Introduction
Myasthenia gravis (MG) is an autoimmune disease characterized by dysfunction at the neuromuscular junction. Treatment frequently includes corticosteroids (CSs) and IV immunoglobulin (IVIG). Treatment of severe MG or exacerbations frequently includes plasma exchange or IV immunoglobulin (IVIG). Plasma exchange was shown to improve muscle strength in patients with MG. Treatment with IVIG was found to produce effects equivalent to PE with fewer adverse effects. Despite CS being first-line immunosuppressive therapy, long-term CS use is associated with potentially serious side effects.
Objective
This study was conducted to determine whether immune globulin (human), 10% caprylate/chromatography purified (IGIV-C) could facilitate CS dose reduction in CS-dependent patients with MG.
Methods
- In this randomized double-blind placebo-controlled trial, CS-dependent patients with MG (Myasthenia Gravis Foundation of America Class II-Iva; AChR+) received a loading dose of 2 g/kg IGIV-C over 2 days (maximum 80 g/d) or placebo at week 0 (baseline).
- Maintenance doses (1 g/kg IGIV-C or placebo) were administered every 3 weeks through week 36.
- Tapering of CS was initiated at week 9 and continued through week 36 unless the patient worsened (quantitative MG score ≥4 points from baseline).
- CS doses were increased (based on the current CS dose) in patients who shows worsening in symptoms
- Patients were withdrawn if worsening failed to improve within 6 weeks or if a second CS increase was required.
- The primary efficacy end point (at week 39) was a ≥50% reduction in CS dose. Secondary and safety end points were assessed throughout the study and follow-up (weeks 42 and 45).
Results
- The primary efficacy end point was the percentage of patients who achieved a 50% reduction in CS dose (week 39 vs baseline [week 0]). There was no significant difference between the treatment groups in this primary end point (p = 1.00). In the IGIV-C treatment group, 60.0% of the patients reached a 50% reduction in CS dose while 63.3% reached that level in the placebo group.
- Secondary end points analysed in this study were the percent reduction in CS dose and the time to first episode of worsening of MG symptoms. There were no statistically significant differences between the treatment groups in percent reduction in CS dose (52.04% ± 44.49% reduction [mean ± SD] in the IGIV-C arm; 54.69 ± 51.36% reduction in the placebo arm) or time to first episode of worsening (25th percentile of time to first worsening [≥+4 points QMG score] 33.10 weeks IGIV-C; 30.10 weeks placebo).
- The probability of MG worsening over time during the study period was calculated using the Kaplan-Meier method. This analysis showed no difference in the probability of MG worsening between the treatment groups (p = 0.744).
Conclusion
In conclusion, the data from this study suggested no benefit of IGIV-C treatment over placebo in the reduction of daily CS dose. These results suggest that the effects of IGIV-C and CS are not synergistic and may be mechanistically different.