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* immunosuppressive drugs
* immunosuppressive drugs
# Azathioprine: [[Azathioprine]], a [[purine]] analogue which inhibits the [[Nucleic acid|nucleic acids]] synthesis, can cause improvement in about 90 percent of myasthenia gravis patients but the onset of this effect takes at least 6 to 12 month.<ref name="pmid15229791">{{cite journal |vauthors=Saperstein DS, Barohn RJ |title=Management of myasthenia gravis |journal=Semin Neurol |volume=24 |issue=1 |pages=41–8 |date=March 2004 |pmid=15229791 |doi=10.1055/s-2004-829586 |url=}}</ref><ref name="pmid3479940">{{cite journal |vauthors=Matell G |title=Immunosuppressive drugs: azathioprine in the treatment of myasthenia gravis |journal=Ann. N. Y. Acad. Sci. |volume=505 |issue= |pages=589–94 |date=1987 |pmid=3479940 |doi= |url=}}</ref><ref name="pmid6951493">{{cite journal |vauthors=Mertens HG, Hertel G, Reuther P, Ricker K |title=Effect of immunosuppressive drugs (azathioprine) |journal=Ann. N. Y. Acad. Sci. |volume=377 |issue= |pages=691–9 |date=1981 |pmid=6951493 |doi= |url=}}</ref><ref name="pmid3062134">{{cite journal |vauthors=Mantegazza R, Antozzi C, Peluchetti D, Sghirlanzoni A, Cornelio F |title=Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis |journal=J. Neurol. |volume=235 |issue=8 |pages=449–53 |date=November 1988 |pmid=3062134 |doi= |url=}}</ref> [[Azathioprine]] can cause [[macrocytosis]] (increased [[MCV]]) and [[Malignancy|malignancies]] such as [[Non hodgkin lymphoma|non-hodgkin lymphoma]].<ref name="pmid3762975">{{cite journal |vauthors=Witte AS, Cornblath DR, Schatz NJ, Lisak RP |title=Monitoring azathioprine therapy in myasthenia gravis |journal=Neurology |volume=36 |issue=11 |pages=1533–4 |date=November 1986 |pmid=3762975 |doi= |url=}}</ref><ref name="pmid10805346">{{cite journal |vauthors=Herrlinger U, Weller M, Dichgans J, Melms A |title=Association of primary central nervous system lymphoma with long-term azathioprine therapy for myasthenia gravis? |journal=Ann. Neurol. |volume=47 |issue=5 |pages=682–3 |date=May 2000 |pmid=10805346 |doi= |url=}}</ref>   
# Azathioprine: [[Azathioprine]], a [[purine]] analogue which inhibits the [[Nucleic acid|nucleic acids]] synthesis, can cause improvement in about 90 percent of myasthenia gravis patients but the onset of this effect takes at least 6 to 12 month.<ref name="pmid15229791">{{cite journal |vauthors=Saperstein DS, Barohn RJ |title=Management of myasthenia gravis |journal=Semin Neurol |volume=24 |issue=1 |pages=41–8 |date=March 2004 |pmid=15229791 |doi=10.1055/s-2004-829586 |url=}}</ref><ref name="pmid3479940">{{cite journal |vauthors=Matell G |title=Immunosuppressive drugs: azathioprine in the treatment of myasthenia gravis |journal=Ann. N. Y. Acad. Sci. |volume=505 |issue= |pages=589–94 |date=1987 |pmid=3479940 |doi= |url=}}</ref><ref name="pmid6951493">{{cite journal |vauthors=Mertens HG, Hertel G, Reuther P, Ricker K |title=Effect of immunosuppressive drugs (azathioprine) |journal=Ann. N. Y. Acad. Sci. |volume=377 |issue= |pages=691–9 |date=1981 |pmid=6951493 |doi= |url=}}</ref><ref name="pmid3062134">{{cite journal |vauthors=Mantegazza R, Antozzi C, Peluchetti D, Sghirlanzoni A, Cornelio F |title=Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis |journal=J. Neurol. |volume=235 |issue=8 |pages=449–53 |date=November 1988 |pmid=3062134 |doi= |url=}}</ref> [[Azathioprine]] can cause [[macrocytosis]] (increased [[MCV]]) and [[Malignancy|malignancies]] such as [[Non hodgkin lymphoma|non-hodgkin lymphoma]].<ref name="pmid3762975">{{cite journal |vauthors=Witte AS, Cornblath DR, Schatz NJ, Lisak RP |title=Monitoring azathioprine therapy in myasthenia gravis |journal=Neurology |volume=36 |issue=11 |pages=1533–4 |date=November 1986 |pmid=3762975 |doi= |url=}}</ref><ref name="pmid10805346">{{cite journal |vauthors=Herrlinger U, Weller M, Dichgans J, Melms A |title=Association of primary central nervous system lymphoma with long-term azathioprine therapy for myasthenia gravis? |journal=Ann. Neurol. |volume=47 |issue=5 |pages=682–3 |date=May 2000 |pmid=10805346 |doi= |url=}}</ref>   
# Mycophenolate: [[Mycophenolate]] mofetil, a [[purine]] synthesis blocker in [[Lymphocyte|lymphocytes]], is proven to be effective in reducing the [[Symptom|symptoms]] of [[Myasthenia gravis|MG]] patients and their need to [[glucocorticoids]].