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CLINICAL NEWS |
“ We were surprised to find differences in variables related to response between [ pomalidomide and placebo ].”
— AYALEW TEFFERI , MD
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of transfusion-independence response criteria that were more stringent than recent criteria published by the International Working Group for MPN Research and Treatment . “ The criteria we used do not reflect the clinical benefit physicians expect , wherein a > 50 percent reduction in RBC transfusion |
intensity may be considered beneficial depending on the baseline intensity ,” the authors wrote . “ Consequently , the strength of our conclusion of no efficacy should be downgraded according to the [ Grading of Recommendations Assessment , Development and Evaluation ] criteria .” ● |
REFERENCE
Tefferi A , Al-Ali HK , Barosi G , et al . A randomized study of pomalidomide vs placebo in persons with myeloproliferative neoplasm-associated myelofibrosis and RBC-transfusion dependence . Leukemia . 2017 ; 31:896-902 .
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( including neutralizing antibody ) positivity in an assay may be influenced by several factors including assay methodology , sample handling , timing of sample collection , concomitant medications , and underlying disease . For these reasons , comparison of the incidence of antibodies to Kogenate FS with the incidence of antibodies to other products may be misleading .
6.2 Postmarketing Experience Because adverse reactions are reported voluntarily from a population of uncertain size , it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure . The following adverse reaction has been identified during post approval use of Kogenate FS :
Sensory System – Dysgeusia Immunogenicity – Postmarketing Registries Data from the Research of Determinants of Inhibitor Development ( RODIN ) study 7 , French National Registry ( FranceCoag ) 8 and United Kingdom Haemophilia Centre Doctors ’ Organisation ( UKHCDO ) 9 registry reported an inhibitor development rate in PUPs for Kogenate FS of 38 %, 50 % and 35 %, respectively , which is comparable to previously-reported inhibitor rates 10 for FVIII products . These registry studies show a trend towards an increased risk of inhibitor development in PUPs , as compared to the reference rFVIII product . A survey of Canadian hemophilia centers 11 ( 2005 to 2012 ) and available data from the European Haemophilia Safety Surveillance ( EUHASS ) 12 registry from 2009 to 2013 , reported an inhibitor development rate in PUPs for Kogenate FS of 42 % and 31 %, respectively , with no statistically significant differences observed across FVIII products .
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C . Animal reproduction studies have not been conducted with Kogenate FS . It is also not known whether Kogenate FS can cause fetal harm when administered to a pregnant woman or affect reproductive capacity . Kogenate FS should be given to a pregnant woman only if clearly needed .
8.2 Labor and Delivery There is no information available on the effect of factor VIII replacement therapy on labor and delivery . Kogenate FS should be used only if clinically needed .
8.3 Nursing Mothers It is not known whether this drug is excreted into human milk . Because many drugs are excreted into human milk , caution should be exercised if Kogenate FS is administered to a nursing woman .
8.4 Pediatric Use Safety and efficacy studies have been performed in previously untreated and minimally treated pediatric patients . Children , in comparison to adults , present higher factor VIII clearance values and , thus , lower half-life and recovery of factor VIII . This may be due to differences in body composition . 13 Account for this difference in clearance when dosing or following factor VIII levels in the pediatric population [ see Clinical Pharmacology ( 12.3 )].
Routine prophylactic treatment in children ages 0 – 2.5 years with no pre-existing joint damage has been shown to reduce spontaneous joint bleeding and the risk of joint damage . This data can be extrapolated to ages > 2.5 – 16 years for children who have no existing joint damage [ see Clinical Studies ( 14 )].
8.5 Geriatric Use Clinical studies with Kogenate FS did not include patients aged 65 and over . Dose selection for an elderly patient should be individualized .
15 REFERENCES
1 . White GC , Rosendaal F , Aledort LM , Lusher JM , Rothschild C , Ingerslev J , for the Factor VIII and Factor IX Subcommittee of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis . Definitions in hemophilia . Thromb Haemost 85:560-75 , 2001 .
2 . Abildgaard CF , Simone JV , Corrigan JJ , et al : Treatment of hemophilia with glycine-precipitated Factor VIII . N Engl J Med 275 ( 9 ): 471 – 5 , 1966 .
3 . Schwartz RS , Abildgaard CF , Aledort LM , et al : Human recombinant DNAderived antihemophilic factor ( factor VIII ) in the treatment of hemophilia A . Recombinant Factor VIII Study Group . N Engl J Med 323 ( 26 ): 1800-5 , 1990 .
4 . White GC 2nd , Courter S , Bray GL , et al : A multicenter study of recombinant factor VIII ( Recombinate ) in previously treated patients with hemophilia A . The Recombinate Previously Treated Patient Study Group . Thromb Haemost 77 ( 4 ): 660-667 , 1997 .
