Jasińska-Stroschein Magdalena, Stawarczyk Karolina, Stępień Anna, Orszulak-Michalak Daria
Department of Biopharmacy, Medical University of Lodz, Lodz, Poland.
Arch Med Sci. 2020 Jun 5;20(1):167-188. doi: 10.5114/aoms.2020.96143. eCollection 2024.
The objective of this study was to estimate the safety profile of pulmonary hypertension-specific therapies using placebo-controlled and active comparator trials.
The search corpus comprised Medline, Scopus, Embase and Clinical Trials databases. A systematic review and meta-analysis was performed to assess the relative risk of severe events and discontinuations as well as of adverse drug reactions (ADRs) classified into 26 categories and 21 subcategories defined by the Medical Dictionary for Regulatory Activities (MedRA).
Pulmonary hypertension-specific therapies had the greatest effect on such events as flushing and headache as well as jaw pain, limb pain and myalgia or gastrointestinal disorders. The relative risk for ADRs in patients receiving monotherapy (vs. placebo/supportive therapies) and combined regimens (vs. monotherapy) was significantly increased. The risk of cessation for the combined regimen was slightly higher (Q, = 0.0778). Such ADRs as blood and lymphatic system disorders with the anemia subgroup, gastrointestinal disorders with diarrhea and nausea subgroups, respiratory and thoracic diseases or nervous system disorders with headache tended to occur more often in combination regimens as compared to monotherapy.
About half of the main categories and subcategories of adverse reactions according to MedRA were associated with a relatively high frequency and hazard ratio. Their risk can be increased when combination regimens are used, especially.
本研究的目的是通过安慰剂对照试验和活性对照试验评估肺动脉高压特异性治疗的安全性。
检索库包括Medline、Scopus、Embase和临床试验数据库。进行了一项系统评价和荟萃分析，以评估严重事件和停药以及根据《药物监管活动医学词典》（MedRA）分类为26个类别和21个子类别的药物不良反应（ADR）的相对风险。
肺动脉高压特异性治疗对潮红、头痛以及颌部疼痛、肢体疼痛、肌痛或胃肠道疾病等事件影响最大。接受单药治疗（与安慰剂/支持性治疗相比）和联合治疗方案（与单药治疗相比）的患者发生ADR的相对风险显著增加。联合治疗方案停药的风险略高（Q = 0.0778）。与单药治疗相比，联合治疗方案中贫血亚组的血液和淋巴系统疾病、腹泻和恶心亚组的胃肠道疾病、呼吸和胸部疾病或头痛的神经系统疾病等ADR往往更常发生。
根据MedRA，约一半的主要不良反应类别和亚类与相对较高的频率和风险比相关。特别是使用联合治疗方案时，其风险可能会增加。
