Inhibitor epidemiology and genetic‐related risk factors in people with haemophilia from Côte d’Ivoire

Abstract

Introduction In Sub‐Saharan Africa, inhibitor prevalence data in people with haemophilia (PWH) are scarce, as are data on genetic or treatment‐related risk factors. Aims and methods We performed a prospective study on PWH from Côte d’Ivoire to collect data into inhibitor prevalence, create a database of haemophilia genotypes, establish correlations between inhibitor presence and genetic variants identified amongst Ivoirian PWHs and evaluate exposure to CFCs. Results The study included 54 unrelated participants (43 severe, four moderate, two mild haemophilia A and five severe haemophilia B). PWH were treated on‐demand with various product types for short periods, non‐intensively, and using low‐dose regimens. We reported similar distributions of intron 22 inversions (39.5%), point pathogenic variants (32.6%) and rearrangements in Ivoirian severe haemophilia A patients versus non‐African ethnic groups. The haplotypes H1 (29.6%), H2 (36.3%) and H3 (34.1%) frequencies in haemophilia A were consistent with results published on African populations. We identified eight new causal variants. An inhibitor was found in 12% of haemophilia A patients previously exposed to replacement therapies. Among PWH with inhibitors, 66.7% had a positive intron 22 inversion and 50% the H1 haplotype. Conclusion This study provides original data on molecular diagnosis of haemophilia, inhibitor prevalence and risk factors for inhibitor development previously associated with inhibitors in Côte d’Ivoire. The low inhibitor prevalence likely reflects the limited exposure to replacement therapy in Côte d’Ivoire. Further larger, multicentric and international studies are needed to gain more insight on inhibitor incidence and risk factors in African PWH.

Feasibility and outcomes of low‐dose and low‐frequency prophylaxis with recombinant extended half‐life products (Fc‐rFVIII and Fc‐rFIX) in Ivorian children with hemophilia: Two‐year experience in the setting of World Federation of Haemophilia humanitarian aid programme

“…In our population, we observed during the 2 years of study period a low rate of inhibitor incidence (12.5% with 8.3% of persistent inhibitor). This is in line with previous published data from Ivory Coast but lower than reported in studies conducted on genetic risk factors for inhibitors among black PWHs in North America 14,25 . Data on inhibitors in African PWHs are, however, scarce, and more insight on the inhibitors' incidence and risk factor development is needed in this population 14 .…”

“…Infusions were firstly performed by a HCP, and progressively some highly motivated parents (33% at T2) were trained to infuse their children. The median [range] follow-up duration was 17 [11][12][13][14][15][16][17][18][19][20][21][22][23][24] months. Outcome data at T1 and T2 were available in 24 participants, since one BWH was lost to follow-up after moving to Senegal (Figure 1).…”

“…The causal genetic variant was available in 76% of the participants, these data having been previously studied across the Ivorian haemophilia population. 14 With respect to the treatment prior to inclusion to the study, all the BWHs were treated on-demand with standard half-life CFCs, with a majority (84%) of minimally treated BWHs having less than 15 consultation. Peripheral venous access was easy for the majority and difficult but achievable in one BWH.…”

“…12 In 2014, a WFH twinning was established between the Yopougon haemophilia treatment centre (HTC) in Abidjan, Ivory Coast, and the international HTC of the Cliniques universitaires Saint-Luc in Brussels, Belgium. In this setting, several initiatives were launched including a systematic clinical and molecular characterization of all identified Ivorian haemophilia patients, 13,14 the introduction since January 2016 of the use of paper logbooks to systematically record treated and untreated bleeds and their treatments, 15 the development and implementation of culturally adapted educational materials 16 and self-rehabilitation programmes 17 as well as regular inhibitor screening. These initiatives and a concomitant increase in the WFH humanitarian CFCs allocation 18 contributed to develop a favourable environment to start prophylaxis in Ivory Coast in January 2018.…”

“…Mean (SD) age at inclusion was 5.6 (2.5) years. The median [range] follow-up duration was 17 [11][12][13][14][15][16][17][18][19][20][21][22][23][24] months.Regimen of prophylaxis was 20 IU kg −1 1×/week in haemophilia A and every 10 days in haemophilia B. We observed a maximal reduction by 87.6% of the annual spontaneous joint bleeding rate and a slight decrease in the total HJHS scores (p = .047).Adherence problems related to parents' low education level and shortage in CFCs were the main issues to carry out the programme.…”