(25-26)
# Mycophenolate: [[Mycophenolate]] mofetil, a [[purine]] synthesis blocker in [[Lymphocyte|lymphocytes]], is proven to be effective in reducing the [[Symptom|symptoms]] of [[Myasthenia gravis|MG]] patients and their need to [[glucocorticoids]].<ref name="pmid11148242">{{cite journal |vauthors=Chaudhry V, Cornblath DR, Griffin JW, O'Brien R, Drachman DB |title=Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases |journal=Neurology |volume=56 |issue=1 |pages=94–6 |date=January 2001 |pmid=11148242 |doi= |url=}}</ref><ref name="pmid11148243">{{cite journal |vauthors=Ciafaloni E, Massey JM, Tucker-Lipscomb B, Sanders DB |title=Mycophenolate mofetil for myasthenia gravis: an open-label pilot study |journal=Neurology |volume=56 |issue=1 |pages=97–9 |date=January 2001 |pmid=11148243 |doi= |url=}}</ref>
# Cyclosporine: [[Cyclosporine]], an immunomodulatory agent which blocks the production of [[Interleukin 2|interleukin-2]] and inhibits the function of [[T helper cell|T helper cells]], can cause improvement in about 90 percent of [[Myasthenia gravis|MG]] patients after 1 to 2 months of start but the maximum effect will appear after 7 months.(32-33-34 chronic) This drug can cause [[nephrotoxicity]] (37), [[tremor]], [[nausea]], [[Myalgia|myalgias]], [[gingival hyperplasia]], [[hypertrichosis]] and [[Malignancy|malignancies]] such as [[squamous cell skin cancer]] and [[lymphoma]].(34)
# Cyclosporine: [[Cyclosporine]], an immunomodulatory agent which blocks the production of [[Interleukin 2|interleukin-2]] and inhibits the function of [[T helper cell|T helper cells]], can cause improvement in about 90 percent of [[Myasthenia gravis|MG]] patients after 1 to 2 months of start but the maximum effect will appear after 7 months.<ref name="pmid3547126">{{cite journal |vauthors=Tindall RS, Rollins JA, Phillips JT, Greenlee RG, Wells L, Belendiuk G |title=Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis |journal=N. Engl. J. Med. |volume=316 |issue=12 |pages=719–24 |date=March 1987 |pmid=3547126 |doi=10.1056/NEJM198703193161205 |url=}}</ref><ref name="pmid8357194">{{cite journal |vauthors=Tindall RS, Phillips JT, Rollins JA, Wells L, Hall K |title=A clinical therapeutic trial of cyclosporine in myasthenia gravis |journal=Ann. N. Y. Acad. Sci. |volume=681 |issue= |pages=539–51 |date=June 1993 |pmid=8357194 |doi= |url=}}</ref><ref name="pmid10932288">{{cite journal |vauthors=Ciafaloni E, Nikhar NK, Massey JM, Sanders DB |title=Retrospective analysis of the use of cyclosporine in myasthenia gravis |journal=Neurology |volume=55 |issue=3 |pages=448–50 |date=August 2000 |pmid=10932288 |doi= |url=}}</ref> This drug can cause [[nephrotoxicity]] (37), [[tremor]], [[nausea]], [[Myalgia|myalgias]], [[gingival hyperplasia]], [[hypertrichosis]] and [[Malignancy|malignancies]] such as [[squamous cell skin cancer]] and [[lymphoma]].(34)
# Tacrolimus: [[Tacrolimus]], an immunosuppressive macrolid can significantly reduce the requirement to [[prednisolone]] and [[Myasthenia gravis|MG]] [[Symptom|symptoms]] in almost 67 to 87 percent of patients with less [[nephrotoxicity]] than [[cyclosporine]].(37-38-40 ta44 chronic) the side effects of this drug include [[hyperglycemia]], [[hypomagnesemia]], [[Paresthesia|paresthesias]] and [[tremor]].(45)
# Tacrolimus: [[Tacrolimus]], an immunosuppressive macrolid can significantly reduce the requirement to [[prednisolone]] and [[Myasthenia gravis|MG]] [[Symptom|symptoms]] in almost 67 to 87 percent of patients with less [[nephrotoxicity]] than [[cyclosporine]].(37-38-40 ta44 chronic) the side effects of this drug include [[hyperglycemia]], [[hypomagnesemia]], [[Paresthesia|paresthesias]] and [[tremor]].(45)
# Rituximab: [[Rituximab]], a [[Monoclonal antibodies|monoclonal antibody]] against [[B cell]] membrane marker [[CD20]] can be used in refractory myasthenia gravis. This drug is also effective in patients with anti [[MuSK]] antibody.(46-47-48-49-50 chronic)
# Rituximab: [[Rituximab]], a [[Monoclonal antibodies|monoclonal antibody]] against [[B cell]] membrane marker [[CD20]] can be used in refractory myasthenia gravis. This drug is also effective in patients with anti [[MuSK]] antibody.(46-47-48-49-50 chronic)

