Treatment Of Refractory Myasthenia Gravis Research Articles

Diagnostic value of antibody concentration ratio for treatment-refractory myasthenia gravis.

This study aimed to assess the diagnostic potential of the Antibody concentration ratio in identifying treatment-refractory myasthenia gravis (MG). A retrospective analysis was conducted on 116 MG patients who underwent antibody detection at least twice between June 1, 2015, and June 1, 2023. Demographic and clinical characteristics were collated to ascertain their association with refractory MG. The Antibody Concentration Ratio was applied to determine treatment response, using the International Consensus Guidance criteria as the reference standard. The area under nonparametric receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy were calculated to assess the diagnostic efficacy of the Antibody concentration ratio following consecutive immunotherapy relative to initial antibody concentrations for refractory MG. 19 out of 116 patients were unequivocally diagnosed with refractory MG. A significant correlation was found between the Antibody Concentration Ratio and refractory MG status in treatment-refractory and treatment-responsive patients. Subsequently, the AUC demonstrated the robust diagnostic capability of the Antibody concentration ratio for refractory MG, with an AUC of 0.8709 (95% CI: 0.7995-0.9422, p < 0.0001). The optimal cut-off value stood at 0.8903, exhibiting a sensitivity of 94.74% (95% CI: 75.36%-99.73%), a specificity of 68.04% (95% CI: 58.23%-76.48%), and accuracy of 72.41% (95% CI: 64.28%-80.54%). Elevated Antibody Concentration Ratio is intrinsically linked with refractory MG and exhibits potential as an diagnostic biomarker for the condition.

Rituximab as a sole steroid-sparing agent in generalized myasthenia gravis: Long-term outcomes.

Rituximab, a B-cell depleting monoclonal antibody, represents an option for the treatment of refractory myasthenia gravis (MG). Its use is more established in muscle-specific tyrosine kinase positive (MuSK +) patients, while its role in managing acetylcholine receptor positive (AChR +), or double seronegative (DSN) patients, remains less clear. This study evaluates the long-term effectiveness and safety of rituximab in MG of various serotypes. We conducted an open-label study of MG patients receiving rituximab. Adults with generalized refractory MG, either anti-AChR + or DSN, and anti-MuSK + , refractory or not, who had follow-up > 12months were selected. Change in quantitative myasthenia gravis (QMG) score at last follow-up, compared with baseline was a primary outcome, as well as factors affecting response to treatment. Secondary outcomes included, long-term safety, the steroid-sparing effect and relapse rates post-rituximab. Thirty patients (16 anti-AChR + , 6 anti-MuSK + , 8 DSN) followed for a mean of 33.3months were included. Mean scores pre-rituximab compared to last follow-up significantly decreased (p < 0.001), from 11 ± 4.1 to 4.3 ± 3.8, and from 1.9 to 0.3 regarding QMG and relapse rate per patient/year, respectively, while in 93.1% a daily steroid dose ≤ 10mg was achieved. Antibody status was the only factor independently influencing several endpoints. Throughout the study period no crises or deaths occurred. The present study supports that rituximab is an effective and well tolerated treatment for refractory anti-AChR + and DSN MG patients, while anti-MuSK + remains the group experiencing the greater benefits.

