Anti-CD20 antibody therapy and risk of infection in patients with demyelinating diseases

Abstract

Background: Anti-CD20 antibody therapy may be associated with an increased risk of infections. We therefore investigated risk factors for infection in patients with demyelinating diseases treated with anti-CD20 antibody therapy. Methods: In this retrospective uncontrolled study, patients ever treated with anti-CD20 antibodies at an academic clinic were identified through the Danish Multiple Sclerosis Registry (DMSR). Data were collected from medical charts and the DMSR. We assessed occurrence of severe infections (requiring hospitalization), varicella zoster virus (VZV), major comorbidities and routine laboratory values for lymphocytes, IgG and IgM. Results: A total of 447 patients ever treated with anti-CD20 antibody therapy were identified; of these 416 with 649 patient years of follow-up were still under therapy. In this group, seven patients had VZV infections, and 16 patients had been hospitalized with infections during up to three years of follow-up on anti-CD20 therapy. Comorbidity was recorded in 80 patients. The risk of severe infection was associated with comorbidities, higher age, longer duration of treatment, and higher Expanded Disability Status Scale (EDSS) scores. In multivariable analyses treatment duration, EDSS scores and presence of comorbidity were independently associated with risk of severe infections. Serum concentrations of IgG and IgM decreased with increasing duration of therapy but were not associated with risk of severe infections. Patients with VZV infection had lower lymphocyte counts and lower serum concentrations of IgM. In multivariable analyses only lymphocyte counts were independently associated with risk of VZV infection. Conclusions: In this retrospective study of patients treated with anti-CD20 antibodies, the risk of infections requiring hospitalization was independently associated with comorbidities, duration of treatment, and higher EDSS scores. Risk of VZV infection was independently associated with lymphopenia. Future studies investigating strategies for mitigating risk of infection in patients treated with anti-CD20 antibodies are warranted, especially for older patients, patients with higher levels of disability and for patients with a longer duration of treatment.

Baseline Inflammatory Status Reveals Dichotomic Immune Mechanisms Involved In Primary-Progressive Multiple Sclerosis Pathology

“…Regarding serum immunoglobulins in the four groups of patients, ocrelizumab induced a decrease in serum IgM levels, with no changes in IgG values, as previously reported for patients treated with anti-CD20 antibodies ( 9 , 20 ). Likewise, all groups of patients showed a decrease in the IgG/IgM and IgA/IgM ratios.…”

Hypogammaglobulinemia, infections and COVID-19 in people with multiple sclerosis treated with ocrelizumab

“…( Seery et al, 2021 Aug ) Another study showed that pwMS with an infection requiring hospitalization were older, more commonly had comorbidities, had longer duration of treatment and higher EDSS scores. ( Oksbjerg et al, 2021 Jul ) Similarly, we have also shown that older age increases the risk for infections requiring hospitalization. In our cohort we didn't find association between IgG levels and infections, however, we found that smaller drop in IgM before 3 rd ocrelizumab cycle increased the risk for infection requiring hospitalization.…”

“…( Seery et al, 2021 Aug ) Data from the Danish MS registry showed that the rates of low levels of IgM and IgG among pwMS treated with CD20 depleting therapies (rituximab, ocrelizumab and ofatumumab) were 28% and 5%, respectively. ( Oksbjerg et al, 2021 Jul ) Overall, the largest body of evidence related to immunoglobulin levels exists for rituximab. When looking at the different classes of immunoglobulins, IgM was the most frequently affected immunoglobulin whose levels tend to stay low for longer periods than IgG after rituximab cessation and often remain low even after the level of B cells have returned to normal.…”

Die Corona-Pandemie und Multiple Sklerose: Impfungen und deren Implikationen für Patienten – Teil 1: Empfehlungen

“…Infektionen bergen generell ein Risiko für MS-Patienten, da sie nicht nur einen Pseudoschub auslösen können, sondern auch mit Krankheitsprogression und reduzierter Lebenserwartung assoziiert sind [ 40 , 46 , 82 ]. Dieses infektionsassoziierte Risiko kann sich durch entsprechende Begleiterkrankungen und krankheitsmodifizierende Therapien (DMTs) nochmals weiter erhöhen [ 23 , 39 , 54 , 62 , 81 ]. Darüber hinaus existieren verschiedene Theorien zur Beteiligung von Infektionen an der Immunpathogenese der MS. Diese umfassen u. a. folgende Mechanismen: „molecular mimicry“, „bystander activation“ und „epitope spreading“ [ 44 ].…”