Benefits of prophylaxis versus on-demand treatment in adolescents and adults with severe haemophilia A: the POTTER study

2015 ◽  
Vol 114 (07) ◽  
pp. 35-45 ◽  
Author(s):  
Giulio Feola ◽  
Angelo Claudio Molinari ◽  
Cristina Santoro ◽  
Gianna Franca Rivolta ◽  
Dorina Bianca Cultrera ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Secondary Prophylaxis ◽  
Annual Number ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Open Label ◽  
On Demand ◽  
Adolescents And Adults ◽  
Bleeding Episodes

SummaryRigorous 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 (Clinical-Trials.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.

Effects of primary and secondary prophylaxis on the clinical expression of joint damage in children with severe haemophilia A

2008 ◽  
Vol 99 (01) ◽  
pp. 71-76 ◽  
Author(s):  
Karin Kurnik ◽  
Frauke Friedrichs ◽  
Susan Halimeh ◽  
Anne Krümpel ◽  
Christoph Bidlingmaier ◽  
...  
Keyword(s):  
Bleeding Episode ◽  
Joint Damage ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Outcome Variable ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
On Demand ◽  
Haemophilic Arthropathy ◽  
Bleeding Episodes

SummaryPatients with severe haemophilia A (HA) can either be treated by regular FVIII infusions twice or three times per week (prophylaxis), or only in case of bleeding episodes (on-demand). Whereas prophylaxis reduces the number of bleeding episodes and may therefore prevent the development of haemophilic arthropathy, there is still a lot of controversy surrounding recommendations on age and dose at start of prophylactic regimens. The present database study was performed to investigate the role of primary versus secondary prophylaxis in HA children. The outcome variable was imaging-proven haemophilic joint damage. Forty-two children were initially treated with primary prophylaxis following the first bleeding episode, and were frequency-matched (year of birth, catchment area) to 67 pa- tients receiving “on-demand” therapy with an early switch to “secondary prophylaxis”. In multivariate analysis adjusted for the HA mutation type and the presence or absence of thrombophilia, the Pettersson score investigated at a median age of 12.5 years in joints with at least one documented bleeding episode was not significantly different between the two patient groups (p=0.944),and no statistically significant differences were found in patients with target joints (p=0.3), nor in children in whom synovitis had occurred (p=0.77). No conclusion can be drawn from the data presented herein whether primary prophylaxis or an early start of secondary prophylaxis is superior with respect to joint outcome in children with severe HA.

Secondary prophylaxis treatment versus on-demand treatment for patients with severe haemophilia A: comparisons of cost and outcomes in Taiwan

Haemophilia ◽  
2010 ◽  
Vol 17 (1) ◽  
pp. 45-54 ◽  
Author(s):  
W.-S. LIOU ◽  
T.-C. TU ◽  
S.-N. CHENG ◽  
T.-Y. CHOU ◽  
C.-F. LEE ◽  
...  
Keyword(s):  
Secondary Prophylaxis ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
On Demand

Discontinuing early prophylaxis in severe haemophilia leads to deterioration of joint status despite low bleeding rates

2016 ◽  
Vol 115 (05) ◽  
pp. 931-938 ◽  
Author(s):  
Annelies Nijdam ◽  
Wouter Foppen ◽  
Piet de Kleijn ◽  
Evelien P. Mauser-Bunschoten ◽  
Goris Roosendaal ◽  
...  
Keyword(s):  
Functional Limitations ◽  
Objective Assessment ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
On Demand ◽  
Recommended Treatment ◽  
Objective Monitoring ◽  
Joint Health ◽  
Observational Cohort

SummaryProphylaxis is the recommended treatment for children with severe haemophilia A, but whether prophylaxis should be continued in adulthood is still under debate. Previous studies with limited follow-up have suggested that some patients may be able to stop prophylaxis in adulthood, while maintaining good joint health. This single-centre observational cohort study examined patients with severe haemophilia A born 1970–1988 without inhibitor development, and assessed the long-term consequences of discontinuing prophylaxis. Patient-initiated changes in prophylaxis, including all switches to on-demand treatment lasting a minimum of two consecutive weeks, were recorded from the time self-infusion began until the last evaluation. Sixty-six patients were evaluated at a median age of 32.4 years: 26 of patients had stopped prophylaxis for a median of 10 years, 15 had interrupted prophylaxis and 59 had continued prophylaxis. Annual joint bleeding rate (AJBR), Haemophilia Joint Health Score (HJHS-2.1; 0–124 points), radiological Pettersson score (0–78 points) and Haemophilia Activities List score (HAL; 100–0 points) were compared between patients who stopped and patients who continued prophylaxis. Although self-reported bleeding rates and functional limitations were similar in both groups (AJBR: 1.5 vs 1.2 and HAL: 84 vs 84 for those who stopped and continued prophylaxis, respectively), objective assessment of joint status showed increased arthropathy after 10 years of on-demand treatment in patients who stopped prophylaxis compared with those who continued (HJHS: 23 vs. 14 and Pettersson: 16 vs 5, respectively; P< 0.01). These results support continuation of long-term prophylaxis in adults and demonstrate the need for objective monitoring of joint status.Trial registration: Dutch Trial Registry number 3098; UTN U1111–1121–7069.

