Doctors in Melbourne have reported a rare success treating relapsed primary focal segmental glomerulosclerosis (FSGS) with rituximab, offering hope for patients for whom steroid toxicity has caused serious harm.
A case report published in Nephrology [link here] by clinicians at Western Health describes a woman in her late twenties whose FSGS relapsed despite maintenance tacrolimus – and for whom high-dose glucocorticoids were considered unsafe after she previously developed severe steroid-induced hypomania.
During that relapse she had been treated with intravenous methylprednisolone 500 mg daily for three days, followed by oral prednisolone 60 mg daily. What followed was severe steroid-induced hypomania that required two voluntary psychiatric admissions, the first over concerns she might engage in ‘behaviour harmful to herself both reputationally and financially’, and the second after a paracetamol overdose with suicidal intent, report clinicians.
Her steroid-induced hypomania was managed with olanzapine 10 mg BD and rapid prednisolone tapering. Tacrolimus 3 mg BD was introduced as a steroid-sparing agent, and within four months of starting treatment she achieved complete remission of her FSGS. Prednisolone was ceased, and tacrolimus was continued with a target trough level of 4-6.
When her disease relapsed several years later, the history of psychiatric toxicity made high-dose glucocorticoids an unacceptable risk. Instead, she was started on low-dose prednisolone with Olanzapine 5mg BD whilst on glucocorticoids aiming to prevent any mood disturbance. Tacrolimus was continued with a target trough level of 4-6 and Rituximab 1000mg IV was administered with a further dose of 1000mg two weeks later.
The decision was anchored in emerging evidence that a subset of primary FSGS may be autoantibody-mediated and responsive to B-cell depletion.
According to the authors, her clinical response was rapid. Two weeks after the second rituximab dose, investigators recorded “a marked improvement in proteinuria (UPCR 14 mg/mmol) and normalisation of serum albumin.” At two months, she had “no proteinuria and normal serum albumin,” and by nine months her remission “remained intact with no proteinuria (UPCR 1 mg/mmol) and stable renal function”.
The authors say the case strengthens the argument for steroid-sparing strategies in carefully selected patients.
Primary FSGS is notoriously difficult to manage, they note, often relapsing and frequently progressing to end-stage kidney disease. While glucocorticoids remain the cornerstone of treatment, the report notes “there is minimal evidence supporting the use of rituximab as an alternative to high-dose glucocorticoids to achieve remission.”
“Given that relapses and steroid dependence are common in primary FSGS necessitating exposure to long-term glucocorticoids, steroid-sparing therapies are needed to reduce glucocorticoid adverse effects”, they argue adding that the condition’s underlying biology makes B-cell depletion a biologically plausible option.
Primary FSGS, they write, “has long been postulated [to occur] due to a circulatory permeability factor causing podocyte injury,” and emerging data suggest rituximab “may have an additional mechanism in modulating podocyte function to reduce apoptosis… rather than simply an immune modulatory effect.”
But, pointing out that most existing literature evaluates rituximab alongside high-dose steroids, they say it’s difficult to disentangle which therapy is driving remission. Meanwhile, evidence where rituximab is used without high-dose glucocorticoids remains limited and mixed, with small case series showing both successes and failures.
A small but growing body of research suggests its effects may differ depending on steroid responsiveness. The authors point to one study that, “interestingly, found those with steroid-dependent primary FSGS achieved complete remission with the addition of rituximab, while those with steroid-resistant primary FSGS demonstrated nil response.” Meanwhile, the recent RITERM study – a retrospective cohort of 64 patients – found that 82% achieved complete or partial remission at six months on rituximab-based regimens.
Acknowledging that further studies are required to determine which patients are most likely to benefit from rituximab administration, the Western Health team say their patient’s remission, achieved without exposure to toxic steroid doses, is an important addition to the debate.
“In the absence of randomised controlled trials B-cell depletion therapy with rituximab may be effective at achieving remission, particularly in patients whereby high-dose glucocorticoids are contraindicated,” they conclude.