An update on evolving treatment algorithms for NMOSD and MOGAD

Prof. Jeffrey Bennett (University of Colorado, CO, USA) reviewed the acute and preventative strategies for the treatment of aquaporin (AQP)4 IgG seropositive (AQP4+) neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and added his expert opinion [1].

NMOSD and MOGAD are clinically overlapping CNS disorders against distinct glial antigens: AQP4 and MOG. Prof. Bennett argued that the acute treatment of both conditions is relatively similar, while differences are more evident in the preventative treatment. Acute relapses of both conditions respond to high-dose corticosteroids, but results are generally better in MOGAD patients. In a French cohort, return to baseline EDSS score after corticosteroid treatment was achieved by 14 of 121 (12.1%) NMOSD patients versus 20 of 67 (33.3%) MOGAD patients [2]. “Quick action,” was the overall message concerning acute treatment, according to Prof. Bennett, who added that “avoiding delay is shown to have a benefit both for high-dose corticosteroids and plasma exchange/apheresis. Particularly in NMOSD, early use of plasma exchange can result in better outcomes than corticosteroids.” Prof. Bennett also noted that acute care for NMOSD and MOGAD attacks needs further optimisation.

Prophylactic treatment of NMOSD is initiated after the first relapse and is usually lifelong; in MOGAD, it is usually reserved for (confirmed) relapse. Prof. Bennett discussed 3 prophylactic treatment options: immunosuppressive agents, immunomodulation, and complement inhibition. Available immunosuppressive treatments are azathioprine and mycophenolate. “These are reasonable first-line therapies in MOGAD, but I would consider them – if available – second-line therapies in NMOSD, considering the open-label experience and the use of new monoclonal antibodies that are approved for NMOSD,” Prof. Bennett noted.

Moving on to immunomodulation, intravenous immunoglobulin has shown promise for MOGAD. For AQP4+ NMOSD relapse prevention, 4 therapies have now been approved worldwide. Mechanisms include B-cell depletion, IL-6 receptor blockade, and complement inhibition. B-cell depletion (inebilizumab) is more effective in NMOSD than in MOGAD; IL-6R blockade (satralizumab) may be equally effective in both conditions. For NMOSD, complement inhibition is a third option. “Both ravulizumab and eculizumab have shown promise and very potent relapse inhibition in NMOSD,” reported Prof. Bennett, stressing that inebilizumab, satralizumab, and eculizumab also have been shown to be effective in open-label extension studies (data on ravulizumab not yet available), limiting the annualised relapse rate to <0.1. Previous therapies that are now off-label show a higher annualised relapse rate, which in most cases is similar or even higher than in the placebo groups of the large registration trials for the new options for AQP4+ NMOSD. “So we may not be doing as well as we think with these off-label therapies,” concluded Prof. Bennett.

Large, prospective placebo-controlled trials for IL-6R (satralizumab) and neonatal Fc receptor inhibition (rozanolixizumab) for MOGAD relapse prevention are underway.

Prof. Bennett presented treatment algorithms for both NMOSD and MOGAD, in which he added off-line options in case registered therapies are not available (see Figures 1 & 2).

Figure 1: Treatment algorithm for NMOSD [1]



Ig, immunoglobulin; IV, intravenous.

Figure 2: Treatment algorithm for MOGAD [1,3]



Ig, immunoglobulin; IV, intravenous; MOGAD, myelin oligodendrocyte glycoprotein antibody-associated disease; PLEX, plasma exchange.

1. Bennett JL. Treatment of NMOSD and MOGAD: an update. O167, MSMilan 2023, 11–13 October, Milan, Italy.
2. Demuth S, et al. J Neuroinflammation. 2022;19:62.
3. Bruijstens AL, et al. Eur J Paediatr Neurol. 2020 Nov;29:2-13.

 

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Posted on 4 December, 20234 December, 2023