MG-BNMA
(2026)Objective
Compare efficacy and safety of generalized myasthenia gravis (gMG) treatments while accounting for differences in trial designs and populations, given the absence of head-to-head studies.
Study Summary
• MG-ADL reduction vs placebo: FcRn inhibitors −1.93 (95% CrI −2.21 to −1.65); CD19+ BCDT −1.91 (−2.97 to −0.84); C5i −1.84 (−2.48 to −1.19).
• Safety: FcRn inhibitors had higher TRAE odds vs placebo (OR 2.20, 1.52–3.38); C5i and CD19+ BCDT TRAE odds comparable to placebo.
Intervention
Bayesian network meta-analysis of 27 placebo-controlled RCTs comparing FcRn inhibitors, C5 complement inhibitors, CD19+/CD20+ B-cell depletion, IVIg, CD40 inhibitor, IL-6 signaling inhibitor, BAFF inhibitor, and immunosuppressive therapies for generalized MG.
Inclusion Criteria
Prospective placebo-controlled RCTs of adults (≥18 y) with generalized MG reporting mean treatment difference (with SE/SD/CI) in MG-ADL or QMG change from baseline.
Study Design
Arms: 17 active treatment regimens across 9 mechanism-of-action classes vs placebo + standard of care
Patients per Arm: Treatment n=1,232 ; Placebo n=1,086 (27 RCTs, 1987–2025)
Outcome
• MG-ADL mean difference vs placebo: FcRn −1.93 (−2.21 to −1.65); CD19+ BCDT −1.91 (−2.97 to −0.84); C5i −1.84 (−2.48 to −1.19).
• Phase-3-only subset: FcRn QMG −4.03 (−4.93 to −3.13), MG-ADL −2.27 (−2.92 to −1.63); C5i QMG −2.42 (−3.33 to −1.54), MG-ADL −1.71 (−2.44 to −0.97); CD19+ BCDT QMG −2.5 (−3.96 to −1.04), MG-ADL −1.9 (−3.02 to −0.79).
• MuSK+ patients: rozanolixizumab 7 mg/kg had greatest MG-ADL reduction −9.42 (−15.07 to −3.67).
• TRAE odds ratio vs placebo: IVIg 3.62 (1.01–13.21); IL-6i 3.24 (1.29–8.29); FcRn 2.20 (1.52–3.38); C5i and CD19+ BCDT comparable to placebo; CD20+ BCDT lowest (SUCRA 0.735).
Clinical Question
Among therapies for generalized myasthenia gravis (gMG), how do FcRn inhibitors, C5 complement inhibitors, B-cell depletion therapies, IL-6 inhibitors, IVIg, and conventional immunosuppressants compare in efficacy (QMG and MG-ADL change from baseline) and safety (treatment-related adverse events) when accounting for differences in trial populations?
Bottom Line
FcRn inhibitors, C5 complement inhibitors, and CD19+ B-cell depletion therapy show comparable efficacy on QMG and MG-ADL reduction in gMG (differences between classes below minimum clinically important thresholds), and FcRn inhibitors carry higher odds of treatment-related adverse events than placebo, whereas C5i and CD19+ BCDT do not.
Major Points
- Bayesian NMA of 27 placebo-controlled RCTs (1987–2025; 17 treatments across 9 mechanism classes) in generalized MG, including recently approved targeted biologics.
- FcRn inhibitors produced the largest QMG reduction vs placebo (−3.63; 95% CrI −4.43 to −2.77), followed by C5 complement inhibitors (−2.59; −3.92 to −1.28) and CD19+ B-cell depletion (−2.50; −5.11 to 0.12).
- MG-ADL reductions were similar across FcRn (−1.93), CD19+ BCDT (−1.91), and C5i (−1.84) — none exceeded the 2-point clinically meaningful difference between active arms.
- Higher percentage of female patients and greater enrollment age were associated with greater QMG reduction (sex β = −3.16; age β = 2.09), suggesting population differences may confound between-trial comparisons.
- In an AChR-antibody–positive subgroup analysis, FcRn inhibitors showed the greatest treatment effect (QMG −3.81; MG-ADL −2.20) with CD19+ BCDT and C5i showing broadly comparable magnitudes.
- Treatment-related adverse events: FcRn inhibitors (OR 2.20; 1.52–3.38), IL-6 signaling inhibitors (OR 3.24; 1.29–8.29), and IVIg (OR 3.62; 1.01–13.21) had higher TRAE odds than placebo; CD20+ B-cell depletion (SUCRA 0.735) and IST (SUCRA 0.690) had the lowest odds of TRAE.
Study Design
- Study Type
- Bayesian Network Meta-Analysis of Randomized Controlled Trials
- Randomization
- No
- Blinding
- N/A (meta-analysis; included trials were placebo-controlled and mostly double-blind)
- Sample Size
- 2318
- Follow-up
- Included trials 4–52 weeks (outcome time points at which QMG/MG-ADL treatment effects were reported)
- Centers
- Multiple (across 27 RCTs)
- Countries
- Multinational (varied by included trial; several US, European, and Chinese trials)
Primary Outcome
Definition: Mean treatment difference in QMG score change from baseline vs placebo (all-phase, unadjusted)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Placebo + standard of care (reference) | FcRn inhibitors: −3.63 pts | C5i: −2.59 pts | CD19+ BCDT: −2.50 pts | - (FcRn −4.43 to −2.77 ; C5i −3.92 to −1.28 ; CD19+ BCDT −5.11 to 0.12 (95% credible intervals)) | Bayesian NMA — significance interpreted by credible intervals excluding zero (FcRn and C5i significant; CD19+ BCDT crossed zero) |
Limitations & Criticisms
- Excluded pivotal azathioprine and thymectomy RCTs and one 2008 international phase 3 mycophenolate mofetil trial because they reported medians or did not report change from baseline — limits comparison with foundational MG therapies.
- Meta-analysis of aggregate data, not individual-patient data — precluded sensitivity analyses for disease duration, early-onset vs late-onset MG, refractoriness, or thymectomy status.
- Covariate-adjusted treatment effects are model-based predictions and should not be interpreted as Class I subgroup evidence.
- Bayesian hierarchical models limited to simple linear meta-regression due to computational constraints; more complex interactions were not modeled.
- TRAE reporting was inconsistent across trials — only 18 of 27 trials contributed to safety analysis; batoclimab phase 3 disproportionately drove the FcRn TRAE signal, and IVIg TRAE OR came from a single trial.
- Heterogeneity in trial length (4–52 weeks), assessment timepoints, and mechanism-specific temporal response patterns (e.g., cyclical FcRn effect vs sustained CD19+ BCDT benefit) complicate direct efficacy comparison.
- For some studies, MG-ADL/QMG data had to be extracted from published figures using an online tool (graphreader) — introduces potential measurement error, notably for efgartigimod phase 2/3 week-4 data.
- Several IST trials (2 MMF, 2 cyclosporine, 1 tacrolimus, 2 batoclimab) were single-country studies, limiting generalizability.
Citation
Neurology. 2026 Aug 11;107(3):e218351.