Treatment response to cyclophosphamide, rituximab, and bortezomib in chronic immune-mediated sensorimotor neuropathies: a retrospective cohort study.

Background: Up to 20% of patients with chronic immune-mediated sensorimotor neuropathies (CIN) do not respond adequately to first-line therapies. However, studies on further treatment are scarce.
Methods: We analyzed retrospectively 200 CIN patients regarding disease characteristics and response to therapy with cyclophosphamide (CYP), rituximab (RTX), and bortezomib (BTZ). Treatment response was defined as improvement or stabilization of inflammatory neuropathy cause and treatment overall disability score (INCAT-ODSS).
Results: A total of 48 of 181 patients (26.5%) received therapy with CYP, RTX, or BTZ. The most frequently and first used therapy was CYP (69%). More than 40% of patients needed a second or third treatment. Overall, 71 treatments were applied in 48 patients. The combination of up to all three treatments enhanced the response-rate to 90%. Treatment within 24 months after initial diagnosis resulted in significantly higher response rate than late treatment (79% versus 50 %, p  = 0.04, χ ² -test, n  = 46) and in lower disability in long-term follow up (INCAT-ODSS 3.8 versus 5.8, p  = 0.02, t -test, n  = 48). Patients with Lewis-Sumner syndrome ( n  = 9) and autoantibody mediated neuropathies ( n  = 13) had excellent response rates after treatment with RTX (90-100%). In contrast, typical chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed a response rate of 64% in CYP, 64% in RTX, and 75% in BTZ.
Conclusion: Treatment with CYP, RTX, or BTZ was effective in this cohort of CIN refractory to first-line treatment. Our data increase evidence for an early use of these therapies. High efficacy of RTX in Lewis-Sumner syndrome in contrast to typical CIDP suggests a distinct pathophysiology.
Competing Interests: Conflict of interest statement: Jeremias Motte: received travel grants from Biogen idec, Novartis AG, Teva, and Eisai GmbH, his research is funded by Klaus Tschira Foundation and Ruhr-University, Bochum (FoRUM-program); none related to this work. Anna Lena Fisse: received research funding by Georgius Agricola Stiftung Ruhr and Ruhr-University, Bochum (FoRUM-program), received honoraria and travel grants from Novartis AG, Sanofi, and Eisai GmbH, none related to this work. Owns shares of Fresenius SE & Co., Gilead Sciences, Medtronic PLC, and Novartis AG. Nuray Köse: none Thomas Grüter: received travel reimbursement from Sanofi Genzyme and Biogen Idec, none related to this manuscript. Hannah Mork: none Diamantis Athanasopoulos: none Miriam Fels: none Susanne Otto: none Ines Siglienti: none Christiane Schneider-Gold: has received a FoRUM grant (F 701-2010) from the Ruhr-University of Bochum and consulting and speaker’s honoraria from Alexion Pharmaceuticals, Amicus Therapeutics, Bayer Schering, CSL Behring, Grünenthal, Lupin Pharmaceuticals, and TEVA. Kerstin Hellwig: Received speaker honoraria, consultancy fees and research support from Bayer Healthcare, Biogen, Novartis, Merck, Teva, and Roche. Min-Suk Yoon has received speaker honoraria from CSL Behring and Grifols, a scientific grant from CSL Behring, none related to this manuscript. Ralf Gold: Serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis, none related to this manuscript. Because this author is the Editor-in-Chief of Therapeutic Advances in Neurological Disorders, the peer review process was managed by alternative members of the Board and the submitting Editor was not involved in the decision-making process. Kalliopi Pitarokoili: received travel funding and speaker honoraria from Biogen Idec, Novartis and Bayer Schering Pharma and funding from the Ruhr-University, Bochum (FORUM-Program), none related to this work.
(© The Author(s), 2021.)