Mycophenolate mofetil in the therapy of severe myasthenia gravis

Mycophenolate mofetil is a novel immunosuppressive drug already established in transplantation medicine. Recently, results of three open clinical trials on mycophenolate mofetil in myasthenia gravis have been reported. Mycophenolate mofetil in a dose of 1.0-2.0 g/day was given in 2 patients with severe refractory myasthenia gravis and in 1 patient with myasthenia gravis-polymyositis syndrome. Apart from dose-dependent reversible hemolytic anemia in 1 patient, no severe side effects occurred. Considerable improvement of myasthenic symptoms was seen in all patients within 3-6 months after the initiation of this therapy. Mycophenolate mofetil may be considered as a useful alternative in the treatment of severe myasthenia gravis when standard therapeutic regimens fail. It is usually well tolerated and its application is simple.     

Treatment of myasthenia gravis with mycophenolate mofetil: a case report

We report a patient with myasthenia gravis (MG) who had marked clinical benefit in response to treatment with mycophenolate mofetil as documented by serial quantitative measures of strength and muscle fatigue. Our patient had experienced either adverse side effects or a suboptimal response to the usual immunosuppressive agents used in MG. Mycophenolate mofetil was used in combination with cyclosporine and prednisone and allowed for significant reductions in dosage of these immunosuppressants. We conclude that mycophenolate mofetil deserves further study as a therapeutic agent in MG. In particular, its role as a steroid-sparing agent and as a drug to be used in combination immunotherapy in more severe or refractory cases of MG should be investigated.     

Primary CNS lymphoma complicating treatment of myasthenia gravis with mycophenolate mofetil

Mycophenolate mofetil (MM), an immunosuppressant used after organ transplantation, is also used for treatment of autoimmune myasthenia gravis (MG). A patient with generalized MG was effectively managed with MM but developed CNS lymphoma after 3 years of treatment. Primary CNS lymphoma regressed on withdrawal of MM. Despite minimal short-term side effects and apparent efficacy, chronic treatment of MG with MM may be associated with increased risk of lymphoproliferative disorders.     

T‐cell lymphoproliferative disorder following mycophenolate treatment for myasthenia gravis

Immunosuppressive therapies are critical in the management of numerous conditions including myasthenia gravis. Mycophenolate mofetil is a widely used, oral immunosuppressive agent that is considered to have few adverse effects compared with similar drugs. We report the case of a patient who developed T‐cell lymphoproliferative lesions following long‐term treatment with mycophenolate mofetil and prednisone for myasthenia gravis. The lesions resolved following cessation of the treatment. This case highlights a serious complication of a commonly used drug. Muscle Nerve, 2009     

Mycophenolate (CellCept) treatment of myasthenia gravis, chronic inflammatory polyneuropathy and inclusion body myositis

We report favorable results of the long term use of mycophenolate in the treatment of three patients with myasthenia gravis (MG), two patients with chronic inflammatory demyelinating polyneuropathy (CIDP), one patient with secondary polymyositis (PM), and one patient with inclusion body myositis (IBM). Side effects were mild. Mycophenolate appears to be a useful addition to the armamentarium of immunosuppressants for treatment of chronic immunologically mediated neuromuscular diseases.     

Idiopathic hypertrophic pachymeningitis responsive to mycophenolate

Idiopathic hypertrophic pachymeningitis (IHP) represents a rare inflammatory condition that affects the central nervous system, often difficult to treat. We report the case of a patient who presented with difficulty in swallowing, slurred speech and ataxia associated with headache, vomiting and weight loss. He was diagnosed with IHP. He deteriorated despite treatment with high dose steroids and other immunosuppressants, including pulsed cyclophosphamide. Mycophenolate mofetil was therefore administered resulting in improvement and stabilization. This is the first report in English literature of the use of mycophenolate mofetil in the treatment of IHP and could stimulate further research in its efficacy in managing this condition.     