5 . Manco-Johnson MJ , Abshire TC , Shapiro AD , Riske B , Hacker MR , Kilcoyne R , et al . Prophylaxis versus episodic treatment to prevent joint disease in boys with severe hemophilia . N Engl J Med 2007 ; 357 ( 6 ): 535-44 .
6 . Kasper CK : Complications of hemophilia A treatment : factor VIII inhibitors . Ann NY Acad Sci 614:97-105 , 1991 .
7 . Gouw SC , van den Berg HM , et al : Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A : the RODIN study . Blood 121 ( 20 ): 4046-4055 , 2013 .
8 . Calvez T , Chambost H , et al : Recombinant factor VIII products and inhibitor development in previously untreated boys with severe hemophilia A . Blood 124 ( 23 ): 3398-3408 , 2014 .
9 . Collins PW , Palmer BP , et al : Factor VIII brand and the incidence of factor VIII inhibitors in previously untreated UK children with severe hemophilia A , 2000-2011 . Blood 124 ( 23 ): 3389-3397 , 2014 .
10 . Franchini M , Coppola A , et al : Systematic Review of the Role of FVIII Concentrates in Inhibitor Development in Previously Untreated Patients with Severe Hemophilia A : A 2013 Update . Semin Throm Hemost ( 39 ): 752-766 , 2013 .
11 . Vezina C , Carcao M , et al : Incidence and risk factors for inhibitor development in previously untreated severe haemophilia A patients born between 2005 and 2010 . Haemophilia 20 ( 6 ): 771-776 , 2014 .
12 . Fisher K , Lassila , R , et al . Inhibitor development in haemophilia according to concentrate : Four-year results from the European HAemophilia Safety Surveillance ( EUHASS ) project . Thromb Haemost 113.4 , 2015 .
13 . Barnes C , Lillicrap D , Pazmino-Canizares J , et al : Pharmacokinetics of recombinant factor VIII ( Kogenate-FS ® ) in children and causes of interpatient pharmacokinetic variability . Haemophilia 12 ( Suppl . 4 ): 40-49 , 2006 .
14 . Lawn RM , Vehar GA : The molecular genetics of hemophilia . Sci Am 254 ( 3 ): 48 – 54 , 1986 .
15 . Stenland CJ , et al : Partitioning of human and sheep forms of the pathogenic prion protein during the purification of therapeutic proteins from human plasma . Transfusion 42 ( 11 ): 1497-500 , 2002 .
16 . Lee DC , Miller JL , Petteway SR : Pathogen safety of manufacturing processes for biological products : special emphasis on KOGENATE ® Bayer . Haemophilia 8 ( Suppl . 2 ): 6-9 , 2002 .
17 . Lee DC , Stenland CJ , Miller JL , et al : A direct relationship between the partitioning of the pathogenic prion protein and transmissible spongiform encephalopathy infectivity during the purification of plasma proteins . Transfusion 41 ( 4 ): 449-55 , 2001 .
18 . Cai K , Miller JL , Stenland CJ , et al : Solvent-dependent precipitation of prion protein . Biochim Biophys Acta 1597 ( 1 ): 28-35 , 2002 .
19 . Trejo SR , Hotta JA , Lebing W , et al : Evaluation of virus and prion reduction in a new intravenous immunoglobulin manufacturing process . Vox Sang 84 ( 3 ): 176-87 , 2003 .
20 . Nuss R , Kilcoyne RF , Geraghty S , et al : MRI findings in haemophilic joints treated with radiosynoviorthesis with development of an MRI scale of joint damage . Haemophilia 6:162-169 , 2000 .
21 . Pettersson H , Ahlberg A , Nilsson IM : A radiologic classification of hemophilia arthropathy . Clin Orthop Relat Res 149:153-159 , 1980 .
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17 PATIENT COUNSELING INFORMATION
• Advise the patient to read the FDA-approved patient labeling ( Patient Information and Instructions for Use ).
• Advise patients to report any adverse reactions or problems following Kogenate FS administration to their physician or healthcare provider .
• Allergic-type hypersensitivity reactions have been reported with Kogenate FS . Warn patients of the early signs of hypersensitivity reactions [ including hives ( rash with itching ), generalized urticaria , tightness of the chest , wheezing , hypotension ] and anaphylaxis . Advise patients to discontinue use of the product if these symptoms occur and seek immediate emergency treatment with resuscitative measures such as the administration of epinephrine and oxygen .
• Inhibitor formation may occur at any time in the treatment of a patient with hemophilia A . Advise patients to contact their physician or treatment center for further treatment and / or assessment , if they experience a lack of clinical response to factor VIII replacement therapy , as this may be a manifestation of an inhibitor .
• Advise patients to consult with their healthcare provider prior to travel . While traveling advise patients to bring an adequate supply of Kogenate FS based on their current regimen of treatment .
Bayer HealthCare LLC Whippany , NJ 07981 USA
U . S . License No . 8 ( License Holder : Bayer Corporation )
http :// www . kogenatefs . com / 6709904BS
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