Complement inhibition in Myasthenia – from basics to RCT data

Myasthenia gravis (MG) is the prototypic autoimmune neurological disorder causing fatiguable muscle weakness either limited to the ocular muscles or becoming generalised involving the limb and bulbar muscles. Nine out of 10 generalised MG patients have IgG1 or IgG3 antibodies against the acetylcholine receptor (AChR). AChR antibodies cause neuromuscular weakness by internalisation of AChR, receptor blockade and by activating the complement pathway. Complement activation causes formation of the membrane attack complex (MAC) leading to degradation of the neuromuscular junction (NMJ). Several animal models have confirmed the role of complement in the pathogenesis of MG, with the experimental models (EAMG) often needing complement inhibitory therapies to prevent or reverse the disease. Various molecules that target the complement system have now been developed to treat myasthenia gravis. The vast majority of the currently studied molecules target the C5 protein, thereby preventing the formation of MAC and subsequent NMJ destruction. The currently studied anti-complement therapies for MG include Eculizumab, Zilucoplan, Ravulizumab, Pozelimab, Cemdisiran, Gefurilimab, Danicopan and few others in the pipeline. Eculizumab has been shown in clinical trials to be effective in the treatment of refractory MG, but further sub-group analysis and real-life experience have shown that this can be beneficial in various patients including those receiving regular IVIG, plasma exchange or Rituximab. It was approved for use by FDA in Oct 2017. Ravulizumab is a long-acting monoclonal antibody which has similar mechanism of action to Eculizumab and was approved for use in MG by FDA in April 2022. Zilucoplan is a macrocyclic peptide which binds to C5 and C5b thus preventing terminal complement activation, which can be given subcutaneously (FDA new drug application accepted in Nov 2022). Many of these have also been shown to have long term benefit in different sub-groups of patients with MG. Patients would need to be vaccinated against Neisseria meningitidis because of the risk of Gram-negative septicaemia, although no major safety signatures have been noted in the studies so far. Future studies may be able to identify specific biomarkers which might aid in selecting the most appropriate patients who might respond to these therapies.

P.035 Autologous hematopoietic stem cell transplant for the treatment of refractory myasthenia gravis with anti-muscle specific kinase antibodies

Background: Several case series describe patients with refractory acetylcholine receptor antibody-positive (AChR) myasthenia gravis (MG) treated with hematopoietic stem cell transplant (HSCT). In this report, we describe four patients with anti-muscle-specific kinase (MuSK)MG treated with HSCT. Methods: We reviewed the records of all patients undergoing HSCT for MG in the Alberta Blood and Bone Marrow Transplant Program and identified 4 patients with anti-MuSK MG. Results: All 4 patients had severe disease (Myasthenia Gravis Foundation of America score IVb-V) and were refractory to multiple treatments, including rituximab. 3 patients improved with no clinical manifestations or mild symptoms and remained as such for 2, 3.5, and 5.5 years. In these 3 patients, adverse events ranged from treatable infections and transient dyspnea to persistent fatigue and premature menopause. The average worst Myasthenia Gravis Activities of Daily Living (MG-ADL) scores improved from 14.7 before to 0.3 after HSCT while their mean worst Myasthenia Gravis Quality of Life Questionnaire (MG-QoL15) scores improved from 26.7 to 0. The fourth patient developed pneumonia and passed away from respiratory failure 8 weeks post-transplant. Conclusions: In patients with severe refractory anti-MuSK MG, it may be reasonable to consider HSCT but with an appreciation of the associated risks.

Novel Immunotherapies for Myasthenia Gravis.

Myasthenia gravis (MG), a prototype autoimmune neurological disease, had its therapy centred on corticosteroids, non-steroidal broad-spectrum immunotherapy and cholinesterase inhibitors for several decades. Treatment-refractory MG and long-term toxicities of the medications have been major concerns with the conventional therapies. Advances in the immunology and pathogenesis of MG have ushered in an era of newer therapies which are more specific and efficacious. Complement inhibitors and neonatal Fc receptor blockers target disease-specific pathogenic mechanisms linked to myasthenia and have proven their efficacy in pivotal clinical studies. B cell-depleting agents, specifically rituximab, have also emerged as useful for the treatment of severe MG. Many more biologicals are in the pipeline and in diverse stages of development. This review discusses the evidence for the novel therapies and the specific issues related to their clinical use.

The Clinical Outcome in AChR-Positive Generalized Myasthenia Gravis: A Retrospective Observational Study.

