Promising Experimental Treatments for Lupus Nephritis: Key Talking Points and Potential Opportunities

Abstract

Lupus nephritis (LN) is a frequent and serious complication of systemic lupus erythematosus (SLE), impairing patients' quality of life and significantly increasing mortality. Despite optimizing the use of conventional immunosuppressants and other biological drugs, its management remains unsatisfactory. This is mainly due to the heterogeneity of SLE, but also to insufficiently effective treatment regimens and clinical trial limitations (strict criteria, low number of patients included, and side effects). Most clinical trials of new biological therapies have failed to meet their primary endpoints in both general SLE and LN, with only two biological drugs (belimumab and anifrolumab) being approved by the Food and Drug Administration (FDA) for the treatment of SLE. Recently, several Phase II randomized controlled trials have evaluated the efficacy and safety of new biologics in LN, and some of them have demonstrated an improvement in clinical and laboratory measures. Multi-target therapies are also being successfully developed and encourage a belief that there will be an improvement in LN outcomes.

Clinico-serological associations of urinary activated leukocyte cell adhesion molecule in systemic lupus erythematosus and lupus nephritis

“…In Lupus Nephritis, the ALCAM, also known as CD166, plays a pathogenic role. This has been demonstrated by blocking the ALCAM-CD6 pathway with anti-CD6 monoclonal antibodies, resulting in a reduction in T cell count infiltrating the kidneys, which leads to a decrease in renal impairment and LN severity [ 14 ].…”

Nefritis Lúpica : Una Revisión Sistemática de su Manejo

“…Con respecto a las terapias emergentes, guselkumab, un anticuerpo monoclonal dirigido contra IL-23, ha completado exitosamente un ensayo aleatorizado de fase II para evaluar su eficacia y seguridad en pacientes con NL, aunque los resultados aún no han sido publicados. (3) En contraste, ustekinumab, otro anticuerpo monoclonal que inhibe tanto IL-12 como IL-23, y que afecta la actividad de Th17, mostró cumplimiento con sus objetivos en un ensayo de fase II en pacientes sin NL, pero no en otro ensayo de fase II relacionado con NL, lo que ha llevado al abandono de estudios adicionales en esta área. (3) Resulta crucial garantizar una dosificación adecuada de los medicamentos inmunosupresores para prevenir efectos secundarios graves; esto se puede lograr mediante la medición de los niveles plasmáticos del medicamento, como en el caso del MMF, y al brindar un plan educacional amplio sobre la cumplimiento y apego adecuados al tratamiento.…”