Aflibercept – Eye Inflammation
Mepolizumab – COPD
Buprenorphine – Acute Pain
Tafenoquine – Malaria Prevention
Sildenafil – FGR Study Halted
Clinical Trials – New Horizons
~ Pharmacology News ~
Targeting Blood Pressure to 120 mmHg Lowers Risk of Mild Cognitive Impairment
July 25th, AAIC Meeting: Intensive blood pressure control targeted at a systolic pressure of 120 mmHg was associated with a 19% lower risk of mild cognitive impairment compared with less intensive blood pressure control (target blood pressure 140 mmHg). RCT, SPRINT MIND trial (9,361 patients).
Numerous Cases of Inflammation Associated with Aflibercept Injections
July 21st/July 23rd, Medscape: Nearly 100 cases of eye inflammation, in some instances involving loss of visual acuity, have been attributed to aflibercept (a VEGF decoy receptor) injections. Although fewer than 1/5 American ophthalmologists use aflibercept to treat neovascular age-related macular degeneration, 82% of reported adverse reactions to intravitreal drugs involved use of this medication.
FDA Committee Recommends Against Expanding Mepolizumab Indications to Include COPD
July 26th, FDA: An FDA advisory committee has voted 3 to 16 not to recommend mepolizumab, an anti-IL-5 monoclonal antibody, as an add-on therapy for reducing exacerbations in patients with COPD + high circulating eosinophil counts. Mepolizumab is already approved for eosinophilic subtypes of asthma and granulomatosis with polyangiitis.
FDA Advisory Panel Votes Against Buprenorphine Sublingual-Spray for Pain Management
July 27th, FDA: A US FDA advisory panel has voted 18-to-1 against the approval of buprenorphine sublingual spray (Buvaya, by INSYS Therapeutics) for the treatment of moderate-to-severe pain. The committee expressed concern over the safety and efficacy of the formulation.
FDA Advisory Panel Votes in Favor of Second Tafenoquine Antimalarial Product
July 26th, FDA: A US FDA advisory committee has voted in favor of the efficacy and safety of a second tafenoquine product (Arakoda) as a once weekly malaria prophylactic. This vote comes on the heels of the approval of a single-dose tafenoquine product (Krintafel) indicated for the radical cure of plasmodium vivax malaria.
Sildenafil Trial Halted Following Infant Deaths
July 25th, BMJ: The STRIDER trial of 183 pregnant women assigned to sildenafil or placebo for the prevention of fetal growth restriction has been discontinued following a high incidence of lung complications and neonatal death in the treatment arm.
~ Clinical Trials: New Horizons ~
SubQ Apomorphine Infusion Reduces “Off Time” in Parkinson’s Disease
July 25th, The Lancet Neurology: Subcutaneous infusion of apomorphine, a nonspecific dopamine agonist, in patients with Parkinson’s disease was found to reduce off time (periods where antiparkinsons medications cease to adequately control symptoms) by nearly 2 hours/day. RCT (106 patients).
Plasma Administration During Air Transport Associated with Lower 30-Day Mortality in Trauma Patients
July 25th NEJM: Administration of plasma during standard traumatic resuscitation in severely injured patients receiving air medical transport was associated with a 10% lower 30-day mortality compared with patients treated with standard resuscitation measures alone. RCT (501 patients).
Plasma Administration During Ground Transport Not Associated with Lower 28-Day Mortality in Trauma Patients
July 19th, The Lancet: Administration of plasma during standard traumatic resuscitation in severely injured patients receiving ground medical transport was not associated with a lower 28-day mortality than patients treated with saline during standard resuscitation. RCT (144 patients).
High-Dose PPI + Aspirin Associated with Improved Outcomes in Barrett’s Esophagus
July 26th, The Lancet: High-dose esomeprazole (40 mg PO BID) + 300-325 mg aspirin was associated with a 59% longer event-free period than low-dose esomeprazole (20 mg PO QD) without aspirin in patients with Barrett’s esophagus. RCT, AspECT Phase III trial (2557 patients).
Novel Anti-VEGF Drug Abicipar Demonstrates Efficacy in Age-Related Macular Degeneration
July 19th, Allergan & Molecular Partners: Abicipar, a novel anti-VEGF DARPin (an antibody mimetic), was found in two Phase III RCTs to be non-inferior to ranibizumab, a previously approved intravitreous anti-VEGF drug. Abicipar required fewer injections to meet the same efficacy endpoint as rabinizumab, but was associated with higher rates of intraocular inflammation.