Prophylactic versus on-demand treatment strategies for severe haemophilia: a comparison of costs and long-term outcome

Haemophilia ◽  
2002 ◽  
Vol 8 (6) ◽  
pp. 745-752 ◽  
Author(s):  
K. Fischer ◽  
J. G. Van der Bom ◽  
P. Molho ◽  
C. Negrier ◽  
E. P. Mauser-Bunschoten ◽  
...  
Keyword(s):  
Treatment Strategies ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Term Outcome ◽  
Long Term Outcome ◽  
On Demand

Secondary prophylaxis in an adult patient with severe haemophilia A

2013 ◽  
Vol 33 (03) ◽  
pp. 241-244 ◽  
Author(s):  
C. Schubert ◽  
S. Schlenkrich
Keyword(s):  
Factor Viii ◽  
Prospective Studies ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Bleeding Rate ◽  
On Demand ◽  
Optimal Dosing ◽  
Joint Protection

SummaryPrimary prophylaxis has been proven as the gold standard for preserving joint function in severe haemophilia. Secondary prophylaxis in children has also been shown to have a more beneficial effect on joint protection as on-demand treatment. The outcome of delayed secondary prophylaxis started in adulthood is rarely studied. The case of a man (age: 47 years) with severe haemophilia A demonstrates the successful switch from on-demand therapy to prophylaxis with sub-sequent reduction of annual bleeding rate and number of days of work lost. The small increase of factor VIII consumption (16%) and the decrease of bleeding rate are compared with data from two recently published prospective studies.An optimal dosing schedule needs to be discussed and larger and longer prospective studies targeting the benefits of secondary prophylaxis with factor VIII started in adulthood are necessary.

scholarly journals Long-term safety and efficacy of turoctocog alfa in prophylaxis and treatment of bleeding episodes in severe haemophilia A: Final results from the guardian 2 extension trial

Haemophilia ◽  
2018 ◽  
Vol 24 (6) ◽  
pp. e391-e394 ◽  
Author(s):  
Steven R. Lentz ◽  
Dragana Janic ◽  
Kaan Kavakli ◽  
Predrag Miljic ◽  
Johannes Oldenburg ◽  
...  
Keyword(s):  
Haemophilia A ◽  
Severe Haemophilia ◽  
Safety And Efficacy ◽  
Bleeding Episodes ◽  
The Guardian ◽  
Extension Trial

Long-term cariprazine treatment for the prevention of relapse in patients with schizophrenia: A randomized, double-blind, placebo-controlled trial

2020 ◽  
pp. 27-37
Author(s):  
Suresh Durgam ◽  
Willie Earley ◽  
Rui Li ◽  
Dayong Li ◽  
Kaifeng Lu ◽  
...  
Keyword(s):  
Safety Profile ◽  
Relapse Prevention ◽  
Controlled Trial ◽  
Fixed Dose ◽  
Open Label ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Randomized Controlled ◽  
Time To Relapse

Cariprazine, a dopamine D3/D2 receptor partial agonist with preference for D3 receptors, has demonstrated efficacy in randomized controlled trials in schizophrenia. This multinational, randomized, double-blind, placebo-controlled, parallel-group study evaluated the efficacy, safety, and tolerability of cariprazine for relapse prevention in adults with schizophrenia; total study duration was up to 97 weeks. Schizophrenia symptoms were treated/stabilized with cariprazine 3—9 mg/d during 20-week open-label treatment consisting of an 8-week, flexible-dose run-in phase and a 12-week fixed-dose stabilization phase. Stable patients who completed open-label treatment could be randomized to continued cariprazine (3, 6, or 9 mg/d) or placebo for double-blind treatment (up to 72 weeks). The primary efficacy parameter was time to relapse (worsening of symptom scores, psychiatric hospitalization, aggressive/violent behavior, or suicidal risk); clinical measures were implemented to ensure safety in case of impending relapse. A total of 264/765 patients completed open-label treatment; 200 eligible patients were randomized to double-blind placebo (n = 99) or cariprazine (n = 101). Time to relapse was significantly longer in cariprazine — versus placebo-treated patients (P = .0010, log-rank test). Relapse occurred in 24.8% of cariprazine- and 47.5% of placebo-treated patients (hazard ratio [95% CI] = 0.45 [0.28, 0.73]). Akathisia (19.2%), insomnia (14.4%), and headache (12.0%) were reported in ≥ 10% of patients during open-label treatment; there were no cariprazine adverse events ≥ 10% during double-blind treatment. Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia. The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials. ClincalTrials.gov identifier: NCT01412060. Key words: schizophrenia; cariprazine; long-term treatment; relapse prevention; randomized controlled trial; oral antipsychotics

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