Myasthenia gravis (MG) is an autoimmune disease affecting the neuromuscular junction, and in over 80% of cases, antibodies are identified against the nicotinic type of acetylcholine receptor (AChR) on the muscle endplate. Despite the availability of various treatment options, patients with MG experience relapses and remission during the course of the disease. Aims and Objective: To understand the clinical profile, predictors of outcomes in acetyl choline receptor (AChR) antibody positive generalized MG. This is a retrospective, single-centre, observational study of 108 patients with AChR positive generalized MG. We collected data on clinical and demographical profiles, treatments received, and treatment responses from those who fulfilled inclusion criteria over a mean follow up period of 33.75 ±7.30 months. Clinical outcomes were studied in terms of the type of remission and crisis or disease exacerbations patients had, considering different variables and treatment received. We found the commonest initial symptoms were ocular or oculo-bulbar, which progressed to generalized MG in the first year of disease onset. 36 (33.3%) patients experienced a crisis requiring mechanical ventilation within a mean period of 9.4 ±4.77 months from the disease onset. Multivariate regression analysis showed late-onset MG (age of onset between 50-70 years) and treatment with rituximab were better correlated with remission, (odd ratio of 4.7; 95 % CI ,1.12 -12.6; P value < 0.05 and odd ratio of 4.56; 95 % CI ,1.2 -10.04; P value < 0.05) respectively. While treatment with Mycofenolate Mofetile (MMF) was associated with a higher number of relapses (odd ratio of 1.8; 95 % CI ,0.08 -0.96; P value < 0.05). Treatment with Rituximab showed a higher rate of remission as compared to treatment refractory (TR) on conventional immunosuppressant therapy (IST). Out of 35(32 %) thymoma patients, 21 patients underwent thymectomy and these patients showed significantly greater rate of remission as compared both thymoma patients who denied thymectomy as a treatment option (N = 10 ;55.60 % vs N = 4; 23.50%). In this study of AChR antibody positive generalized MG patients, we found that nearly one-third of them experienced myasthenic crisis despite receiving the best medical care. Rituximab appeared to be effective in the treatment of refractory MG and those who failed thymectomy. Thymectomy was associated with better outcomes in patients, both with or without a thymoma.

Autologous hematopoietic stem cell transplant for the treatment of refractory myasthenia gravis with anti-muscle specific kinase antibodies.

Up to 25% of patients with myasthenia gravis (MG) have refractory disease despite trials of multiple immunosuppressants. Several case series describe acetylcholine receptor antibody-positive (AChR) MG patients treated with autologous hematopoietic stem cell transplant (HSCT). In this report, we describe three patients with anti-muscle-specific kinase (MuSK) MG treated with HSCT. We included all patients who had undergone HSCT with anti-MuSK myasthenia gravis identified through the records of the Alberta Blood and Marrow Transplant Program. We collected demographic and clinical data including validated MG scales as well as questionnaire data. All 3 patients had severe disease (Myasthenia Gravis Foundation of America score IVb-V) and were refractory to multiple treatments, including rituximab. All patients improved with no clinical manifestations or mild symptoms and remained as such for 2, 3.5, and 5.5y. Adverse events ranged from treatable infections and transient dyspnea to persistent fatigue and premature menopause. The average worst Myasthenia Gravis Activities of Daily Living (MG-ADL) scores improved from 14.7 before to 0.3 after HSCT. The mean worst Myasthenia Gravis Quality of Life Questionnaire (MG-QoL15) scores improved from 26.7 to 0. All patients reported they would undergo transplant again for their MG. We describe three patients with anti-MuSK MG treated with HSCT, all of whom became symptom free from MG with a tolerable side effect profile. In patients with severe refractory anti-MuSK MG, it may be reasonable to consider HSCT.

Effect of tacrolimus on soluble costimulatory molecules in patients with refractory myasthenia gravis