Neurosarcoidosis treated with mycophenolate mofetil: two cases

INTRODUCTION: Neurosarcoidosis is a rare (5 cases for one million) immune-mediated disease generally observed in young adults. Neurological symptoms are present in the half of patients, and symptoms remain limited to neurological system in 10p.cent. Histological criteria are mandatory to prove the diagnosis. The sensitivity and complications of biopsy are variable. The best sensitivity appears to be achieved with muscle biopsies which in addition have a lower risk of complications. Neurosarcoidosis is usually treated with corticosteroid therapy and immunosuppressive drugs (cyclophosphamide, cyclosporine, aziathoprine, methotrexate), but frequently resists standard schedules. In addition the many contraindications, side effects and cumulated toxicities of immunosuppressive drugs compromises their use. Knowledge of the effectiveness of other treatments would therefore be useful. Mycophenolate mofetil (MMF) has been used for treatment of many immune-mediated neurological diseases, like polymyositis, multifocal motor neuropathy, myasthenia or chronic inflammatory demyelinating polyradiculoneuropathy. MMF is efficient and well tolerated, but there is no case-report about neurosarcoidosis. CASE REPORT: We report two observations of young patients (14 and 27 years) with a diagnosis of resistant neurosarcoidosis treated with MMF (2 g/j) and corticosteroids. A significant and rapid effectiveness was clinically and radiologically observed, with good clinical and hematologic tolerance. CONCLUSION: The MMF seems to be an interesting rescue treatment for neurosarcoidosis. Further evaluation is needed.     

Therapy in myasthenia gravis and Lambert-Eaton myasthenic syndrome

Myasthenia gravis (MG) is a heterogeneous disorder, a fact that needs to be kept in mind when considering treatment. Most patients benefit from pyridostigmine. In nonthymomatous ocular MG, prednisolone is often effective. Thymectomy is indicated for thymoma and is an option for acetylcholine receptor antibody-positive patients with generalized weakness developing under the age of 45 years. In older patients and in those failing to respond to thymectomy, prednisone alone or combined with azathioprine is the treatment of choice. Mycophenolate mofetil is an option in those intolerant of azathioprine. Lambert-Eaton myasthenic syndrome (LEMS) can exist in paraneoplastic (P-) and nonparaneoplastic (NP-) forms. Most patients benefit from 3,4-diaminopyridine. In P-LEMS, treatment of the tumor often results in neurological improvement. In both forms, prednisone alone is an option or combined with azathioprine in NP-LEMS. In both MG and LEMS, where weakness is severe, plasma exchange or intravenous immunoglobulin treatment may provide short-term benefit.     

Inflammatory myopathies: how to treat the difficult cases.

The initial approach to the treatment of patients with inflammatory myopathy is critical in determining the subsequent course and outcome. Prolonged administration of high doses of corticosteroids should be avoided and a second-line agent such as methotrexate or azathioprine should be introduced earlier rather than later. Intravenous immunoglobulin therapy has an important place if the myositis remains active, particularly in patients with dermatomyositis, and is the treatment of choice in patients with immunodeficiency who are not controlled by corticosteroids. In more resistant cases of polymyositis or dermatomyositis it may be necessary to use cyclophosphamide, cyclosporin or the promising newer immunosuppressive agents mycophenolate mofetil or tacrolimus to achieve disease control. The treatment of inclusion body myositis remains unsatisfactory but a trial of prednisolone and methotrexate is warranted in selected patients.     

Mycophenolate mofetil and tacrolimus: new therapeutic options in neuroimmunological diseases

Mycophenolate mofetil (MMF) and tacrolimus are novel immunosuppressive drugs, both first established in transplantation medicine and now used increasingly in neuroimmunological diseases including myasthenia gravis, dysimmune polyneuropathies, and myositis. In myasthenia gravis, the efficacy and safety of MMF has been shown by one open-label trial; one small, double-blind, placebo-controlled trial; and a few retrospective analyses. Similarly, for tacrolimus the greatest experience and evidence for efficacy and safety have been gathered in myasthenia gravis. MMF and tacrolimus have both been used as an alternative treatment for various other autoimmune diseases in which azathioprine or cyclosporine were not sufficiently effective. However, experience with tacrolimus in dysimmune polyneuropathies and myositis is limited. At this time, the available data suggest that MMF and tacrolimus are well suited for long-term immunosuppression in patients with myasthenia gravis. The spectrum of neuroimmunological diseases in which these drugs may be used has not been finally delineated and will require further controlled studies.     

A patient of infantile polymyositis triggered by respiratory syncytium virus infection

An 11-month-old boy developed acute polymyositis about 1 week after respiratory syncytium virus (RSV) pneumonia. He was admitted to our hospital because of interstitial pneumonia. RSV infection was confirmed by the presence of its antigen in his nasal discharge. Two weeks later, his chest X-ray findings improved and RSV antigen became negative, but severe generalized muscle weakness developed, causing respiratory failure. Muscle biopsy demonstrated inflammatory cellular infiltration with occasional fiber necrosis. Intravenous steroid pulse therapy was remarkably effective resulting in complete recovery of his muscle power. In this patient polymyositis was preceded with RSV infection, suggesting a close relationship between polymyositis and RSV infection. Although many patients of viral myositis have been reported to be associated with coxsackie B, HCV and HTLV-1 viruses, our patient is the first infantile polymyositis secondary to RSV infection.     

