Lack of seasonal variation in bleeding and patient-assessed pain patterns in patients with haemophilia B receiving on-demand therapy

Abstract

Spontaneous haemorrhage in patients with haemophilia is generally considered to occur randomly and without a predictable temporal or seasonal pattern; however, there is a lack of evidence in the literature on the effects of weather, temperature and atmosphere on bleeding episodes. This post hoc analysis of a multicentre, open-label crossover study examined the influence of seasonality on bleeding frequency and patient-assessed pain in patients with moderately severe and severe (FIX C ≤ 2%) haemophilia B. Fifty patients were enrolled and treated on-demand for 16 weeks; 47 were subsequently randomized to one of two prophylactic regimens (nonacog alfa 100 IU kg(-1) once weekly or 50 IU kg(-1) twice weekly) for 16 weeks. Patients then underwent an 8-week washout period of on-demand therapy before being crossed over to the other prophylactic regimen for 16 weeks. Bleeding episodes during the on-demand treatment periods were analysed. To assess for temporal trends, data were graphed as scatter plots. The primary end point was the annualized bleeding rate (ABR). Additional measures included raw and median pain scores during every joint bleeding event (spontaneous or traumatic), with pain scored using the Brief Pain Inventory (0 = 'no pain' to 10 = 'pain as bad as you can imagine'). The observed ABRs during the on-demand periods showed no distinguishable trend over time. Analysis of pain associated with joint bleeding episodes also did not demonstrate any discernible temporal trend. No apparent seasonal variation in bleeding pattern or patient-reported pain was observed in this analysis of patients with haemophilia B.

Trial registration: ClinicalTrials.gov NCT00364182.

Keywords: factor IX; haemophilia B; pain; recombinant factor IX; seasonality.

Figure 1

Study design. PI, principal investigator; R, randomization.

Figure 2

Distribution of annualized bleeding events for on-demand period 1 vs. on-demand period 2 for each patient.

Figure 3

(a) Distribution of annualized bleeding events in each on-demand treatment period per patient, by day of the year. Data from both on-demand periods were pooled so that all months could be represented. Each circle represents up to two data values for an individual patient. The time point represents the midpoint of the patient's participation in that period. (b) Proportion of joint bleeding episodes associated with pain per patient in each on-demand treatment period, by day of the year. Each circle represents the proportion of joint bleeding episodes for which the patient answered ‘Yes’ to question 1 on the BPI (‘Have you experienced significant pain today?’), plotted at the midpoint of the patient's participation in that period. (c) Raw pain scores for patients reporting pain from a joint bleeding episode during either on-demand period, by day and year of occurrence, for each reported episode. Each circle represents a raw pain score, which is plotted on the day of occurrence. (d) Median pain score in each on-demand treatment period per patient, by day of the year. Each point represents the median pain score for each patient, plotted at the midpoint of the patient's participation in that period. A pain score of 0 was imputed for any joint bleeding episode for which a patient reported no significant pain.