Induction intravenous cyclophosphamide followed by maintenance oral immunosuppression in refractory myasthenia gravis

Buzzard, Katherine; Meyer, Nicholas J.; Hardy, Todd A.; Riminton, Sean; Reddel, Stephen W.

doi:10.1002/mus.24536

Cited by 36 publications

(24 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…MG-ADL, QMG, and MGC assessments were performed weekly from week 1 through week 3. MG-ADL, QMG, MGC, and MG-QOL15 assessments were then performed at weeks 4,8,12,16,20,26,40, and 52 in year 1, every 6 months thereafter, and at each patient's end of study visit. These same 4 efficacy measures were used in the REGAIN study.…”

Section: Methodsmentioning

confidence: 99%

“…Muscle Nerve 60: [14][15][16][17][18][19][20][21][22][23][24]2019 Generalized myasthenia gravis (gMG) is a chronic, rare autoimmune disorder that is characterized by severe muscle weakness. 1 Autoantibodies to the acetylcholine receptor are present in 73%-88% of patients with gMG.…”

mentioning

confidence: 99%

“…1,[8][9][10][11][12][13] The complement-mediated pathological membrane changes reduce the efficiency of neurotransmission at the neuromuscular junction, resulting in the characteristic muscle weakness and fatigability that are observed in patients with MG. 1,14 Some patients (10%-15%) with MG do not respond adequately to long-term treatment with corticosteroids or multiple steroid-sparing immunosuppressive therapies (IST), experience intolerable side effects, or require ongoing treatment with intravenous immunoglobulin (IVIg) or plasma exchange. 1,[15][16][17][18] Persistent myasthenic symptoms [14][15][16]18,19 can adversely affect activities of daily living, including breathing, talking, swallowing, walking, and functional muscle strength as well as quality of life. 15 Patients also have increased risks of myasthenic exacerbations and crises; an increased requirement for rescue therapies; and more frequent inpatient hospitalizations, intensive care unit admissions, and emergency room visits.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Long‐term safety and efficacy of eculizumab in generalized myasthenia gravis

et al. 2019

View full text Add to dashboard Cite

Introduction : Eculizumab is effective and well tolerated in patients with antiacetylcholine receptor antibody‐positive refractory generalized myasthenia gravis (gMG; REGAIN; NCT01997229). We report an interim analysis of an open‐label extension of REGAIN, evaluating eculizumab's long‐term safety and efficacy. Methods : Eculizumab (1,200 mg every 2 weeks for 22.7 months [median]) was administered to 117 patients. Results : The safety profile of eculizumab was consistent with REGAIN; no cases of meningococcal infection were reported during the interim analysis period. Myasthenia gravis exacerbation rate was reduced by 75% from the year before REGAIN ( P < 0.0001). Improvements with eculizumab in activities of daily living, muscle strength, functional ability, and quality of life in REGAIN were maintained through 3 years; 56% of patients achieved minimal manifestations or pharmacological remission. Patients who had received placebo during REGAIN experienced rapid and sustained improvements during open‐label eculizumab ( P < 0.0001). Discussion : These findings provide evidence for the long‐term safety and sustained efficacy of eculizumab for refractory gMG. Muscle Nerve 2019

show abstract

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Long‐term safety and efficacy of eculizumab in generalized myasthenia gravis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Cyclophosphamide has been proposed as an option for treatment refractory MG. 137 It is best reserved as a third-line immunosuppressant choice given its significant side effects, which include bone marrow suppression, risk of infection, and risk of bladder cancer. Induction IV cyclophosphamide followed by oral maintenance has been reported to successfully treat six patients that had failed conventional immunotherapy.…”

Section: Cyclophosphamidementioning

confidence: 99%

“…Induction IV cyclophosphamide followed by oral maintenance has been reported to successfully treat six patients that had failed conventional immunotherapy. 137 With the use of IV cyclophosphamide, remission is achievable though short (mean 20.3 months in one trial). 138 Cyclophosphamide is a cell-cycle nonspecific antiproliferative agent that damages DNA structure by cross-linking nucleic acids.…”

Section: Cyclophosphamidementioning

confidence: 99%

Myasthenia Gravis

Gwathmey

Burns

2015

Semin Neurol

View full text Add to dashboard Cite

Myasthenia gravis is an autoimmune neuromuscular disease caused by antibodies directed against the postsynaptic muscle membrane. The clinical hallmark of the disease is fluctuating and fatigable weakness that affects the ocular muscles (resulting in diplopia and ptosis), the bulbar muscles (causing dysphagia, dysarthria, and dyspnea), and extremity muscles. The diagnosis is most often made with serological testing that identifies either acetylcholine receptor antibodies or muscle-specific tyrosine kinase antibodies. Electrodiagnostic testing has a role in supporting the diagnosis. There are many available treatments that result in improvement of function and quality of life. Treatment should be individualized after consideration of many factors, including disease distribution and severity, patient comorbidities, age, serological status, and what is known about the efficacy and safety of the various treatments.

show abstract

Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Mantegazza¹,

O’Brien²,

Yountz³

et al. 2020

Ann Clin Transl Neurol

View full text Add to dashboard Cite

Objective To assess whether eculizumab, a terminal complement inhibitor, improves patient‐ and physician‐reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods Patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open‐label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open‐label extension were analyzed. Results Of the 125 patients who participated in REGAIN, 117 enrolled in the open‐label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open‐label extension. Interpretation Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis.

show abstract

Induction intravenous cyclophosphamide followed by maintenance oral immunosuppression in refractory myasthenia gravis

Abstract: Remission-induction IV CYC followed by oral immunosuppression is a rapid, effective, and durable treatment for refractory MG. Adding a post-CYC immunosuppressant may account for low relapse rates compared with other published series.

Cited by 36 publications

References 28 publications

Long‐term safety and efficacy of eculizumab in generalized myasthenia gravis

Long‐term safety and efficacy of eculizumab in generalized myasthenia gravis

Myasthenia Gravis

Consistent improvement with eculizumab across muscle groups in myasthenia gravis

Contact Info

Product

Resources

About