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MG Expert Series: Patient Reported Experiences as reported by an International MG Patient Council

MG Expert Series: Patient Reported Experiences as reported by an International MG Patient Council

In a unique analysis led by an international group of professional MG advocates who also have MG themselves, Law et al.iii sought to identify common experiences as described by patients who are diagnosed with MG, with the hope that it will enhance the understanding of MG. Data on patient reported experiences was gathered from three different resources: prospective interviews between Nov 2019 & Jan 2020, a Patient Council meeting report from September 2019, and 32 peer-reviewed research publications that present patient-reported outcomes or experiences of living with MG.

 

The collated insights and quotes were organized based on how the Patient Council members considered them to represent the patient perspective of MG. Domains were constructed at the start of analysis and adjusted during the analysis to help consolidate common themes identified in the patient insights. The authors clarify that care was taken to accurately represent source data, minimize researcher interpretation and avoid changing the meaning of the insights. Quotes were used to explain the insights. 

 

114 insights and 50 quotes were recorded from 54 people affected by MG. This included 48 people with generalized MG and six caregivers. Nine domains were identified: physical; psychological; social; reproduction and parenting; activities and participation; controlled and not controlled; flare-ups and myasthenic crises; treatment burden; and unmet needs.

The Patient Council identified five themes that best represented the patient experience: (1) living with fluctuating and unpredictable symptoms, (2) a constant state of adaptation, continual assessment and trade-offs in all aspects of life, (3) treatment inertia, often resulting in under-treatment, (4) a sense of disconnect with healthcare professionals, (5) feelings of anxiety, frustration, guilt, anger, loneliness and depression. The Patient Council also identified several positive outcomes observed in patients with MG, including opportunities for personal growth, better coping strategies and the opportunity to help others through peer-support. 

 

While the Patient Council took extra steps to maintain accuracy and limit researcher bias, they acknowledge that the inherent nature of the study design may limit the variability of responses and decontextualize insights during data extraction. The small number of patients included in the study may also limit generalizability of the study. Nonetheless, the authors’ hope is that this novel, patient-led patient reported experience summary may lead to better understanding of what it is like to be living with MG. 

 

The long awaited BeatMG study results: Rituximab for AChR Antibody positive generalized Myasthenia Gravis did not show benefit in achieving favorable outcome compared to placebo 

 

Rituximab has been used for many antibody mediated illnesses, including neuromuscular diseases. In this phase 2 controlled clinical trial,iv the BeatMG study team sought to clarify if administration of rituximab for AChR antibody positive generalized MG would lead to more frequent achievement of favorable outcome defined as tapering of prednisone and improvement of disease severity. Participants were randomized to receive rituximab or placebo, with stratified randomization based on baseline prednisone and concomitant immunosuppressive therapy so that participants in both groups have similar baseline treatments.

 

The treatment group was given a dose of four weekly rituximab infusions followed by a second cycles of four weekly infusions six months later while the placebo group received vehicle components (without true medicine). If the patient had stable or improved disease based on the Myasthenia Gravis Composite (MGC) score at week 8, prednisone dose was tapered. The primary outcome was the proportion of participants with greater than or equal to 75% reduction in mean daily prednisone at weeks 49 to 52 compared to the baseline without disease worsening.  Another primary outcome was the safety of rituximab treatment. The trial used a futility design to determine whether larger phase 3 trial is warranted or not.  

 

Total 52 participants were randomized, 25 to rituximab and 27 to placebo groups. Participants were enrolled at 16 centers across the United States between August 2014 and July 2016 and followed for 52 weeks. Mean age was 55 ranging from 21 to 90. Baseline immunosuppressive therapy was well matched between groups. Disease severity was predominantly mild (MGFA class II by approximately 60% in each group). Placebo group had significantly lower disease burden at baseline compared to rituximab group based on disease severity scales and proportion of participants with minimal symptom.

 

The primary outcome of effective steroid taper with stable disease was achieved in 60% of subjects in the rituximab group versus 56% in the placebo group. Since the groups responded similarly, the futility endpoint was achieved (p = 0.03). This result means that it is unlikely that the subsequent larger trial would demonstrate a clinically meaningful steroid sparing effect of rituximab.  

 

Despite this negative trial, researchers have learned many valuable lessons. The trial design and the milder disease severity of participants may have limited the ability to measure a clinically significant response. The dramatic response rate and disproportionate fraction of individuals with milder disease in the placebo group were unanticipated and likely affected the study results.

Although most of the primary and secondary outcomes were comparable between groups, the rate of MG exacerbation requiring rescue therapy was threefold higher in the placebo group when compared to the rituximab group, when baseline differences were accounted for. This observation suggests that the disease course was more stable in the rituximab group compared to the placebo group while tapering the prednisone. Safety profile was similar between rituximab and placebo groups. Further studies including the ongoing observational post-intervention study are needed to define role of rituximab in generalized AChR MG treatment. 

 

[1]Kim Y, Li X, Huang Y, Kim M, Shaibani A, Sheikh K, Zhang GQ, Nguyen TP. COVID-19 Outcomes in Myasthenia Gravis Patients: Analysis From Electronic Health Records in the United States. Front Neurol. 2022 Mar 28;13:802559. doi: 10.3389/fneur.2022.802559. PMID: 35418937; PMCID: PMC8996116.

[1]Farina A, Falso S, Cornacchini S, Spagni G, Monte G, Mariottini A, Massacesi L, Barilaro A, Evoli A, Damato V. Safety and tolerability of SARS-Cov-2 vaccination in patients with myasthenia gravis: A multicenter experience. Eur J Neurol. 2022 Apr 7. doi: 10.1111/ene.15348. Epub ahead of print. PMID: 35390184.

[1]Law N, Davio K, Blunck M, Lobban D, Seddik K. The Lived Experience of Myasthenia Gravis: A Patient-Led Analysis. Neurol Ther. 2021 Dec;10(2):1103-1125. doi: 10.1007/s40120-021-00285-w. Epub 2021 Oct 23. PMID: 34687427; PMCID: PMC8540870.

[1]Nowak RJ, Coffey CS, Goldstein JM, Dimachkie MM, Benatar M, Kissel JT, Wolfe GI, Burns TM, Freimer ML, Nations S, Granit V, Smith AG, Richman DP, Ciafaloni E, Al-Lozi MT, Sams LA, Quan D, Ubogu E, Pearson B, Sharma A, Yankey JW, Uribe L, Shy M, Amato AA, Conwit R, O'Connor KC, Hafler DA, Cudkowicz ME, Barohn RJ; NeuroNEXT NN103 BeatMG Study Team. Phase 2 Trial of Rituximab in Acetylcholine Receptor Antibody-Positive Generalized Myasthenia Gravis: The BeatMG Study. Neurology. 2021 Dec 2;98(4):e376–89. doi: 10.1212/WNL.0000000000013121. Epub ahead of print. PMID: 34857535; PMCID: PMC8793103.

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