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. 2025 Mar;32(3):e70049.
doi: 10.1111/ene.70049.

Is a Benign Disease Course Possible in Untreated AQP4-IgG NMOSD?

Pakeeran Siriratnam  1   2   3 , Chiara Rocchi  2 , Emily Gibbons  2 , Patricia Kelly  2 , Samantha Linaker  2 , Saif Huda  2
Affiliations

Is a Benign Disease Course Possible in Untreated AQP4-IgG NMOSD?

Pakeeran Siriratnam et al. Eur J Neurol. 2025 Mar.

Abstract

Background: Most patients with aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD) require life-long immunosuppression to prevent relapses. Patients who are untreated or undergo de-escalation of therapy typically experience severe disabling relapses. We present a series of patients who, despite not receiving immunosuppression, developed minimal disability.

Methods: Case series from a UK national NMOSD referral centre. We defined benign disease as an estimated disability status scale score of ≤ 3 after a minimum of 4 years without immunotherapy.

Results: Of 153 AQP4-IgG NMOSD patients, 8 (5.2%) had a benign disease course after a median follow-up of 7.5 years (Q1: 5.8, Q3: 13.3) without immunotherapy. All patients were female, and 7/8 were of White racial background. Clinical attacks included isolated optic neuritis, transverse myelitis, area postrema syndrome or combinations of these syndromes.

Conclusion: The presence of benign NMOSD and the potential for safe de-escalation of therapy in NMOSD remains unclear. This study suggests that both may be possible. Further studies of similar cases could provide valuable insights and identify biomarkers for safe treatment discontinuation.

Keywords: AQP4; EDSS; NMOSD; benign; disability.

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Conflict of interest statement

P.S. has received travel support from Novartis and Biogen; S.H. is partly funded by the National Institute for Health Research SCPRA grant and NHS England Highly Specialised Services. The remaining authors declare no conflicts of interest with respect to the research, authorship and/or publication of this article.

Figures

FIGURE 1
FIGURE 1
Disability score changes following acute relapses and treatments. Continuous lines represent EDSS changes with each attack (at nadir and recovery). Dashed lines represent attack‐free follow‐up. The colour of treatment symbols and corresponding lines are unique to each patient. Vertical lines during the patient course represent treatment discontinuation points. Patient 6 had a relapse on azathioprine and patient 8 had a relapse on Rituximab. All other relapses occurred off long‐term immunotherapy. EDSS, estimated disability status scale.
See this image and copyright information in PMC

References

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