|Year : 2021 | Volume
| Issue : 2 | Page : 127-131
Perception to hydroxyurea therapy in patients with sickle cell disease: Report from 3 centers
Kaladada I Korubo1, Nkemsinachi Maryanne Onodingene2, Helen Chioma Okoye3, Hannah E Omunakwe4
1 Department of Medicine and Community Medicine, College of Health Sciences, Usmanu Danfodiyo University, Renal Centre, Sokoto, Sokoto State, Nigeria
2 Department of Specialist Hospital, Sokoto, Sokoto State, Nigeria
3 Sir Yahaya Memorial Hospital, Birnin Kebbi, Kebbi State, Nigeria
4 Federal Medical Centre, Birnin Kebbi, Kebbi State; Ahmad Sani Yariman Bakura Hospital, Gusau, Zamfara State, Nigeria
|Date of Submission||06-May-2020|
|Date of Acceptance||24-Aug-2020|
|Date of Web Publication||30-Jun-2021|
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Hydroxyurea (HU) is an hemoglobin F inducing agent used in the treatment of sickle cell disease (SCD). Aim: The aim of this study is to determine the perception of HU by people living with SCD. Materials and Methods: A pretested questionnaire was self-administered to known cases of SCD attending pediatrics and adult hematology clinics in three participating centers. Mothers of children <18 years responded on their behalf. Results: There were 101 responders, 49 (48.5%) males and 52 (51.5%) females, of which 24 (23.8%) were children <18 years and 77 (76.2%) were adults. The majority (n = 73, 72.3%) knew their phenotype. Up to 63 (62.4%) had crises in the past 3 months. Only 35 (34.7%) had heard of HU, many through their doctor (n = 16, 45.7%), 8 (22.9%) through online resources, and 7 (20%) from friends. Only 12 (11.9%) had been exposed to HU therapy, of which 5 (41.7%) had discontinued therapy mostly due to side effects (n = 2, 40%). The seven patients (58.3%) on continuous HU therapy for a duration of 6 months to over 5 years, all reported reduced hospital admissions and frequency of crises as benefits of the drug, whereas 4 (57.1%) had stopped requiring blood transfusion since starting therapy. Of those who had never taken HU, 53 (52.5%) believed that HU should be used in treating SCD and majority (n = 32, 60.4%) would want to be commenced on the drug. However, 8 (15.1%) would decline therapy (mostly due to perceived associated side effects; n = 4; 50%). Six (11.3%) were unsure if they would want the drug and 7 (13.2%) would have to discuss the decision first with their family. There were 8 (8.9%) responders who did not think HU will be beneficial in SCD and would decline treatment, while 26 (29.2%) were unsure of both the benefits of the drug or of commencing therapy. Conclusion: The findings from this study suggest that HU is beneficial for patients with SCD; however, the awareness of this medication among SCD patients is still low in our environment. Some SCD patients would decline the use of HU due to perceived side effects. We recommend that more awareness on HU be created and coordinated multi-center studies on the efficacy of HU in the Nigerian population be carried out.
