Reappraisal of Oral Steroid Therapy for Myasthenia Gravis

Abstract

Treatment with oral corticosteroids at high doses with an escalation and de-escalation schedule is effective against myasthena gravis (MG). In fact, the use of corticosteroids has led to a reduction in mortality to below 10% after the 1960s. However, long-term use of oral steroids above a certain dosage level is known to cause a number of problems. In 2014, the Japanese clinical guidelines for MG proposed that the first goal in MG treatment (treatment target) should be set at minimal manifestations (MM) with oral prednisolone (PSL) 5 mg/day or below, and that treatment strategies should strive to attain this level as rapidly as possible. In 2015, a multicenter, cross-sectional study revealed that higher PSL dose and longer PSL treatment do not ensure better outcome. In the absence of good response, the PSL dose should be decreased by combining with modalities such as plasma exchange/plasmapheresis and intravenous immunoglobulin (fast-acting treatments). In 2018, we conducted a multicenter, cross-sectional study in a large population of Japanese patients with generalized MG, aiming to elucidate the correlation between oral PSL regimens and achievement of treatment goals. The ORs for low vs. high dose to achieve treatment goals at 1, 2, and 3 years were 10.4, 2.75, and 1.86, respectively, whereas the corresponding ORs for low vs. medium dose were 13.4, 3.99, and 4.92. Early combination with fast-acting therapy (OR 2.19 at 2 years, 2.11 at 3 years) or combination with calcineurin inhibitors (OR 2.09 at 2 years, 2.36 at 3 years) were also positively associated with achieving treatment goals. These results indicate that early combination of low-dose PSL regimens with other therapies is the key for early achievement of treatment goals in generalized MG. However, even with this regimen, ~35% of patients did not achieve the treatment target after 3 years. These results suggest the limitation of the current oral corticosteroid therapy. We need to develop new treatment options to increase the rate of satisfactory outcome.

Keywords: cross-sectional study; logistic regression analysis; myasthenia gravis; oral corticosteroids; treatment strategies.

Figure 1

Classification of 472 MG patients treated with prednisolone according to the present disease status in a multicenter, cross-sectional study in 2015. MG, myasthenia gravis; PSL, prednisolone; CSR, complete stable remission; PR, pharmacological remission; MM, minimal manifestations; I, improved; U, unchanged; W, worse; E, exacerbation. This figure is drawn from data published in (32).

Figure 2

Changes of therapeutic strategy. (A) The traditional strategy with high-dose oral corticosteroids with escalation and de-escalation schedule. (B) The new strategy with low-dose oral corticosteroids. PE, plasma exchange; PP, plasmapheresis; IVIg, intravenous immunoglobulin; mPSL, methylprednisolone; CNI, calcineurin inhibitor. This figure is drawn from data published in (32).

Figure 3

Classification of 590 prednisolone-treated generalized MG patients according to the present disease status in a multicenter, cross-sectional study in 2018. MG, myasthenia gravis; PSL, prednisolone; CSR, complete stable remission; PR, pharmacological remission; MM, minimal manifestations; I, improved; U, unchanged; W, worse; E, exacerbation. This figure is drawn from data published in (47).