MOGAD-PLEX
(2026)Objective
Evaluate the effectiveness and safety of plasmapheresis (plasma exchange/immunoadsorption) in patients with acute myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) attacks, including optic neuritis, myelitis, and cerebral presentations.
Study Summary
• Isolated optic neuritis subgroup: excellent recovery 81% (95% CI 33–100%; 4 studies; n=116 attacks) at 3–6 months.
• Plasmapheresis-related adverse events 3% (95% CI 1–14%; 4 studies; 24/444 patients); serious AEs 0.5% (95% CI 0–2%; 2/444).
Intervention
Plasmapheresis (plasma exchange [PLEX] or immunoadsorption [IA]), typically a median of 5 sessions (IQR 5–7, range 3–11) on alternate days, given as escalation after intravenous methylprednisolone (IVMP), simultaneously with IVMP, or as monotherapy for acute MOGAD attacks.
Inclusion Criteria
Studies with ≥5 patients meeting 2023 MOGAD diagnostic criteria (or MOG-IgG-positive by cell-based assay with MOGAD-typical syndrome for pre-2023 studies) treated with IVMP, IVIG, or plasmapheresis for an acute attack; any language; adult or pediatric.
Study Design
Arms: Plasmapheresis-containing regimens (PLEX/IA alone, IVMP then PLEX, IVMP simultaneously with PLEX, IVMP+IVIG then PLEX) vs IVMP-only comparison groups; observational comparison, no randomization
Patients per Arm: Overall 1,045 patients / 1,368 attacks (SR); 710 patients / 1,033 attacks in meta-analysis; PLEX-containing 517 attacks (~50.1%); IVMP-only 487 attacks; from 10 studies across >120 centers in 14 countries
Outcome
• Steroid-refractory logMAR mean difference 1.22 (0.92–1.52), p=0.73 (I²=0%).
• Excellent recovery PLEX 47% (23–71%) vs IVMP-alone 76% (2–100%).
• Good recovery PLEX 94% (88–100%) vs IVMP-alone 73% (21–100%).
• Isolated ON excellent recovery 81% (33–100%) at 3–6 mo.
• PLEX-related AEs 3% (1–14%); serious AEs 0.5% (0–2%); reported events included transient rash, fresh frozen plasma reaction, and internal jugular vein thrombosis leading to early PLEX termination in single cases.
• Overall GRADE certainty low to very low; substantial heterogeneity (I² typically 73–99%) reflecting variable design, timing, phenotype, and severity.
Clinical Question
In adults and children with acute myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) attacks (optic neuritis, myelitis, or cerebral presentations), does plasmapheresis (plasma exchange or immunoadsorption) — administered as escalation after IVMP, simultaneously with IVMP, or as monotherapy — improve visual and neurologic recovery, and what is its safety profile?
Bottom Line
In this systematic review and meta-analysis of 10 observational studies (1,045 patients, 1,368 attacks; >120 centers, 14 countries), plasmapheresis was associated with clinically meaningful visual and neurologic recovery in acute MOGAD attacks — particularly in isolated optic neuritis (excellent recovery 81%) and steroid-refractory presentations (logMAR mean difference 1.22; I²=0%) — with a low adverse-event rate (3%) and rare serious events (0.5%); however, the evidence is low-to-very-low certainty (GRADE), all included studies are observational with moderate risk of bias, and randomized trials are needed to define patient selection and timing.
Major Points
- Systematic review and meta-analysis (PROSPERO CRD420251169201) searching PubMed, Embase, Web of Science, and Cochrane Library from inception through October 20, 2025; PRISMA 2020 methodology; 2,744 records screened → 10 studies (n=1,045 patients / 1,368 attacks) in qualitative synthesis; 8 studies (n=710 / 1,033 attacks) in the meta-analysis.
- All included studies observational (7 retrospective, 3 prospective); multicenter in 7, single-center in 3; representing >120 centers across 14 countries; publications 2016–2025; 4 studies (65.6% of attacks) used the 2023 MOGAD diagnostic criteria.
- Baseline: mean age 35 ± 17 years, 56.5% female; attack manifestations dominated by optic neuritis (41%) and combined ON+myelitis±cerebral (29.4%); mean time from clinical onset to plasmapheresis 15.2 ± 13 days; PLEX regimens median 5 sessions (IQR 5–7, range 3–11) on alternate days.
- Primary efficacy — visual acuity (logMAR) pre vs post-PLEX: mean difference 1.43 (95% CI 0.63–2.24; Q=19.38, p<0.0001; I²=90%; 3 studies; 341 optic neuritis attacks). In steroid-refractory subgroup (PLEX after IVMP), mean difference 1.22 (95% CI 0.92–1.52; Q=0.12, p=0.73; I²=0%; 2 studies; 249 attacks) — heterogeneity resolved.