Cabozantinib Extends Survival in Hepatocellular Carcinoma
July 5th, NEJM: Cabozantinib, a tyrosine kinase inhibitor (including VEGFR1/2/3, MET, AXL) extended median overall survival by 2.2 months in patients with previously-treated advanced hepatocellular carcinoma. RCT, CELESTIAL trial (707 patients).
Atezolizumab Improves Survival in Metastatic Lung Cancer
June 14th, NEJM: Atezolizumab, an anti-PD-L1 antibody, combined with bevacizumab, carboplatin, and paclitaxel was associated with a 1.5 month longer median survival in patients with metastatic non-small cell lung cancer (NSCLC), compared with metastatic NSCLC patients receiving only bevacizumab, carboplatin, and paclitaxel. RCT, IMPower50 (356 patients).
Synthetic Cannabinoid Nabilone Associated with Lower Rates of Agitation in Alzheimer’s Disease
July 24th, AAIC Conference: Twice as many patients (47%) with Alzheimer’s Disease experienced clinically meaningful improvement in agitation compared with those receiving placebo (23%). RCT (39 patients).
Brigatinib Demonstrates Superiority to First-Line Drug in Advanced Non-Small Cell Lung Cancer
July 25th, Takeda Pharmaceutical: Brigatinib (Alunbrig, an anaplastic lymphoma kinase (ALK) inhibitor) has demonstrated superiority to the first-line treatment crizotinib, another ALK-inhibitor, in patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) who are ALK-inhibitor therapy naive. Brigatinib is currently approved only as a second-line therapy, for patients who are not responsive or cannot tolerate crizotinib. RCT (275 patients).
Pembrolizumab Monotherapy Improves Overall Survival in Head and Neck Squamous Cell Carcinoma
July 25th, Merck: Pembrolizumab (Keytruda, an anti-PD-L1 monoclonal antibody) was effective as first-line monotherapy in patients with head and neck squamous cell carcinoma (HNSCC) whose tumors express PL-L1 ligand. Patients receiving pembrolizumab experienced improved overall survival compared with patients treated with the current standard-of-care (cetuximab + platinum chemotherapy + 5-FU). Pembrolizumab is currently approved for HNSCC only in patients who experienced disease progression on a platinum-based chemotherapy regimen. KEYNOTE-048, Phase III RCT (~825 patients).
~ Clinical Research ~
Protease Inhibitors Associated with Worse Outcomes in Patients with HIV + Heart Failure
July 23rd, JACC: Patients with HIV and heart failure treated with protease Inhibitor-based antiretroviral therapy had a two-fold higher rates 30-day heart-failure readmission and cardiovascular mortality compared with patients receiving non-protease-inhibitor antiviral regimens. Observational retrospective (394 patients).
Ondansetron Associated with Slightly Increased Risk of Cleft-Palate and Renal Birth Defects
July 25th, Journal Obstetrics and Gynecology: Off-label use of ondansetron to treat first-trimester nausea and vomiting was associated with a slightly increased likelihood of cleft palate and renal agenesis-dysgenesis. Observational retrospective (Two cohorts, 35,824 total participants).
“Enhanced” Surgery Recovery Protocol Decreases Post-Operative Opioid Use
July 25th, Journal Obstetrics and Gynecology: Implementation of a multidisciplinary perioperative care program (ERAS) involving nutritional counseling, goal-directed fluid therapy, perioperative opioid-sparing analgesia, emphasis on early ambulation, and restriction of the use of surgical drains resulted in a 72% reduction in median opioid consumption compared with patients receiving conventional post-operative recovery measures. Observational, interventional - before/after ERAS implementation. (607 patients).
Mediterranean Diet Adherence Associated with Less Severe Psoriasis
July 26th, JAMA Dermatology: In a survey-based study, patients who adhered to a Mediterranean diet were nearly 30% less likely to have severe psoriasis than patients who did not adhere closely to a Mediterranean diet. Cross-sectional observational, NutriNet-Sante Cohort (35,735 survey participants, 3557 reported having psoriasis.)
Antidepressant Use Associated with Slightly Worse Outcomes in COPD
July 27th, European Respiratory Journal: Recent initiation of selective serotonin reuptake inhibitor (SSRI) or serotonin/norepinephrine reuptake inhibitor (SNRI) medications in older patients with chronic obstructive pulmonary disease (COPD) was associated with a 20% higher mortality rate compared to propensity-matched controls who had not recently started SSRI/SNRI therapy. Retrospective observational (131,718 patients).
