Research Studies

Objective:

Hemophilia is marked by frequent joint bleeding, resulting in acute and chronic pain and functional impairment. Surveys in US adults with hemophilia demonstrate suboptimal pain management and quality of life (QoL). The objective of P-FiQ was to methodologically assess QoL parameters, including functional impairment and pain, and pain management strategies.

Methods:

Adult men with mild-severe hemophilia with a history of joint pain and/or bleeding completed a hemophilia/pain history and various patient-reported outcome assessments (completed twice in “retest” population of initially enrolled patients).

Summary:

Of 164 adults with hemophilia (median age 34) in the “retest” population, more had hemophilia A (74%) than B (26%); 6% had inhibitors. Most had some college-or-above education (63%), 81% were employed, 61% were overweight/obese, and 61% self-reported arthritis/bone/joint problems. Current patient-reported treatment regimens were prophylaxis (42%), on-demand (39%), or mostly on-demand (19%; 25/31 using infusions ahead of activity). One-third (32.9%) reported unrestricted school/work/recreational activities in the prior 6 months; 6.2% reported needing assistance for school/work/self-care, or did not participate in recreational activities because of pain, loss of motion, and weakness. Some patients (31.3%) reported using a cane/crutches/walker (3.8% always) and 7.6% a wheelchair (1.3% always), and 47.0% reported a history of joint surgery (41 knee, 37 ankle, 29 elbow). Patients reported losing an average of 3.7 and 1.8 school/work days in the previous 6 months due to lower and upper extremity problems, respectively. Patients reported that during the prior 6 months they had experienced acute pain only (24%), chronic pain only (33%), or both (29%); 15% reported no pain. Acute pain was most frequently described as sharp (77%), aching (66%), shooting (57%), and throbbing (55%), and chronic pain as aching (74%), nagging (49%), throbbing (44%), and sharp (40%). Most common analgesics in the past 6 months for acute/chronic pain were acetaminophen (69%/58%), NSAIDs (40%/52%), hydrocodone-acetaminophen (29%/33%), oxycodone (12%/11%), and oxycodone- acetaminophen (9%/8%). Most common nonanalgesic treatment strategies reported for acute/chronic pain in the past 6 months were ice (73%/37%), rest (48%/34%), factor or bypassing agent (48%/24%), elevation (34%/28%), relaxation (31%/23%), compression (27%/21%), and heat (25%/15%); other reported strategies include medical marijuana (17%/9%), physical therapy (12%/9%), prayer (11%/8%), faith (9%/8%), alcohol (8%/7%), aquatherapy (5%/6%), illicit drugs (4%/2%), acupuncture (2%/1%), hypnosis (2%/1%), and biofeedback (1%/1%).

Conclusions:

Initial data corroborate the high prevalence of pain and functional disability in adults with hemophilia and highlight opportunities to address clinical assessment, patient dialogue, and management strategies to improve outcomes.

Objective:

The ongoing rFIXFc extension study, B-YOND (clinicaltrials.gov #NCT01425723), evaluates the long-term safety and efficacy of rFIXFc for the treatment of severe hemophilia B. Here we report interim safety and efficacy data for adults and adolescents enrolled in B- YOND.

Methods:

Upon completing B-LONG, eligible subjects could enroll in one of 4 treatment groups in B-YOND: weekly prophylaxis (20 to 100 IU/kg every 7 days), individualized prophylaxis (100 IU/kg every 8 to 16 days, or twice monthly), modified prophylaxis (a prophylaxis regimen different from weekly or individualized prophylaxis), or episodic treatment. Subjects could change treatment groups at any point in the study. The primary endpoint was development of inhibitors. Secondary outcomes included annualized bleeding rate (ABR) and rFIXFc exposure days (EDs).

Summary:

93/115 subjects (80.9%) who completed B-LONG enrolled in B-YOND. As of the interim data cut (17 October 2014), 18 subjects had completed, 7 had discontinued, and 68 remained on study (median time on study, 119.9 weeks). From the start of B-LONG to the B- YOND interim data cut, the median time on rFIXFc was 171.6 weeks and 68 subjects (73%) had ≥100 cumulative rFIXFc EDs. 29/90 subjects (32%) from Arms 1-3 of B-LONG changed treatment groups at the start of or during B-YOND, including 9/19 subjects who changed from episodic to prophylactic treatment (1 subject changed back to episodic treatment before the interim data cut). In the weekly prophylaxis group, the median (IQR) average weekly prophylactic dose was 49.5 (21.0, 105.6) IU/kg. The median (IQR) average dosing intervals in the individualized and modified prophylaxis groups were 13.7 (10.1, 14.0) days and 6.9 (4.9, 7.0) days, respectively (a reduction in annual infusions of ~75% and ~50%, respectively, compared with twice-weekly administration of a standard half-life FIX product). As of the B- YOND interim data cut, no inhibitors were observed, and there were no reports of anaphylaxis or serious hypersensitivity reactions associated with rFIXFc, and no thrombotic events. Adverse events were generally typical of the hemophilia B population; no subject discontinued due to an adverse event. Median ABRs were low with rFIXFc prophylaxis (Table). 97.2% of bleeding episodes were controlled with 1 or 2 infusions.

Conclusions:

Interim data from B- YOND confirm the long-term safety of rFIXFc and the maintenance of a low ABR with prophylactic dosing every 1 to 2 weeks.

Introduction and Objectives:

The phase 3 A-LONG and Kids A-LONG studies demonstrated the safety and efficacy of rFVIIIFc for the control and prevention of bleeding episodes in subjects with severe hemophilia A. This subgroup analysis of A-LONG and Kids A-LONG examined bleeding frequency with rFVIIIFc prophylaxis in subjects with target joints at baseline.

Methods:

A-LONG (≥12 y) and Kids A-LONG (<12 y) subjects with a history of target joints (a major joint with ≥3 bleeding episodes in a 6-month period) who were previously treated with FVIII and received on-study rFVIIIFc prophylaxis were identified. Self-reported pre-study 12- month bleeding history and on-study annualized bleeding rate (ABR) for all bleeds were evaluated.

Results:

93/141 subjects in A-LONG and 13/69 subjects in Kids A-LONG had target joints at baseline. The most prevalent locations of pre-study target joints identified at baseline among subjects in A-LONG were the elbow (61.7%) and ankle (59.6%). Similarly, in Kids A-LONG, these were the ankle (69.2%) and elbow (30.8%). A total of 59.7% and 52.4% of subjects receiving individualized (Arm 1) and weekly (Arm 2) rFVIIIFc prophylaxis in A-LONG, respectively, and 53.8% of subjects receiving rFVIIIFc prophylaxis in Kids A-LONG with target joints at baseline had no target joint bleeding episodes on-study. Median on-study ABRs with rFVIIIFc prophylaxis tended to be lower than pre-study bleeding rates in subjects with target joints at baseline (Table).

Conclusions:

For subjects with severe hemophilia A who had target joints at baseline, rFVIIIFc prophylaxis lowered bleeding rates across age groups compared with pre-study FVIII treatment.