| Abstract in French|| |
Contexte: L'hydroxyurée (HU) est un agent inducteur de l'hémoglobine F utilisé dans le traitement de la drépanocytose (SCD). Objectif: le but de cette L'étude vise à déterminer la perception de l'HU par les personnes atteintes de SCD. Matériel et Méthodes: un questionnaire pré-testé a été auto-administré aux cas connus de SCD fréquentant des cliniques de pédiatrie et d'hématologie pour adultes dans trois centres participants. Les mères d'enfants de moins de 18 ans ont répondu en leur nom. Résultats: Il y avait 101 répondants, 49 (48,5%) hommes et 52 (51,5%) femmes, dont 24 (23,8%) étaient des enfants de moins de 18 ans et 77 (76,2%) étaient des adultes. La majorité (n = 73, 72,3%) connaissait leur phénotype. Jusqu'à 63 (62,4%) ont eu des crises au cours des 3 derniers mois. Seulement 35 (34,7%) avaient entendu parler de HU, beaucoup par l'intermédiaire de leur médecin (n = 16, 45,7%), 8 (22,9%) par des ressources en ligne et 7 (20%) par des amis. Seulement 12 (11,9%) avaient été exposés à un traitement par HU, dont 5 (41,7%) avaient arrêté le traitement principalement en raison d'effets secondaires (n = 2, 40%). Les sept patients (58,3%) sous traitement HU continu pendant une durée de 6 mois à plus de 5 ans, tous ont signalé une réduction des hospitalisations et de la fréquence des crises comme bienfaits du médicament, alors que 4 (57,1%) avaient cessé de nécessiter une transfusion sanguine depuis le début du traitement. De ceux qui n'avaient jamais prises HU, 53 (52,5%) estimaient que HU devrait être utilisée dans le traitement de la drépanocytose et la majorité (n = 32, 60,4%) souhaiterait commencer le médicament. Cependant, 8 (15,1%) refuseraient le traitement (principalement en raison des effets secondaires associés perçus; n = 4; 50%). Six (11,3%) ne savaient pas siils voudraient le médicament et 7 (13,2%) devraient d'abord discuter de la décision avec leur famille. Il y avait 8 répondants (8,9%) quine pense pas que l'HU sera bénéfique dans la drépanocytose et refuserait le traitement, tandis que 26 (29,2%) n'étaient pas certains des avantages du médicament ou commencer la thérapie. Conclusion: Les résultats de cette étude suggèrent que l'HU est bénéfique pour les patients atteints de SCD; cependant, la conscience de ce médicament chez les patients SCD est encore faible dans notre environnement. Certains patients SCD refuseraient l'utilisation de l'HU en raison du côté perçu effets. Nous recommandons qu'une plus grande sensibilisation à l'HU soit créée et coordonne des études multicentriques sur l'efficacité de l'HU au Nigéria. population être effectuée.
Keywords: Hydroxyurea, sickle cell crises, sickle cell disease
|How to cite this article:|
Korubo KI, Onodingene NM, Okoye HC, Omunakwe HE. Perception to hydroxyurea therapy in patients with sickle cell disease: Report from 3 centers. Ann Afr Med 2021;20:127-31
|How to cite this URL:|
Korubo KI, Onodingene NM, Okoye HC, Omunakwe HE. Perception to hydroxyurea therapy in patients with sickle cell disease: Report from 3 centers. Ann Afr Med [serial online] 2021 [cited 2022 Aug 15];20:127-31. Available from: https://www.annalsafrmed.org/text.asp?2021/20/2/127/320043
| Introduction|| |
Sickle cell anemia (SCA) is a genetic disorder characterized by the presence of the sickle globin gene, where due to replacement of thymine for adenine at position 6 of the beta-globin chain, the amino acid valine is substituted for glutamine. This leads to the polymerization of deoxyhemoglobin and ultimately brings about the sequel of the disease. Nigeria has one of the largest burdens of SCA; there is a high carrier rate with 20%–30% of the population having the sickle cell trait while about 2%–3% of the population affected by the disease. Although the clinical severity of the disease varies from patient to patient, the chronicity of the disease coupled with associated morbidity affects the quality of life of people living with SCA.,
Hydroxyurea (HU) is a myelosuppressive agent that was found to induce HbF, thereby ameliorating the clinical severity of adult SCA patients in the 1980s in clinical trials. It was first approved for the management of adult patients with a clinically severe form of SCA by the United States Food and Drug Administration in 1998. The mechanism of action of HU in sickle cell is not limited to HbF induction because the clinical benefits of HU may be seen before significant elevation of HbF. Other mechanisms of action of HU in SCA include; red cell hydration, improved deformability, and rheology, increased nitric oxide availability, cytotoxicity, thereby causing the reduction in the production of neutrophils, reticulocytes, and platelets which are mediators of inflammation. HU reduces the frequency and severity of acute pain crises and acute chest syndrome; it reduces the mean number of days of hospitalization and mortality associated with SCA by 40%. The use of HU has expanded since the initial indication for adults with clinically severe forms of SCA to include; adults and children with pain that interferes with daily activities or quality of life, adults, and children with 3 or more moderate-to-severe pain crises within 12 months, adults and children with severe or recurrent acute chest syndrome or symptomatic anemia, children aged 9–42 months (irrespective of clinical severity) and children >42 months, adolescents or adults should be offered HU because of the impact of its effect on reducing the mortality of SCA.