Opportunistic infections in myasthenia gravis treated with mycophenolate mofetil

Mycophenolate mofetil (MMF) is used for immunosuppression in myasthenia gravis (MG). Although there are numerous data on associated infection and prophylaxis in transplant patients who are on MMF, data in MG remains lacking. We report two elderly seropositive MG patients who developed cytomegalovirus (CMV) enteritis and Epstein-Barr virus (EBV) encephalitis while on MMF for 5months and 1year, respectively. Chronic MMF therapy in MG patients may trigger life-threatening infections including CMV and EBV diseases, especially in the elderly. Similar to the practice in transplant patients, viral serology testing and appropriate prophylactic regimen with antiviral agents should be considered, particularly in older MG patients.     

Mycophenolate mofetil for myasthenia gravis: a clear and present controversy

Mycophenolate mofetil (MMF) has been used to treat myasthenia gravis (MG) for over 10 years. MMF’s use in the MG population stems from its theoretical mechanism of action and the medical literature that supports its benefit in MG patients. Recently, two large, double-blinded, placebo-controlled, randomized clinical trials were initiated to study the effectiveness of MMF for MG. One of these studies found no benefit in taking MMF with 20 mg of prednisone as compared to taking prednisone alone, while the other study demonstrated no advantage in taking MMF against placebo during a 36-week prednisone taper. This article critically reviews the medical literature on MMF’s use in MG and suggests further research avenues on this topic.     

A study of vascular permeability in normal skeletal muscle and inflammatory myopathies using a fluorescein dye technique with percutaneous needle biopsy

Percutaneous needle biopsy of the vastus lateralis muscle was performed immediately prior to the intravenous injection of 5 ml of 20% fluorescein sodium, in 2 control subjects and 2 patients with polymyositis. Repeat biopsies were performed 5, 10 and 15 minutes after injection. Similar biopsies were taken prior to, and 10 minutes after, fluorescein injection in 1 control subject and 15 patients with a variety of inflammatory muscle conditions including polymyositis, some of whom were on treatment with corticosteroids. Apart from one patient, with polymyalgia rheumatica, increased penetration of dye was found only in those patients with polymyositis, particularly around areas of cellular infiltration, necrosis and phagocytosis and in the periphery of muscle fibres. Corticosteroid therapy appeared to reduce the amount of dye permeating muscle tissue in patients with polymyositis. It is suggested that reducing the abnormally increased vascular permeability in damaged muscle from patients with polymyositis may represent one mode of action of corticosteroids in this condition, and that the amount of fluorescein permeating muscle may be helpful in the diagnosis where conventional clinical and histological criteria are not conclusive.     

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

Immunosuppressives have been used in multiple sclerosis (MS) since 1966. Today, we have many treatments for the relapsing forms of the disease, including 8 US Food and Drug Administration-approved therapies, with more soon to be introduced. Given the current treatment landscape what place do immunosuppressants have in combating MS? Trial work and our experience suggest that immunosuppressives still have an important role in treating MS. Cyclophosphamide finds use in treating patients with severe, inflammatory relapsing remitting MS or those suffering from a fulminant attack. We tend to employ mycophenolate mofetil as an add-on to injectable therapy for patients experiencing breakthrough activity. Some progressive (primary progressive multiple sclerosis or secondary progressive multiple sclerosis) patients may stabilize after treatment with either cyclophosphamide or mycophenolate. We rarely employ mitoxantrone because of potential cardiac or carcinogenic effects. We prefer to use cyclophosphamide or mycophenolate mofetil in preference to methotrexate because evidence of efficacy is limited for this drug. We have less experience with azathioprine, but it may be an alternative for patients with limited options who are unable to tolerate conventional therapies.     

