Serum immunoglobulin levels and risk of serious infections

Patients with MS have a higher risk of infections and hospital admission rates for infection compared with the general population [1]. The risk of serious infections is influenced by diverse factors, such as age, body weight, comorbidities (e.g. diabetes), disability level, concomitant treatments (e.g. steroids), and neutrophil and lymphocyte count [1,2]. “This is true for the general population, but also for MS patients”, Prof. Tobias Derfuss (University Hospital Basel, Switzerland) mentioned.

Immunoglobulins also play a major role in adaptive immunity. The risk of certain types of infection is increased when immunoglobulin levels are low [3]. Reduced blood concentration of IgG, IgM, and/or IgA is known to occur in patients treated with B-cell-depleting therapy, including ocrelizumab [4,5].

In clinical trials evaluating ocrelizumab in MS patients, infections were one of the most frequently reported adverse events. In phase 3 trials, rates of serious infections were low, and there was no increased risk compared with IFN-beta-1a and placebo observed. In an open-label extension analysis of the OPERA I and II and ORATORIO trials, evaluating patients with relapsing-remitting MS and primary progressive MS respectively, Prof. Derfuss and others assessed serum Ig levels over 5.5 years and evaluated a potential association between a decrease in IgG, IgM, or IgA levels and serious infections.

Over 5.5 years of ocrelizumab treatment, the reduction in serum levels (relative reduction from baseline to 264 weeks) were:

• In relapsing MS: IgG, 17.0%; IgA, 21.3%; and IgM, 58.1%; and
• In primary progressive MS: IgG, 16.9%; IgA, 20.5%; IgM, 56.3% [6].

At week 264, the proportions of patients reaching IgG, IgA, and IgM levels under the lower limit of normal (<LLN) were 5.7%, 5.4% and 29.2%, respectively.

After approximately 6 years of ocrelizumab exposure, rates of serious infections remained low and consistent with rates of infection-related hospitalisations in real-world MS cohorts. Overall, 14 serious infections occurred during a drop in IgG levels

1. Wijnands JM, et al. Mult Scler. 2017;23:1506-1516.
2. Md Yusof MY, et al. Arthritis Rheumatol. 2019 May 27.
3. Furst DE. Semin Arthritis Rheum. 2009;39:18-29.
4. Kim SH, et al. JAMA Neurol. 2013;70:1110-7.
5. Tallantyre EC, et al. J Neurol. 2018;265:1115-1122.
6. Derfuss T, et al. ECTRIMS 2019, abstract 65.

Posted on 8 November, 201925 March, 2024