Methods of Treating Multiple Sclerosis
Provided herein are methods of treating multiple sclerosis with a fumarate, wherein the fumarate is a dialkyl fumarate, a monoalkyl fumarate, a combination of a dialkyl fumarate and a monoalkyl fumarate, a prodrug of monoalkyl fumarate, a deuterated form of any of the foregoing, or a pharmaceutically acceptable salt, clathrate, solvate, tautomer, or stereoisomer of any of the foregoing, or a combination of any of the foregoing. The methods provided herein improve the safety of treatment by informing and monitoring patients undergoing treatment regarding progressive multifocal leukoencephalopathy, and/or by monitoring lymphocyte count.
1 - 313 . (canceled)
314 . A method of treating a patient with multiple sclerosis, comprising the steps of:
(a) administering a pharmaceutical composition comprising a fumarate to the patient; wherein the fumarate is dimethyl fumarate, monomethyl fumarate, a combination of dimethyl fumarate and monomethyl fumarate, or a clathrate, solvate, tautomer, or stereoisomer of any of the foregoing; with the proviso that a fumarate salt is not present in the pharmaceutical composition;
(b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; and
(c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5×10 9 /L persisting for more than six months.
315 . The method of claim 314 , wherein the fumarate is dimethyl fumarate, monomethyl fumarate or a combination of dimethyl fumarate and monomethyl fumarate.
316 . The method of claim 314 , wherein the fumarate is dimethyl fumarate.
317 . The method of claim 314 , wherein the fumarate is monomethyl fumarate.
318 . The method of claim 314 , wherein the administering is done orally.
319 . The method of claim 316 , wherein the administering is of 240 mg dimethyl fumarate twice daily orally.
320 . The method of claim 318 , wherein the administering is of not greater than 480 mg daily total fumarates.
321 . A method of treating a patient with multiple sclerosis, comprising the steps of:
(a) administering a pharmaceutical composition comprising a fumarate to the patient; wherein the fumarate is dimethyl fumarate, monomethyl fumarate, a combination of dimethyl fumarate and monomethyl fumarate, or a pharmaceutically acceptable salt, clathrate, solvate, tautomer, or stereoisomer of any of the foregoing; with the proviso that an ethyl hydrogen fumarate salt is not present in the pharmaceutical composition;
(b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; and
(c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5×10 9 /L persisting for more than six months.
322 . The method of claim 321 , wherein the fumarate is dimethyl fumarate, monomethyl fumarate or a combination of dimethyl fumarate and monomethyl fumarate.
323 . The method of claim 321 , wherein the fumarate is dimethyl fumarate.
324 . The method of claim 321 , wherein the fumarate is monomethyl fumarate.
325 . The method of claim 321 , wherein the administering is done orally.
326 . The method of claim 323 , wherein the administering is of 240 mg dimethyl fumarate twice daily orally.
327 . The method of claim 325 , wherein the administering is of not greater than 480 mg daily total fumarates.
328 . A method of treating a patient with multiple sclerosis, comprising the steps of:
(a) administering a pharmaceutical composition comprising a fumarate to the patient; wherein the fumarate is dimethyl fumarate, monomethyl fumarate, a combination of dimethyl fumarate and monomethyl fumarate, or a pharmaceutically acceptable salt, clathrate, solvate, tautomer, or stereoisomer of any of the foregoing; with the proviso that ethyl hydrogen fumarate calcium salt, ethyl hydrogen fumarate magnesium salt, ethyl hydrogen fumarate zinc salt, and ethyl hydrogen fumarate copper salt are not present in the pharmaceutical composition;
(b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; and
(c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5×10 9 /L persisting for more than six months.
329 . The method of claim 328 , wherein the fumarate is dimethyl fumarate, monomethyl fumarate or a combination of dimethyl fumarate and monomethyl fumarate.
330 . The method of claim 328 , wherein the fumarate is dimethyl fumarate.
331 . The method of claim 328 , wherein the fumarate is monomethyl fumarate.
332 . The method of claim 328 , wherein the administering is done orally.
333 . The method of claim 330 , wherein the administering is of 240 mg dimethyl fumarate twice daily orally.
334 . The method of claim 332 , wherein the administering is of not greater than 480 mg daily total fumarates.
335 . A method of treating a patient with multiple sclerosis, comprising the steps of:
(a) administering a pharmaceutical composition consisting essentially of dimethyl fumarate and/or monomethyl fumarate to the patient;
(b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; and
(c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5×10 9 /L persisting for more than six months.
336 . The method of claim 335 , wherein the pharmaceutical composition consists essentially of dimethyl fumarate and monomethyl fumarate.
337 . The method of claim 335 , wherein the pharmaceutical composition consists essentially of dimethyl fumarate.
338 . The method of claim 335 , wherein the pharmaceutical composition consists essentially of monomethyl fumarate.
339 . The method of claim 335 , wherein the administering is done orally.
340 . The method of claim 337 , wherein the administering is of 240 mg dimethyl fumarate twice daily orally.
341 . The method of claim 339 , wherein the administering is of not greater than 480 mg daily total fumarates.
342 . The method of claim 341 , wherein the pharmaceutical composition consists essentially of dimethyl fumarate.
343 . The method of claim 341 , wherein the pharmaceutical composition consists essentially of monomethyl fumarate.