Clinical outcome measures following plasma exchange for MG exacerbation

Raja, Shruti; Howard, James F.; Juel, Vern C.; Massey, Janice M.; Chopra, Manisha; Guptill, Jeffrey T.

doi:10.1002/acn3.50901

Cited by 14 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The available phase 1 and phase 2 clinical trial data for anti-FcRn monoclonal antibodies consistently demonstrate the ability to reduce and maintain total IgG and/or AChR autoantibodies at levels associated with efficacy for PLEX (5,36). In general, all of the available therapeutics reduce IgG levels by 60-80% from baseline at the doses studied, with modest effects on albumin.…”

Section: Clinical Development Summarymentioning

confidence: 89%

Antagonism of the Neonatal Fc Receptor as an Emerging Treatment for Myasthenia Gravis

Gable

Guptill

2020

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

Myasthenia gravis is an autoimmune disease in which immunoglobulin G (IgG) autoantibodies are formed against the nicotinic acetylcholine receptor (AChR) or other components of the neuromuscular junction. Though effective treatments are currently available, many commonly used therapies have important limitations and alternative therapeutic options are needed for patients. A novel treatment approach currently in clinical trials for myasthenia gravis targets the neonatal Fc receptor (FcRn). This receptor plays a central role in prolonging the half-life of IgG molecules. The primary function of FcRn is salvage of IgG and albumin from lysosomal degradation through the recycling and transcytosis of IgG within cells. Antagonism of this receptor causes IgG catabolism, resulting in reduced overall IgG and pathogenic autoantibody levels. This treatment approach is particularly intriguing as it does not result in widespread immune suppression, in contrast to many therapies in routine clinical use. Experience with plasma exchange and emerging phase 2 clinical trial data of FcRn antagonists provide proof of concept for IgG lowering in myasthenia gravis. Here we review the IgG lifecycle and the relevance of IgG lowering to myasthenia gravis treatment and summarize the available data on FcRn targeted therapeutics in clinical trials for myasthenia gravis.

show abstract

Section: Clinical Development Summarymentioning

confidence: 89%

Antagonism of the Neonatal Fc Receptor as an Emerging Treatment for Myasthenia Gravis

Gable

Guptill

2020

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Despite treatment with rozanolixizumab resulting in up to 68% reduction in anti-AChR autoantibodies, no consistent correlation with clinical effects was observed. These data are consistent with previous studies reporting no associations between anti-AChR antibodies and clinical improvements in MG. 12 – 14 …”

Section: Discussionmentioning

confidence: 99%

“…Despite treatment with rozanolixizumab resulting in up to 68% reduction in anti-AChR autoantibodies, no consistent correlation with clinical effects were observed. These data are consistent with previous studies reporting no associations between anti-AChR antibodies and clinical improvements in MG. [12][13][14] In addition to issues around timing of efficacy assessments, it should also be considered whether there is a need for more robust MG endpoints. It is known that the clinical significance of a change in QMG score can be affected by baseline disease severity and that subtleties exist when assessing treatment response with QMG (percentage change or point-change from baseline).…”

