and SLEDAI domains. Logistic regression models with Simes-Hochberg correction revealed that renal phenotypes were strongly associated with mycophenolate initiation (OR = 4.09, p < 0.001), musculoskeletal phenotypes with methotrexate (OR = 4.86, p < 0.001). Belimumab was preferentially initiated in patients with musculoskeletal involvement and high SLEDAI scores (OR = 1.84, p = 0.03; OR = 2.03, p = 0.03, respectively). Notably, the association between mycophenolate and the renal phenotype persisted in the presence of comorbidities but was not observed in patients with SLICC-DI > 0 or more than one hospitalization in the previous year. Similarly, methotrexate and belimumab associations were diminished in patients with a Charlson comorbidity index > 1 or damage (SLICC-DI > 0). This study offers novel insights into the clinical determinants of immunosuppressive therapy selection in SLE and underscore the potential for tailoring treatment strategies to individual patient profiles.

Keywords: Comorbidity; Lupus erythematosus; Organ damage; Treatment.

Fig. 1

Correspondence analysis: association between variables is represented as distance in a two dimensional space, the closer two variables are, the stronger the positive association is. The figure illustrates the phenotypic clustering of SLE manifestations and their corresponding therapeutic associations, emphasizing the strong phenotype-driven rationale in treatment selection, particularly the alignment of renal phenotypes with MMF, CYC, and TAC, and musculoskeletal phenotypes with MTX and BEL. AZA Azathioprine, BEL Belimumab, CYC Cyclophosphamide, CYA Cyclosporine A, LEF Leflunomide, MMF Mycophenolate mofetil, MTX Methotrexate, RTX Rituximab, TAC Tacrolimus.