1.
Molecular therapies for HCC: Looking outside the box.
Faivre, S, Rimassa, L, Finn, RS
Journal of hepatology. 2020;(2):342-352
Abstract
Over the past decade, sorafenib has been the only systemic agent with proven clinical efficacy for patients with unresectable hepatocellular carcinoma (HCC). Recently, lenvatinib was shown to be non-inferior to sorafenib, while regorafenib, cabozantinib, and ramucirumab were shown to be superior to placebo in patients failing sorafenib. In addition, trials of immune checkpoint inhibitors reported encouraging efficacy signals. However, apart from alpha-fetoprotein, which is used to select patients for ramucirumab, no biomarkers are available to identify patients that may respond to a specific treatment. Different synergisms have been postulated based on the potential interplay between antiangiogenic drugs and immunotherapy, with several clinical trials currently testing this hypothesis. Indeed, encouraging preliminary results of phase I studies of bevacizumab plus atezolizumab and lenvatinib plus pembrolizumab have led to the design of ongoing phase III trials, including both antiangiogenics and immune checkpoint inhibitors in the front-line setting. Other important phase II studies have tested molecular therapies directed against different novel targets, such as transforming growth factor-beta, MET (hepatocyte growth factor receptor), and fibroblast growth factor receptor 4. These studies integrated translational research with the aim of better defining the biological tumour profile and identifying tumour and blood biomarkers that select patients who may really benefit from a specific molecular therapy. Importantly, good safety profiles make these drugs suitable for future combinations. In this review, we discuss the most recent data on novel combination strategies and targets, as well as looking ahead to the future role of molecular therapies in the treatment of patients with advanced HCC.
2.
A systematic review on the off-label use of montelukast in atopic dermatitis treatment.
Chin, WK, Lee, SWH
International journal of clinical pharmacy. 2018;(5):963-976
Abstract
Background Atopic dermatitis (AD) is the most common form of eczema. As leukotriene mediators are involved in the inflammatory phase of atopic dermatitis, montelukast has been suggested as a possible therapy. Aim of the review To evaluate the safety and efficacy of montelukast off-label use for the treatment atopic dermatitis. Method A search was performed from database inception until March 2018 in six electronic databases for randomized-controlled-trials examining the use of montelukast for AD. Results Among 301 articles screened, 11 studies met the inclusion criteria and were included in the review. The study populations consist of paediatric and adult subjects with moderate-to-severe AD. Montelukast use was shown to improve symptoms such as pruritus in four studies. Another 2 studies reported that montelukast could improve symptoms similar to the standard regimen of topical steroid and oral antihistamine. However, five studies reported that montelukast had no effects in symptoms alleviation. The use of montelukast was associated with a similar safety profile to placebo and well-tolerated with minimal adverse effects. Conclusion There is limited evidence to suggest that the off-label use of montelukast is effective in treating moderate-to-severe AD. Further research with larger study populations employing standardized endpoint measuring instrument is warranted to further investigate the off-label use of montelukast in AD treatment. Until then, the use of conventional treatments including optimal daily skin hydration should remain the mainstay in the management of atopic dermatitis. In fact, for moderate-to-severe condition, steroid sparing immune-suppressants should still be used clinically until more effective and safer alternative is discovered.
3.
[Micro-invasive embedding combined with montelukast sodium for children cough variant asthma:a randomized controlled trial].
