Prednisone

Prednisone is a man-made corticosteroid used in the treatment of Lambert-Eaton myasthenic syndrome (LEMS). It acts in a similar way to the corticosteroid hormones synthesized by the outer layer of the adrenal glands, such as cortisol.

How prednisone works

LEMS is caused by autoantibodies generated against a protein called the voltage-gated calcium channels (VGCC) found in nerve cell endings. These autoantibodies bind to the VGCC and prevent the uptake of calcium by the nerve cells. Calcium is required for the release of vesicles containing a neurotransmitter, or cell-signaling molecule, called acetylcholine into the neuromuscular junction, the point where nerve and muscle cells meet. Acetylcholine controls muscle contraction by mediating the communication between the nerve cells and the muscle cells.

Prednisone, like the corticosteroid hormones, has anti-immune and anti-inflammatory effects; it suppresses the production of autoantibodies by cells of the immune system called B cells, thereby alleviating symptoms associated with LEMS.

Mechanistically, prednisone is metabolized by the liver into prednisolone, the active compound with therapeutic effects. Prednisolone can easily pass through the membrane of cells, where it binds to glucocorticoid receptors in the cytoplasm. The glucocorticoid receptor-prednisolone complex then enters the cell nucleus, where it regulates gene expression. For example, it shuts off the activity of genes that are required for the synthesis of antibodies in B cells.

Prednisone in clinical trials

In LEMS patients, treatment with Firdapse has emerged as the first line of treatment. If Firdapse satisfactorily controls the symptoms of LEMS, no further treatment is needed. However, if symptoms remain, long-term treatment with prednisone and azathioprine is preferred.

A study published in the journal Neurology, Neurosurgery & Psychiatry showed that prednisone in combination with azathioprine was needed in 80 of 114 (70 percent) patients with non-cancer LEMS, and in 46 of 104 (44 percent) patients with cancer-mediated LEMS.

The study also showed that LEMS patients require longer treatment with immunosuppressive agents such as prednisolone and azathioprine compared to patients with another related autoimmune disease, myasthenia gravis, to control symptoms of the disease.  Only 14 percent of LEMS patients did not require prednisolone to remain in remission after three years compared to 67 percent of myasthenia gravis patients. Most myasthenia gravis patients achieved remission within the first year of treatment, which was markedly quicker than the remission time of one to four years for LEMS patients.

The effectiveness of the combined prednisone-azathioprine therapy has only been shown in a retrospective study, but is supported by the positive results of the combined treatment in myasthenia gravis.

Therefore, prednisone alone or in combination with azathioprine can be used for the treatment of patients with both cancer-related and non-cancer forms of LEMS.

Other details

Prednisone treatment can cause side effects such as osteoporosis, mood disturbances, gastrointestinal problems, weight gain, high blood pressure, cataracts, and stunted growth in children.

To avoid the side effects, especially when longer treatment is required, a low dosage of prednisolone may be combined with other non-steroid immunosuppressive medications such as azathioprine.

 

Last updated: July 23, 2019

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