Myasthenia Gravis

The primary goals for MG therapy are to induce and then maintain remission, and to make use of immunosuppressive treatments as early as possible to reduce the likelihood of epitope spreading. Secondary goals are to manage disease symptoms. Most current MG treatments are immunosuppressive, with either of two types of treatment effects: rapid but short lived and long term.18'19'47

Acetylcholinesterase inhibitors (e.g., pyridostigmine) are the first-line therapy for recently diagnosed MG patients (see Figure 1 and Table 2); they are palliative treatments, bringing symptomatic relief, and are effective early in the disease course or in patients with mild disease, when the number of AChRs is sufficient to elicit a response. However, they have side effects (particularly at high doses), erratic absorption profiles, and short-lived effects (a few hours), thus requiring frequent administration. A greater worry perhaps is that their use can mask disease progression. Anti-sense technology is being used to develop a novel cholinesterase inhibitor, Monarsen (EN101), which is being tested in a Phase IIb clinical trial in Israel. Monarsen is reported to have a longer duration of efficacy than conventional inhibitors, with fewer side effects and equal or greater efficacy.

One immunosuppressive strategy for MG is thymectomy, the classic long-term treatment. Thymectomy appears to increase the likelihood of remission or remission maintenance and reduce or preclude the use of steroids, and is most effective when performed early in the disease. It is indicated for patients with neoplastic thymoma (thymomatous MG), but also for patients with thymic hyperplasia or no thymic abnormalities. There are, however, adverse effects, and little controlled randomized trial data to support its use for nonthymomatous MG; to address this issue, a clinical trial, testing the efficacy of thymectomy for nonthymomatous MG will begin shortly.

Corticosteroids, usually prednisone, are a short-term treatment that have been used for decades to treat MG, often in combination with thymectomy; numerous observational studies and expert opinion support their efficacy.48 However, there is little or no evidence from randomized controlled clinical trials to clearly demonstrate their efficacy or suggest the optimal dosage or route of administration. The onset is slow, with improvement noted by about 6 weeks, and remission by 3 months. Once remission occurs, the steroid administration is slowly and gradually tapered until the patient shows signs of relapse; some patients can be completely weaned from steroids. During tapering, azathioprine, which has fewer side effects than corticosteroids, can be used to increase the success of this phase. Cyclophosphamide tends to only be used for patients with severe MG who do not tolerate or respond well to high-dose corticosteroids. Other short-term treatments include IVIg and PE, which tend to be used for patients with an actual or impending myasthenic crisis; they are often administered in response to an exacerbation during the tapering phase of corticosteroids.

Mycophenolate mofetil is indicated for patients with poorly controlled disease in combination with the therapeutics described above. Randomized controlled clinical trial data are lacking for nearly all MG therapies, and there are currently only a handful of clinical trials for MG - one testing IVIg and the others mycophenolate mofetil.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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