Is it time to say goodbye to weekly rituximab in ANCA vasculitis?
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LETTER TO THE EDITOR
Is it time to say goodbye to weekly rituximab in ANCA vasculitis? Benzeeta Pinto 1
&
Aadhaar Dhooria 2
Received: 6 August 2020 / Revised: 6 August 2020 / Accepted: 20 August 2020 # International League of Associations for Rheumatology (ILAR) 2020
Sir, We read with great interest the observational study by Mittal et al. on the effectiveness of rituximab biosimilars in ANCA vasculitis [1]. Rituximab biosimilars are widely used in India owing to cost effectiveness despite a paucity of safety and efficacy data [2]. We would like to highlight the induction regimen used in this study, i.e., 1000 mg × 2 doses, 15 days apart. Even though this regimen is widely used in rheumatoid arthritis, both RAVE and RITUXVAS employed a weekly regimen of 375 mg/m2 × 4 [3, 4]. The choice of regimen, unfortunately, is not based on robust pharmacokinetic data. Rituximab demonstrates biphasic pharmacokinetics with a long half-life of 3 weeks [5]. The initial rapid clearance is due to binding of the antibody to its target antigen while subsequent elimination is linear due to non-specific catabolism. Cornec et al. explored the pharmacokinetics of rituximab in patients with ANCA-associated vasculitis enrolled in RAVE study. They reported highly variable serum levels of rituximab despite using a body-surface-area-based dosing regimen. In their study, male gender and newly diagnosed disease correlated with lower serum levels, however, the serum levels did not have any effect on clinical outcomes [6]. The weekly regimen makes sense in hemato-oncology practice where increased binding in patients with high tumor burden invariably culminates in increased clearance. This “sink effect” is unlikely in rheumatic diseases. In the present study by Mittal et al., the 1000 mg × 2 regimen lead to a remission rate of 60% at 6 months which is similar to that achieved in the RAVE trial with weekly infusions with better results in patients with relapsing or refractory disease [1]. Ekbote et al. also reported excellent results (remission in 17/19 patients at 6 months) in
* Benzeeta Pinto [email protected] 1
2
Department of Clinical Immunology and Rheumatology, St John’s Medical College, Sarjapur Road, Bengaluru 560034, India Department of Clinical Immunology and Rheumatology, Santokba Durlabhji Memorial Hospital, Jaipur, India
patients of ANCA vasculitis with relapsing or refractory disease who received the same regimen [7]. Not only does the weekly regimen result in increased hospital visits (two extra infusions), the dose of rituximab administered is also 25% more (assuming an average body surface area 1.7 m 2; 2550 mg versus 2000 mg). In the absence of any conclusive evidence of superiority, it seems pragmatic to adopt 1000 mg × 2 as the standard rituximab induction regimen for patients with ANCA vasculitis.
Compliance with ethical standards Disclosures None.
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Mittal S, Naidu GSRSNK, Jha S, Rathi M, Nada R, Minz RW, Sharma K, Dhir V, Jain S, Sharma A (2020) Experience with similar biologic rituxima
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