Select Myasthenia Gravis Rx on Case-by-Case Basis : Prednisone is the most commonly used agent and most patients will require long-term, low-dose Tx.

MIAMI BEACH — The off-label use of immunosuppressive agents for myasthenia gravis can significantly decrease the need for steroids, while improving symptoms.

However, compared with prednisone, other immunosuppressants are much more expensive and carry their own risks of adverse events, so their use should be carefully evaluated on a case-by-case basis, Gil Wolfe, M.D., said at the annual meeting of the American Academy of Neurology.

Since acetylcholinesterase inhibitor monotherapy controls the symptoms of no more than 40% of myasthenia gravis (MG) patients, most patients will end up taking prednisone or other immunosuppressive agents, either alone or in combination, said Dr. Wolfe, a neurologist and codirector of the Muscular Dystrophy Association clinic at the University of Texas Southwestern Medical Center in Dallas.

▸ Prednisone—started low and slowly titrated, and tapered down very slowly after symptom improvement—is the most commonly used regimen. But few patients will be able to taper off prednisone completely; the rest will require long-term, low-dose therapy. Other immunosuppressants may be added to prednisone to act as steroid-sparing agents and to assist in successful prednisone discontinuation, Dr. Wolfe said.

▸ Azathioprine is used as a steroid-sparing agent for patients who relapse during a prednisone taper and for those who have adverse events during long-term steroid use. “Up to 90% of patients respond well to [azathioprine], if they can tolerate it,” he said. “In those who can, it can reduce steroid consumption by up to 80% by 2 years.” One small study concluded that 63% of those who took azathioprine for 36 months had completely tapered off prednisone, compared with 20% of those who took prednisone alone.

The major cause for discontinuation is a flulike reaction, seen in 10%–20% of patients. The drug also has a long onset of action—maximum benefit may not be seen for up to 2 years.

▸ Cyclosporine works more rapidly, with maximum benefit seen by 3 months. Patients who are refractory to other agents may respond to cyclosporine; this drug is as effective as azathioprine in symptom improvement, judging from the findings of a recent study. However, cyclosporine is less well tolerated than azathioprine, and some studies suggest that about half of patients discontinue the medication because of adverse events.

“It's important not to mix different cyclosporine preparations, because the different brands are not bioequivalent,” Dr. Wolfe added.

▸ Mycophenolate mofetil has shown promise as the newest immunosuppressive agent commonly used for MG, he said. A recent open-label study showed that 73% of patients achieved pharmacologic remission, minimal manifestation status, or symptom improvement with mycophenolate. The drug has a rapid onset of action, with improvement seen in 9–11 weeks and maximum effect by 6 months. “You may be able to decrease steroids by up to 50% in most patients with this drug,” Dr. Wolfe said.

Mycophenolate is well tolerated. Its main adverse events are diarrhea, vomiting, increased risk of infection, and rarely, leukopenia; only about 6% of patients discontinue the drug because of an adverse event. Switching to dosing three times daily may decrease the incidence of diarrhea.

▸ Cyclophosphamide is used mainly for refractory MG patients. “This drug has a lot of potential for adverse events,” Dr. Wolfe said. “But IV pulse therapy looks like it could be safer than daily oral therapy, because there is a lower cumulative dose.” However, cyclophosphamide should be considered a third-line therapy.

▸ Intravenous gamma globulin is employed as a lower-risk alternative to plasma exchange. An analysis of eight retrospective studies indicated that 73% of patients responded well to intravenous gamma globulin, and did so very quickly—in about 4–5 days. The beneficial effects can last up to several months. “IV gamma globulin is a particularly attractive alternative to plasma exchange for patients with poor venous access, hemodynamic instability, or other contraindications to plasmapheresis,” he said.

▸ Investigational agents include tacrolimus, rituximab, and monarsen. Tacrolimus has demonstrated efficacy as a monotherapy or in combination with corticosteroids, in a few recent open trials. It has a similar mechanism of action to cyclosporine but appears less nephrotoxic. However, hyperglycemia may occur. Rituximab has been reported in just a few MG cases and was associated with substantial clinical improvement at 4 weeks and with no complications or adverse events. Monarsen is being investigated in preliminary MG studies. In an open trial of 16 patients, 15 who discontinued the antiacetylcholinesterase pyridostigmine demonstrated improvement while using monarsen.

