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

• Published in: Nephrology (Carlton, Vic.) Vol. 24; no. 12; pp. 1241 - 1247
• Main Authors: Ramachandran, Raja, Bharati, Joyita, Rao, Indu, Kashif, Ahmed W, Nada, Ritambhra, Minz, Ranjana, Gupta, Krishan L, Kohli, Harbir S
• Format: Journal Article
• Language: English
• Published: Melbourne John Wiley & Sons Australia, Ltd 01-12-2019; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Antigens, CD19 - analysis; Biopsy; Calcineurin; calcineurin inhibitor; Calcineurin inhibitors; Calcineurin Inhibitors - administration & dosage; Calcineurin Inhibitors - adverse effects; Candidiasis; Costs and Cost Analysis; Dose-Response Relationship, Drug; Drug Monitoring - methods; Drug Resistance; Female; focal segmental glomerulosclerosis; Glomerulosclerosis, Focal Segmental - complications; Glucocorticoids - therapeutic use; Humans; Immunologic Factors - administration & dosage; Immunologic Factors - adverse effects; Immunologic Factors - economics; Immunotherapy; India; Male; minimal change disease; Monoclonal antibodies; Nephrosis, Lipoid - complications; Nephrotic syndrome; Nephrotic Syndrome - drug therapy; Nephrotic Syndrome - etiology; Nephrotic Syndrome - immunology; Remission; Respiratory tract diseases; Rituximab; Rituximab - administration & dosage; Rituximab - adverse effects; Rituximab - economics; steroid dependent; steroid resistant; Treatment Outcome; India; steroid resistant; minimal change disease; calcineurin inhibitor; steroid dependent; focal segmental glomerulosclerosis; rituximab
• ISSN: 1320-5358; 1440-1797
• DOI: 10.1111/nep.13554

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.
SUMMARY AT A GLANCE
This paper shows that rituximab, a monoclonal antibody‐based therapy that depletes CD‐19 and CD‐20‐positive B cells, may be an alternative approach to maintain remission in calcineurin‐inhibitor dependent podocytopathies.