- Excellent recovery: plasmapheresis 47% (95% CI 23–71%; Q=730.56, p<0.0001; I²=99%; 10 study groups; 244/491 attacks); IVMP alone 76% (2–100%; I²=98%; 3 groups; 120/211). PLEX-after-IVMP subanalysis: 29% (14–45%; I²=84%; 6 groups; 134/366). Isolated optic neuritis PLEX excellent recovery 81% (33–100%; I²=79%; 4 groups; 109/116 attacks) at 3–6 mo follow-up.
- Good recovery: plasmapheresis 94% (95% CI 88–100%; Q=26.30, p=0.0004; I²=73%; 8 groups; 439/473 attacks); IVMP alone 73% (21–100%; I²=96%; 5 groups; 143/182). PLEX-after-IVMP subanalysis 81% (60–100%; I²=78%; 6 groups; 120/334).
- Safety: plasmapheresis-related adverse events 3% (95% CI 1–14%; I²=0%; 4 studies; 24/444 patients); serious AEs 0.5% (95% CI 0–2%; 2/444). Reported complications included transient rash, fresh frozen plasma reaction (1 patient, PLEX stopped after 4 cycles), and internal jugular vein thrombosis leading to premature PLEX termination in a single case (Schwake 2024).
- Meta-regression showed no clear association between baseline logMAR severity and magnitude of improvement (slope 0.10 per unit baseline; 95% CI −10.07 to 10.26; p=0.92) — but result was highly imprecise given few studies. Publication bias assessment by funnel plot; Egger regression not performed (<10 studies).
- Quality: all studies classified as moderate risk of bias by ROBINS-I (confounding [D1] and selection of reported results [D7] were dominant domains). GRADE overall certainty of evidence for both effectiveness and safety was low to very low.
Study Design
- Study Type
- Systematic Review and Random-Effects Meta-Analysis of Observational Studies (PROSPERO CRD420251169201)
- Randomization
- No
- Blinding
- N/A (meta-analysis of observational studies; no randomized trials included)
- Sample Size
- 1045
- Follow-up
- Overall 11 ± 12.2 months (n=836); primary outcome at last follow-up (mean 6 ± 2.2 months); individual studies ranged from 3 months to 43 ± 30 months
- Centers
- >120 centers across included studies (7 multicenter, 3 single-center)
- Countries
- 14 countries across the included studies (multicontinental)
Primary Outcome
Definition: Change in visual acuity measured as logMAR (pretreatment minus follow-up) after plasmapheresis in patients with optic neuritis — random-effects unpaired inverse-variance mean difference
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| IVMP alone (comparison not statistically computable due to lack of baseline + follow-up logMAR in IVMP-only cohorts) | Plasmapheresis (PLEX or IA) | - (0.63 to 2.24) | <0.0001 |
Limitations & Criticisms
- All 10 included studies were observational (7 retrospective, 3 prospective); no randomized trials of plasmapheresis in MOGAD exist — findings should be considered hypothesis-generating rather than definitive.
- GRADE certainty of evidence for both effectiveness and safety was low to very low; ROBINS-I rated all studies at moderate risk of bias, dominated by confounding (D1) and selection of reported results (D7).
- Extreme heterogeneity across pooled outcomes (I² 73–99% for most efficacy analyses), reflecting variability in study design, populations, criteria for diagnosis/relapse/recovery, treatment timing, dosing, sequencing, phenotype (ON vs myelitis vs cerebral), and baseline severity.
- Indication bias / confounding by severity: patients selected for plasmapheresis had more severe or steroid-refractory attacks than IVMP-only cohorts, biasing direct comparisons and paradoxically resulting in a lower pooled 'excellent recovery' rate for PLEX (47%) than for IVMP-alone (76%).
- Meta-analysis relies on indirect comparisons across cohorts rather than head-to-head randomized data; transitivity and consistency assumptions may not be satisfied.
- Only 3 studies contributed to the primary logMAR analysis (n=341 optic neuritis attacks); comparison group logMAR was not statistically computable due to absent baseline + follow-up VA measurements in IVMP-only cohorts.
- EDSS scores were insufficiently reported for pooled analysis; medians/IQRs were approximated to means/SDs in 2 studies, imprecise for skewed data.
- Data insufficient to formally analyze the isolated myelitis phenotype or to compare plasmapheresis vs IVIG; also insufficient granularity for the most clinically informative subgroups (severe baseline VA, IVMP failure with treatment ≤2 weeks of onset, ≥4 PLEX sessions).
- Definitions of 'steroid-refractory' varied substantially across studies (typically VA ≤20/200, <3-line Snellen improvement, or failure to regain function), complicating cross-study synthesis.
- Non-serious adverse events are known to be incompletely reported in retrospective studies — safety estimate (3%) may be an underestimate.
- Publication bias assessed only by funnel plot (Egger regression not performed given <10 studies per outcome); gray literature was excluded.
- Real-world generalizability limited by heterogeneous demographic composition (ages, ethnicities) and reliance on centers with expertise in MOGAD care.
Citation
Neurology. 2026 Aug 11;107(3):e218300. Published online 2026 Jul 22.