MIAMI BEACH — The off-label use of immunosuppressive agents for myasthenia gravis can significantly decrease the need for steroids, while improving symptoms.

However, compared with prednisone, other immunosuppressants are much more expensive and carry their own risks of adverse events, so their use should be carefully evaluated on a case-by-case basis, Gil Wolfe, M.D., said at the annual meeting of the American Academy of Neurology.

Since acetylcholinesterase inhibitor monotherapy controls the symptoms of no more than 40% of myasthenia gravis (MG) patients, most patients will end up taking prednisone or other immunosuppressive agents, either alone or in combination, said Dr. Wolfe, a neurologist and codirector of the Muscular Dystrophy Association clinic at the University of Texas Southwestern Medical Center in Dallas.

▸ Prednisone—started low and slowly titrated, and tapered down very slowly after symptom improvement—is the most commonly used regimen. But few patients will be able to taper off prednisone completely; the rest will require long-term, low-dose therapy. Other immunosuppressants may be added to prednisone to act as steroid-sparing agents and to assist in successful prednisone discontinuation, Dr. Wolfe said.

▸ Azathioprine is used as a steroid-sparing agent for patients who relapse during a prednisone taper and for those who have adverse events during long-term steroid use. “Up to 90% of patients respond well to [azathioprine], if they can tolerate it,” he said. “In those who can, it can reduce steroid consumption by up to 80% by 2 years.” One small study concluded that 63% of those who took azathioprine for 36 months had completely tapered off prednisone, compared with 20% of those who took prednisone alone.

The major cause for discontinuation is a flulike reaction, seen in 10%–20% of patients. The drug also has a long onset of action—maximum benefit may not be seen for up to 2 years.

▸ Cyclosporine works more rapidly, with maximum benefit seen by 3 months. Patients who are refractory to other agents may respond to cyclosporine; this drug is as effective as azathioprine in symptom improvement, judging from the findings of a recent study. However, cyclosporine is less well tolerated than azathioprine, and some studies suggest that about half of patients discontinue the medication because of adverse events.

“It's important not to mix different cyclosporine preparations, because the different brands are not bioequivalent,” Dr. Wolfe added.

▸ Mycophenolate mofetil has shown promise as the newest immunosuppressive agent commonly used for MG, he said. A recent open-label study showed that 73% of patients achieved pharmacologic remission, minimal manifestation status, or symptom improvement with mycophenolate. The drug has a rapid onset of action, with improvement seen in 9–11 weeks and maximum effect by 6 months. “You may be able to decrease steroids by up to 50% in most patients with this drug,” Dr. Wolfe said.

Mycophenolate is well tolerated. Its main adverse events are diarrhea, vomiting, increased risk of infection, and rarely, leukopenia; only about 6% of patients discontinue the drug because of an adverse event. Switching to dosing three times daily may decrease the incidence of diarrhea.

▸ Cyclophosphamide is used mainly for refractory MG patients. “This drug has a lot of potential for adverse events,” Dr. Wolfe said. “But IV pulse therapy looks like it could be safer than daily oral therapy, because there is a lower cumulative dose.” However, cyclophosphamide should be considered a third-line therapy.

▸ Intravenous gamma globulin is employed as a lower-risk alternative to plasma exchange. An analysis of eight retrospective studies indicated that 73% of patients responded well to intravenous gamma globulin, and did so very quickly—in about 4–5 days. The beneficial effects can last up to several months. “IV gamma globulin is a particularly attractive alternative to plasma exchange for patients with poor venous access, hemodynamic instability, or other contraindications to plasmapheresis,” he said.

▸ Investigational agents include tacrolimus, rituximab, and monarsen. Tacrolimus has demonstrated efficacy as a monotherapy or in combination with corticosteroids, in a few recent open trials. It has a similar mechanism of action to cyclosporine but appears less nephrotoxic. However, hyperglycemia may occur. Rituximab has been reported in just a few MG cases and was associated with substantial clinical improvement at 4 weeks and with no complications or adverse events. Monarsen is being investigated in preliminary MG studies. In an open trial of 16 patients, 15 who discontinued the antiacetylcholinesterase pyridostigmine demonstrated improvement while using monarsen.

