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Rituximab/tocilizumab Cellulitis facialis, infections and late-onset neutropenia following an off-label use: 4 case reports

In an observational retrospective study of all consecutive unselected adult patients (data obtained from the local European Database for Multiple Sclerosis (EDMUS), which included all patients treated with tocilizumab in the Toulouse University Hospital Pharmacy prescription database in France, between 2014 and 2020) 4 patients (3 women and 1 man) aged 22–52 years were described, who developed recurrent gynecologic infections, late-onset neutropenia after rituximab therapy (LONART), tooth infections, hypertriglyceridaemia or cellulitis facialis following an off-label therapy with rituximab or tocilizumab for myelin oligodendrocytes antibodies associated disease (MOGAD) or neuromyelitis optica spectrum disorders (NMOSD) [times to reactions onsets not stated; not all dosages, routes and outcomes stated]. The patients had underlying MOGAD or NMOSD with positive aquaporin 4 antibodies. The patients initially received off-label rituximab (3 patients), and off-label rituximab and azathioprine (1 patient). However, two of the 4 patients developed LONART in the setting of rituximab therapy, while the remaining 2 patients developed recurrent gynecologic infections, suspected to be due to rituximab. Rituximab therapy was withdrawn, and the LONART events resolved. Thereafter, the patients started receiving off-label therapy with IV tocilizumab 8 mg/Kg monthly for a total of 4–16 cycles. Three of the 4 patients received off-label SC tocilizumab 162mg weekly (for a total of 28–76 cycles) after completion of IV tocilizumab administration. Length of tocilizumab administration ranged at 4–29 months in these 4 patients. However, three of the 4 patients developed tooth infections (1 patient), hypertriglyceridaemia (1 patient) and cellulitis facialis (1 patient) due to tocilizumab. In the patient with recurrent gynecologic infections due to rituximab, tocilizumab (though did not contributed to any adverse reactions) was discontinued during the follow-up, as investigations revealed non-infectious vulvar pathology, which was not directly due to tocilizumab but required specific therapy with unspecified TNF-α inhibitors. Among the 3 patients of tocilizumab related events, tocilizumab was continued in 2 patients, and transient tocilizumab interruption was required in the facial cellulitis patient. Tocilizumab proved to be effective against underlying MOGAD or NMOSD. Rigal J, et al. Off-label use of tocilizumab in neuromyelitis optica spectrum disorders and MOG-antibody-associated diseases: A case-series. Multiple Sclerosis and Related 803515796 Disorders 46: Nov 2020. Available from: URL: http://doi.org/10.1016/j.msard.2020.102483

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Reactions 21 Nov 2020 No. 1831