Flavonoid Ingestion Associated with Decreased Risk of AMD
July 6th, American Journal of Clinical Nutrition: A correlation has been observed between flavonoid – a type of dietary phytochemical antioxidant present in oranges and some other fruits and vegetables - ingestion and a decreased risk of age-related macular degeneration (AMD). Each standard-deviation increase in flavonoid intake was associated with a 34% lower odds ratio of developing AMD. Observational retrospective (2,856 patients).
Norepinephrine Associated with Lower Risk of Refractory Shock than Epinephrine Following Myocardial Infarction
July 10th, JACC: Administration of norepinephrine and was associated with similar vascular and cardiac effects as administration of epinephrine in patients with cardiogenic shock following myocardial infarction. Norepinephrine was associated with a significantly lower risk of refractory shock (7% of patients) compared with epinephrine (37% of patients). RCT, OptimaCC Clinical Trial (57 patients).
Low-Dose Rivaroxaban Associated with Higher Risk of Myocardial Infarction in Asians with Atrial Fibrillation
July 24th, JACC: Compared to standard-dose rivaroxaban (Xarelto, a direct factor Xa inhibitor), 10 mg/day rivaroxaban was associated with an approximately two-fold higher risk of myocardial infarction in Asian patients with atrial fibrillation. Retrospective observational (6,558 patients).
Dolutegravir Antiretroviral Therapy Associated with Increased Risk of Neural Tube Defects
July 24th, NEJM: Infants born to HIV-positive women receiving dolutegravir (Tivicay, an HIV integrase inhibitor)-based antiretroviral therapy from the time of conception were found to have an 82% increased risk of neural tube defects compared with infants born to women receiving other antiretroviral therapies. Observational (88,755 births, 86 neural-tube defects).
Two-Drug HIV Antiretroviral Regimen Non-Inferior to Three-Drug Regimen
July 25th, ViiV Healthcare: A two-drug dolutegravir and lamivudine (integrase inhibitor and reverse transcriptase inhibitor, respectively) combination was found to be non-inferior compared to the standard, first-line three drug dolutegravir/tenofovir/emtricitabine (integrase inhibitor + two reverse transcriptase inhibitors) combination therapy with respect to viral load in HIV infected individuals after 48 weeks of treatment. Two RCTS, GEMINI I/II (~1,400 participants).
Escitalopram Following Acute Coronary Syndrome Associated with Improved Outcomes
July 24th, JAMA: 24 weeks of escitalopram (Lexapro, a selective serotonin reuptake inhibitor) in patients experiencing depression following a recent episode of acute coronary syndrome was associated with an 18% decrease in all-cause mortality compared with patients receiving placebo. RCT (300 patients).
Rabinizumab and Panretinal Photocoagulation Similarly Effective in Proliferative Diabetic Retinopathy
July 24th, JAMA Opthalmology: Panretinal photocoagulation (PRP) therapy and rabinizumab were similarly effective in delaying the progression of diabetic proliferative retinopathy 5 years after initation of therapy. Patients treated with rabinizumab were 40% as likely to develop vision-impairing macular edema as those treataed with PRP. RCT, 5-year follow-up (184 participants -initial cohort size: 305).
~ Reviews ~
Shorter Duration of Antifungal Therapy More Effective in HIV-Associated Cryptococcal Meningitis
July 25th, Cochrane: 1 week of intravenous amphotericin B deoxycholate + oral flucytosine followed by 1 week of oral fluconazole was associated with lower 10-week mortality than guideline-recommended 2 weeks of IV amphotericin B deoxycholate + oral flucytosine. In circumstances where IV amphotericin is unavailable, a two week regimen of oral flucytosine + fluconazole may be comparably effective. Systematic review and meta-analysis (13 studies, 2426 participants).
Vancomycin + Pip-Tazo Associated with Increased Risk of Kidney Injury
July 27th, Annals of Emergency Medicine: Combination vancomycin and piperacillin-tazobactam was associated with a significantly higher risk acute kidney injury than vancomycin/piperacillin-tazobactam monotherapy, vancomycin + cefepime, or vancomycin + carbapenem combination therapy. Systematic review and meta-analysis (15 studies, 17 abstracts – 24,799 patients).
Link to study
Depression, Anti-Depressant Use Associated with Increased Venous Thromboembolic Risk
July 12, Annals of Medicine: Antidepressants of several classes were associated with a 12-59% increased risk of venous thromboembolism (VTE). Analysis of a subset of studies suggested a 31% higher risk of VTE in patients with depression, compared with those without depression, regardless of antidepressant use. Systematic review and meta-analysis (8 observational studies, 960,113 participants.)