MIAMI BEACH — The off-label use of immunosuppressive agents for myasthenia gravis can significantly decrease the need for steroids, while improving symptoms.

However, compared with prednisone, other immunosuppressants are much more expensive and carry their own risks of adverse events, so their use should be carefully evaluated on a case-by-case basis, Gil Wolfe, M.D., said at the annual meeting of the American Academy of Neurology.

Since acetylcholinesterase inhibitor monotherapy controls the symptoms of no more than 40% of myasthenia gravis (MG) patients, most patients will end up taking prednisone or other immunosuppressive agents, either alone or in combination, said Dr. Wolfe, a neurologist and codirector of the Muscular Dystrophy Association clinic at the University of Texas Southwestern Medical Center in Dallas.

▸ Prednisone—started low and slowly titrated, and tapered down very slowly after symptom improvement—is the most commonly used regimen. But few patients will be able to taper off prednisone completely; the rest will require long-term, low-dose therapy. Other immunosuppressants may be added to prednisone to act as steroid-sparing agents and to assist in successful prednisone discontinuation, Dr. Wolfe said.

▸ Azathioprine is used as a steroid-sparing agent for patients who relapse during a prednisone taper and for those who have adverse events during long-term steroid use. “Up to 90% of patients respond well to [azathioprine], if they can tolerate it,” he said. “In those who can, it can reduce steroid consumption by up to 80% by 2 years.” One small study concluded that 63% of those who took azathioprine for 36 months had completely tapered off prednisone, compared with 20% of those who took prednisone alone.

The major cause for discontinuation is a flulike reaction, seen in 10%–20% of patients. The drug also has a long onset of action—maximum benefit may not be seen for up to 2 years.

▸ Cyclosporine works more rapidly, with maximum benefit seen by 3 months. Patients who are refractory to other agents may respond to cyclosporine; this drug is as effective as azathioprine in symptom improvement, judging from the findings of a recent study. However, cyclosporine is less well tolerated than azathioprine, and some studies suggest that about half of patients discontinue the medication because of adverse events.

“It's important not to mix different cyclosporine preparations, because the different brands are not bioequivalent,” Dr. Wolfe added.

▸ Mycophenolate mofetil has shown promise as the newest immunosuppressive agent commonly used for MG, he said. A recent open-label study showed that 73% of patients achieved pharmacologic remission, minimal manifestation status, or symptom improvement with mycophenolate. The drug has a rapid onset of action, with improvement seen in 9–11 weeks and maximum effect by 6 months. “You may be able to decrease steroids by up to 50% in most patients with this drug,” Dr. Wolfe said.

Mycophenolate is well tolerated. Its main adverse events are diarrhea, vomiting, increased risk of infection, and rarely, leukopenia; only about 6% of patients discontinue the drug because of an adverse event. Switching to dosing three times daily may decrease the incidence of diarrhea.

▸ Cyclophosphamide is used mainly for refractory MG patients. “This drug has a lot of potential for adverse events,” Dr. Wolfe said. “But IV pulse therapy looks like it could be safer than daily oral therapy, because there is a lower cumulative dose.” However, cyclophosphamide should be considered a third-line therapy.

▸ Intravenous gamma globulin is employed as a lower-risk alternative to plasma exchange. An analysis of eight retrospective studies indicated that 73% of patients responded well to intravenous gamma globulin, and did so very quickly—in about 4–5 days. The beneficial effects can last up to several months. “IV gamma globulin is a particularly attractive alternative to plasma exchange for patients with poor venous access, hemodynamic instability, or other contraindications to plasmapheresis,” he said.

▸ Investigational agents include tacrolimus, rituximab, and monarsen. Tacrolimus has demonstrated efficacy as a monotherapy or in combination with corticosteroids, in a few recent open trials. It has a similar mechanism of action to cyclosporine but appears less nephrotoxic. However, hyperglycemia may occur. Rituximab has been reported in just a few MG cases and was associated with substantial clinical improvement at 4 weeks and with no complications or adverse events. Monarsen is being investigated in preliminary MG studies. In an open trial of 16 patients, 15 who discontinued the antiacetylcholinesterase pyridostigmine demonstrated improvement while using monarsen.