Sunday, November 15, 2009

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. 

+ four more.

1 comment:

Unknown said...

I was wondering if you had heard about using rituximab for treatment of autoimmune encephalitis, specifically paraneoplastic limbic encephalitis? My mother (51 years old) is currently suffering from this disease and for the past 2 weeks has been in a coma. They are currently doing plasma phoresis, but so far no changes are noted. They have identified the autoantibodies as CRMP-5. As for some background info, she had a thymoma removed last January and was starting to recover muscle function slowly until about in September when she became very fatigued and acquired shingles and then memory loss began. She has been in the hospital for about 3.5 weeks now.
Thanks for considering this. Any feedback appreciated