MINT
Inebilizumab for the Treatment of Autoimmune Generalized Myasthenia Gravis
Clinical Question
Does inebilizumab, a CD19+ B-cell–depleting monoclonal antibody, improve symptoms and function in patients with autoimmune generalized myasthenia gravis who are positive for anti–AChR or anti–MuSK antibodies compared with placebo?
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.
Design
Study Type: Randomized, double-blind, placebo-controlled, phase 3 trial
Randomization: 1
Blinding: Participants, investigators, and study personnel blinded
Enrollment Period: June 2021 – April 2023
Follow-up Duration: 52 weeks
Centers: 88
Countries: Multiple countries (not specified in extracted text)
Sample Size: 208
Analysis: Mixed-model repeated-measures analysis; intention-to-treat population
Inclusion Criteria
- Age ≥18 years
- Diagnosis of autoimmune generalized myasthenia gravis
- Positive for anti–AChR or anti–MuSK antibodies
Exclusion Criteria
- History of thymoma requiring treatment within the past year
- Receipt of B-cell–depleting therapy within 6 months before screening
- Use of intravenous immunoglobulin or plasma exchange within 4 weeks before randomization
Arms
| Field | Inebilizumab | Control |
|---|---|---|
| Intervention | Intravenous inebilizumab 300 mg on days 1 and 15; AChR-positive participants received an additional dose on day 183 | Matching intravenous placebo infusions |
| Duration | 52 weeks | 52 weeks |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Mean change from baseline in MG-ADL score at week 26 | Primary | -2.3 | -4.0 | <0.001 | |
| QMG score change at week 26 | Secondary | -3.1 | -5.4 | <0.001 | |
| Time to sustained ≥3-point improvement in MG-ADL | Secondary | Not reached | Median 12 weeks | HR 1.8 | <0.001 |
| Any adverse event | Adverse | 78% | 80% | ||
| Serious adverse events | Adverse | 6% | 7% | ||
| Infusion-related reaction | Adverse | 3% | 4% |
Subgroup Analysis
Greater magnitude of benefit in AChR-antibody–positive patients; MuSK subgroup too small for definitive conclusions.
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
Funding
Sponsored by Horizon Therapeutics
Based on: MINT (New England Journal of Medicine, 2025)
Authors: James F. Howard Jr., MD; Renato Mantegazza, MD; Jing Jing Wang, ..., MD; and the MINT Trial Investigators
Citation: N Engl J Med 2025;392:1353-1365
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