Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis

Hewett, K.; Sanders, Donald B.; Grove, Richard; Broderick, Christine L.; Rudo, Todd; Bassiri, Ashlyn Eaton; Zvartau-Hind, Marina; Bril, Vera

doi:10.1212/wnl.0000000000005323

Cited by 98 publications

(71 citation statements)

References 34 publications

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“…Importantly, corticosteroids remain indispensable and the most effective drug for treating MG [6 , 7] . New drugs with a more favorable safety profile would be very welcome, but in recent years several promising candidate drugs unexpectedly failed to prove efficacy in clinical trials [8][9][10][11][12] . To test https://doi.org/10.1016/j.nmd.2019.12.003 0960-8966/© 2019 The Author(s).…”

Section: Introductionmentioning

confidence: 99%

Emerging therapies for autoimmune myasthenia gravis: Towards treatment without corticosteroids

Tannemaat

Verschuuren

2020

Neuromuscular Disorders

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Myasthenia gravis is an autoimmune disease characterized by dysfunction of the neuromuscular junction. Current treatment is based on lifestyle advice, symptomatic treatment, immunosuppressive drugs and thymectomy. Corticosteroids remain the cornerstone of treatment beside symptomatic medication due to their low cost, wide availability and fast mode of action. However, long term steroid use carries substantial risks of severe adverse side effects. Therefore, non-steroidal immunosuppressive drugs are commonly added to the treatment. Unfortunately, they have a delayed-onset effect and evidence of their efficacy appears to be difficult to obtain. Several trials using drugs that have had clear positive results in other immunological disorders have failed in myasthenia. This failure may in part be related to difficulties in the design of clinical trial for myasthenia, which has a fluctuating disease course involving weakness that may be difficult to assess quantitively. This problem is exacerbated by the tendency of most clinical trials to select patients with a stable, but severe disease. Future trials should: select patients with weakness and fatigability that is completely explained by their myasthenia gravis, use a design that avoids the exclusion of patients with recent changes in medication, and explore the possibilities to completely avoid the use of corticosteroids.

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Section: Introductionmentioning

confidence: 99%

Emerging therapies for autoimmune myasthenia gravis: Towards treatment without corticosteroids

Tannemaat

Verschuuren

2020

Neuromuscular Disorders

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“…MTX was comparable with AZA in the primary (−0.058, −0.98 to 0.92) and secondary (0.20, −0.99 to 1.36) outcome measures including safety in HR (1.09, 0.28 to 4.29). BLM, a human monoclonal antibody against B‐cell activating factor (BAFF), is an effective therapy for SLE. It was demonstrated that the level of CD19 + BAFFR + B cells was elevated in MG patients, verifying the increased activation of B‐cell maturation .…”

Section: Discussionmentioning

confidence: 99%

“…The data from the two studies by Sanders 21,22 were not pooled for different participant cohorts, neither were the data from the four studies by Howard 23,24 or Tindall 25,26 for different time points. Finally, 14 studies [21][22][23][24][25][26][27][28][29][30][31][32][33][34] were included in the NMA of our study.…”

Section: Study Characteristicsmentioning

confidence: 99%

Immunosuppressive and monoclonal antibody treatment for myasthenia gravis: A network meta‐analysis

Wang

Huan

et al. 2019

CNS Neurosci Ther

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Summary Background We intended to compare and rank all the immunotherapies including immunosuppressant agents or monoclonal antibodies for myasthenia gravis (MG). Methods A network meta‐analysis was performed to synthesize the direct evidence and indirect evidence. Quantitative MG score (QMGS) was defined as the primary outcome. The secondary outcomes included the glucocorticoid reduction and hazard ratios (HR) from the counts of adverse events (AEs). Results We identified 14 studies including 808 MG patients. For the primary outcome, cyclosporine A (CsA) was hierarchically the best with statistical significances of −1.18 (−1.81, −0.59) vs placebo (PLA), −0.98 (−1.72, −0.23) vs mycophenolate mofetil, and −0.77 (−1.57, −0.032) vs tacrolimus (TAC). When the intervention periods were controlled, both eculizumab (ECZ) of −1.50 (−2.81, −0.18) and CsA of −1.23 (−1.81, −0.64) vs PLA reached a statistical significance. Belimumab and ECZ ranked the most tolerable therapies while CsA of 2.41 (0.58, 10.01) ranked the last vs PLA. Conclusion These findings demonstrated that ECZ represented the most effective and tolerable therapeutic alternative to be recommended for refractory MG. TAC may be a beneficial therapy to treat MG extensively while the efficacy of CsA and cyclophosphamide may be limited by their multiple or severe AEs.

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“…BAFF also has a role in MG development and progression (41). Although belimumab treatment in patients with SLE had moderate efficacy in a multicenter phase 3 trials, treatment in an FDA-approved randomized MG study did not produce significant effects in patients with either AChR-MG or MuSK-MG (42).…”

Section: B Cell-activating Factor (Baff)-targeting Mabmentioning

confidence: 99%

New Approaches to Targeting B Cells for Myasthenia Gravis Therapy

Huda

2020

Front. Immunol.

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Current therapies for myasthenia gravis (MG) are limited, and many investigations have recently focused on target-specific therapies. B cell-targeting monoclonal antibody (mAb) therapies for MG are increasingly attractive due to their specificity and efficacy. The targeted B cell biomarkers are mainly the cluster of differentiation (CD) proteins that mediate maturation, differentiation, or survival of pathogenic B cells. Additional B cell-directed therapies include non-specific peptide inhibitors that preferentially target specific B cell subsets. The primary goals of such therapies are to intercept autoantibodies and prevent the generation of an inflammatory response that contributes to the pathogenesis of MG. Treatment of patients with MG using B cell-directed mAbs, antibody fragments, or selective inhibitors have exhibited moderate to high efficacy in early studies, and some of these therapies appear to be highly promising for further drug development. Numerous other biologics targeting various B cell surface molecules have been approved for the treatment of other conditions or are either in clinical trials or preclinical development stages. These approaches remain to be tested in patients with MG or animal models of the disease. This review article provides an overview of B cell-targeted treatments for MG, including those already available and those still in preclinical and clinical development. We also discuss the potential benefits as well as the shortcomings of these approaches to development of new therapies for MG and future directions in the field.

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Randomized study of adjunctive belimumab in participants with generalized myasthenia gravis

Cited by 98 publications

References 34 publications

Emerging therapies for autoimmune myasthenia gravis: Towards treatment without corticosteroids

Emerging therapies for autoimmune myasthenia gravis: Towards treatment without corticosteroids

Immunosuppressive and monoclonal antibody treatment for myasthenia gravis: A network meta‐analysis

New Approaches to Targeting B Cells for Myasthenia Gravis Therapy

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