ObjectivesTo investigate the expression and possible role of soluble costimulatory molecules in the treatment of refractory myasthenia gravis. MethodsThirty-two patients with refractory myasthenia gravis were enrolled into this study and given tacrolimus 3 mg/day. At the beginning of treatment and 12 months follow-up period, clinical data were collected and recorded. The clinical classification of myasthenia gravis Foundation (MGFA) was performed. The MGFA-quantitative myasthenia gravis score (MGFA-QMGS), manual muscle test (MMT), MG activity of daily living (MG-ADL) and the activity of daily living (MG-ADL), the 15-item myasthenia gravis quality of life (MG QOL-15) and the dose change of prednisone were used to evaluate the efficacy. The expression levels of soluble costimulatory molecules and their ligands (sPD-1/sPD-L1, sICOS/sICOSL, sCD40/sCD40L), soluble CD25 and IL-2 in serum were determined by enzyme-linked immunosorbent assay (ELISA). ResultsWe observed that oral administration of 3 mg tacrolimus daily for 1 year can significantly improve the clinical symptoms of patients with refractory myasthenia gravis, which is characterized by a significant reduction in clinical scores, such as QMG, MMT, ADL, MGQOL-15, and a reduction daily oral prednisolone (PSL) dose (P < 0.0001).We also found that the levels of plasma sPD-1, sCD40, IL-2 in refractory MG patients increased significantly, and those decreased significantly 12 months after tacrolimus treatment (P < 0.05). The level of sCD25 was negatively correlated with clinical severity scores (P < 0.05). After tacrolimus treatment, the level of sPD-L1 increased although there was no significant difference. ConclusionTacrolimus could relieve the symptoms of refractory MG and significantly decrease the levels of plasma sPD-1, sICOSL, sCD40, sCD25 and IL-2. Soluble costimulatory molecules might be potential biomarkers for MG and tacrolimus treatment.

A retrospective longitudinal cohort study of the clinical burden in myasthenia gravis

BackgroundPatients with generalized myasthenia gravis (MG) often experience debilitating exacerbations, with the possibility of life-threatening respiratory crises requiring hospitalization. Long-term longitudinal studies are needed to understand the burden of MG, including in patients whose disease is refractory to conventional treatment.MethodsA retrospective, longitudinal, cohort study was conducted of patients in England aged ≥ 18 years with treatment-refractory or non-refractory MG, using data recorded during 1997–2016 in the Clinical Practice Research Datalink and the Hospital Episode Statistics databases. A control cohort of patients without MG, matched to the patients in the treatment-refractory MG cohort, was also identified. Outcome measures included myasthenic crises, MG exacerbations, MG-related hospitalizations, comorbidities, and all-cause mortality. Descriptive statistics were calculated for the overall MG population. For continuous variables, between-cohort comparisons were made using t tests for normally distributed data and Mann–Whitney U tests for non-normally distributed data. For categorical data, the comparisons were made by chi-squared tests. Differences in clinical outcomes between cohorts were modeled using negative binomial regression.ResultsA total of 1149 patients with MG were included. Overall, 18.4% of patients experienced myasthenic crises, 24.6% experienced exacerbations, and 38.6% underwent MG-related hospitalizations. Most of these events occurred within 2–3 years of diagnosis. Patients with MG refractory to conventional treatment (n = 66) experienced more exacerbations and MG-related hospitalizations than patients with non-refractory disease (n = 1083). Patients with refractory MG experienced a higher frequency of renal disease and hypertension compared with patients with non-refractory MG, and with matched patients without MG. They were also more likely to have diabetes and congestive heart failure than the matched controls. Rates of all-cause mortality during the follow-up period did not differ between patients with refractory MG and non-refractory MG.ConclusionsThese results show that conventional treatments for MG are not adequately managing patients’ symptoms and that patients with refractory MG are more likely to experience certain comorbidities than those with non-refractory MG or matched controls without MG. Future research should focus on the impact of newer targeted therapies on long-term clinical outcomes and comorbid conditions.

Treatment of refractory myasthenia gravis by double-filtration plasmapheresis and rituximab: A case series of nine patients and literature review.