Polymyositis masquerading as motor neuron disease

BACKGROUND: Several conditions have been reported to mimic motor neuron disease (MND), and misdiagnosis remains a common clinical problem. OBJECTIVE: To report a case of bulbar-onset polymyositis where the initial clinical presentation was suggestive of MND. CASE DESCRIPTION: A 73-year-old woman was admitted for investigation of acute-onset dysphagia without dysarthria. Examination revealed nasal dysphonia and severe oropharyngeal weakness. Subtle upper-limb weakness, brisk tendon reflexes, and fasciculations in the right deltoid muscle were also demonstrated. A clinical diagnosis of MND was entertained. The serum creatine kinase value was within the reference range. Findings from electromyographic studies, however, were suggestive of a myopathic rather than a neurodegenerative process, and a muscle biopsy specimen was diagnostic of polymyositis. The dysphagia rapidly resolved upon treatment with corticosteroids and azathioprine. CONCLUSIONS: Bulbar-onset polymyositis may mimic MND, particularly in the absence of inflammatory markers or elevated muscle enzyme levels. Caution should be exercised in the clinical diagnosis of bulbar dysfunction, and further investigations such as electromyography and muscle biopsy are indicated to confirm the diagnosis.     

Can mycophenolate mofetil be tapered safely in myasthenia gravis? A retrospective,multicenter analysis

Introduction: Mycophenolate mofetil (MMF) is frequently used to treat myasthenia gravis, but there is little information to guide clinicians on the safety of reducing the dose in well‐controlled patients. Methods: This retrospective chart review at 3 institutions identified 92 patients who had undergone MMF taper after achieving either pharmacologic remission or minimal manifestations status. Statistical analysis was performed to assess differences in patient characteristics between patients who had successfully tapered MMF and those who relapsed. Results: Of 92 patients undergoing a taper, 30 relapsed. The relapses were mild, transient, and usually responded to increased MMF dose. MG crisis did not occur. The mean dose at time of relapse was 888 mg/day. Patients with relapses were tapered more quickly (8.4 vs. 62.4 months). Conclusions: Tapering MMF appears safe after years of disease stability. Reducing the dose at a dose of only 500 mg/day every 12 months is recommended. Muscle Nerve 52 : 211–215, 2015     

Corticosteroids in the treatment of myasthenia gravis. Study of 12 cases with review of the literature]

The results of treatment of myasthenia gravis in 12 patients are reported. There were 10 cases with severe generalized form and two cases with moderate generalized form, one of which associated with polymyositis. Seven patients had prior thymectomy and one of them had a thymoma. All the patients were receiving anticholinesterase drugs with poor response or without any response. One patient received a short, intensive course of dexametazone, and other patient used prednisone after a more prolonged dexametazone course. The remaining patients received prednisone, always beginning with high (100 mg) alternate day oral single-doses. This therapy has been maintained for a period thought to be sufficient to suppress the symptoms, as well as to allow remission or an improvement for remaining even when prednisone had been slowly decreased, after a scheduled of one to two years of treatment.     

Inflammatory myopathies: clinical,diagnostic and therapeutic aspects

The three major forms of immune-mediated inflammatory myopathy are dermatomyositis (DM), polymyositis (PM), and inclusion-body myositis (IBM). They each have distinctive clinical and histopathologic features that allow the clinician to reach a specific diagnosis in most cases. Magnetic resonance imaging is sometimes helpful, particularly if the diagnosis of IBM is suspected but has not been formally evaluated. Myositis-specific antibodies are not helpful diagnostically but may be of prognostic value; most antibodies have low sensitivity. Muscle biopsy is mandatory to confirm the diagnosis of an inflammatory myopathy and to allow unusual varieties such as eosinophilic, granulomatous, and parasitic myositis, and macrophagic myofasciitis, to be recognized. The treatment of the inflammatory myopathies remains largely empirical and relies upon the use of corticosteroids, immunosuppressive agents, and intravenous immunoglobulin, all of which have nonselective effects on the immune system. Further controlled clinical trials are required to evaluate the relative efficacy of the available therapeutic modalities particularly in combinations, and of newer immunosuppressive agents (mycophenolate mofetil and tacrolimus) and cytokine-based therapies for the treatment of resistant cases of DM, PM, and IBM. Improved understanding of the molecular mechanisms of muscle injury in the inflammatory myopathies should lead to the development of more specific forms of immunotherapy for these conditions.     

Mycophenolate mofetil – as an adjunctive immunosuppressive therapy in refractory myasthenia gravis: The Singapore experience

We report our experience, using mycophenolate mofetil (MyM) as an adjunctive immunosuppressive therapy in patients with severe, refractory and high dose steroid-dependant myasthenia gravis (MG). Five patients were commenced on MyM in addition to other immunosuppressive therapies. All had significant clinical improvement and no subsequent myasthenic crisis requiring intensive care unit admission. MyM was well tolerated and no serious adverse effects were observed. MyM is an effective adjunctive therapy for the treatment of severe, refractory and steroid-dependant MG in our experience.