DataSheet_1_Biological drugs for systemic lupus erythematosus or active lupus nephritis and rates of infectious complications. Evidence from large clinical trials.pdf

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that frequently affects the kidneys, known as lupus nephritis (LN). Such patients are treated with antimalarials, corticosteroids or immunosuppressive drugs, and more recently, target-specific biological drugs. Although efficacy of these therapies improved SLE-related outcomes, SLE remains associated with higher rates of infections. Here, we performed a comprehensive systemic review of infectious complications in clinical trials covering drug interventions for SLE or specifically for active LN. Our search in 15 online registries yielded a total of 1477 studies of which 14 matched our prespecified criteria. These covered the biological drugs anifrolumab, belimumab, and rituximab that were tested in patients with non-renal SLE and active LN.The available safety data from the SLE trials indicated that infectious complications such as herpes zoster, upper respiratory tract infection, nasopharyngitis, bronchitis, and urinary tract infection in patients receiving placebo were quite prevalent especially in the EXPLORER (rituximab) trial. Infections occurred mostly during the first year of LN therapy. Serious adverse events and infectious complications occurred more frequently in placebo-treated patients with active LN, especially in the BLISS-LN (belimumab) and LUNAR (rituximab) trials. Anifrolumab and rituximab increased the number of clinically relevant episodes of herpes zoster compared to belimumab in patients with active LN. Anifrolumab displayed a similar trend for influenza infections, which is consistent with the specific mechanisms-of-action of anifrolumab; highlighting drug-specific effects on infectious complications. In addition, standard-of-care therapy, e.g., MMF and immunosuppressants, as well as a longer SLE duration may also affect the incidence of serious adverse events and certain infectious complications in SLE patients with active LN.Infectious complications are common in SLE but even more common in patients with active LN, especially herpes zoster is strongly associated with active LN and anifrolumab therapy (OR 2.8, 95% CI 1.18 to 6.66, p = 0.018). Immunotherapy seems to impose unspecific and specific risks for infections. The latter may imply specific precautions such as preemptive vaccination and individual risk-benefit assessments.

系统性红斑狼疮（SLE）是一种多系统性的自身免疫性疾病，常累及肾脏，称为狼疮性肾炎（LN）。此类患者接受抗疟药、皮质类固醇或免疫抑制剂的治疗，而近年来，靶向性生物制剂亦被应用于治疗。尽管这些疗法的疗效有所提升，SLE仍与感染的高发生率相关。本研究对涉及SLE或特定于活动性LN的药物干预的临床试验中的感染并发症进行了全面的系统性回顾。在15个在线注册库中，我们共检索到1477项研究，其中14项符合我们预设的标准。这些研究涵盖了在非肾脏SLE和活动性LN患者中测试的生物制剂anifrolumab、belimumab和rituximab。从SLE试验中可获得的安全性数据表明，接受安慰剂治疗的患者中，感染并发症如带状疱疹、上呼吸道感染、鼻咽炎、支气管炎和尿路感染的发生率相当普遍，尤其是在EXPLORER（rituximab）试验中。感染主要发生在LN治疗的头一年。在BLISS-LN（belimumab）和LUNAR（rituximab）试验中，接受安慰剂治疗的活动性LN患者中，严重不良事件和感染并发症的发生频率更高。与belimumab相比，anifrolumab和rituximab在活动性LN患者中增加了带状疱疹的临床相关病例数。anifrolumab在流感感染方面也显示出类似的趋势，这与anifrolumab特定的作用机制一致；突显了药物对感染并发症的特异性影响。此外，标准治疗方案，例如霉酚酸酯和免疫抑制剂，以及更长的SLE病程也可能影响活动性LN的SLE患者的严重不良事件和某些感染并发症的发生率。感染并发症在SLE中较为常见，但在活动性LN患者中更为普遍，尤其是带状疱疹与活动性LN及anifrolumab治疗之间存在强烈的关联（OR 2.8，95% CI 1.18至6.66，p = 0.018）。免疫疗法似乎对感染产生非特异性和特异性的风险。后者可能意味着需要采取特定的预防措施，如预防性疫苗接种和个体风险效益评估。