Are all anti-CD20 antibodies created equal?

A

Rituximab is part mouse part human antibody and ocelizumab is humanised. They bind to similar regions of CD20 on B cells but ocrelizumab is much better at depleting B cells due to augmented killing activity. This was seen here in a real life study.

There was a small drop in IgM for both treatments and a small drop in IgG within 12 months with ocrelizumab. In the phase III this was by less than 10% in the first year.

Antibody levels for ocrelizumab where slightly lower than with rituzimab in people over 50 years old. This may suggest that age should be considered when deciding on doses and dosing intervals with B cell depleting drugs in order to reduce the risks of developing IgG deficiency, since it tends to be long-lasting even after drug administration has been terminated.

The capacity to make IgM and IgG capacity maybe a issue for the long term use of anti CD20. If it drops you may be more open to infection. The manufacturers have trial data on this. It was presented at ECTRIMS ages ago. Time to get this published and easily visible.

A comparative study of tolerability and effects on immunoglobulin levels and CD19 cell counts with ocrelizumab vs low dose of rituximab in multiple sclerosis.Evertsson B, Hoyt T, Christensen A, Nimer FA, Foley J, Piehl F.Mult Scler J Exp Transl Clin. 2020 6(4):2055217320964505.

Background: Rituximab (RTX) and ocrelizumab (OCR) are two anti-CD20 biologics used in MS; however, comparisons on safety and efficacy are rare.

Objective: To compare treatment outcomes over the first year with RTX and OCR.

Methods: Retrospective cohort study comprising MS patients initiating RTX at the Karolinska University Hospital (Sweden; n = 311) and OCR at Rocky Mountain MS Clinic (Utah, USA; n = 161), respectively.

Results: Levels of immunoglobulin G measured in blood dropped 0.16 g/L (95% confidence interval 0.01 to 0.31) with each OCR infusion, but remained stable with RTX. In contrast, levels of immunoglobulin M decreased to a similar extent with both drugs. Ten and 15% of patients discontinued treatment with RTX and OCR, respectively (n.s), however, adverse events leading to treatment discontinuation were more common with OCR (6.8% vs 2.6%; p = 0.026). Only 3.1 and 1.6% discontinued OCR and RTX, respectively, due to lack of effect (n.s). The degree of B cell depletion was superior with OCR.

Conclusion: Overall, differences between the two treatments were small. Although the study design precludes robust conclusions regarding the risk-benefit with the studied therapies, our findings indicate that the tolerability and safety with RTX is not inferior to OCR.

About the author

MouseDoctor

4 comments

  • As with most drugs, companies are loathe to doing head to head trials for obvious reasons.

    As for age and Ab production, here is something I cullled.

    Both humoral and cellular immune responses are impaired in aged individuals, leading to decreased vaccine responses. Although T cell defects occur, defects in B cells play a significant role in age-related humoral immune changes. The ability to undergo class switch recombination (CSR), the enzyme for CSR, AID (activation-induced cytidine deaminase) and the transcription factor E47 are all decreased in aged stimulated B cells.

    So I guess folks have looked into this and therefore, B cell mediated responses to OCR or RTX falling off the ledge is no surprise.

  • Further reading and thanks to computers one needs to do no reading !!!!
    Even our residents in hospitals look up stuff. Why not ? So long as you know what to search for and what to look for, right ? Read on……..

    Aging affects the humoral immune response both quantitatively and qualitatively, as specificity and class of antibody produced are changed (Frasca and Blomberg, 2009; Linton and Dorshkind, 2004). The changes in the humoral immune response during aging significantly contribute to the increased susceptibility of the elderly to infectious diseases and reduce the protective effects of vaccination (McElhaney and Effros, 2009). Not only decreased antibody production but also reduced duration of protective immunity following immunization has been reported (Steger et al., 1996).

    High-affinity protective antibodies are produced in the germinal centers (GC) of secondary lymphoid tissue during affinity maturation processes which are characterized by somatic hypermutation (SHM) of immunoglobulin (Ig) genes and subsequent selection of the genes encoding the best antibodies (Klein and Dalla-Favera, 2008; Longerich et al., 2006).

  • Like this bit

    Conclusion: Overall, differences between the two treatments were small. Although the study design precludes robust conclusions regarding the risk-benefit with the studied therapies, our findings indicate that the tolerability and safety with RTX is not inferior to OCR.

    Its 2000 euros versus 60000 euros

    What will you choose?

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives