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NASHVILLE, Tennessee — In a multicenter collaboration, patients with multiple sclerosis (MS) who developed hypogammaglobulinemia (HGG) after treatment with ocrelizumab or ofatumumab were found to have about a twofold increase in the risk for serious infection.

Just under 10% of those who received either of the B-cell–depleting monoclonal antibody therapies developed HGG, the study showed. This correlated with the depletion of B cells and reductions in the immunoglobulin (Ig) G and IgA.

The rate of serious infection among those who developed HGG on ocrelizumab or ofatumumab was 16.8% — more than double that of patients without HGG.

Although the association between rituximab and HGG has been well documented, the growing use of the monoclonal antibodies targeting B cells in MS suggests more data are needed to understand the risk for HGG "in the real world," investigator Kiranpal S. Sangha, PharmD, a clinical pharmacy specialist at the Waddell Center for Multiple Sclerosis, University of Cincinnati, Cincinnati, told Medscape Medical News.

"The use of anti-CD20 therapies in MS, particularly prescriptions for ocrelizumab and ofatumumab, has been increasing," he said. "There are no studies comparing rates of serious infection in MS patients on one of these commonly used therapies."

The findings were presented on May 30 at the Consortium of Multiple Sclerosis Centers (CMSC) 2024 Annual Meeting.

Well-Known Risk

The data for this retrospective study, called REPLACE-MS, were pooled from Sangha's Institution, MS clinics associated with University Hospitals of Case Western Reserve University, Cleveland, and the Medical College of Wisconsin, Milwaukee, Wisconsin.

Of 911 patients, 832 were treated with ocrelizumab and 179 with ofatumumab. The rates of HGG were 9.9% and 8.9%, respectively, a difference on univariate analysis that was not significant (P = .676).

Compared with patients on one of the two drugs who did not develop HGG, those who did were slightly older (48 vs 45 years; P = .03), more likely to be White (92% vs 71%; P = .00001), and had a longer treatment duration (1130 vs 927 days; P = .0016).

There was no difference between groups in mean body mass index, the presence of a progressive phenotype, or sex.

After adjusting for confounders, increased risk for HGG while taking ocrelizumab or ofatumumab was significantly higher among people age 50 years or older (adjusted odds ratio [aOR], 1.61; P = .0386), White (aOR, 4.51; P = .0002), and those with a treatment duration of longer than 3 years (aOR, 1.97; P = .009).

Overall, 73 patients developed a serious infection and 836 did not, irrespective of HGG status.

Among those treated with ocrelizumab or ofatumumab, the rate of infection was 16.8% in patients with HGG vs 7.1% in those without the condition (P = .001), Sangha said.

On multivariate analysis, factors associated with infection risk included HGG (aOR, 2.55; P = .0057), > 3 years on therapy (aOR, 1.77; P = .04), previous disease-modifying therapy (aOR, 2.66; P = .0021), and progressive phenotype (aOR, 3.62; P < .001). Lymphopenia (defined as ALC, < 1000/µL) was also a significant predictor (aOR, 3.19; P < .001).

More Data Needed

Commenting on the findings for Medscape Medical News, Enrique Alvarez, MD, PhD, vice chair of clinical research in the Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, noted that there is broad agreement that patients should be monitored regularly for changes in IgG levels and for infection.

In a recent review article published in Multiple Sclerosis and Related Disorders on the risk for HGG in patients with MS on anti-CD20 therapy, Alvarez and coauthors also concluded that the risk for serious infection is not trivial even if the benefits of these therapies typically provide a favorable benefit-to-risk ratio.

Alvarez noted that there were inconsistences regarding HGG risk from a series of small initial studies, but "as we look at these larger studies, the association with infection is becoming clearer," he said.

He suggested evaluations in patients with MS on B-cell–depleting therapies should be conducted "at least yearly," but cautioned that there is not full agreement about when biomarkers, such as IgG or HGG, are low enough to warrant a change in management of MS.

Based on his analysis, Alvarez agreed that "the risks go up in patients who have been treated for the longest and those with higher levels of disability," he said.

As a result, these might be factors guiding how often to monitor patients with MS on a B-cell–depleting therapy for infection risk, but more data are needed to generate guidelines, Alvarez added.

Sanha reported no potential conflicts of interest. Alvarez reported financial relationships with Alexion, Biogen, Celgene/Bristol Myers Squibb, EMD Serono, Genentech, Novartis Sanofi, and TG Therapeutics.