Rituximab Treatment Associated with Reduced Relapse Rate in AQP4-IgG Positive NMOSD and MOGAD

A study using patient data from John Hopkins showed that rituximab treatment was associated with reduced annualized relapse rates in AQP4-IgG seropositive NMOSD and MOGAD.

Paula Barreras, MD, neurologist, Johns Hopkins University School of Medicine

Paula Barreras, MD

A recent retrospective observational study from Johns Hopkins resulted in rituximab treatment being significantly associated with a reduced relapse rate for patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Previous data on using rituximab in long-term, such as with the effectiveness and safety of the treatment, were limited.1

After rituximab was initiated in both NMOSD (median, annualized relapse rate [ARR]: pre treatment, 1.1; post treatment, 0; P <.001) and MOGAD (median ARR: pretreatment, 1.9, post treatment, 0.3; P = .002), the ARR decreased. Relapses on rituximab occurred in 28% of NMOSD patients (n = 31) and 61% of MOGAD patients (n = 14).

Seventy-seven percent of NMOSD treatment failures happened in the setting of delayed/missed rituximab doses and/or peripheral B cell reconstitution (24 relapses) or within the initial 6-months after starting rituximab (13 relapses). Whereas the patients with MOGAD had a treatment failure rate of 54%, a smaller proportion.

Lead investigator, Paula Barreras, MD, neurologist, Johns Hopkins University School of Medicine, and colleagues wrote, “In MOGAD, while a reduction in relapses was observed after initiation of rituximab, this association appeared to be less robust than in AQP4-IgG seropositive NMOSD. Severe infections and hypogammaglobulinemia occurred in a significant proportion of patients, highlighting the need for close monitoring of infectious complications.”

A retrospective chart review was performed between January 2010 and June 2021 of patients with aquaporin 4 seropositive (AQP4-IgG+) NMOSD (n = 111) or MOGAD (n = 23) at the Johns Hopkins Neuromyelitis Optica Clinic which had patients included who received at least 1 dose of rituximab. Other criteria for participants’ data included treatment with at least 1 dose of rituximab with diagnostic and therapeutic records, and at least 1 clinic visit after starting rituximab.

The median for the duration of rituximab treatment on patients with NMOSD was 3.7 years (range, 0.5-13.2) and for patients with MOGAD was 2.1 years (range, 0.5-7.0). In addition, the risk of relapse on rituximab was greater for patients with MOGAD compared with patients with NMOSD (HR, 2.8; 95%CI, 1.5-5.2; P =.001). Thirteen percent of patients required hospitalization because of infection and IgG hypogammaglobulinemia occurred in 17% of patients. Notably, the median for the rituximab treatment duration before IgG hypogammaglobulinemia was 5.4 years (IQR, 3.8-7.7).

Barreras et al wrote, “we observed that the vast majority of relapses occurring during rituximab treatment occurred either within the first 6 months after initiation, or in the setting of missed/delayed infusions and/or peripheral blood B-cell reconstitution. Importantly, no relapses were observed in patients who remained on rituximab and had been continuously treated for at least 2.5 years.”

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Other notable findings include that there was a large proportion of relapses in patients with MOGAD that occurred in the absence of missed doses or peripheral blood B cell reconstitution. Also, the patients with MOGAD continued to experience relapses while on treatment, relapsed within the first 6-months of initiating treatment and remained on rituximab. Hence, the investigators concluded that there should be a low threshold maintained to switch from rituximab to another agent for patients with MOGAD who experience relapses on rituximab.

This study is supported by prior findings in which suggested that rituximab could be useful maintenance therapy for individuals with NMOSD who are AQP4-IgG+.2 The limitations of the study included that it was restricted to relapses and adverse events documented from the medical record, participants with MOGAD constituted a relatively small fraction of the cohort, and the laboratory data was not available for all of the patients.

Barreras et noted, “Given the relatively large proportions of patients experiencing hypogammaglobulinemia, lymphopenia and infection requiring hospitalization, especially in patients with more severe disability, infection risk in patients treated with B-cell depleting therapies is an important consideration when counseling patients regarding treatment selection, and patients should be closely monitored during follow-up.” Further study is needed on the use of concurrent corticosteroids within the first 6-months of rituximab therapy to mitigate early relapse risk.

REFERENCES
1. Ringelstein M, Ayzenberg I, Lindenblatt G, et al. Interleukin-6 Receptor Blockade in Treatment-Refractory MOG-IgG-Associated Disease and Neuromyelitis Optica Spectrum Disorders. Neurol Neuroimmunol Neuroinflamm. 2021;9(1):e1100. doi:10.1212/NXI.0000000000001100
2. Tahara M, Oeda T, Okada K, et al. Safety and efficacy of rituximab in neuromyelitis optica spectrum disorders (RIN-1 study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2020;19(4):298-306. doi:10.1016/S1474-4422(20)30066-1

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