Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms

Lorenzoni, Paulo José; Kay, Cláudia Suemi Kamoi; Zanlorenzi, Marcelo Farago; Ducci, Renata Dal‐Prá; Werneck, Lineü Cesar; Scola, Rosana Hermínia

doi:10.1016/j.jns.2020.116734

Cited by 15 publications

(13 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This study is a double-blind test. [12] is as follows: Xu's 5-point clinical score was adopted to judge the severity of the disease, and the clinical relative score was adopted to evaluate the therapeutic effect. (1) The clinical absolute scoring method is divided into 8 items, namely, ptosis point, ptosis time, horizontal eye movement and diplopia, facial muscle weakness, fatigue test of the upper and lower limbs, and evaluation of chewing, swallowing, and respiratory function.…”

Section: Methodsmentioning

confidence: 99%

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Peng

Xie

Tan

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

Background. Myasthenia gravis (MG) is an acquired autoimmune disease. The main clinical features of MG are skeletal muscle fatigue and pathological fatigue, which worsen at night or after fatigue, such as dyspnea, dysphagia, and systemic weakness. Plasma exchange (PE) is often used in patients with acute exacerbation of MG. Intravenous immunoglobulin (IVIG) is a collection of immunoglobulins from thousands of donors. IVIG can replace a variety of immunosuppressants or PE. However, the effect of PE or IVIG on patients’ consciousness, immune function, and prognosis is not clear. Objective. A prospective randomized test of the effects of PE combined with immunoglobulin on consciousness, immune function, and prognosis in patients with myasthenia gravis crisis (MGC). Methods. Sixty patients with MGC treated from February 2019 to April 2021 were enrolled in our hospital. The cases who received PE were set as the PE group, and those who received PE combined with immunoglobulin were set as the PE+immunoglobulin group. The efficacy, clinical score, state of consciousness, immune function, acetylcholine receptor antibody (AChR-Ab), lymphocyte (LYM), albumin (ALB) levels, and the incidence of adverse reactions were compared. Results. The improvement rate was 100.005% in the treatment group and 83.33% in the PE group. After treatment, the clinical score of the PE+immunoglobulin group was lower than that of the PE group, and the clinical relative score of the PE+immunoglobulin group was higher than that of the PE group ( P < 0.05 ). The number of conscious people in the PE+immunoglobulin group was more than that in the PE group ( P < 0.05 ). Immunoglobulin A, immunoglobulin M, immunoglobulin G, and immunoglobulin G in the PE+immunoglobulin group were higher than those in the PE group ( P < 0.05 ). The levels of AChR-Ab and ALB in the PE+immunoglobulin group were higher than those in the PE group, while the level of LYM in the PE+immunoglobulin group was lower than that in the PE group. The incidence of skin system, gastrointestinal system, nervous system, and systemic damage in the PE+immunoglobulin group was lower than that in the PE group ( P < 0.05 ). Conclusion. The treatment of MGC with PE combined with immunoglobulin can not only effectively enhance the consciousness and immune function of patients but also effectively promote the prognosis, and the safety of treatment can be guaranteed.

show abstract

Section: Methodsmentioning

confidence: 99%

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Peng

Xie

Tan

et al. 2022

Computational and Mathematical Methods in Medicine

View full text Add to dashboard Cite

show abstract

“…We advocate checking thiopurine S-methyltransferase (TPMT) levels (24) prior to initiating azathioprine treatment. If levels are in the normal range, we initiate azathioprine at 25 mg daily and increase weekly by 25 mg until target dose is reached, with blood monitoring carried out in primary practice.…”

Section: Steroid Sparing Immunosuppressive Agentsmentioning

confidence: 99%

A Practical Approach to Managing Patients With Myasthenia Gravis—Opinions and a Review of the Literature

Farrugia

Goodfellow

2020

Front. Neurol.

View full text Add to dashboard Cite

When the diagnosis of myasthenia gravis (MG) has been secured, the aim of management should be prompt symptom control and the induction of remission or minimal manifestations. Symptom control, with acetylcholinesterase inhibitors such as pyridostigmine, is commonly employed. This may be sufficient in mild disease. There is no single universally accepted treatment regimen. Corticosteroids are the mainstay of immunosuppressive treatment in patients with more than mild MG to induce remission. Immunosuppressive therapies, such as azathioprine are prescribed in addition to but sometimes instead of corticosteroids when background comorbidities preclude or restrict the use of steroids. Rituximab has a role in refractory MG, while plasmapheresis and immunoglobulin therapy are commonly prescribed to treat MG crisis and in some cases of refractory MG. Data from the MGTX trial showed clear evidence that thymectomy is beneficial in patients with acetylcholine receptor (AChR) antibody positive generalized MG, up to the age of 65 years. Minimally invasive thymectomy surgery including robotic-assisted thymectomy surgery has further revolutionized thymectomy and the management of MG. Ocular MG is not life-threatening but can be significantly disabling when diplopia is persistent. There is evidence to support early treatment with corticosteroids when ocular motility is abnormal and fails to respond to symptomatic treatment. Treatment needs to be individualized in the older age-group depending on specific comorbidities. In the younger age-groups, particularly in women, consideration must be given to the potential teratogenicity of certain therapies. Novel therapies are being developed and trialed, including ones that inhibit complement-induced immunological pathways or interfere with antibody-recycling pathways. Fatigue is common in MG and should be duly identified from fatigable weakness and managed with a combination of physical therapy with or without psychological support. MG patients may also develop dysfunctional breathing and the necessary respiratory physiotherapy techniques need to be implemented to alleviate the patient's symptoms of dyspnoea. In this review, we discuss various facets of myasthenia management in adults with ocular Farrugia and Goodfellow Practical Approaches to Myasthenia Management and generalized disease, including some practical approaches and our personal opinions based on our experience.

