Usefulness of Low Dose Topoisomerase I Inhibitor (Irinotecan) as Add on Therapy Along with Low Dose Rituximab in Lupus Nephritis Flare Patients with Deteriorating Renal Function - Our Initial Experience - Abstract
Effective therapy for a lupus nephritis flare is still elusive. Topoisomerase I inhibitor irinotecan as add on therapy is shown to have favourable outcome in lupus nephritis but its use in lupus nephritis flare is not reported. Objective: To study the usefulness, safety, and outcome of low dose irinotecan topoisomerase I inhibitor as add on therapy in a lupus nephritis flare. Method: From January 2018 through December 2022, 4 patients with lupus nephritis who had a lupus flare and a rise in serum creatinine were administered low-dose irinotecan along with low dose rituximab (RTX). Other conventional immunosuppressants were continued. All patients were followed up minimum one year. In the event of a repeat flare, the same regimen is to be repeated. Renal function, routine clinical and blood parameters, and the urine protein to creatinine ratio (upcr) recorded at regular intervals during follow up. Kidney biopsy to be done when indicated. Results: Patient-1 on presentation had a urine protein/creatinine ratio upcr 1.05 after 4 doses of 100 mg/week irinotecan and 200 mg of single dose RTX; upcr reduced to 0.7; it further reduced to 0.2 end of six months on follow up. Renal function improved from 2.1 mg/dl serum creatinine (s.cr) on presentation to 0.8 mg/dl end of three months and remained stable. Patient has proteinuric flare two years subsequently and received second dose of irinotecan and RTX. Upcr from 2.30 reduced to 0.50 end of four weeks and in eight weeks urine albumin was found trace. The skin rash at the presentation also disappeared. Patient 2, a lupus nephritis patient, had a rise in s.cr from 2.6 to 6.1 mg/dl and her upcr 1.56. At end of eight weeks after low dose irinotecan and RTX single dose, her s.cr came down to 2.9 with PCR of 0.85 and blood pressure well controlled. Patient-3 In spite of four doses of irinotecan given alongwith inj RTX 200mg single dose her creatinine remained at 5.89mg/dl and progressed to ESRD in one year. Patient 4, who required hemodialysis upon a lupus flare, was withdrawn from hemodialysis after receiving four doses of irinotecan and 200 mg of RTX single dose. His upcr was 0.75 in last follow up and s.cr 5.8 mg/ dl down from 8.7 mg/dl. Conclusion: Irinotecan, a non immunosuppressive add on drug, along with low dose rituximab, was useful in our patient during a flare of lupus nephritis. Further study is needed to understand its use in lupus nephritis patients.