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

Abstract

The present invention provides a 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 titration package for 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 titration package comprises interferon-β-1a and delivery 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 7.5 μg of interferon-β-1a to the patient in week one; 
 a second delivery device for intramuscular administration of 15 μg of interferon-β-1a to the patient in week two; and 
 a third delivery device for intramuscular administration of 22.5 μg of interferon-β-1a to the patient in week three; 
 wherein the severity of the flu-like symptoms is reduced 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 when compared to the severity of flu-like symptoms at 4-6 hours and 12-15 hours after each administration of interferon-β-1a to the patient according to 
 (i) 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 to 
 (ii) 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 . (canceled) 
     
     
         3 . The titration package of  claim 1 , wherein the interferon is provided in vials in lyophilized form. 
     
     
         4 . The titration package of  claim 3 , further comprising a vial adapter and the delivery devices are syringes pre-filled with a diluent for said lyophilized interferon. 
     
     
         5 . The titration package of  claim 1 , wherein the delivery devices are pre-filled syringes containing correct dosages of interferon-β-1a in liquid form. 
     
     
         6 . (canceled) 
     
     
         7 . (canceled) 
     
     
         8 . The titration package of  claim 1 , wherein the delivery device comprises an auto-injector. 
     
     
         9 . The titration package of  claim 1 , wherein the delivery device is needle-free. 
     
     
         10 . The titration package of  claim 1 , wherein the delivery device is a pen. 
     
     
         11 . The titration package of  claim 1 , further comprising a needle stick prevention device. 
     
     
         12 . The titration package of  claim 11 , wherein the needle-stick prevention device comprises a needle shield. 
     
     
         13 . The titration package of  claim 12 , wherein the shield is activated manually by the patient. 
     
     
         14 . The titration package of  claim 12 , wherein the shield is automated. 
     
     
         15 . The titration package of  claim 14 , wherein the automated shield is activated by the patient. 
     
     
         16 . The titration package of  claim 14 , wherein the needle is automatically shielded without any action by the patient. 
     
     
         17 . The titration package of  claim 14 , wherein the needle is shielded without any action by the patient. 
     
     
         18 . The titration package of  claim 1 , wherein the package further comprises a dose-limiting titration device. 
     
     
         19 . The titration package of  claim 1 , further comprising an analgesic or anti-inflammatory drug, or a mixture thereof. 
     
     
         20 . The titration package of  claim 19 , wherein the drug is a steroid. 
     
     
         21 . The titration package of  claim 19 , wherein the drug is a non-steroidal anti-inflammatory agent. 
     
     
         22 . The titration package of  claim 19 , wherein the drug is acetaminophen. 
     
     
         23 . The titration package of  claim 19 , wherein the drug is ibuprofen. 
     
     
         24 . The titration package of  claim 1 , further comprising instructions for intramuscular administration of the interferon-β-1a during the titration period.