Method for reducing flu-like symptoms associated with intramuscular administration of interferon using a fast titration escalating dosing regimen

Abstract

A combination and method for treating multiple sclerosis (MS), and for reducing flu-like symptoms associated with administration of an interferon to a patient with MS. The method involves intramuscularly administering the interferon to the MS patient according to an escalating dosing regimen in weeks 1 to 3, and a full therapeutically effective dose of interferon in week 4. In one embodiment of the invention, the escalating dosing regimen comprises administering one quarter of the therapeutically effective dose in week 1, half of the therapeutically effective dose in week 2, and three-quarters of the therapeutically effective dose in week 3. Also provided are titration packages for enabling compliance with a regimen of changing dosage of an interferon over a period of time.

1 . A combination of delivery devices and dose-limiting accessory devices for use in reducing the severity of flu-like symptoms associated with treating a patient having multiple sclerosis with intramuscularly administered interferon-β-1a over an eight week period,
 wherein the combination comprises interferon-β-1a, delivery devices and dose-limiting accessory devices for once a week intramuscular administration to a patient having multiple sclerosis according to a first schedule comprising: 
 a first delivery device for intramuscular administration of interferon-β-1a to the patient and a first dose-limiting accessory configured to limit dispensing of the first titration dose from the first delivery device to 7.5 μg of the interferon-β-1a in week one; 
 a second delivery device for intramuscular administration of interferon-β-1a to the patient and a second dose-limiting accessory configured to limit dispensing of the second titration dose from the second delivery device to 15 μg of the interferon-β-1a in week two; 
 a third delivery device for intramuscular administration of interferon-β-1a to the patient and a third dose-limiting accessory configured to limit dispensing of the third titration dose from the third delivery device to 22.5 μg of the interferon-β-1a in week three; and 
 a fourth delivery device for intramuscular administration of 30 μg interferon-β-1a to the patient; 
 wherein the combination reduces severity of the flu-like symptoms at 4-6 hours and at 12-15 hours after each intramuscular administration of interferon-β-1a throughout an eight week period which includes once a week intramuscular administration of 30 μg of interferon-β-1a to the patient in weeks four through eight 
 (i) when compared to the severity of the flu-like symptoms at 4-6 hours and at 12-15 hours after each intramuscular administration of interferon-β-1a in a second schedule comprising once a week intramuscular administration of 30 μg of interferon-β-1a to a patient having multiple sclerosis for eight weeks; and 
 (ii) when compared to the severity of the flu-like symptoms at 4-6 hours and at 12-15 hours after each intramuscular administration of interferon-β-1a in a once a week intramuscular administration of the medicament to a patient having multiple sclerosis according to a third schedule comprising: 
 intramuscular administration of 7.5 μg of interferon-β-1a to the patient in weeks one and two; 
 intramuscular administration of 15 μg of interferon-β-1a to the patient in weeks three and four; 
 intramuscular administration of 22.5 μg of interferon-β-1a to the patient in weeks five and six; and 
 intramuscular administration of 30 μg of interferon-β-1a to the patient in weeks seven and eight. 
 
     
     
         2 . The combination of  claim 1 , further comprising vials containing the interferon-β-1a in lyophilized form. 
     
     
         3 . The combination of  claim 2 , further comprising a vial adapter and the delivery devices are syringes pre-filled with a diluent for said lyophilized interferon-β-1a. 
     
     
         4 . The combination of  claim 1 , wherein the delivery devices are pre-filled syringes containing interferon-β-1a in liquid form. 
     
     
         5 . The combination of  claim 1 , wherein the delivery device comprises an auto-injector. 
     
     
         6 . The combination of  claim 1 , wherein the delivery device is needle-free. 
     
     
         7 . The combination of  claim 1 , wherein the delivery device is a pen. 
     
     
         8 . The combination of  claim 1 , further comprising a needle stick prevention device. 
     
     
         9 . The combination of  claim 1 , wherein the needle-stick prevention device comprises a needle shield. 
     
     
         10 . The combination of  claim 9 , wherein the shield is configured to be activated manually by a user. 
     
     
         11 . The combination of  claim 9 , wherein the shield is automated. 
     
     
         12 . The combination of  claim 11 , wherein the automated shield is configured to be activated by a user. 
     
     
         13 . The combination of  claim 11 , wherein the needle is configured to be automatically shielded without any action by the user.