Revision as of 18:51, 21 June 2018

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Medical Therapy

The mainstays of medical therapy for myasthenia gravis are:

Symptomatic treatments

An oral anticholinesterase like pyridostigmine is usually the first drug in MG patients.[1] These drugs can reduce the degradation of Ach in the synaptic cleft.[2]

Chronic immunomodulating treatments

  1. Azathioprine: Azathioprine, a purine analogue which inhibits the nucleic acids synthesis, can cause improvement in about 90 percent of myasthenia gravis patients but the onset of this effect takes at least 6 to 12 month.[16][17][18][19] Azathioprine can cause macrocytosis (increased MCV) and malignancies such as non-hodgkin lymphoma.[20][21]
  2. Mycophenolate: Mycophenolate mofetil, a purine synthesis blocker in lymphocytes, is proven to be effective in reducing the symptoms of MG patients and their need to glucocorticoids.[22][23]
  3. Cyclosporine: Cyclosporine, an immunomodulatory agent which blocks the production of interleukin-2 and inhibits the function of T helper cells, can cause improvement in about 90 percent of MG patients after 1 to 2 months of start but the maximum effect will appear after 7 months.[24][25][26] This drug can cause nephrotoxicity (37), tremor, nausea, myalgias, gingival hyperplasia, hypertrichosis and malignancies such as squamous cell skin cancer and lymphoma.(34)
  4. Tacrolimus: Tacrolimus, an immunosuppressive macrolid can significantly reduce the requirement to prednisolone and MG symptoms in almost 67 to 87 percent of patients with less nephrotoxicity than cyclosporine.(37-38-40 ta44 chronic) the side effects of this drug include hyperglycemia, hypomagnesemia, paresthesias and tremor.(45)
  5. Rituximab: Rituximab, a monoclonal antibody against B cell membrane marker CD20 can be used in refractory myasthenia gravis. This drug is also effective in patients with anti MuSK antibody.(46-47-48-49-50 chronic)
  6. Methotrexate: Methotrexate is an immunosuppressant agent which suggested to be effective as a second line immunosuppressant for MG patients.(51-52)
  7. Etanercept: Etanercept is made of TNF receptor linked to Fc portion of human IgG1. This drug can inhibit TNF-alpha which is a proinflammatory cytokine, and improve the symptoms of MG patients.(53)
  8. Cyclophosphamide: Cyclophosphamide is an alkylating agent which inhibits the proliferation of B and T cells. Monthly high dose intravenous administration of this drug is proved to be more effective than daily oral type.(54) the side effects of this drug include anorexia, nausea and vomiting, leukopenia, alopecia and hemorrhagic cystitis and it can also increase the risk of malignancies.(54-55)