Although the benefits and safety of HU in SCA have been widely documented in Europe, America, and Jamaica for over 30 years since its approval, the use of the drug is still suboptimal in Nigeria, which has a high burden of the disease. Reasons for this may include a lack of awareness, unavailability, cost, and concerns about potential side effects, including the risk of secondary malignancies.,,
This study was aimed to determine the perception of the use of HU for the treatment of SCA by people living with the disease.
| Materials and Methods|| |
A pretested structured questionnaire was self-administered to known cases of sickle cell disease (SCD) attending either the pediatric or adult hematology clinics in three different centers (University of Port Harcourt Teaching Hospital Port Harcourt, Rivers State University Teaching Hospital Port Harcourt and University of Nigeria Teaching Hospital Enugu) located in South-South and Eastern Nigeria, for 6 months. Adult patients responded to the questionnaires themselves, while mothers of children <18 years responded on their behalf. Data were analyzed using SPSS software Version 22 (IBM, Chicago, Illinois, USA) and expressed in figures and tables.
| Results|| |
There were 101 responders, 49 (48.5%) males and 52 (51.5%) females, of which 24 (23.8%) were children <18 years and 77 (76.2%) were adults [Figure 1]. Majority (n = 94, 93.1%) had received formal education. There were 51 (56%) students, while 37 (40.1%) responders were employed and 3 (3.3%) unemployed. Although the majority (n = 73, 72.3%) knew their hemoglobin phenotype as Haemoglobin SS (HbSS), more than a quarter (n = 28, 27.7%) of the responders did not. Up to 63 (62.4%) had a crisis in the preceding 3 months, while more than half (n = 61, 60.4%) had been hospitalized at least once within the preceding 12 months. [Table 1] shows the type of health workers the responders sought treatment from most frequently.
Only 35 (34.7%) had heard of HU, 66 (65.3%) had never heard of HU. Almost half of those who knew of HU heard about it from their doctor (n = 16, 45.7%), 8 (22.9%) through online resources, 8 (22.9%) through a family member or friend while 3 (8.6%) did not specify how they heard of HU. Of the total responders, only 12 (11.9%) had been prescribed HU therapy [Figure 2]. Five of the 12 (41.7%) were commenced on therapy by hematologists, another 5 (41.7%) were commenced by a nonspecialist physician, 1 (8.3%) by a pediatrician, while 1 person did not respond. The dose of HU at the initiation of therapy ranged from 500 mg for 5 responders (41.7%) to 1000 mg for 7 responders (58.3%). Indications for HU included severe, frequent crises in 8 cases (66.7%), severe anemia for 3 cases (25%), whereas one responder (16.7%) was commenced on the drug for both severe anemia and frequent vaso-occlusive crises. The median duration of HU therapy was 8.5 months (interquartile range 34 months).
Of the 12 who were exposed to HU, 5 (41.7%) had discontinued therapy [Figure 2]. Benefits of HU before discontinued therapy included the reduced number of crises, reduced hospital admission rate, and fewer blood transfusions in 3 (60%) persons. Reasons for discontinuing the drug included adverse effects (n = 4, 80%) and drug unavailability (n = 1, 20%). None of those who had discontinued HU had dose escalation during the period of therapy.
Seven (58.3%) of the 12 who had been on HU were still on the drug at the time of this survey, the duration of therapy was 6 months to 65 months. They all reported reduced hospital admission rates and frequency of crises as benefits of the drug, whereas 4 (57.1%) had stopped requiring blood transfusion since starting therapy. Five of them (71.4%) had dose escalation, while on the drug with increments between 500 mg and 1500 mg over a mean period of 28.3 months.