Section: A C C E P T E Dmentioning

confidence: 99%

Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis

et al. 2021

View full text Add to dashboard Cite

ObjectiveTo explore the clinical efficacy and safety of subcutaneous (SC) rozanolixizumab, an anti-neonatal Fc receptor humanized monoclonal antibody, in patients with generalized myasthenia gravis (gMG).MethodsIn this phase 2a, randomized, double-blind, placebo-controlled, 2-period, multicenter trial (NCT03052751), patients were randomized (1:1) in period 1 (days 1–29) to 3 once-weekly (Q1W) SC infusions of rozanolixizumab 7 mg/kg or placebo. In period 2 (days 29–43), patients were re-randomized to either rozanolixizumab 7 mg/kg or 4 mg/kg (3 Q1W SC infusions), followed by an observation period (days 44–99). Primary endpoint: change from baseline to day 29 in Quantitative Myasthenia Gravis (QMG) score. Secondary endpoints: change from baseline to day 29 in MG-Activities of Daily Living (MG-ADL) and MG-Composite (MGC) scores; safety.ResultsForty-three patients were randomized (rozanolixizumab: 21 patients; placebo: 22 [period 1]). Least squares (LS) mean change from baseline to day 29 for rozanolixizumab vs placebo: QMG (LS mean: −1.8 vs −1.2; difference: −0.7; 95% UCL: 0.8; p = 0.221; not statistically significant), MG-ADL (LS mean: −1.8 vs −0.4; difference: −1.4; 95% UCL: −0.4), and MGC (LS mean: −3.1 vs −1.2; difference: −1.8; 95% UCL: 0.4) scores. Efficacy measures continued to improve with rozanolixizumab 7 mg/kg in period 2. The most common adverse event in period 1 was headache (rozanolixizumab: 57%; placebo: 14%).ConclusionWhile change from baseline in QMG was not statistically significant, the data overall suggest rozanolixizumab may provide clinical benefit in patients with gMG and was generally well tolerated. Phase 3 evaluation is ongoing (NCT03971422).Classification of evidenceThis study provides class I evidence that for patients with gMG, rozanolixizumab is well tolerated, but did not significantly improve QMG score.

show abstract

“…However, in a study by Raja and colleagues, there was poor correlation between between AChR antibody titer and MG-composite score at baseline (R 2 = 0.022) and at 2 weeks post-TPE (R 2 = 0.093) and between AChR antibody titer and MG-ADL at baseline (R 2 < 0.0001) and at 2 weeks post-TPE (R 2 = 0.198) [31].…”

Section: Discussionmentioning

confidence: 94%

Determinants of quality of life changes with plasmapheresis in patients with myasthenia gravis

Al-Ahmer

Elshony

2021

Egypt J Neurol Psychiatry Neurosurg

View full text Add to dashboard Cite

Background Immunomodulation, including IVIG and plasma exchange, is useful for a crisis or severe exacerbation. Plasma exchange may be slightly faster and more effective in a myasthenic crisis than IVIG. The aim of the current study was to determine the changes in the quality of life (QOL) after plasmapheresis and factors influencing these changes. Results This study was conducted on 98 MG patients diagnosed as moderate to severe myasthenia gravis (according to Myasthenia Gravis Foundation of America classification), 81 patients received alternate day 5 sessions plasmapheresis (TPE group) and 17 patients were on medical treatment only (control group). All patients were subjected to full history, through clinical neurological evaluation and scored with quantitative myasthenia gravis (QMG) score for MG severity at start and after 1 m. Both groups completed the QOL questionnaire at baseline and after 1 month. The MG-QOL-15 scores were computed and we analyzed the change in the QOL scores from baseline to after plasmapheresis groups and compared it with the results for the control group. The scores in QOL scales had significantly decreased after plasmapheresis, and the improvement in QOL scores had a good correlation with the decrease in QMGS. The improvement in QOL and QMG was significantly correlated with younger age, female gender, shorter duration of the illness, presence of AchR antibodies, antibody titer, and thymus hyperplasia. Conclusion Plasmapheresis is effective in improving quality of life in myasthenia gravis patients and this improvement influenced by age, gender, duration of illness, presence of AchR antibodies and their titer, and the thymus pathology.

show abstract

Clinical outcome measures following plasma exchange for MG exacerbation

Cited by 14 publications

References 20 publications

Antagonism of the Neonatal Fc Receptor as an Emerging Treatment for Myasthenia Gravis

Antagonism of the Neonatal Fc Receptor as an Emerging Treatment for Myasthenia Gravis

Efficacy and Safety of Rozanolixizumab in Moderate to Severe Generalized Myasthenia Gravis

Determinants of quality of life changes with plasmapheresis in patients with myasthenia gravis

Contact Info

Product

Resources

About