Human interleukin-2 biosimilar(Xiamen Amoytop Biotech Co. Ltd.)

Background. The results of previous clinical trials evaluating the efficacy and safety of recombinant human interleukin-2 (rhuIL-2) for adult patients with pulmonary tuberculosis showed inconsistent results. Accordingly, a comprehensive systematic review and meta-analysis was performed. Methods. Relevant randomized controlled trials (RCTs) were retrieved by searching the PubMed, Embase, Cochrane’s Library, Web of Science, Wanfang, and CNKI databases. A random-effects model was used to combine the results. Results. 18 RCTs with 2630 patients were included in this meta-analysis. Pooled results showed that adjunctive rhuIL-2 significantly increased the odds of sputum culture conversion to negative (risk ratio [RR]: 1.27, 95% CI: 1.09 to 1.47, $p=0.002$, I2 = 80%), sputum smear conversion to negative (RR: 1.35, 95% CI: 1.17 to 1.57, $p<0.001$, I2 = 83%), radiographic focus absorption (RR: 1.17, 95% CI: 1.06 to 1.30, $p=0.002$, I2 = 72), and cavity closure (RR: 1.24, 95% CI: 1.09 to 1.40, $p<0.001$, I2 = 23). The use of rhuIL-2 was not related to any severe adverse events which led to discontinuation of the treatment. Results showed that rhuIL-2 was related to an increased risk of fever (RR: 2.46, 95% CI: 1.29 to 4.70, $p=0.006$, I2 = 0%). The incidence of other adverse events, such as musculoskeletal pain, hepatic injury, and renal toxicity, was not significantly different between groups ($p$ all >0.05). Conclusions. rhuIL-2 is an effective adjunctive immunotherapy for patients with pulmonary tuberculosis.

E7777 is a recombinant cytotoxic fusion protein composed of the diphtheria toxin fragments A and B and human interleukin‐2. It shares an amino acid sequence with denileukin diftitox, but has improved purity and an increased percentage of active monomer. We undertook a multicenter, single‐arm phase II study of E7777 in patients with relapsed or refractory peripheral T‐cell lymphoma (PTCL) and cutaneous T‐cell lymphoma (CTCL) to evaluate its efficacy, safety, pharmacokinetics, and immunogenicity. A total of 37 patients were enrolled, of which 17 and 19 patients had PTCL and CTCL, respectively, and one patient with another type of lymphoma (extranodal natural killer/T‐cell lymphoma, nasal type), diagnosed by the Central Pathological Diagnosis Committee. Among the 36 patients with PTCL and CTCL, objective response rate based on the independent review was 36% (41% and 31%, respectively). The median progression‐free survival was 3.1 months (2.1 months in PTCL and 4.2 months in CTCL). The common adverse events (AEs) observed were increased aspartate aminotransferase (AST) / alanine aminotransferase (ALT), hypoalbuminemia, lymphopenia, and pyrexia. Our results indicated that a 9 µg/kg/d dose of E7777 shows efficacy and a manageable safety profile in Japanese patients with relapsed or refractory PTCL and CTCL, with clinical activity observed across the range of CD25 expression. The common AEs were manageable, but increase in ALT / AST, hypoalbuminemia, and capillary leak syndrome should be carefully managed during the treatment.