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The online version of the original article can be found at https://doi.org/10.1007/s10067-021-06003-z B Correction to: Clinical Rheumatology b https://doi.org/10.1007/s10067-021-06003-z In the original published version of the above article contained the following errors and should have been corrected. 4 Pooled estimates of relative risk of major cardiovascular events in rheumatoid arthritis patients, stratifed by JAK inhibitor treatment The original article has been corrected. [Extracted from the article]

Objectives: Janus kinase (JAK) inhibitors are a new class of medication for treatment of rheumatoid arthritis (RA), and such inhibitors alter levels of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) in RA patients. However, the extent of such changes has not been systematically reviewed. Method: A systematic review and network meta-analysis was performed on randomized trials in RA patients in response to JAKi identified from Pubmed, Medline, Embase, and Cochrane Controlled Trials Register. The primary outcome was mean change of HDL-C and LDL-C from baseline. Mean treatment differences and the rank of the effect of various JAKi on HDL-C and LDL-C were estimated. Results: Based on data from 18 unique studies involving five approved JAK inhibitors and 6697 RA patients (JAKi = 3341, placebo = 3356), such inhibitors led to a mean increase of 8.11 mg/dl (95% CI 6.65–9.58, I2 = 82%) in HDL levels from baseline, and a mean increase of 11.37 mg/dl (95% CI 7.84–14.91, I2 = 88%) in LDL levels from baseline. Cardiovascular disease risk did not differ significantly between patients who received JAK inhibitors or those who received placebo or active agents. Conclusions: Our analysis suggests that, at their recommended doses, all five JAK inhibitors lead to an increase in HDL and LDL levels in RA patients. Further long-term research is required to extend these results and understand whether changes in lipid levels in RA patients can affect cardiovascular risk. Key Points • This is the first systematic review and NMA examining the effect of all five clinically approved JAK inhibitors on lipid levels in RA patients. • Recommended doses of JAK inhibitors used for the treatment of RA patients can induce a significant increase in HDL and LDL levels. • Indirect pairwise comparisons suggest that only upadacitinib and peficitinib have significantly different ability to induce LDL change in RA patients. [ABSTRACT FROM AUTHOR]

Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. To observe the clinical safety and tolerability of CALAS. Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies. [ABSTRACT FROM AUTHOR]

Alstonia scholaris could be used as a traditional medicinal plant in China for the treatment of acute respiratory, which might be caused by respiratory tract infections. The investigation tested the anti-infective effects of total alkaloids extract (TA) from leaves of A. scholaris, and as a result, TA inhibited herpes simplex virus type 1 (HSV-1), respiratory syncytial virus (RSV) and influenza A virus (H1N1) in vitro respectively. In addition, the survival days of mice were prolonged, and the lung weights and mortality of mice were decreased significantly, after oral administrated TA in H1N1 and beta-hemolytic streptococcus infectious models in vivo respectively. The finding supported partly the traditional usage of A. scholaris in the treatment of respiratory infections. [ABSTRACT FROM AUTHOR]

Background: This study aims to assess the tolerability and safety of DQTM tablet, which contains a complex mixture of Salvia miltiorrhiza salvianolic acids and Panax notoginseng saponins. Methods: A double-blind, randomized, placebo-controlled phase I dose escalation study was conducted in 84 healthy volunteers. In a single ascending dose study, active ingredients were administered in various doses (90, 270, 540, 1080, 1800, 2880, 4320 or 5760 mg) to 60 subjects in cohorts 1–8. In a multiple ascending dose study, active ingredients were administered at doses of 360, 720 or 2160 mg twice daily to 24 subjects in cohorts 9–11 for 14 consecutive days. Safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiography, laboratory tests and adverse events. Results: No serious adverse events or clinically significant changes in vital signs or electrocardiography were observed. One subject experienced mildly elevated levels of alanine aminotransferase and aspartate transaminase but recovered spontaneously. Five subjects experienced a small increase in the number of daily stools. Conclusions: DQTM tablet was well tolerated at single doses of up to 5760 mg and twice-daily doses of up to 2160 mg for 14 consecutive days. The most frequent adverse event was an increase in the number of daily stools. [ABSTRACT FROM AUTHOR]

