Treatment of severe community acquired pneumonia

Abstract

The present invention provides for a new therapeutic tools capable of treating infectious diseases, in particular, a new pharmaceutical composition comprising an IgM-enriched immunoglobulin preparation for use in the adjunctive treatment of severe Community Acquired Pneumonia (sCAP).

1 . A human plasma-derived 1 gM-enriched immunoglobulin preparation, said immunoglobulin preparation not having been chemically modified and/or treated with beta-propiolactone, for use in adjunctive treatment of severe Community Acquired Pneumonia (sCAP) in a patient, wherein said patient has a serum CRP level of at least 50 mg/ml to at least 100 mg/I and/or a serum PCT level of at least 1.0 ng/ml to at least 5.0 ng/ml. 
     
     
         2 . The immunoglobulin preparation for use according to  claim 1 , wherein the immunoglobulin preparation comprises from 10 to 40%, preferably from 18 to 28% by weight lgM of the total immunoglobulin content. 
     
     
         3 . The immunoglobulin preparation for use according to  claim 1 , wherein the serum CRP-level is at least 50 mg/I, or at least 70 mg/I, or at least 75 mg/I, or at least 80 mg/I, or at least 100 mg/I, and/or wherein the serum PCT level is at least 1.0 ng/ml, or at least 1.5 ng/ml, or at least 2.0 ng/ml, or at least 5 ng/ml. 
     
     
         4 . The immunoglobulin preparation for use according to  claim 1 , wherein said serum PCT and/or CRP level is present at the time of sCAP diagnosis particularly is present at least once within 24 hours before to 24 hours after start of vasopressor therapy and/or start of invasive mechanical ventilation. 
     
     
         5 . The immunoglobulin preparation for use according to  claim 1 , wherein the patient has a serum lgM level of equal to or lower than 0.4 g/I to equal to or lower than 1.5 g/I, and/or a serum lgG level of equal to or lower than 5 g/I to equal to or lower than 10 g/I, and/or a serum lgA level of equal to or lower than 4.0 g/I, equal to or lower than 3.5 g/I, equal to or lower than 3 g/I, equal to or lower than 2.5 g/I, or equal to or lower than 2.0 g/I. 
     
     
         6 . The immunoglobulin preparation for use according to  claim 1 , wherein the serum lgM level is equal to or lower than 1.0 g/I, equal to or lower than 0.8 g/I, or equal to or lower than 0.7 g/I, or equal to or lower than 0.5 g/I, and/or wherein the lgG level is equal to or lower than 9 g/I, or equal to or lower than 8 g/I, or equal to or lower than 7 g/I, or equal to or lower than 7 g/I, or equal to or lower than 6 g/I. 
     
     
         7 . The plasma-derived lgM-enriched immunoglobulin preparation for use according to  claim 1 , wherein said treatment is adjunctive to antibiotic therapy. 
     
     
         8 . The immunoglobulin preparation for use according to  claim 5 , wherein said serum lgM, lgG, or lgA level is present at the time of sCAP diagnosis, more particularly is present at least once within 24 hours before to 24 hours after the start of vasopressor therapy or invasive mechanical ventilation. 
     
     
         9 . The immunoglobulin preparation for use according to  claim 1 , wherein the immunoglobulin preparation has not been treated with beta-propiolactone. 
     
     
         10 . The immunoglobulin preparation for use according to  claim 1 , wherein the immunoglobulin preparation comprises from 10 to 40%, preferably from 18 to 28% by weight lgM of the total immunoglobulin content. 
     
     
         11 . The immunoglobulin preparation for use according to  claim 1 , wherein the immunoglobulin preparation comprises from 15 to 27% by weight lgA of the total immunoglobulin content. 
     
     
         12 . The immunoglobulin preparation for use according to  claim 1 , wherein the immunoglobulin preparation comprises from 48 to 66% by weight lgG of the total immunoglobulin content. 
     
     
         13 . The immunoglobulin preparation for use according to  claim 1 , wherein the immunoglobulin preparation has a total immunoglobulin content of at least 90%, preferably at least 95% by weight of the total protein content. 
     