show abstract

“…U ovu terapiju spadaju azatioprin, ciklosporin A, mikofenolat mofetil i takrolimus, kao najčešće primenjivani imunomodulatorni lekovi kod SAMG, ali i ciklofosfamid, metotreksat, leflunomid i drugi [20][21][22][23][25][26][27][28] . Ovi lekovi se mogu dati odmah, praktično istovremeno sa steroidnom terapijom, ili se daju naknadno, kod pacijenata kod kojih kortikosteroidi nisu dali pun terapijski učinak, kod kojih je redukcija kortikosteroidne terapije dovela do pogoršanja SAMG ili su se pojavili značajni neželjeni efekti kortikosteroida koji su zahtevali redukciju ili potpunu obustavu ove terapije.…”

Section: Terapija Samgunclassified

Treatment of acquired autoimmune myasthenia gravis: Where are we today?

Lavrnić¹

2022

Galenika Med J

View full text Add to dashboard Cite

Acquired autoimmune myasthenia gravis (MG) is a prototype of autoimmune disease in which autoantibodies directed against various antigens of the neuromuscular junction, leading to impaired neuromuscular transmission with clinical presentation of fluctuating weakness and excessive fatigue of transverse striated skeletal muscles. In 85% of patients with MG there are antibodies to the nicotine acetylcholine receptor of the postsynaptic muscle membrane (nAChR), in 5-8% of patients there are antibodies to muscle-specific tyrosine kinase (MuSK), in 1-2% of antibodies to low-density lipoprotein receptor-related protein 4 (LRP4), while in the remaining 10% none of the mentioned autoantibodies can be detected, and these patients are classified in the group of so-called "seronegative" MG. It is well known that this antigenic specificity affects both the clinical presentation and the therapeutic response, course and prognosis of the disease, which is why the early serological confirmation of the diagnosis is important. In this way, determining the exact profile of autoantibodies can provide a significantly more efficient, personalized therapeutic approach for each patient, and thus improve the prognosis and quality of life of these patients. In general, when a patient is diagnosed with MG, the goal is to alleviate the symptoms of the disease as soon as possible, as well as to induce remission or minimal manifestations of the disease in the following period. MG therapy can be roughly divided into symptomatic therapy, which includes drugs that alleviate the symptoms of weakness and fatigue, causal therapy, which immunomodulates the pathogenetic process that affects the course of MG and temporary therapeutic procedures to achieve rapid improvement in patients to avoid or treatment of the most severe clinical manifestations, the so-called "crisis" of MG. Symptomatic MG therapy involves the use of acetylcholinesterase inhibitors, represented by pyridostigmine bromide. It works by relieving the symptoms of MG in a short period of time, 4-8 hours. Causal therapy acts on the pathogenetic process on the basis of MG and it includes corticosteroids as first-line drugs and immunosuppressive drugs: azathioprine, cyclosporine A, mycophenolate mofetil, etc, while temporary therapeutic procedures include therapeutic plasma changes and intravenous immunoglobulins. All the above mentioned MG therapies are is effective in most patients with this disease, but it should be emphasized that, on the one hand, to achieve its full effect usually takes several months, and on the other hand, that such prolonged therapy is often followed by the occurrence of various side effects that require its reduction or complete cessation. With advances in immunology, molecular biology, and rapid drug development, new agents are being developed today that have much more selective immune targets, save the rest of the immune system, have lower toxicity, and a much faster onset of action MG. Some of these drugs are already being used successfully today, but we can freely say that the door to highly selective immunotherapy in MG has just been opened and that this is certainly the therapy of the future.

show abstract

Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms

Cited by 15 publications

References 29 publications

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

Effects of Plasma Exchange Combined with Immunoglobulin Therapy on Consciousness, Immune Function, and Prognosis in Patients with Myasthenia Gravis Crisis: A Prospective Randomized Test

A Practical Approach to Managing Patients With Myasthenia Gravis—Opinions and a Review of the Literature

Treatment of acquired autoimmune myasthenia gravis: Where are we today?

Contact Info

Product

Resources

About