ABSTRACT
Background: Thymosin alpha 1 (Tα1) is widely used to treat patients with COVID-19 in China; however, its efficacy remains unclear. This study aimed to explore the efficacy of Tα1 as a COVID-19 therapy. Methods: We performed a multicenter cohort study in five tertiary hospitals in the Hubei province of China between December 2019 and March 2020. The patient non-recovery rate was used as the primary outcome. Results: All crude outcomes, including non-recovery rate (65/306 vs. 290/1,976, p = 0.003), in-hospital mortality rate (62/306 vs. 271/1,976, p = 0.003), intubation rate (31/306 vs. 106/1,976, p = 0.001), acute respiratory distress syndrome (ARDS) incidence (104/306 vs. 499/1,976, p = 0.001), acute kidney injury (AKI) incidence (26/306 vs. 66/1,976, p < 0.001), and length of intensive care unit (ICU) stay (14.9 ± 12.7 vs. 8.7 ± 8.2 days, p < 0.001), were significantly higher in the Tα1 treatment group. After adjusting for confounding factors, Tα1 use was found to be significantly associated with a higher non-recovery rate than non-Tα1 use (OR 1.5, 95% CI 1.1-2.1, p = 0.028). An increased risk of non-recovery rate associated with Tα1 use was observed in the patient subgroups with maximum sequential organ failure assessment (SOFA) scores ≥2 (OR 2.0, 95%CI 1.4-2.9, p = 0.024), a record of ICU admission (OR 5.4, 95%CI 2.1-14.0, p < 0.001), and lower PaO2/FiO2 values (OR 1.9, 95%CI 1.1-3.4, p = 0.046). Furthermore, later initiation of Tα1 use was associated with a higher non-recovery rate. Conclusion: Tα1 use in COVID-19 patients was associated with an increased non-recovery rate, especially in those with greater disease severity.
Subject(s)
COVID-19 Drug Treatment , Respiratory Distress Syndrome/epidemiology , Thymalfasin/adverse effects , Adult , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , Female , Hospital Mortality , Humans , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Logistic Models , Male , Middle Aged , Organ Dysfunction Scores , Prognosis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/prevention & control , Retrospective Studies , Risk Assessment/statistics & numerical data , Thymalfasin/administration & dosage , Treatment OutcomeABSTRACT
BACKGROUND: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients. METHODS: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification. RESULTS: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa02/FiO2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×109/L, neutrophil >5.3×109/L, lymphocyte < 0.73 × 109/L, PaO2/FiO2 < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7. CONCLUSION: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.
Subject(s)
Adjuvants, Immunologic/therapeutic use , Coronavirus Infections/drug therapy , Critical Care/methods , Pneumonia, Viral/drug therapy , Thymalfasin/therapeutic use , APACHE , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Aged , Betacoronavirus , COVID-19 , China/epidemiology , Cohort Studies , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Critical Illness , Female , Humans , Male , Middle Aged , Mortality/trends , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Proportional Hazards Models , Retrospective Studies , SARS-CoV-2 , Thymalfasin/administration & dosage , Thymalfasin/adverse effectsABSTRACT
BACKGROUND: Immune checkpoint blockade antibodies (imAbs), such as the anti Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) ipilimumab (IPI) raised overall survival (OS) in metastatic melanoma (MM). Further, long-term OS is a crucial endpoint in MM. Thymosin alpha-1 (Tα1) with dacarbazine (DTIC) showed activity in a phase II trial and a compassionate use program (EAP). We report on long-term follow-up of patients treated with Tα1 to investigate the preconditioning role of Tα1 in imAbs-treated patients. METHODS: Records of patients with melanoma treated with Tα1 within a phase II trial and EAP program were reviewed comparing median OS among patients that sequentially received anti-CTLA-4 imAb and Tα1. Further, the effect of Tα1 on IPI long-term survivor patients was investigated. RESULTS: Among patients treated with Tα1, 21/61 patients received sequentially even anti CTLA-4 imAbs. Median OS at the data cut-off was 57.8 and 7.4 months in patients treated sequentially with anti-CTLA-4 imAbs or not, respectively. Moreover, pretreatment with Tα1 in all (95) IPI-evaluable patients confirmed a significant increase in long-term OS. CONCLUSION: This is the first report on long-term follow-up of Tα1-treated patients. Moreover, an advantage in OS in patients sequentially treated with Tα1 and IPI was seen that suggests a synergistic effect.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ipilimumab/administration & dosage , Melanoma/drug therapy , Protein Kinase Inhibitors/administration & dosage , Skin Neoplasms/drug therapy , Thymalfasin/administration & dosage , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Cell Cycle Checkpoints/drug effects , Cell Cycle Checkpoints/immunology , Clinical Trials, Phase II as Topic , Dacarbazine/administration & dosage , Dacarbazine/adverse effects , Drug Synergism , Female , Follow-Up Studies , Humans , Ipilimumab/adverse effects , Male , Melanoma/mortality , Melanoma/pathology , Middle Aged , Neoplasm Metastasis , Protein Kinase Inhibitors/adverse effects , Randomized Controlled Trials as Topic , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Survival Analysis , Thymalfasin/adverse effects , Time Factors , Young AdultABSTRACT
ABSTRACT Background: Thymosin alpha-1 (Ta-1) suppresses HBV viral replication, while the evidence of combination effect with nucleoide is still limited. We aimed to investigate the efficacy and safety of combination therapy of Ta-1 with entecavir (ETV) in patients with compensated liver cirrhosis. RESEARCH DESIGN AND METHODS: A total of 690 patients were randomized to receive Ta-1 plus ETV (n = 351) or ETV monotherapy (n = 339) for 52 weeks after 26 weeks of ETV treatment, followed by continued entecavir therapy. The primary endpoint was defined as liver decompensation, hepatocellular carcinoma (HCC) or death. RESULTS: The median followed up was 38.2 months. The cumulative incidence of liver decompensation, HCC, or death were similar between two groups. During the Ta-1 combination treatment, the HCC incidence was 1.7% in combination group and 2.1% in ETV group, without new HCC cases developed during week 39 to week 77 in combination group. The virologic response, serologic response, biochemical response was similar between two groups at week 104. Both therapies were well-tolerated. CONCLUSION: There was no significant difference between two groups in endpoint events, while combination therapy with Ta-1 has a tendency to inhibit the development of HCC.