     
         14 . The immunoglobulin preparation for use according to  claim 1 , being in the form of a solution for intravenous administration comprising between 40 and 100 gram immunoglobulin per liter solution, preferably between 40 and 60 gram immunoglobulin per liter solution. 
     
     
         15 . The human immunoglobulin preparation for use according to  claim 1 , wherein said immunoglobulin preparation is administered in 3 to 10 daily doses over 21 days, preferably with a first daily dose within 24 hours, preferably between 1 and 12 hours, after start of vasopressor therapy and/or invasive mechanical ventilation, 
     
     
         16 . The human immunoglobulin preparation for use according to  claim 1 , wherein said immunoglobulin preparation is administered according to the following treatment regimen: a first daily dose to be administered within 24 hours, preferably between 1 and 12 hours after start of vasopressor therapy and/or invasive mechanical ventilation, followed by 3 to 10, preferably 3 to 6, consecutive daily infusions, and optionally one or more maintenance infusions at 10 to 18 days after the first administration with said immunoglobulin preparation. 
     
     
         17 . The human immunoglobulin preparation for use according to  claim 1 , wherein the daily dosage administered is between 30 and 80 mg lgM/kg bodyweight, preferably between 35 and 65 mg lgM/kg bodyweight 
     
     
         18 . The human immunoglobulin preparation for use according to  claim 1 , wherein the initial daily dose administered is between 50 and 80 mg lgM/kg bodyweight, preferably between 60 and 65 mg lgM/kg bodyweight. 
     
     
         19 . The immunoglobulin preparation for use according to  claim 1 , wherein the infusion rate is equal or less than 6 mg lgM/min, more preferably the initial infusion rate is equal or less than 2 mg/lgM/min. 
     
     
         20 . The immunoglobulin preparation for use according to  claim 1 , characterized in that the number of plasma donors from which the immunoglobulin preparation is derived is at least 500, at least 1500, more preferably at least 2500. 
     
     
         21 . A container suitable for infusion comprising the immunoglobulin preparation or pharmaceutical composition for use according to  claim 1 . 
     
     
         22 . A package or kit comprising a single or multiple container(s) according to  claim 21 , and instructions for administration, preferably with instructions for administration. 
     
     
         23 . A method for identifying an sCAP patient who would benefit from adjunctive treatment with a human plasma-derived lgM-enriched immunoglobulin preparation, said immunoglobulin preparation not having been chemically modified or treated with betapropiolactone, comprising the steps of determining serum CRP level, and/or serum PCT level, and/or serum lgM level, and/or serum lgG level, and/or serum lgA level, or any combination thereof in a blood sample of the patient, wherein any one or more of: (1) a serum CRP level of at least 50 mg/I to at least 100 mg/I; (2) a serum PCT level of at least 1.0 to at least 5.0 ng/ml; (3) a serum lgM level of equal to or lower than 0.5 to at least 1.5 g/I; (4) a serum lgG level of equal to or lower than 5 to at least 10 g/I; (5) a serum lgA level of equal to or lower than 4.0 g/I, equal to or lower than 3.5 g/I, equal to or lower than 3 g/I, equal to or lower than 2.5 g/I, or equal to or lower than 2.0 g/I; is indicative that the patient may benefit from such treatment. 
     
     
         24 . The method according to  claim 23 , wherein said level of PCT, CRP, lgM, lgG, or lgA is present at the time of sCAP diagnosis, more particularly at present least once within 24 hours before to 24 hours after the start of vasopressor therapy or invasive mechanical ventilation. 
     
     
         25 . The method according to  claim 23 , wherein the measurements are done prior to the intended start of treatment with the lgM-enriched immunoglobulin preparation as defined herein. 
     
     
         26 . The preparation according to  claim 1 , wherein the patient is male and/or wherein the patient is not older than 65 years. 
     
     
         27 . The method according to  claim 23 , wherein the patient is male and/or wherein the patient is not older than 65 years.