Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD

Mears, Veronica; Jakubecz, Collin; Seeco, Catherine; Woodson, Sophia; Serra, Alessandro; Abboud, Hesham

doi:10.1016/j.jneuroim.2023.578066

Cited by 14 publications

(11 citation statements)

References 11 publications

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“…We used the ROB2 tool for six RCTs; three of them were rated as good quality ( 24 , 26 , 51 ), and the other three studies were of low quality ( 23 , 36 , 46 ) due to the limited available data in the studies. We used the NIH tool for 30 Cohort and cross-sectional studies, 19 of them were of good quality ( 14 , 15 , 17–22 , 25 , 27 , 28 , 32 , 35 , 37 , 40 , 41 , 47 , 50 , 52 ), 11 studies were of fair quality ( 16 , 29 , 30 , 38 , 39 , 42–45 , 48 , 49 ). Three studies were assessed using the Newcastle-Ottawa Scale, with two scoring nine stars ( 31 , 33 ), and one scoring eight stars ( 34 ).…”

Section: Resultsmentioning

confidence: 99%

“…Even after 48 weeks from rituximab discontinuation, B-cell levels were merely 30.7% of baseline values ( 57 ). Another explanation involves certain B-cell subsets experiencing impaired reconstitution; for instance, post-rituximab therapy, regenerated B cells mainly comprise naïve B cells with fewer differentiated memory B cells ( 40 , 62 ). These regenerated naive B cells display reduced ability to become plasma cells, leading to decreased IgG and IgA production while still capable of producing IgM ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies in the literature have sought to investigate the potential association between low IgG levels and demographic characteristics of patients. In a study by Mears et al ( 40 ) involving 184 patients treated with rituximab and ocrelizumab, 22 patients experienced hypogammaglobulinemia. Those with hypogammaglobulinemia were more likely to be aged ≥50 years and exhibited lower initial IgG levels.…”

Section: Discussionmentioning

confidence: 99%

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Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients

Elgenidy,

Abdelhalim,

Al-kurdi

et al. 2024

Front. Neurol.

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BackgroundRecent years have seen the emergence of disease-modifying therapies in multiple sclerosis (MS), such as anti-cluster of differentiation 20 (anti-CD20) monoclonal antibodies, aiming to modulate the immune response and effectively manage MS. However, the relationship between anti-CD20 treatments and immunoglobulin G (IgG) levels, particularly the development of hypogammaglobulinemia and subsequent infection risks, remains a subject of scientific interest and variability. We aimed to investigate the intricate connection between anti-CD20 MS treatments, changes in IgG levels, and the associated risk of hypogammaglobulinemia and subsequent infections.MethodPubMed, Scopus, Embase, Cochrane, and Web of Science databases have been searched for relevant studies. The “R” software utilized to analyze the occurrence of hypogammaglobulinemia, infections and mean differences in IgG levels pre- and post-treatment. The subgrouping analyses were done based on drug type and treatment duration. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model.ResultsThirty-nine articles fulfilled our inclusion criteria and were included in our review which included a total of 20,501 MS patients. The overall prevalence rate of hypogammaglobulinemia was found to be 11% (95% CI: 0.08 to 0.15). Subgroup analysis based on drug type revealed varying prevalence rates, with rituximab showing the highest at 18%. Subgroup analysis based on drug usage duration revealed that the highest proportion of hypogammaglobulinemia occurred in individuals taking the drugs for 1 year or less (19%). The prevalence of infections in MS patients with a focus on different infection types stratified by the MS drug used revealed that pulmonary infections were the most prevalent (9%) followed by urinary tract infections (6%), gastrointestinal infections (2%), and skin and mucous membrane infections (2%). Additionally, a significant decrease in mean IgG levels after treatment compared to before treatment, with a mean difference of 0.57 (95% CI: 0.22 to 0.93).ConclusionThis study provides a comprehensive analysis of the impact of anti-CD20 drugs on serum IgG levels in MS patients, exploring the prevalence of hypogammaglobulinemia, based on different drug types, treatment durations, and infection patterns. The identified rates and patterns offer a foundation for clinicians to consider in their risk-benefit.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=518239, CRD42024518239.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients

Elgenidy,

Abdelhalim,

Al-kurdi

et al. 2024

Front. Neurol.

