1.
Comparative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for active rheumatoid arthritis.
Ho Lee, Y, Gyu Song, G
Journal of clinical pharmacy and therapeutics. 2020;(4):674-681
Abstract
WHAT IS KNOWN AND OBJECTIVE Several clinical trials have attempted to evaluate the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy in patients with active rheumatoid arthritis (RA), but their relative efficacy and safety as monotherapy remain unclear due to the lack of data from head-to-head comparison trials. The relative efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy for rheumatoid arthritis (RA) were assessed. METHODS We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) and examine the efficacy and safety of tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy relative to placebo in patients with RA. RESULTS AND DISCUSSION Five RCTs comprising 1547 patients met the inclusion criteria. Compared with placebo, tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib as monotherapy showed a significantly higher American College of Rheumatology 20% (ACR20) response rate. Peficitinib 150 mg monotherapy showed the highest ACR20 response rate (odds ratio, 17.24.39; 95% credible interval, 6.57-51.80). The ranking probability based on the surface under the cumulative ranking curve indicated that peficitinib 150 mg had the highest probability of being the best treatment for achieving the ACR20 response rate, followed by peficitinib 100 mg, filgotinib 200 mg, filgotinib 100 mg, tofacitinib 5 mg, upadacitinib 15 mg, baricitinib 4 mg and placebo. However, the number of patients who experienced serious adverse events did not differ significantly between the JAK inhibitors, except for tofacitinib 5 mg, and placebo. WHAT IS NEW AND CONCLUSION All five JAK inhibitors-tofacitinib, baricitinib, upadacitinib, filgotinib and peficitinib-were efficacious monotherapy interventions for active RA, and differences were noted in their efficacy and safety in monotherapy.
2.
Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials.
Stein, EA, Giugliano, RP, Koren, MJ, Raal, FJ, Roth, EM, Weiss, R, Sullivan, D, Wasserman, SM, Somaratne, R, Kim, JB, et al
European heart journal. 2014;(33):2249-59
Abstract
AIMS: Prior trials with monoclonal antibodies to proprotein convertase subtilizin/kexin type 9 (PCSK9) reported robust low density lipoprotein cholesterol (LDL-C) reductions. However, the ability to detect potentially beneficial changes in other lipoproteins such as lipoprotein (a), triglycerides, high-density lipoprotein cholesterol (HDL-C), and apolipoprotein (Apo) A1, and adverse events (AEs) was limited by sample sizes of individual trials. We report a pooled analysis from four phase 2 studies of evolocumab (AMG 145), a monoclonal antibody to PCSK9. METHODS AND RESULTS The trials randomized 1359 patients to various doses of subcutaneous evolocumab every 2 weeks (Q2W) or 4 weeks (Q4W), placebo, or ezetimibe for 12 weeks; 1252 patients contributed to efficacy and 1314, to safety analyses. Mean percentage (95% CI) reductions in LDL-C vs. placebo ranged from 40.2% (44.6%, 35.8%) to 59.3% (63.7%, 54.8%) among the evolocumab groups (all P < 0.001). Statistically significant reductions in apolipoprotein B (Apo B), non-high-density lipoprotein cholesterol (non-HDL-C), triglycerides and lipoprotein (a) [Lp(a)], and increases in HDL-C were also observed. Adverse events (AEs) and serious AEs with evolocumab were reported in 56.8 and 2.0% of patients, compared with 49.2% and 1.2% with placebo. Adjudicated cardiac and cerebrovascular events were reported in 0.3 and 0% in the placebo and 0.9 and 0.3% in the evolocumab arms, respectively. CONCLUSION In addition to LDL-C reduction, evolocumab, dosed either Q2W or Q4W, demonstrated significant and favourable changes in other atherogenic and anti-atherogenic lipoproteins, and was well tolerated over the 12-week treatment period.
3.
Effects of ezetimibe, simvastatin and ezetimibe/simvastatin on correlations between apolipoprotein B, LDL cholesterol and non-HDL cholesterol in patients with primary hypercholesterolemia.
Farnier, M, Guyton, JR, Jensen, E, Polis, AB, Johnson-Levonas, AO, Brudi, P
Atherosclerosis. 2013;(2):415-22
Abstract
BACKGROUND/SYNOPSIS Apolipoprotein (apo) B is highly predictive of coronary risk, especially in patients with high triglycerides (TG). This post hoc analysis evaluated the effects of lipid-lowering therapy on correlations between apoB and low-density lipoprotein cholesterol (apoB:LDL-C) and non-high-density lipoprotein cholesterol (apoB:non-HDL-C) in patients with TG< and ≥ 200 mg/dL. METHODS This analysis used data from 3 randomized clinical trials in patients with primary hypercholesterolemia receiving placebo, ezetimibe (EZE), simvastatin (SIMVA) or EZE/SIMVA for 12 weeks. Simple linear regression analyses predicted LDL-C and non-HDL-C levels corresponding to apoB values (80 mg/dL) at baseline and Week 12. RESULTS ApoB correlated with LDL-C (r ≥ 0.76) and non-HDL-C (r ≥ 0.86) at baseline. The correlations were strengthened with SIMVA and EZE/SIMVA at Week 12 (r ≥ 0.88 for LDL-C and r ≥ 0.94 for non-HDL-C). The predicted LDL-C and non-HDL-C values were lower following treatment with SIMVA or EZE/SIMVA than for placebo and EZE. For SIMVA and EZE/SIMVA, the predicted LDL-C and non-HDL-C values were closer to more aggressive LDL-C and non-HDL-C levels (i.e., 70 and 100 mg/dL, respectively). The apoB:LDL-C and apoB:non-HDL-C correlations were weaker and the predicted LDL-C values were generally lower in high TG patients than in low TG patients both at baseline and Week 12. In contrast, the predicted non-HDL-C values were generally higher in high versus low TG patients at baseline but less so at Week 12. CONCLUSION After treatment with EZE, SIMVA, or EZE/SIMVA, a given apoB value corresponds to lower LDL-C and non-HDL-C levels than those obtained from untreated patients.