Predicting Response to IVIG or Plasmapheresis in Myasthenia Gravis
Abstract & Commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports no financial relationships relevant to this field of study.
Synopsis: Clinical examination severity appears to be the best predictor of response to immunotherapy in patients with myasthenia gravis.
Source: Katzberg HD, et al. Predictors of response to immunomodulation in patients with myasthenia gravis. Muscle Nerve 2012;45;648-652.
Which factors predict a positive response to intravenous immunoglobulin (IVIG) or plasma exchange (PLEX) in a patient with myasthenia gravis (MG)? To address this question, data were collected from two trials comparing IVIG or PLEX to placebo, that included patients 18 years or older, with a quantitative MG score of 10.5 or greater, whose weakness worsened and thus required alteration of treatment, as determined by a neuromuscular expert. MG diagnosis was based on clinical evaluation and positive findings on repetitive nerve stimulation studies and single fiber electromyography. Negative antibody studies did not preclude the diagnosis. Exclusionary criteria encompassed worsening of symptoms due to infection or medication (e.g., aminoglycosides), hepatic, renal, or cardiac disease, hypercoagulability, hyperviscosity, pregnancy, breastfeeding, or history of anaphylaxis. Patients received either IVIG 1 g/kg/day for 2 consecutive days, or five plasma exchange procedures, performed every other day, with weekend breaks allowed. Change in quantitative MG score from baseline to 2 weeks following full therapy was the primary endpoint measure, and secondary outcome measures included quantitative MG score at 3 and 4 weeks, improvement in repetitive nerve stimulation decremental response and single fiber electromyography jitter, and change in acetylcholine receptor (AchR) antibody titers at days 28 and 60. Statistical analysis included analysis of variance (ANOVA), multivariate ANOVA for repeated measures, and analysis of covariance (ANCOVA). Chi square testing was performed and P < 0.05 was considered statistically significant.
Among 63 MG patients treated with IVIG and 42 treated with PLEX, mean age was 57 years, disease duration was approximately 5 years, and gender was equally divided among men and women. Both groups included those with or without AchR and muscle-specific kinase (MuSK) antibodies, prior thymoma or thymectomy, as well as patients currently treated with prednisone, azathioprine, or mycophenolate mofetil. Compared to non-responders, patients who responded to IVIG or PLEX were more likely to be seropositive for AchR, but not MuSK, antibodies, tended to have higher baseline quantitative MG score, and greater jitter on single fiber electromyography, but not more significant decrement of repetitive nerve stimulation studies. Ultimately, using multivariate regression, only baseline quantitative MG score proved to be a significant predictor of response to IVIG or PLEX in MG.
For MG patients refractory to IVIG or PLEX, rituximab (RTX), a chimeric monoclonal antibody against surface B cell protein CD20, appears to be an effective alternative.1 Among 13 refractory MG patients treated over 2 years in a retrospective, observational, multicenter study in France, 7 were able to discontinue prednisone treatment within a year following RTX induction, accomplished either by administering 375 mg/m2 weekly for 4 consecutive weeks, followed by 375 mg/m2 every 3 months, or by administering two 1 g infusions, 2 weeks apart, followed by 1 g infusions, as needed, if symptoms warranted. Refractory patients had all previously undergone thymectomy, had received at least 6 months of prednisone and one other immunosuppressive agent, comprising azathioprine, mycophenolate mofetil, cyclosporine, or cyclophosphamide, and either IVIG or PLEX. RTX was well tolerated with no side effects being reported, except for one case of spondylodiskitis, occurring a year following the last RTX infusion. RTX appears to be a good alternative for refractory MG. It is safe, well tolerated, and demonstrated to be efficacious in a non-randomized case series.
1. Collongues N, et al. Rituximab in refractory and non-refractory myasthenia: A retrospective multicenter study. Muscle Nerv 2012 doi:10.1002/mus.23412. Available at: http://onlinelibrary.wiley.com/doi/10.1002/mus.23412/pdf. Accessed June 15, 2012.