Kimutai Robert, Musa Ahmed M, Njoroge Simon, Omollo Raymond, Alves Fabiana, Hailu Asrat, Khalil Eltahir A G, Diro Ermias, Soipei Peninah, Musa Brima, Salman Khalid, Ritmeijer Koert, Chappuis Francois, Rashid Juma, Mohammed Rezika, Jameneh Asfaw, Makonnen Eyasu, Olobo Joseph, Okello Lawrence, Sagaki Patrick, Strub Nathalie, Ellis Sally, Alvar Jorge, Balasegaram Manica, Alirol Emilie, Wasunna Monique
Centre for Clinical Research, Kenya Medical Research Institute, PO Box 20778-00202, Off Mbagathi Rd, Nairobi, Kenya.
Drugs for Neglected Diseases Initiative (DNDi), Nairobi, Kenya.
Clin Drug Investig. 2017 Mar;37(3):259-272. doi: 10.1007/s40261-016-0481-0.
In 2010, WHO recommended a new first-line treatment for visceral leishmaniasis (VL) in Eastern Africa. The new treatment, a combination of intravenous (IV) or intramuscular (IM) sodium stibogluconate (SSG) and IM paromomycin (PM) was an improvement over SSG monotherapy, the previous first-line VL treatment in the region. To monitor the new treatment's safety and effectiveness in routine clinical practice a pharmacovigilance (PV) programme was developed.
A prospective PV cohort was developed. Regulatory approval was obtained in Sudan, Kenya, Uganda and Ethiopia. Twelve sentinel sites sponsored by the Ministries of Health, Médecins Sans Frontières (MSF) and Drugs for Neglected Diseases initiative (DNDi) participated. VL patients treated using the new treatment were consented and included in a common registry that collected demographics, baseline clinical characteristics, adverse events, serious adverse events and treatment outcomes. Six-monthly periodic safety update reports (PSUR) were prepared and reviewed by a PV steering committee.
Overall 3126 patients were enrolled: 1962 (62.7%) from Sudan, 652 (20.9%) from Kenya, 322 (10.3%) from Ethiopia and 190 (6.1%) from Uganda. Patients were mostly male children (68.1%, median age 11 years) with primary VL (97.8%). SSG-PM initial cure rate was 95.1%; no geographical differences were noted. HIV/VL co-infected patients and patients older than 50 years had initial cure rates of 56 and 81.4%, respectively, while 1063 (34%) patients had at least one adverse event (AE) during treatment and 1.92% (n = 60) had a serious adverse event (SAE) with a mortality of 1.0% (n = 32). There were no serious unexpected adverse drug reactions.
This first regional PV programme in VL supports SSG-PM combination as first-line treatment for primary VL in Eastern Africa. SSG-PM was effective and safe except in HIV/VL co-infected or older patients. Active PV surveillance of targeted safety, effectiveness and key VL outcomes such us VL relapse, PKDL and HIV/VL co-infection should continue and PV data integrated to national and WHO PV databases.
2010年，世界卫生组织（WHO）推荐了一种用于东非内脏利什曼病（VL）的新一线治疗方案。这种新疗法是静脉注射（IV）或肌肉注射（IM）葡萄糖酸锑钠（SSG）与肌肉注射巴龙霉素（PM）的联合使用，相较于该地区之前的一线VL治疗方案SSG单药治疗有了改进。为了监测这种新疗法在常规临床实践中的安全性和有效性，制定了一项药物警戒（PV）计划。
建立了一个前瞻性PV队列。在苏丹、肯尼亚、乌干达和埃塞俄比亚获得了监管批准。由各国卫生部、无国界医生组织（MSF）和被忽视疾病药物研发倡议（DNDi）赞助的12个哨点参与其中。使用新疗法治疗的VL患者签署知情同意书后被纳入一个共同登记册，该登记册收集人口统计学信息、基线临床特征、不良事件、严重不良事件和治疗结果。PV指导委员会每六个月编写并审查一次定期安全性更新报告（PSUR）。
总共纳入了3126例患者：1962例（62.7%）来自苏丹，652例（20.9%）来自肯尼亚，322例（10.3%）来自埃塞俄比亚，190例（6.1%）来自乌干达。患者大多是男性儿童（68.1%，中位年龄11岁），患有原发性VL（97.8%）。SSG-PM初始治愈率为95.1%；未发现地理差异。HIV/VL合并感染患者和50岁以上患者的初始治愈率分别为56%和81.4%，而1063例（34%）患者在治疗期间至少出现了一次不良事件（AE），1.92%（n = 60）出现了严重不良事件（SAE），死亡率为1.0%（n = 32）。未出现严重的意外药物不良反应。
这项VL领域的首个区域PV计划支持将SSG-PM联合疗法作为东非原发性VL的一线治疗方案。除了HIV/VL合并感染患者或老年患者外，SSG-PM是有效且安全的。应继续对目标安全性、有效性和关键VL结局（如VL复发、PKDL和HIV/VL合并感染）进行积极的PV监测，并将PV数据整合到国家和WHO的PV数据库中。
