Table II.

Some clinical studies of primary/early secondary prophylaxis in children with haemophilia

Author, year Country [ref.]	Patients	Median age at start of prophylaxis, years; (range)	Main results
Nillsson, 1992 Sweden [1]	35 (30 HA, 5 HB)* 3 cohorts, age at study evaluation 3–6, 7–12 and 13–17 years	1.1 (1–1.5), n=6 1.2 (0.5–2), n=9 2.6 (1–4.5), n=20	The two younger cohorts, starting prophylaxis before the age of 2, minimised joint bleeds (median 0.1/year) and maintained OJS and PS 0, with higher F VIII/IX consumption compared to patients who started prophylaxis later, and experienced a higher frequency of joint bleeds (median 3/year) and worse joint status (median OJS and PS 1.2 and 4.8, respectively).
Aledort, 1994 Multi-national [5]	48 HA**	na.	At the 6-year follow-up absence of progression of OJS and PS was correlated to significantly lower frequency of joint bleeds (mean, 1.8 vs. 11.2, p=0.0001) and higher use of prophylaxis longer than 45 weeks/year (9 vs 0, p=0.002).
Kreuz, 1998	14 (11 HA, 3 HB)*	1.75 (1–2.5), n=8	At study entry the median OJS and PS was 0 in both groups; at the 4-year follow-up the frequency of joint bleeds was similar (0. 14 vs 0.22/year) but the joint outcome was better (median PS 0 vs 4) in the first group, starting prophylaxis earlier and with history of = 1 joint bleed, than in the other group with a median of 6 joint bleeds before prophylaxis.
Van den Berg, 2001 the Netherlands[11]	22 HA	4.0±0.5	At a mean age of 14.7 years, patients, who started prophylaxis after 2–5 joint bleeds and at a mean of 2.3 years after the first bleed, had a mean of 3.2 joint bleeds/year and a mean PS of 2.3.
Panicker, 2002 US [12]	20 (17 HA, 3 HB)	4.5	A reduction of the mean frequency of major bleeds from 15.4 to 1.9/year at a median age of 11.4 years, with significant reductions in target joints and number of visits and hospital admissions, was observed.
Yee, 2002 UK [13]	29 (24 HA, 5 HB)	4.0(2–12.7)	At a median follow-up of 4.1 years (0.3–11.5), median joint bleeds decreased from 3.5 to 0.5/year, 20 children (70%) retained an OJS of 0, while in the other 9 the median OJS was 1.5.

Abbreviations: n.a.: not available; HA: haemophilia A; HB: haemophilia B; OJS: orthopaedic joint score; PS: Pettersson score

^*only patients considered on primary or early secondary prophylaxis from the whole study population (60 patients, 52 HA, 8 HB, in the Swedish study, 21 patients, 18 HA, 3 HB in the German study) are mentioned.

^**the subgroup of children with orthopaedic and Pettersson scores 0 at study entry is considered.