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“…Nevertheless, our patients only received ofatumumab for a maximum of 335 days, in comparison to the approval study that monitored patients for up to 30 months [ 27 , 52 ]. Altogether, monitoring lymphocytes and immunoglobulin levels under B cell depletion therapy remains relevant as the infection risk has been shown to be associated with lymphopenia and long-term therapy that is associated with hypogammaglobulinaemia [ 53 , 54 ]. Long-term observation will enlighten us as to whether one or the other form of application might prevail in balancing needed immunosuppressive effects with a sustained level of immune defence.…”

Section: Discussionmentioning

confidence: 99%

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis—A Real-World Scenario

Schraad,

Runkel,

Hitzler

et al. 2024

Vaccines

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Immunomodulatory and immunosuppressive therapy is needed in people with a chronic neuroinflammatory disease of the central nervous system such as multiple sclerosis (MS). Therefore, MS requires monitoring for and preventing against infectious diseases like SARS-CoV-2. Vaccination and anti-viral treatments are, in particular, recommended for elderly people and people at risk of a severe course of infection and of MS. Here, we asked whether repetitive infection or vaccination influenced responses upon receiving high efficacy treatments, namely sphingosine-1-phosphate receptor modulator (S1P) or anti-CD20 B cell antibody (anti-CD20) treatments. We performed a prospective real-world study of people with MS (pwMS) under S1P or anti-CD20 with repetitive exposure to the SARS-CoV-2 virus or vaccine. The measurement of anti-SARS-CoV-2 antibody titres was performed by two independent immunoassays after initial immunisation and after booster vaccination or infection. Other laboratory and clinical parameters were included in the analysis of influencing factors. As secondary outcomes, lymphocyte and immunoglobulin levels were observed longitudinally under intravenous and subcutaneous anti-CD20 treatment. In a long-term real-world cohort of 201 pwMS, we found that despite lymphopenia upon S1P drugs, the SARS-CoV-2 immunisation response increased both in selective and non-selective S1P (100% and 88% seroconversion, respectively), whereas those under anti-CD20 therapies merely exhibited a slight long-term increase in antibody titres (52% seroconversion). The latter was independent of immunoglobulin or total lymphocyte levels, which mostly remained stable. If the individual was immunised prior to therapy initiation, their levels of SARS-CoV-2 antibodies remained high under treatment. PwMS under non-selective S1P benefit from repetitive vaccination. The risk of an insufficient vaccination response mirrored by lower SARS-CoV-2 antibodies remains in pwMS receiving anti-CD20 treatment, even after repetitive exposure to the vaccine or virus. Due to the compromised vaccination response in CD20-depleting drugs, prompt antiviral treatment might be necessary.

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“…In a study of patients receiving rituximab or ocrelizumab for MS and other neurological disorders, 12% of patients developed hypogammaglobulinemia (9% in the ocrelizumab group and 25% in the rituximab group, p = 0.0123), with the difference persisting after matching based on time on treatment [ 47 ]. In this study older age (> 50 years), White race and lower baseline IgG and IgA levels were predictors of hypogammaglobulinemia on treatment, while lymphopenia and total time on therapy were found to be predictors of serious infection [ 47 ].…”

Section: Mechanism Of Action and Adverse Eventsmentioning

confidence: 99%

Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

Carlson,

Amin,

Cohen

2024

Drugs

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Currently, there are four monoclonal antibodies (mAbs) that target the cluster of differentiation (CD) 20 receptor available to treat multiple sclerosis (MS): rituximab, ocrelizumab, ofatumumab, and ublituximab. B-cell depletion therapy has changed the therapeutic landscape of MS through robust efficacy on clinical manifestations and MRI lesion activity, and the currently available anti-CD20 mAb therapies for use in MS are a cornerstone of highly effective disease-modifying treatment. Ocrelizumab is currently the only therapy with regulatory approval for primary progressive MS. There are currently few data regarding the relative efficacy of these therapies, though several clinical trials are ongoing. Safety concerns applicable to this class of therapeutics relate primarily to immunogenicity and mechanism of action, and include infusion-related or injection-related reactions, development of hypogammaglobulinemia (leading to increased infection and malignancy risk), and decreased vaccine response. Exploration of alternative dose/dosing schedules might be an effective strategy for mitigating these risks. Future development of biosimilar medications might make these therapies more readily available. Although anti-CD20 mAb therapies have led to significant improvements in disease outcomes, CNS-penetrant therapies are still needed to more effectively address the compartmentalized inflammation thought to play an important role in disability progression.

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Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD

Cited by 14 publications

References 11 publications

Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients

Hypogammaglobulinemia and infections in patients with multiple sclerosis treated with anti-CD20 treatments: a systematic review and meta-analysis of 19,139 multiple sclerosis patients

Long-Term Observation of SARS-CoV-2 Vaccination Response upon High Efficacy Treatment in Multiple Sclerosis—A Real-World Scenario

Drugs Targeting CD20 in Multiple Sclerosis: Pharmacology, Efficacy, Safety, and Tolerability

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