rituxan and MG details

Rituximab for myasthenia gravis developing after bone marrow transplant

Neurology - Volume 55, Issue 7 (October 2000)  Rituximab was administered at a dose of 260 mg/m² iv every 7 days for 4 weeks. 6-Methylprednisolone and pyridostigmine were initially maintained at the pre-rituximab dosage of 0.5 mg/kg daily and 4 mg/kg daily. During and after treatment with rituximab the patient was monitored (figure) for muscular strength and performance status using Karnofsky's scale, ARAb titer every other week using a radio receptor assay (Alifax, Hamburg, Germany; cat. no. RE21023/21), CD 20+ lymphocytes (monthly count), serum Ig level, and 6-methylprednisolone and pyridostigmine dose. Rituximab was well tolerated and no complications or toxic effects were registered in the following 5 months of observation. From the fourth week on the performance status improved and ARAb titer decreased. 6-Methylprednisolone and pyridostigmine dosage were gradually tapered to 0.2 mg/kg daily and 3 mg/kg daily at the sixth month of observation, with a performance status of 80 and a substantial reduction of corticosteroid-related symptoms and signs. After treatment with rituximab we observed no changes in serum Ig level; we documented a substantial and prolonged reduction of CD 20+ lymphocyte count (0.2 × 10⁹ /L pre-rituximab, 0.07 × 10⁹ /L and 0.04 × 10⁹ /L 1 and 5 months after the fourth rituximab infusion).

 

Silvestri NJ, Wolfe GI. Rituximab in treatment refractory myasthenia gravis.  JAMA Neurology 2017; 74: 21-23. RTeview. cites Zaja et al 2000 (above);

Lebrun C, Bourg V, Tieulie N, et al. Successful treatment of refractory generalized  myasthenia gravis with Rituximab.  Eur J Neurol 2009: 16: 246-250.  6 patients with refractory disease after thymectomy , got 375 mg/m2 weekly for four weeks then monthly for for two months, then subsequently based on clinical status.  A few patients needed infusions for 1-2 years. All patients ultimately tapered mestinon and prednisone and other drugs. 


Diaz-Manera J, Martinez Hernandez E, Querol L. et al.  Long lasting treatment effect of rituximab in MuSK myasthenia.  Neurology 2012; 78: 189-193 .  17 patients with resistant MG 9defined as failing 3 second line agents. Rituxan was given 375 mg/m2 for four weeks then monthly for two months, then if intereference with ADL's.  All patients with uSK reached minimal manifestation status by 3 months after treatment, and maintained MMS or remitted by 35 months.  Note-- drug seems best suited for MuSK patients. 

Anderson et al.Rituxan in refractory myasthenia gravis: a prospective open-label study with long term followup.. Ann Clin Trans Neurol 2016; 3: 552-555. Refractory MG given Rituxan by abvove protocol or 750 mg/m2 every 2 weeks x 1 month.  3 people got  additional cycles.  At 22 months all patients improved, and pred, IVIG and PE needs decreased. 

One case exists of PML in a MuSK myasthenic patient (Kanth KM, Solórzano GE, Goldman MD. PML in a patient with myasthenia gravis treated with multiple immunosuppressing agents. Neurol Clin Prac. 2016; 6: e17-e19). 

Durability of responseRobeson KR, Kumar A, Keung B et al.  Durability of the rituximab response in acetylcholine receptor autoantibodfy positive myasthenia gravis. JAMA Neurol 2016 : 4190.
After the first cycle, 63 % had sustained remission, 19 % had pharmacological remission and 19 % MMS not requiring treatment.

Of those who discontinued all other forms of therapy, did so at a mean of 8 months (range 1-13) after the last cycle.  9/16 (56 %) relapsed at aa mean of 36 months, but all improved with further immunosuppressive therapy.  All patietns tolerated it well. 

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