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

Abstract

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.

Immunotherapy choice and maintenance for generalized myasthenia gravis in China

“…Treatments with these agents are commonly initiated in conjunction with steroids so that they may be gradually tapered to a lower maintenance dose, which varies among individual patients 8 . A previous network meta‐analysis showed the efficacy and tolerability of the immunosuppressants were heterogeneous 9 …”

Autoimmune Channelopathies at Neuromuscular Junction

“…It is worth mentioning that eculizumab, one of the latest generation treatment, was approved for the treatment of adults with AChR-associated gMG in the USA (183), AChR-associated refractory gMG in the EU (184) or patients with AChR-associated gMG whose symptoms are difficult to control with high-dose IVIg therapy or PE in Japan (185). One of a latest meta-analysis found that eculizumab is the most effective and tolerable therapeutic for refractory MG and tacrolimus is a beneficial therapy for MG extensively (186). Moreover, some new drugs are also under exploration which need further researches, such as efgartigimod (187).…”

Myasthenia gravis and specific immunotherapy: monoclonal antibodies

“…The complement system comprises more than 20 serum proteins, most of which are synthesized in the liver . These proteins are synthesized as inactive precursor proteins, which can be activated by appropriate stimuli . The activated forms of these proteins act as proteases and cleave other components successively in amplification pathways leading to an exponential generation of final effectors.…”

“…Furthermore, blocking C5 can inhibit the formation of the MAC, dampening the destruction of NMJs and the subsequent production of proinflammatory factors . Molecules aimed at inhibiting complement cascade activation at the NMJ could represent an effective therapeutic approach of major interest .…”

“…Nevertheless, to date, only eculizumab exists as a molecular treatment specifically targeting complement deposition for MG patients. Eculizumab has been approved by the FDA for refractory MG based on a phase III trial . It is a human‐derived mAb developed against complement C5 that specifically binds to C5 and inhibits the breakdown of C5 into C5a and C5b.…”