Of the 101 responders, 89 (88.1%) had never taken HU. After being informed of the benefits and adverse effects of HU, 55 (61.8%) of them were of the opinion that HU should be used in treating SCA. On the other hand, only 35 (39.3%) wanted to commence HU in the index clinic visit, while 13 (14.6%) wanted to discuss the decision first with their family. About 22 (24.7%) declined therapy with HU [Figure 3]. Reasons for declining therapy were; fear of adverse effects (n = 11, 50%), waiting until after childbirth before using the drug (n = 3, 27.3%), no benefit of the drug (n = 2, 9.1%), one person needed more information on the drug (4.5%). In comparison, 5 (22.7%) gave no reason for declining to give consent. When asked if they would tell other people about the drug, 61 (68.5%) would do so, 6 (6.7%) would not, while almost a quarter were undecided (n = 22, 24.7%).
|Figure 3: Response to questions on the use and consent for hydroxyurea therapy in sickle cell|
Click here to view
| Discussion|| |
The majority of the responders in this survey were young adults. There was good knowledge about their hemoglobin phenotype; however, about a quarter of the participants did not know their specific hemoglobin phenotype despite being on follow-up care for SCD. Although all responders were known cases of SCD, many did not know their hemoglobin phenotype just like in a survey of undergraduates that despite a high awareness of SCD, only 135 of 200 knew their hemoglobin phenotype.
The knowledge about HU was poor and for those who had heard of HU, less than half of them heard about it from their doctor. This suggests that doctors managing patients with SCD do not routinely discuss HU as a therapeutic option with their patients; it may also be that many health-care providers do not have enough knowledge about HU; thus patients and families are not offered treatment with HU even when they need it. However, all those who had received HU had been commenced by a doctor. It is pertinent that care-givers in the sphere of SCD in Nigeria attain and maintain competence in the use of HU for the treatment of SCD.
HU has been recommended as the standard-of-care for SCA and is also recommended for early initiation in children because of its ability to enable affected children live longer and healthier lives., A long-term observational follow-up study of mortality in patients with SCD in Boston showed that HU reduced mortality from SCD by 40% yet the use of HU in treatment of SCD is still suboptimal in our environment. Our study showed that only 11.9% of the responders had been prescribed HU, but some discontinued the drug, making the actual number of participants on HU lower. Adherence to HU is important for experiencing the desired effect or benefit. Some studies have shown suboptimal adherence to medication among patients with SCD and their beliefs in the need for these medications affected their adherence., Adherence to HU is also a multi-factorial process that is affected by parental and patient perceptions about HU, SCD severity, or both.
Therapy with HU in SCA involves gradual dose–escalation to a maximally tolerated dose,, but this was not done for all the patients who had received HU. Despite that, those exposed to HU benefitted from the drug because they reported fewer crises, fewer blood transfusions, and reduced hospital admissions.
After being counseled, more than half of the young adults who responded in our survey were willing to take HU as an option to improve their quality of life. Some of the respondents who were not on HU still declined because of fear of adverse effects, concerns about its effect on reproduction and a desire to have more information about the drug. These concerns are similar to those raised in other parts of the world with better uptake of HU in the treatment of SCD. It is important that hematologists discuss the known short-term and long-term adverse effects of HU with patients vis a vis the risk of not treating SCD with HU. It is also important that clinicians prescribing and monitoring HU should also look out for adverse effects and report them so that a more robust experience with HU can be documented globally.
| Conclusion|| |
The findings from this study suggest that HU was beneficial for SCA patients who had been exposed to it; however, the awareness of this medication among SCA patients is still low in these centers. Some SCA patients would decline the use of HU due to perceived side effects. We recommend that more awareness of HU be created, and coordinated multi-center studies on the efficacy of HU in the Nigerian population be carried out.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Adewoyin AS. Management of sickle cell disease: A review for physician education in Nigeria (sub-saharan Africa). Anemia 2015;2015:791498.