Rapid immunomodulating treatments

References

  1. ↑ Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, Kuntz N, Massey JM, Melms A, Murai H, Nicolle M, Palace J, Richman DP, Verschuuren J, Narayanaswami P (July 2016). "International consensus guidance for management of myasthenia gravis: Executive summary". Neurology. 87 (4): 419–25. doi:10.1212/WNL.0000000000002790. PMC 4977114. PMID 27358333.
  2. ↑ Punga AR, Stålberg E (June 2009). "Acetylcholinesterase inhibitors in MG: to be or not to be?". Muscle Nerve. 39 (6): 724–8. doi:10.1002/mus.21319. PMID 19260048.
  3. ↑ Schneider-Gold C, Gajdos P, Toyka KV, Hohlfeld RR (April 2005). "Corticosteroids for myasthenia gravis". Cochrane Database Syst Rev (2): CD002828. doi:10.1002/14651858.CD002828.pub2. PMID 15846640.
  4. ↑ Mann JD, Johns TR, Campa JF (August 1976). "Long-term administration of corticosteroids in myasthenia gravis". Neurology. 26 (8): 729–40. PMID 821005.
  5. ↑ Pascuzzi RM, Coslett HB, Johns TR (March 1984). "Long-term corticosteroid treatment of myasthenia gravis: report of 116 patients". Ann. Neurol. 15 (3): 291–8. doi:10.1002/ana.410150316. PMID 6721451.
  6. ↑ Arsura E, Brunner NG, Namba T, Grob D (December 1985). "High-dose intravenous methylprednisolone in myasthenia gravis". Arch. Neurol. 42 (12): 1149–53. PMID 4062612.
  7. ↑ Fardet L, Flahault A, Kettaneh A, Tiev KP, Généreau T, Tolédano C, Lebbé C, Cabane J (July 2007). "Corticosteroid-induced clinical adverse events: frequency, risk factors and patient's opinion". Br. J. Dermatol. 157 (1): 142–8. doi:10.1111/j.1365-2133.2007.07950.x. PMID 17501951.
  8. ↑ Huscher D, Thiele K, Gromnica-Ihle E, Hein G, Demary W, Dreher R, Zink A, Buttgereit F (July 2009). "Dose-related patterns of glucocorticoid-induced side effects". Ann. Rheum. Dis. 68 (7): 1119–24. doi:10.1136/ard.2008.092163. PMID 18684744.
  9. ↑ Da Silva JA, Jacobs JW, Kirwan JR, Boers M, Saag KG, Inês LB, de Koning EJ, Buttgereit F, Cutolo M, Capell H, Rau R, Bijlsma JW (March 2006). "Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data". Ann. Rheum. Dis. 65 (3): 285–93. doi:10.1136/ard.2005.038638. PMC 1798053. PMID 16107513.
  10. ↑ Wei L, MacDonald TM, Walker BR (November 2004). "Taking glucocorticoids by prescription is associated with subsequent cardiovascular disease". Ann. Intern. Med. 141 (10): 764–70. PMID 15545676.
  11. ↑ Messer J, Reitman D, Sacks HS, Smith H, Chalmers TC (July 1983). "Association of adrenocorticosteroid therapy and peptic-ulcer disease". N. Engl. J. Med. 309 (1): 21–4. doi:10.1056/NEJM198307073090105. PMID 6343871.
  12. ↑ Piper JM, Ray WA, Daugherty JR, Griffin MR (May 1991). "Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs". Ann. Intern. Med. 114 (9): 735–40. PMID 2012355.