Myasthenia gravis (MG) is an autoimmune disease mediated by circulating autoantibodies (anti-AchR, anti-MuSK, etc.). More than 20% of myasthenic patients are refractory to conventional treatments (plasma exchange, IVIg, steroids, azathioprine, mycophenolate mofetil). Rituximab (B-lymphocyte-depleting anti-CD20) and apheresis (double-filtration plasmapheresis [DFPP] and immunoadsorption [IA]) are interesting therapeutic alternatives. This monocentric pilot study included nine refractory myasthenic patients (March 2018 to May 2020) treated by DFPP and/or IA associated with rituximab (375 mg/m2 ). Clinical responses were assessed using the Myasthenia Gravis Foundation of America (MGFA) score. Average age of patients was 53 ± 17 years. Gender ratio (M/F) was 3:6. The combination of apheresis and rituximab reduced median MGFA score from IV to II after 12 months of follow-up. Clinical improvement assessed by MGFA score was sustained in the long-term for all patients, during an average follow-up of 14 ± 9months, allowing them to be self-sufficient and out sick-leave. The median number of apheresis sessions was 7 (5-30). The dose of prednisolone was reduced in two patients from 40 mg/d and 30 mg/d to 7.5mg/d and 10mg/d, respectively. It was stopped in a patient who was taking 30 mg/d. No infectious, bleeding, or thrombosis complications were noted. The combination of rituximab and DFPP was effective to treat refractory MG.

Rituximab in the Treatment of Refractory Myasthenia Gravis: Studying the Outcomes Using MMT Score And Need for Plasmapheresis in Baghdad Teaching Hospital

Introduction: Myasthenia gravis (MG) is an uncommon autoimmune disease that is caused by acetylcholine receptor antibodies (AChRA) at the neuromuscular junction. Its pathogenesis involves complement fixing antibodies directed against acetylcholine receptors, muscle-specific tyrosine kinase or low density lipoprotein receptor–related protein. Method: A descriptive case series study investigating rituximab in refractory MG was conducted in Baghdad teaching hospital .Patients who were included in the study had received a regimen of rituximab that was deemed appropriate by their treating physician. Results: A total of 24 patients with mean disease duration of 6.3 years ±3.6 standard deviation were included in this study. The results showed that the average age of patients was 33.3 ,years ±10.1 SD and 62.5% was females. All twenty four patients showed an obvious improvement in clinical status after finishing the follow-up period. The results demonstrated from all patients that enrolled in our study, only one patient that who was on 14 sessions of plasmapheresis was in need for plasmapheresis after induction of rituximab and this difference was statistically significant. Conclusion: There were a great clinical improvement as shown with MMT score in addition to discontinuation of plasma exchange treatments fallowing treatment with rituximab.

Rituximab in the Treatment of Refractory Myasthenia Gravis : Studying the Outcomes using MMT Score and Need for Plasmapheresis in Baghdad Teaching Hospital

Introduction: Myasthenia gravis (MG) is an uncommon autoimmune disease that is caused by acetylcholine receptor antibodies (AChRA) at the neuromuscular junction. Its pathogenesis involves complement fixing antibodies directed against acetylcholine receptors, muscle-specific tyrosine kinase or low density lipoprotein receptor–related protein. Method: A descriptive case series study investigating rituximab in refractory MG was conducted in Baghdad teaching hospital .Patients who were included in the study had received a regimen of rituximab that was deemed appropriate by their treating physician. Results: A total of 24 patients with mean disease duration of 6.3 years ±3.6 standard deviation were included in this study. The results showed that the average age of patients was 33.3 ,years ±10.1 SD and 62.5% was females. All twenty four patients showed an obvious improvement in clinical status after finishing the follow-up period. The results demonstrated from all patients that enrolled in our study, only one patient that who was on 14 sessions of plasmapheresis was in need for plasmapheresis after induction of rituximab and this difference was statistically significant. Conclusion: There were a great clinical improvement as shown with MMT score in addition to discontinuation of plasma exchange treatments fallowing treatment with rituximab.