Babale SM, Sadiq T, Lawal A. Quality of life assessment among individuals with sickle cell disease attending haematology clinic of a tertiary hospital in Northwest Nigeria. Arch Med Surg 2018;3:49-55.
Nwogoh B, Ofovwe CE, Omoti CE. Health-related quality of life in sickle cell disease subjects in Benin City, Nigeria. Afr J Med Health Sci 2016;15:80-5. [Full text]
McGann PT, Ware RE. Hydroxyurea therapy for sickle cell anemia. Expert Opin Drug Saf 2015;14:1749-58.
Harsey C, Roberts IA. The role of hydroxyurea in sickle cell disease. Br J Haematol 2003;120:177-86.
Agrawal RK, Patel RK, Shah V, Nainiwal L, Trivedi B. Hydroxyurea in sickle cell disease: Drug review. Indian J Hematol Blood Transfus 2014;30:91-6.
Qureshi A, Kaya B, Pancham S, Keenan R, Anderson J, Akanni M, et al
. Guidelines for the use of hydroxycarbamide in children and adults with sickle cell disease. Br J Haematol 2018;181:460-75.
McGann PT, Ware RE. Hydroxyurea for sickle cell anemia: What have we learned and what questions still remain? Curr Opin Hematol 2011;18:158-65.
Adewoyin AS, Oghuvwu OS, Awodu OA. Hydroxyurea therapy in adult Nigerian sickle cell disease: A monocentric survey on pattern of use, clinical effects and patient's compliance. Afr Health Sci 2017;17:255-61.
Akinsegun A, Ebele U, Adedoyin D, Adewumi A, John-Olabode S. Hydroxyurea: Modifier of pathophysiology in sickle cell anemia. Ann Trop Pathol 2018;9:1-5.
Rufai AH, Abdullahi FJ, Matthew SA, Amos S, Niyi MA, Gboye OO. The use of hydroxycarbamide in children with sickle cell anemia. Sahel Med J 2018;21:189-93.
Uche E, Olusola O, Benjamin A, Ayobami I, Akinsegun A, Adedoyin D, et al
. An assessment of knowledge, awareness, and attitude of undergraduates toward sickle cell disease in Lagos, Nigeria. Niger Med J 2017;58:167-72.
] [Full text]
Ware RE. How I use hydroxyurea to treat young patients with sickle cell anemia. Blood 2010;115:5300-11.
Ofakunrin AO, Adekola K, Okpe ES, Oguche S, Afolaranmi T, Diaku-Akinwumi, et al.
Level of utilization and provider-related barriers to hydroxyurea use in the treatment of sickle cell disease in Jos, Nigeria. Blood 2019;134:1029.
Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, et al
. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: Risks and benefits up to 9 years of treatment. JAMA 2003;289:1645-51.
Loiselle K, Lee JL, Szulczewski L, Drake S, Crosby LE, Pai AL. Systematic and meta-analytic review: Medication adherence among pediatric patients with sickle cell disease. J Pediatr Psychol 2016;41:406-18.
Badawy SM, Thompson AA, Liem RI. Beliefs about hydroxyurea in youth with sickle cell disease. Hematol Oncol Stem Cell Ther 2018;11:142-8.
Badawy SM, Thompson AA, Lai J, Penedo FJ, Rychilik K, Liem RI. Adherence to hydroxyurea, health-related quality of life domains, and patients' perceptions of sickle cell disease and hydroxyurea: A cross-sectional study in adolescents and young adults. Health Qual Life Outcomes 2017;15:136.
George A, Tran JN. Safety and efficacy of dose-escalation hydroxyurea therapy in infants and young children: A retrospective cohort study. Blood 2018;132:3658.
Brandow AM, Jirovec DL, Panepinto JA. Hydroxyurea in children with sickle cell disease: Practice patterns and barriers to utilization. Blood 2009;114:242.
[Figure 1], [Figure 2], [Figure 3]