Background: Targeted neutrophil inhibitory-hirulog (TNHH) is a novel hybrid glycoprotein that may be a potential drug candidate for acute ischaemic stroke.Objective: The aim of this study was to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of TNHH in healthy volunteers and thereby determine the dose range for future clinical studies.Methods: This randomized, placebo-controlled study was a single ascending dose design with dose levels of 0.05-1.8 mg/kg (n = 4-6 active, 2 placebos per cohort) in 68 participants. In the TNHH 0.2-1.8 mg/kg and control cohorts, pharmacokinetic and pharmacodynamic blood samples were collected over 168 h after intravenous (IV) administration. TNHH occupancy in peripheral blood neutrophils and blood coagulation were evaluated as the markers of target engagement.Results: Two subjects withdrew from the trial before administration of the study treatment, 66 subjects are included in the data analysis. TNHH was well tolerated in all dose regimens. In total, five mild, self-limiting adverse events (AEs) were observed in 4 of the 66 study subjects. Dose-proportional increases in maximum plasma concentration (Cmax) and area under the curve (AUC0-t) of TNHH were observed. Traces of TNHH were excreted in urine. The elimination half-life (t½) ranged from 0.6 to 1.3 h in the eight groups with ascending dose levels. TNHH combined with CD11b/CD18 quickly achieved > 90% receptor occupancy in groups with doses above 0.2 mg/kg. The Cmax and AUC of binding TNHH with CD11b/CD18 increased with the dose. A significant prolongation with dose was observed on thrombin time (TT), and weak influences were observed on prothrombin time (PT) and activated partial thromboplastin time (APTT).Conclusion: TNHH was well-tolerated following IV infusion. The pharmacokinetic and pharmacodynamic characteristics of TNHH indicate that it merits clinical trials. It is recommended that the single dose of TNHH should be 1.0 mg/kg in future studies, and the expected effect may be achieved after 5-7 days of continuous administration.Trial Registration: The study is registered at http://www.chictr.org.cn as ChiCTR-TQR-14004752. [ABSTRACT FROM AUTHOR]

Aims The aims of the study were to assess the pharmacokinetics, pharmacodynamics, safety and tolerability of a novel, pegylated recombinant human consensus interferon-α variant ( PEG-IFN- SA) in healthy volunteers. A pharmacokinetic and pharmacodynamic comparison of PEG-IFN- SA and peginterferon-α-2a in healthy subjects was evaluated. Methods A randomized, dose-escalating, single administration dose phase I clinical study was conducted. Thirty healthy subjects received PEG-IFN- SA as a single dose of 0.5-2.0 μg kg−1 by subcutaneous (s.c.) injection in four parallel groups. Eight subjects received peginterferon-α-2a as a single dose of 180 μg s.c. Results The incidence rates of adverse events for PEG-IFN- SA and peginterferon-α-2a were 29 of 30 and 7 of 8, respectively. The adverse events for PEG-IFN- SA were mild to moderate and similar to those of peginterferon-α-2a. Within 168 h after injection, the mean values of maximal concentration and area under the plasma concentration-time curve from time of dosing to 168 h [ AUC(0-168h)] for 2′,5′-oligoadenylate, neopterin and β2-microglobulin for PEG-IFN- SA at 1.5 μg kg−1 s.c. were similar to or higher than those for peginterferon-α-2a at a dose of 180 μg s.c. After s.c. injection of PEG-IFN- SA at 1.5 μg kg−1, the mean geometric mean values of plasma half-life, time to maximal concentration, maximal concentration and AUC(0-168h) were 55.3 h, 26.9 h, 0.53 μg l−1 and 44.0 μg l−1 h, respectively. Conclusions The tolerance, pharmacokinetic and pharmacodynamic characteristics of PEG-IFN- SA support its administration by s.c. injection as a single dose of 1.5 μg kg−1 or at 2.0 μg kg−1 per week. [ABSTRACT FROM AUTHOR]