  13. ↑ MacAdams MR, White RH, Chipps BE (May 1986). "Reduction of serum testosterone levels during chronic glucocorticoid therapy". Ann. Intern. Med. 104 (5): 648–51. PMID 3083749.
  14. ↑ Crilly R, Cawood M, Marshall DH, Nordin BE (October 1978). "Hormonal status in normal, osteoporotic and corticosteroid-treated postmenopausal women". J R Soc Med. 71 (10): 733–6. PMC 1436218. PMID 712726.
  15. ↑ Wolkowitz OM, Burke H, Epel ES, Reus VI (October 2009). "Glucocorticoids. Mood, memory, and mechanisms". Ann. N. Y. Acad. Sci. 1179: 19–40. doi:10.1111/j.1749-6632.2009.04980.x. PMID 19906230.
  16. ↑ Saperstein DS, Barohn RJ (March 2004). "Management of myasthenia gravis". Semin Neurol. 24 (1): 41–8. doi:10.1055/s-2004-829586. PMID 15229791.
  17. ↑ Matell G (1987). "Immunosuppressive drugs: azathioprine in the treatment of myasthenia gravis". Ann. N. Y. Acad. Sci. 505: 589–94. PMID 3479940.
  18. ↑ Mertens HG, Hertel G, Reuther P, Ricker K (1981). "Effect of immunosuppressive drugs (azathioprine)". Ann. N. Y. Acad. Sci. 377: 691–9. PMID 6951493.
  19. ↑ Mantegazza R, Antozzi C, Peluchetti D, Sghirlanzoni A, Cornelio F (November 1988). "Azathioprine as a single drug or in combination with steroids in the treatment of myasthenia gravis". J. Neurol. 235 (8): 449–53. PMID 3062134.
  20. ↑ Witte AS, Cornblath DR, Schatz NJ, Lisak RP (November 1986). "Monitoring azathioprine therapy in myasthenia gravis". Neurology. 36 (11): 1533–4. PMID 3762975.
  21. ↑ Herrlinger U, Weller M, Dichgans J, Melms A (May 2000). "Association of primary central nervous system lymphoma with long-term azathioprine therapy for myasthenia gravis?". Ann. Neurol. 47 (5): 682–3. PMID 10805346.
  22. ↑ Chaudhry V, Cornblath DR, Griffin JW, O'Brien R, Drachman DB (January 2001). "Mycophenolate mofetil: a safe and promising immunosuppressant in neuromuscular diseases". Neurology. 56 (1): 94–6. PMID 11148242.
  23. ↑ Ciafaloni E, Massey JM, Tucker-Lipscomb B, Sanders DB (January 2001). "Mycophenolate mofetil for myasthenia gravis: an open-label pilot study". Neurology. 56 (1): 97–9. PMID 11148243.
  24. ↑ Tindall RS, Rollins JA, Phillips JT, Greenlee RG, Wells L, Belendiuk G (March 1987). "Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporine in myasthenia gravis". N. Engl. J. Med. 316 (12): 719–24. doi:10.1056/NEJM198703193161205. PMID 3547126.
  25. ↑ Tindall RS, Phillips JT, Rollins JA, Wells L, Hall K (June 1993). "A clinical therapeutic trial of cyclosporine in myasthenia gravis". Ann. N. Y. Acad. Sci. 681: 539–51. PMID 8357194.
  26. ↑ Ciafaloni E, Nikhar NK, Massey JM, Sanders DB (August 2000). "Retrospective analysis of the use of cyclosporine in myasthenia gravis". Neurology. 55 (3): 448–50. PMID 10932288.

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