Persistent CD‐19 depletion by rituximab is cost‐effective in maintaining remission in calcineurin‐inhibitor dependent podocytopathy

Abstract

Aim A significant proportion of patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are either steroid dependent or steroid resistant, requiring long‐term calcineurin inhibitors (CNI) use. Rituximab has more favourable safety profile. The present study was undertaken to evaluate the efficacy and safety of rituximab in CNI‐dependent patients. Methods This was a prospective observational study conducted from July 2014 to February 2018. Steroid‐dependent nephrotic syndrome or steroid‐resistant nephrotic syndrome (biopsy proven MCD/FSGS), who were CNI dependent were enrolled. Mean age at enrolment was 22.77 ± 7.45 years. All patients received rituximab at a dose of 375 mg/m2 at entry in the study. CD‐19 levels were monitored monthly and patients having CD‐19 levels >5/μL and/or > 1% received additional low‐dose (100 mg) of rituximab. Results A total of 24 patients were followed up for 12 months. At the end of 6 and 12 months, 87.5% and 79.16% of the patients achieved remission, respectively. Eight (33.33%) patients developed relapse. The mean dose of rituximab in the first year was 791 mg. The average cost of rituximab in the first year was 487.17$. Rituximab was well‐tolerated, with mild infusion reactions, respiratory tract infection and oral candidiasis in 5 (20.83%), 5 (20.83%) and 1 (4.17%) patient, respectively. Conclusions CD‐19 targeted rituximab is a safe and cost‐effective agent in remission maintenance in adults with CNI dependent. Over three‐fourths of the patients with CNI‐dependent podocytopathy maintain clinical remission with CD‐19 targeted rituximab therapy.

Rituximab in treatment of collapsing FSGS—A case series

“…Rituximab was given either as targeted therapy or weekly regimen. In targeted therapy, after an initial dose of 375 mg/m 2 , B cell flow cytometry was performed after 1 month; patients having CD‐19 levels >5/μL or >1% received additional low‐dose (100 mg) of rituximab) 23 . Weekly regimen involved weekly administration of 375 mg/m 2 .…”

“…Patient 1 was a 30‐year male with biopsy‐proven cFSGS who achieved remission with 1 mg/g oral steroids but was SD, subsequently treated with tacrolimus and deemed dependent to it. He received CD‐19 targeted rituximab 23 with a cumulative dose of 800 mg (after remission induction with oral prednisolone), the patient‐maintained CR and was weaned off steroids successfully. Patient 2 was a 30‐year male who was resistant to 16 weeks of 1 mg/kg of oral prednisolone.…”

“…He achieved PR with CNI (tacrolimus); however, relapsed on tapering. After inducing remission with tacrolimus again, he received CD‐19 targeted rituximab 23 with a cumulative dosage of 700 mg. He maintained PR and tacrolimus weaning was successful.…”

“…She further received CNI (Tacrolimus) for 6 months to which she was resistant, hence discontinued. With CD‐19 targeted rituximab 23 (cumulative dosage of 1200 mg), she achieved PR. Patient 4 was a 24‐year‐old male with SRNS.…”

“…Patient 4 was a 24‐year‐old male with SRNS. Despite administering of CD‐19 targeted rituximab 23 (cumulative dosage of 600 mg), the patient failed to achieve any meaningful remission, also had a worsening of renal function and progressed to ESRD. Patient 5 was a 30‐year‐old male presented with SRNS; following a weekly regimen of rituximab (500 mg*4); he failed to achieve remission.…”