title: Benefits of prophylaxis versus on-demand treatment in adolescents and adults with severe haemophilia A: the POTTER study.
abstract: Rigorous evidence is lacking on long-term outcomes of factor VIII (FVIII) prophylaxis initiated in adolescent or adult patients with severe haemophilia A. The prospective, open-label Prophylaxis versus On-demand Therapy Through Economic Report (POTTER) study (ClinicalTrials.gov NCT01159587) compared long-term late secondary prophylaxis (recombinant FVIII-FS 20-30 IU/kg thrice weekly) with on-demand treatment in patients aged 12 to 55 years with severe haemophilia A. The annual number of joint bleeding episodes (primary endpoint), total bleeding episodes, orthopaedic and radiologic (Pettersson) scores, health-related quality of life (HRQoL), pharmacoeconomic impact, and safety were evaluated over a > 5-year period (2004-2010). Fifty-eight patients were enrolled at 11 centres in Italy; 53 (27 prophylaxis, 26 on demand) were evaluated and stratified into 2 age subgroups (12-25 and 26-55 years). Patients receiving prophylaxis experienced a significantly lower number of joint bleeding episodes vs the on-demand group (annualised bleeding rate, 1.97 vs 16.80 and 2.46 vs 16.71 in younger and older patients, respectively; p=0.0043). Results were similar for total bleeding episodes. Prophylaxis was associated with significantly fewer target joints (p< 0.001), better orthopaedic (p=0.0019) and Pettersson (p=0.0177) scores, better HRQoL, and fewer days of everyday activities lost (p< 0.0001) but required significantly higher FVIII product consumption. The POTTER study is the first prospective, controlled trial documenting long-term benefits of late secondary prophylaxis in adolescents and adults with severe haemophilia A. The benefits of reduced bleeding frequency, improved joint status, and HRQoL may offset the higher FVIII consumption and costs.
authors: Annarita Tagliaferri, MD, Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, Via Gramsci, 14-43126, Parma, Italy, Tel.: +39 0521 703971, Fax: +39 0521 704332, E-mail: atagliaferri@ao.pr.it.
authors: Annarita
authors: A
authors: Tagliaferri
authors: Giulio
authors: G
authors: Feola
authors: Angelo Claudio
authors: AC
authors: Molinari
authors: Cristina
authors: C
authors: Santoro
authors: Gianna Franca
authors: GF
authors: Rivolta
authors: Dorina Bianca
authors: DB
authors: Cultrera
authors: Fabio
authors: F
authors: Gagliano
authors: Ezio
authors: E
authors: Zanon
authors: Maria Elisa
authors: ME
authors: Mancuso
authors: Lelia
authors: L
authors: Valdré
authors: Luciana
authors: L
authors: Mameli
authors: Susanna
authors: S
authors: Amoresano
authors: Prasad
authors: P
authors: Mathew
authors: Antonio
authors: A
authors: Coppola
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D016527:Drug Costs; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D006395:Hemarthrosis / Q000097:blood / Q000175:diagnosis / Q000191:economics / Q000517:prevention & control*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics; D006490:Hemostatics / Q000008:administration & dosage* / Q000009:adverse effects / Q000191:economics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011788:Quality of Life; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006490:Hemostatics; C078147:F8 protein, human; D005169:Factor VIII
keywords: Bleeding; haemophilia; haemophilic arthropathy; health-related quality of life; prophylaxis