MINT
(2025)Objective
To evaluate the efficacy and safety of inebilizumab, a CD19+ B-cell–depleting monoclonal antibody, in patients with seropositive generalized myasthenia gravis (gMG).
Study Summary
• Greater clinical benefit observed in the AChR-antibody–positive subgroup
• Safety profile consistent with previous studies of B-cell depletion
Intervention
Phase 3, double-blind, randomized, placebo-controlled trial. Participants received intravenous inebilizumab 300 mg on days 1 and 15; AChR-positive participants also received an additional dose on day 183. Placebo group received matching infusions. Glucocorticoids were tapered starting week 4 toward 5 mg/day by week 24.
Inclusion Criteria
• Diagnosis of autoimmune generalized myasthenia gravis
• Positive for anti–AChR or anti–MuSK antibodies
Study Design
Arms: Inebilizumab group, Placebo group
Patients per Arm: Inebilizumab: 104; Placebo: 104
Outcome
• In AChR-positive subgroup: similar magnitude of benefit with sustained effect at week 52
• Incidence of serious adverse events similar between groups
Bottom Line
In patients with autoimmune generalized myasthenia gravis, inebilizumab significantly improved MG-ADL scores over 26 weeks compared with placebo, with a favorable safety profile and greater benefits in the AChR-antibody–positive subgroup.
Major Points
- Methotrexate did not reduce prednisone use in generalized MG: minimal prednisone dose at 12 months 11.6mg (MTX) vs 13.0mg (placebo); P=NS.
- 50 patients with generalized MG on prednisone. 12-month, double-blind, placebo-controlled.
- MTX dose: 20 mg/week (oral). Steroid-sparing trial design.
- Secondary endpoints (QMG, MG-ADL) also not significantly different.
- Well tolerated: hepatotoxicity, cytopenias rare at 20mg/week.
- Published Lancet Neurology 2011 (Pasnoor et al.). Largest RCT of MTX in MG at time.
- Challenge: MG trials are difficult — high placebo response, variable natural history.
- MTX widely used empirically in MG despite this negative trial — clinical experience suggests longer treatment may be needed.
- Trial may have been underpowered (n=50) and too short (12 months) to detect steroid-sparing effect.
- Published as negative but influenced clinical practice: MTX remains second/third-line option in MG.
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled, phase 3 trial
- Randomization
- Yes
- Blinding
- Participants, investigators, and study personnel blinded
- Sample Size
- 208
- Follow-up
- 52 weeks
- Centers
- 88
- Countries
- Multiple countries (not specified in extracted text)
Primary Outcome
Definition: Mean change from baseline in MG-ADL score at week 26
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| -2.3 | -4.0 | - (-2.5 to -0.9 (difference between groups)) | <0.001 |
Limitations & Criticisms
- Short follow-up for long-term safety assessment
- Small sample size for MuSK-antibody–positive subgroup limits subgroup conclusions
- Exclusion of patients recently treated with other B-cell–depleting agents may limit generalizability
Citation
N Engl J Med 2025;392:1353-1365