P12 Clinical responses, B cell depletion and treatment outcomes following rituximab biosimilar switch in RA: is there value in switching back?
Authors: Melville Andrew , Buch Maya , Nam Jackie , Emery Paul , Saleem Benazir , Dass Shouvik 
Published: April 2020

Abstract

Background
There has been a national cost-saving drive to switch from originator rituximab (RTX-O) to biosimilar (RTX-B). Whilst regulatory clinical trials necessitate demonstration of equivalence, subtle physicochemical changes could theoretically alter function, safety and efficacy. Some uncertainty remains amongst clinicians and patients, and real-world studies of non-medical biosimilar switching demonstrate clinically relevant discontinuation rates. Here we present our descriptive experience of switching to RTX-B in rheumatoid arthritis (RA), with a focus on B-cell depletion and inadequate responders (IR) subsequently switched back to RTX-O.

Methods
RA patients in Leeds were switched from RTX-O to RTX-B. Routine clinical data were collated, including baseline characteristics, previous treatment, clinical responses, initial B cell depletion (BCD) by high sensitivity flow cytometry, treatment outcomes. For switch back patients, responses were characterised according to DAS28, EULAR response, and association with BCD.

Results
263 RA patients in total switched to RTX-B. After 1st cycle RTX-B (excluding missing data), 180/241 (74.7%) had clinical response, 213/261 (81.6%) had complete BCD. Subsequent treatment outcomes were as follows: 140/263 (53.2%) re-treated with RTX-B, 57 (21.7%) awaiting re-treatment with RTX-B, 27 (10.3%) switched back to RTX-O for IR, 4 (1.5%) switched back for adverse events, 11 (4.2%) switched to another biologic, 24 (9.1%) treatment discontinued. Response data are currently available for 19/27 RTX-B-IR patients switched back to RTX-O (16/19 female, mean age 66.8, mean RTX cycles 6.7, 14/19 on DMARD, 11/19 osteoarthritis). Regarding RTX-B response, 3 had missing data, 2/16 (12.5%) had good response when EULAR criteria applied (but reduced duration), 4/16 (25%) moderate response (but subjectively poor), 10/16 (62.5%) non-response. Of available data in 10/19 after subsequent RTX-O (9 awaited/missing), 5/10 had EULAR good response, 2/10 moderate, 3/10 non-response. BCD occurred in 13/19 (68.4%) with RTX-B, 17/19 (89.5%) with subsequent RTX-O. All 5 good responders following switch back had EULAR non-response to RTX-B and complete BCD pre/post switch. Interestingly, of a further 19 RTX-B treated patients with incomplete BCD but not switched back, 15/19 had complete depletion with subsequent RTX-B. Of the 4 adverse events, 2 had infusion reactions (1 successfully re-treated with RTX-O, 1 pending), 1 headaches (resolved with RTX-O), 1 worsening hearing loss (likely unrelated).

Conclusion
Some patients with IR to RTX-B had good response after switching back to RTX-O. BCD was not predictive of this response. After incomplete BCD with RTX-B, most subsequently depleted with either RTX-O or RTX-B. RTX-B adverse events were rare; some resolved with RTX-O. Assessment of response in this context is challenging; DAS28 may be less clinically relevant with RTX when aiming to re-treat before flares, and discrepancies arise between DAS28 and subjective responses (e.g., influenced by longstanding disease/treatment, concurrent osteoarthritis, ‘nocebo’ effect). This real-world clinical service evaluation has its limitations; data collection is ongoing.

Disclosures
A. Melville None. M. Buch Honoraria; Abbvie, Astra Zeneca, BMS, Lilly, Roche, Sandoz, UCB. J. Nam None. P. Emery Consultancies; BMS, AbbVie, Pfizer, MSD, Novartis, Roche, UCB. Grants/research support; AbbVie, BMS, Pfizer, MSD, Roche. Other; Undertaken clinical trials and provided expert advice to Pfizer, MSD, Abbvie, BMS, UCB, Roche, Novartis, Samsung, Sandoz and Lilly. B. Saleem Other; Speaker fees (Sanofi). S. Dass Consultancies; Roche. Honoraria; Roche. Other; Speaker fees (Roche).