Frequency and clinical features of treatment-refractory myasthenia gravis

BackgroundTo investigate the frequency and characterize the clinical features of treatment-refractory myasthenia gravis in an Austrian cohort.MethodsPatient charts of 126 patients with generalized myasthenia gravis and onset between 2000 and 2016 were analyzed retrospectively. Patients were classified as treatment-refractory according to strict, predefined criteria. These mandated patients being at least moderately symptomatic (i.e., MGFA class III) or needing either maintenance immunoglobulins or plasma exchange therapy for at least 1 year in spite of two adequately dosed immunosuppressive drugs. Clinical features and outcome at last follow-up were compared to treatment-responsive patients.Results14 out of 126 patients (11.1%) met these criteria of treatment-refractory myasthenia gravis. Treatment-refractory patients had more frequent clinical exacerbations and more often received rescue treatments or a further escalation of immunosuppressive therapies. They also remained more severely affected at last follow-up. An early onset of myasthenia gravis was associated with a higher risk for a refractory course.ConclusionA small subgroup of patients with generalized myasthenia gravis do not respond sufficiently to standard therapies. Refractory disease has considerable implications for both patients and health care providers and highlights an unmet need for new treatment options.

Safety of an Abbreviated Transition Period When Switching From Intravenous Immunoglobulin to Eculizumab in Patients with Treatment-Refractory Myasthenia Gravis: A Case Series.

Case seriesPatient: —Final Diagnosis: Generalized myasthenia gravisSymptoms: Muscle weaknessMedication: IVIg • eculizumabClinical Procedure: Transition from IVIg to eculizumabSpecialty: NeurologyObjective:Unusual setting of medical careBackground:Eculizumab is a terminal complement inhibitor used to treat myasthenia gravis in patients refractory (because of insufficient efficacy or intolerance) to other therapies, including intravenous immunoglobulin. However, information is lacking on how to transition patients from intravenous immunoglobulin to eculizumab, while avoiding a crossover effect of intravenous immunoglobulin and minimizing the risk of a transient worsening of symptoms if treatment that may be at least partially effective is interrupted. The aim of this study was to determine whether eculizumab can be safely initiated before complete intravenous immunoglobulin washout, using a standardized protocol.Case Report:A series of 13 patients with generalized treatment-refractory myasthenia gravis were transitioned to eculizumab 10–14 days after their last intravenous immunoglobulin infusion. Patients’ clinical status was assessed before and 6 weeks after transition using the Myasthenia Gravis Composite Score. Most patients (8/13; 62%) had received ≥3 immunosuppressants as well as intravenous immunoglobulin. The median (range) Myasthenia Gravis Composite Score before and 6 weeks after transition was 21 (11–29) and 12 (6–18), respectively. Clinically significant improvements (score decrease ≥3) were observed in all patients. Two patients experienced mild myalgia during transition.Conclusions:In this case series, patients with treatment-refractory myasthenia gravis were successfully transitioned to eculizumab 10–14 days after their last intravenous immunoglobulin infusion without any significant safety concerns.

Healthcare resource utilization by patients with treatment-refractory myasthenia gravis in England

Aims: To examine healthcare resource utilization associated with refractory myasthenia gravis (MG) in England.Materials and methods: This was a retrospective cohort study of linked data from the Clinical Practice Research Datalink and the Hospital Episode Statistics database collected between 1997 and 2016. Included patients were ≥18 years of age at the index MG diagnosis. Patients with refractory MG were identified using an algorithm based on treatments received. Healthcare resource utilization since the index date was compared between refractory and non-refractory cohorts.Results: The study included 1149 patients with MG, of whom 66 (5.7%) were refractory. Sex and age at diagnosis did not significantly differ between the refractory and non-refractory cohorts. Rates of healthcare resource utilization per person-year were significantly higher (p < .05) for patients with refractory compared to non-refractory MG for GP visits, visits to other healthcare professionals, outpatient visits and inpatient hospitalization. Patients in the refractory cohort spent more total days hospitalized since the index visit than patients in the non-refractory cohort (median, 33 vs. 16 days [p < .0001]).Limitations: The algorithm for identifying refractory patients did not include clinical criteria. Also, treatments administered in hospitals or by specialists were not available in the databases.Conclusions: Patients in England with refractory MG more often visit healthcare providers, are hospitalized and visit an emergency room than patients with non-refractory MG.