Wang, X, Liu, B, Lu, B, Zhang, Y, Wang, L, Li, H, Han, X, Ding, D
Zhongguo zhen jiu = Chinese acupuncture & moxibustion. 2017;(3):259-264
Abstract
OBJECTIVE To observe the effects of micro-invasive embedding combined with montelukast sodium and simple montelukast sodium for children cough variant asthma (CVA). METHODS A total of 240 patients were randomly assigned into an observation group and a control group, 120 cases in each one. Considering of cases dropping, 101 patients in the observation group and 105 cases in the control group were included. Montelukast sodium chewable tablets were applied before sleep for 3 months in the control group, 5 mg a time, once a day. Based on the treatment as the control group, micro-invasive embedding was used for 3 months in the observation group, twice in the first month and once in the other two months. The acupoints were Feishu (BL 13), Danzhong (CV 17), Dingchuan (EX-B 1), and Zusanli (ST 36). Follow-up was conducted 9 months after treatment in the two groups. The cough score, serum immunoglobulin (IgE, IgG, IgA), platelet activating factor (PAF) were observed before and after treatment. The indices were compared before and after treatment and at follow-up, including pulmonary function indices[peak expiratory flow rate (PEF), forced expiratory volume at the 1st second (FEV1)], and small airway function indices[forced expiratory flow rate with remaining 25% vital capacity (MEF25%), forced expiratory flow rate with remaining 50% vital capacity (MEF50%), forced expiratory flow rate with remaining 75% vital capacity (MEF75%) and mid expiratory flow rate (MEF25%-75%)]. Also, the total effects were evaluated. RESULTS ①The total effective rate in the observation group was 93.1% (94/101), which was better than 87.6% (92/105) in the control group (P<0.05). The cough disappearance time of the cured children in the observation group was (10.38±2.64) d, and it was shorter than (10.72 ±2.60) d of those in the control group (P<0.05). After treatment, the cough score apparently decreased compared with those before treatment in the two groups (both P<0.05), with better result in the observation group (P<0.05). At follow-up, the recurrence frequency of the observation group was (1.43±1.20), and it was less than (1.91±1.71) in the control group (P<0.05). ②The levels of serum IgA and IgG after treatment in the two groups increased, and those of serum IgE and PAF decreased, compared with those before treatment. There was statistically significance except IgG in the control group before and after treatment (all P<0.05), with better Results in the observation group after treatment (all P<0.05). ③ Compared with those before treatment, all the pulmonary function indices were improved obviously after treatment and at follow-up in the two groups (all P<0.05), without statistically significance between the two groups (both P>0.05). ④ There was no statistically significance before and after treatment on small airway function indices in the two groups (all P>0.05). The indices at follow-up increased compared with those before treatment in the two groups (all P<0.05), with better Results in the observation group (all P<0.05). CONCLUSIONS Micro-invasive embedding combined with montelukast sodium achieved de-finite effect for children CVA, which can improve the body's immune and microcirculation. The effect is better than that of simple montelukast sodium on improving small airway function, etc.
4.
Effects of pitavastatin and pravastatin on markers of immune activation and arterial inflammation in HIV.
Toribio, M, Fitch, KV, Sanchez, L, Burdo, TH, Williams, KC, Sponseller, CA, McCurdy Pate, M, Aberg, JA, Zanni, MV, Grinspoon, SK
AIDS (London, England). 2017;(6):797-806
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Abstract
OBJECTIVE Persistent immune activation is thought to contribute to increased cardiovascular disease risk in HIV and statins may help modulate systemic immune activation. We aimed to compare the effects of two key statins on markers of systemic immune activation and arterial inflammation in the HIV population. DESIGN Double-blind, active-controlled, parallel-group comparative trial performed in 45 sites. METHODS Two hundred and fifty-two antiretroviral therapy-treated HIV-infected participants with dyslipidemia were randomized (1 : 1) to pitavastatin 4 mg daily vs. pravastatin 40 mg daily in the HIV-infected patieNts and TREatment with PItavastatin vs. pravastatin for Dyslipidemia (INTREPID) trial. In this analysis of the INTREPID trial, we assessed markers of immune activation and arterial inflammation using a modified intent-to-treat population. This trial is registered with ClinicalTrials.gov (NCT01301066). RESULTS One hundred and twenty-six participants were randomized to receive pitavastatin and 126 to pravastatin. Ninety-nine participants in the pitavastatin group and 91 participants in the pravastatin group completed the study. Median age was 50 (45, 56) years [median (interquartile range)]. Baseline, low-density lipoprotein-cholestrol (LDL-C) was 153 (135, 171) mg/dl, log HIV-1 viral load was 1.1 ± 0.2 copies/ml, and CD4 cell count was 580 (439, 794) cells/μl. At week 52, the pitavastatin group had a significantly greater reduction (% change) compared with pravastatin in soluble CD14 (sCD14), (-10.0 vs. 0.6%, P = 0.02), oxidized LDL (oxLDL) (-26.9 vs. -17.5%, P = 0.02), and lipoprotein-associated phospholipase 2 (Lp-PLA2) (-26.6 vs. -15.5%, P = 0.005) (pitavastatin vs. pravastatin). CONCLUSION Fifty-two weeks of pitavastatin 4 mg daily (vs. pravastatin 40 mg daily) led to a greater reduction in select markers of immune activation and arterial inflammation (sCD14, oxLDL, and LpPLA2) among HIV-infected participants. Further work is needed to assess whether immune-modulatory effects of pitavastatin reduce cardiovascular disease risk in HIV.