Predictors of hospitalization due to infection in rituximab-treated MS patients

Jakob Rishovd Karlowicz; Mattias Klakegg; Jan Harald Aarseth; Lars Bø; Kjell-Morten Myhr; Hilde Marie Torgauten; Øivind Torkildsen; Stig Wergeland

doi:10.1016/j.msard.2023.104556

Predictors of hospitalization due to infection in rituximab-treated MS patients

Mult Scler Relat Disord. 2023 Mar:71:104556. doi: 10.1016/j.msard.2023.104556. Epub 2023 Feb 11.

Authors

Jakob Rishovd Karlowicz¹, Mattias Klakegg¹, Jan Harald Aarseth², Lars Bø³, Kjell-Morten Myhr³, Hilde Marie Torgauten³, Øivind Torkildsen³, Stig Wergeland⁴

Affiliations

¹ Department of clinical medicine, University of Bergen, Norway.
² Norwegian MS-registry and biobank, Dept of Neurology, Haukeland University Hospital, Bergen, Norway.
³ Department of clinical medicine, University of Bergen, Norway; Neuro-SysMed, Haukeland University Hospital, Bergen, Norway.
⁴ Department of clinical medicine, University of Bergen, Norway; Norwegian MS-registry and biobank, Dept of Neurology, Haukeland University Hospital, Bergen, Norway; Neuro-SysMed, Haukeland University Hospital, Bergen, Norway. Electronic address: stig.wergeland@helse-bergen.no.

PMID: 36842313
DOI: 10.1016/j.msard.2023.104556

Abstract

Background: Rituximab is extensively used off-label to treat multiple sclerosis (MS), and long-term vigilance for adverse events is needed. This study was conducted to determine frequencies and predictors of hematological adverse events, including hypogammaglobulinemia, severe lymphopenia, neutropenia, and infections leading to hospitalization.

Methods: This retrospective cohort study included all patients with MS initiating rituximab treatment at Haukeland University Hospital between January 1^st, 2017, and July 1^st, 2021. Patients were followed by clinical monitoring and repeated blood sampling every six months. Clinical outcomes and laboratory results were retrieved from the Norwegian MS Registry and Biobank and the patient administrative system at Haukeland University Hospital.

Results: Five hundred and fifty-six patients were included, 515 with relapsing-remitting MS (RRMS) and 41 with progressive MS. Overall, 33 patients (5.9%) experienced 56 episodes of infections requiring hospital admission. Sixty patients (10.8%) had confirmed hypogammaglobulinemia, 17 (3.1%) had confirmed severe lymphopenia, and 10 (1.8%) had confirmed severe neutropenia. Predictors of infection requiring hospital admission were progressive MS (adjusted OR (aOR): 4.81; 95%CI: 1.25-18.48), duration of treatment with rituximab (aOR: 1.52; 95%CI: 1.11-2.09) and confirmed severe lymphopenia (aOR: 13.58; 95%CI: 3.41-54.06) and neutropenia (aOR: 13.40; 95%CI: 2.93-61.25). Of the hematological abnormalities, only hypogammaglobulinemia was associated with treatment duration (aOR: 1.35; 95%CI: 1.09-1.69).

Conclusion: The risk of hospitalization due to infection is associated with time on rituximab treatment, in patients with lympho- or neutropenia, and in patients with primary progressive MS. We observed a time-dependent decline in IgG values, in contrast to neutrophil and lymphocyte count, suggesting a cumulative dose-dependent response. These predictors can assist clinicians in assessing and monitoring MS patients receiving rituximab.

Keywords: Hospitalization; Hypogammaglobulinemia; Multiple sclerosis; Rituximab; Serious infections.

MeSH terms

Agammaglobulinemia* / chemically induced
Agammaglobulinemia* / drug therapy
Agammaglobulinemia* / epidemiology
Hospitalization
Humans
Immunologic Factors / adverse effects
Lymphopenia* / chemically induced
Lymphopenia* / epidemiology
Multiple Sclerosis* / drug therapy
Multiple Sclerosis, Chronic Progressive* / drug therapy
Neutropenia* / chemically induced
Neutropenia* / drug therapy
Neutropenia* / epidemiology
Retrospective Studies
Rituximab / adverse effects

Substances

Rituximab
Immunologic Factors