Advances in rituximab treatment of refractory myasthenia gravis

Myasthenia gravis is an autoimmune disorder of the neuromuscular junction caused by circulating antibodies specific for the post-synaptic receptor.It results in neuromuscular transmission disorders.After optimal treatment with standard drugs, most myasthenia gravis patients can achieve a good life quality.Part of patients cannot get stable clinical remission or minimal manifestation with standard therapy.Rituximab is a chimeric mouse/human antibody specific for the CD20 B-cell surface antigen.Studies have showed that rituximab is effective in the refractory myasthenia gravis.This review mainly discusses about the advances of rituximab in the treatment of refractory myasthenia gravis. Key words: Refractory myasthenia gravis; Rituximab

Myasthenia gravis: current status of antibody diagnostics and aspects on refractory myasthenia gravis

Acquired myasthenia gravis (MG) is an autoimmune disease that leads to fluctuating muscle weakness and fatigue, caused by circulating antibodies against different structures of the neuromuscular junction. In most patients, antibodies against acetylcholine receptor (AChR) can be detected. In a smaller proportion of patients with and without AChR antibodies, antibodies to muscle-specific kinase (MuSK), or related proteins such as agrin, cortactin and low-density lipoprotein receptor-related protein 4 (LRP4), are present. With current therapy, most patients achieve a stable condition with good quality of life and normal life expectancy. Nevertheless, 10 to 15 % of patients fail to respond ad equately to current therapies and are defined as refractory myasthenia gravis. Their clinical course is characterized by recurrent episodes of severe, acute deterioration, which sometimes appear life threatening. This article gives an overview of the current state of myasthenic antibody diagnostics and recommended treatment of refractory myasthenia gravis.

Rituximab in refractory myasthenia gravis: Extended prospective study results.

Rituximab appears to be beneficial in treatment-refractory myasthenia gravis (MG); however, prospective, long-term durability data are lacking. In this prospective, open-label study of rituximab in refractory MG, 22 patients (10 nicotinic acetylcholine receptor, 9 muscle-specific tyrosine kinase, 3 seronegative) received rituximab at baseline, with repeat cycles driven by clinical worsening. Manual muscle testing (MMT) scores and CD19/CD20+ B-cell counts were serially monitored. At mean follow-up of 28.8 ± 19.0 months (range, 6-66), mean MMT scores declined from 10.6 ± 5.4 to 3.3 ± 3.1 (P < 0.0001). Mean prednisone dosage declined from 25.2 ± 15.1 to 7.3 ± 7.1 mg/d (P = 0.002). Ten relapses occurred, with average time to first relapse of 17.1 ± 5.5 months (range, 9-23). CD19/CD20+ count recovery did not predict relapse. Three patients experienced prolonged B-cell depletion (range, 24-45 months) after 1 cycle. Sustained clinical improvement was associated with rituximab after 1 cycle, with prolonged time to relapse and reduction in steroid dosage. Muscle Nerve 58: 453-456, 2018.

Burden of illness in patients with treatment refractory myasthenia gravis.

This study assessed the clinical burden of refractory myasthenia gravis (MG), relative to nonrefractory MG. Rates of myasthenic crises, exacerbations, inpatient hospitalizations, and emergency room (ER) visits over a 1-year period were measured for 403 refractory, 3,811 nonrefractory, and 403 non-MG control patients from two administrative health plan databases. Compared with nonrefractory patients, a significantly greater percentage of refractory patients had at least one myasthenic crisis (21.3% vs. 6.1%; P < 0.001) and at least one exacerbation (71.2% vs. 32.4%; P < 0.001) over a 1-year period. Refractory patients were also significantly more likely to be hospitalized and/or have an ER visit than nonrefractory patients and non-MG controls (P < 0.001 for all). Refractory MG patients have significantly greater clinical burden and are more likely to utilize intensive healthcare resources than nonrefractory patients. Furthermore, refractory patients may be at greater risk of crises throughout the disease course than previous studies have suggested. Muscle Nerve, 2018.

Long-term treatment of refractory myasthenia gravis with subcutaneous immunoglobulin.

Long-term treatment of refractory myasthenia gravis with subcutaneous immunoglobulin.