PML in a patient with myasthenia gravis treated with multiple immunosuppressing agents

Kanth, Kiran M.; Solórzano, G; Goldman, Myla D.

doi:10.1212/cpj.0000000000000202

Cited by 41 publications

(26 citation statements)

References 7 publications

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“…To date, only 1 case of PML after rituximab has been reported in MG, in a 58-year-old woman with seronegative disease given 4 monthly rituximab infusions who was concomitantly undergoing treatment with prednisone, pyridostigmine, and IVIg or PLEX; she had previously received mycophenolate mofetil or azathioprine as steroidsparing agents. 92 The patient died 12 months after completing rituximab therapy; autopsy showed classical PML pathology in the brain. Despite the rarity of reports of PML in rituximab-treated MG patients, extreme and continued vigilance is warranted for early detection of the features of the disease.…”

Section: Discussionmentioning

confidence: 99%

“…Rituximab‐associated PML cases were significantly older, more frequently men, had shorter time to onset after initiation of therapy, and had higher fatality rates, when compared with PML after natalizumab treatment. To date, only 1 case of PML after rituximab has been reported in MG, in a 58‐year‐old woman with seronegative disease given 4 monthly rituximab infusions who was concomitantly undergoing treatment with prednisone, pyridostigmine, and IVIg or PLEX; she had previously received mycophenolate mofetil or azathioprine as steroid‐sparing agents . The patient died 12 months after completing rituximab therapy; autopsy showed classical PML pathology in the brain.…”

Section: Discussionmentioning

confidence: 99%

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Rituximab treatment of myasthenia gravis: A systematic review

et al. 2017

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Rituximab is a chimeric mouse/human anti-CD20 monoclonal immunoglobulin. We reviewed the efficacy and safety of rituximab in 169 myasthenia gravis (MG) patients from case reports and series. Antibodies to the acetylcholine receptor (AChR) were present in 59% and muscle-specific tyrosine kinase (MuSK) in 34%. Modified Myasthenia Gravis Foundation of America postintervention scale of minimal manifestations (MM) or better occurred in 44%, and combined pharmacologic and chronic stable remission in 27% overall; MM or better was achieved in 72% of MuSK MG and 30% of AChR MG (P < 0.001). Posttreatment relapses decreased more in MuSK MG (P = 0.05). Response predictors were MuSK MG, less severe disease, and younger age at treatment. Among a responder subset, 26% of AChR and 82% of MuSK MG patients showed decreased posttreatment antibody titers. Rituximab was generally well tolerated. Detectable serum rituximab and depleted CD20 B-cells were observed up to 20 and 16 weeks, respectively, after 4 weekly infusions. Muscle Nerve 56: 185-196, 2017.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rituximab treatment of myasthenia gravis: A systematic review

et al. 2017

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“…This finding is of particular note because most patients had been treated previously with two or more immunosuppressive therapies. Close follow‐up is recommended, however, as several cases of side effects of rituximab have been reported in patients with MG …”

Section: Discussionmentioning

confidence: 99%

The impact of rituximab infusion protocol on the long‐term outcome in anti‐MuSK myasthenia gravis

Cortés-Vicente

Rojas‐García

Díaz‐Manera

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo evaluate whether the clinical benefit and relapse rates in anti‐muscle‐specific kinase (MuSK) myasthenia gravis (MG) differ depending on the protocol of rituximab followed.MethodsThis retrospective multicentre study in patients with MuSK MG compared three rituximab protocols in terms of clinical status, relapse, changes in treatment, and adverse side effects. The primary effectiveness endpoint was clinical relapse requiring a further infusion of rituximab. Survival curves were estimated using Kaplan–Meier methods and survival analyses were undertaken using Cox proportional‐hazards models.ResultsTwenty‐five patients were included: 11 treated with protocol 4 + 2 (375 mg/m2/4 weeks, then monthly for 2 months), five treated with protocol 1 + 1 (two 1 g doses 2 weeks apart), and nine treated with protocol 4 (375 mg/m2/4 weeks). Mean follow‐up was 5.0 years (SD 3.3). Relapse occurred in 18.2%, 80%, and 33.3%, and mean time to relapse was 3.5 (SD 1.5), 1.1 (SD 0.4), and 2.5 (SD 1.4) years, respectively. Based on Kaplan–Meier estimates, patients treated with protocol 4 + 2 had fewer and later relapses than patients treated with the other two protocols (log‐rank test P = 0.0001). Patients treated with protocol 1 + 1 had a higher risk of relapse than patients treated with protocol 4 + 2 (HR 112.8, 95% CI, 5.7–2250.4, P = 0.002). Patients treated with protocol 4 showed a trend to a higher risk of relapse than those treated with protocol 4 + 2 (HR 9.2, 95% CI 0.9–91.8, P = 0.059).InterpretationThis study provides class IV evidence that the 4 + 2 rituximab protocol has a lower clinical relapse rate and produces a more durable response than the 1 + 1 and 4 protocols in patients with MuSK MG.

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“…Treatment with rituximab is generally well tolerated. However, a few severe side effects have been reported in MG patients (e.g., myocardial infarction, spondylodiscitis, agranulocytosis, and two cases of progressive multifocal leukoencephalopathy). Prolonged B cell depletion has been observed in a patient with MuSK + MG .…”

Section: Therapymentioning

confidence: 99%

Myasthenia gravis with antibodies to MuSK: an update

Evoli

Alboini

Damato

et al. 2017

Annals of the New York Academy of Sciences

113

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Myasthenia gravis with antibodies to the muscle-specific tyrosine kinase (MuSK MG) is a rare disease with distinctive pathogenic mechanisms and clinical features. An acute onset and predominant bulbar muscle weakness are very common and highly suggestive of the disease. On the other hand, a more indolent course, atypical ocular presentation, and signs of cholinergic hyperactivity may complicate the diagnosis. Though MuSK MG is still a severe disease, over the years we have observed a steady reduction in the rate of respiratory crisis and a significant improvement in the clinical outcome, both likely related to earlier diagnosis and timely treatment. Despite the improved management, MuSK MG patients tend to remain dependent on long-term immunosuppressive treatment and may develop permanent disabling weakness. In uncontrolled studies, B cell depletion with rituximab proved effective in most patients with refractory disease, inducing prolonged clinical responses associated with a sustained reduction of serum antibody levels. Promising results from experimental studies and case reports suggest that both 3,4-diaminopyridine and albuterol may be effective as symptomatic agents.

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PML in a patient with myasthenia gravis treated with multiple immunosuppressing agents

Cited by 41 publications

References 7 publications

Rituximab treatment of myasthenia gravis: A systematic review

Rituximab treatment of myasthenia gravis: A systematic review

The impact of rituximab infusion protocol on the long‐term outcome in anti‐MuSK myasthenia gravis

Myasthenia gravis with antibodies to MuSK: an update

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