Clinical Trials – New Horizons
~ Pharmacology News ~
FDA Expands Indication for Cystic Fibrosis Combo Drug
August 8th, FDA: The United States FDA has expanded the indication of the cystic fibrosis drug Orkambi (lumacaftor/ivacaftor combination) to include children aged 2+ with homozygous Δ508 CFTR mutations. The drug was previously approved for patients aged 12+ with two copies of the Δ508 variant.
FDA Approves First Anti-CCR4 Antibody Drug for Sézary, Mycosis Fungoides
August 8th, FDA: The US FDA has approved mogamulizumab, an anti-CCR4 humanized monoclonal antibody, for the treatment of the rare non-Hodgkin lymphomas Sézary syndrome and mycosis fungoides.
FDA Panel Recommends Omadacycline, Novel Antibiotic for Skin Infections and Pneumonia
August 10th, FDA: An FDA advisory panel has voted to recommend a novel antibiotic, the first-in-class aminomethylcycline drug omadacycline, for the treatment of acute bacterial skin infections and community-acquired bacterial pneumonia. Omadacycline is structurally related to tetracycline antibiotics.
FDA Rejects Abuse-Deterrent Oxycodone Formulation
August 6th, FDA: Following a 14-to-3 advisory panel vote against recommending Remoxy ER (an extended-release abuse-deterrent formulation of the opioid drug oxycodone) the US FDA has rejected the New Drug Application for use of the product in the treatment of severe pain.
Opioids After Tooth Extraction Associated with Higher Risk of Persistent Opioid Use
August 7th, JAMA: Patients who received and filled opioid prescriptions following wisdom tooth extraction were more likely to develop persistent opioid use than patients who did not fill perioperative opioid prescriptions. Older age was associated with higher risk of developing persistent opioid use. Observational retrospective (70,942 patient records).
Fewer Opioids Prescribed When Providers Informed of Patient’s Fatal Overdose
August 10th, Science: Clinicians who were notified of a patient’s fatal opioid-related overdose prescribed 9.7% fewer milligram morphine equivalents over 3 months compared with clinicians who did not receive a patient death notification. RCT (861 clinicians, 170 overdoses).
Opioid Use Disorder Rate at Delivery Quadrupled Between 1999 and 2014
August 10th, CDC: The rate of opioid use disorder documented during delivery hospitalization in the United States increased 4-fold between 1999 and 2014. In West Virginia and Vermont the prevalence of neonatal abstinence syndrome was estimated to have risen to >3% during this period.
Methylphenidate Formulation Dosed in Evening Approved by FDA for ADHD
August 9th, Ironshore Pharmaceuticals: A methylphenidate formulation that is dosed once-daily in the evening has been approved by the FDA for use in patients 6 years and older with ADHD.
FDA Approves Migalastat, First Oral Drug for Treatment of Fabry Disease
August 10th, FDA: The US FDA has approved migalastat (Galafold), an orally available novel alpha-galactosidase A (α-GalA) modulator/chaperone for the treatment of patients with variants of Fabry disease whose α-GalA genes have mutations expected to be amenable to the drug.
FDA Approves Combination Hormonal Contraceptive Vaginal Ring
August 10th, FDA: The US FDA has approved the use of the Annovera (combination segesterone acetate and ethinyl estradiol) vaginal ring as a hormonal contraceptive option with a duration of efficacy of up to one year.
FDA Approves First RNAi Agent Patisiran for Treatment of Hereditary Transthyretin Amyloidosis
August 10th, FDA: The US FDA has approved patisiran, an siRNA agent that inhibits translation of transthyretin protein, for the treatment of polyneuropathy in patients with hereditary transthyretin amyloidosis. It is the first RNA interference-based therapeutic to be approved by the FDA.
~ Clinical Trials: New Horizons ~
Anlotinib Extends Survival as Third-Line Agent in Lung Cancer
August 9th, JAMA Oncology: In patients with advanced non-small-cell lung cancer who experienced cancer progression following second-line therapy, administration of the novel tyrosine kinase inhibitor anlotinib was associated with a 3 month longer overall survival than placebo. RCT (439 patients).
Acupuncture Associated with Less Drug-Related Joint Pain in Women with Breast Cancer
July 10th, JAMA: In women with hormone-sensitive early-stage breast cancer who have joint pain related to the aromatase inhibitors anastrozole, exemestane, or letrozole, 12 sessions of true acupuncture over 6 weeks was associated with less joint pain than sham acupuncture. RCT (226 patients).
Moyeam Tea Associated with Short-Term Improvements in Glycemic Control, Renal Parameters in Type II Diabetes
August 8th, EJCN: In patients with type II diabetes mellitus, 1 month of ampelopsis grossedentata (moyeam, putative active ingredient: dihydromyricetin flavonoid) was associated with decreased levels of fasting plasma glucose, glycated albumin, cystatin C, compared with those who were given placebo tea. RCT (70 patients).
Risankizumab Demonstrates Superiority to Placebo, Ustekinumab in Plaque Psoriasis
August 7th, The Lancet: In patients with moderate-severe chronic plaque psoriasis, risankizumab (a monoclonal antibody against IL-23) was found to be superior in reducing symptom severity to ustekinumab (a monoclonal antibody against IL-23/IL-12) and placebo, with similar safety considerations. Risankizumab was associated with a 90% improvement in the psoriasis area severity index in 75% of patients compared with <50% taking ustekinumab and <5% taking placebo. 2 double-blind RCTs, UltIMMa-1/UltIMMa-2 trials (997 patients).
Mogamulizumab Demonstrates Efficacy in Cutaneous T-Cell Lymphomas
August 9th, The Lancet: Mogamulizumab, a novel anti-CCR4 humanized monoclonal antibody, has demonstrated efficacy in the treatment of refractory cutaneous T-cell lymphoma (mycosis fungoides or Sézary syndrome), extending progression-free survival by three months compared to the current standard-of-care, the histone deacetylase inhibitor vorinostat. Open-label RCT, Phase III MAVORIC trial (372 patients).
~ Clinical Research ~
Hydrochlorothiazide Use Associated with Higher Risk of Melanoma
August 6th, JAMA Internal Medicine: Patients who were hydrochlorothiazide (HCTZ) were more likely to develop melanomas than those who used other thiazide diuretics or antihypertensive medications, with an odds ratio of 1.22 for high-users (>50,000 mg cumulative dose) compared with never-users. Observational retrospective (19 273 melanoma cases, 192 730 population controls).
More Overuse of VTE Prophylaxis than Underuse
August 6th, JAMA Internal Medicine: Excessive VTE prophylaxis (prophylaxis for low-risk patient, inappropriate prophylaxis in high-risk patients, or combo pharmacologic and mechanical prophylais in any patient) was observed in 65.3% of hospitalized patients. Conversely, VTE prophylaxis was underused (defined no pharmacologic prophylaxis in high-risk patients without a contraindication to anticoagulation or absent prophylaxis in high-risk patients with a contraindication to anticoagulation) in 22% of patients. Observational (44 775 patients).
Maternal Vitamin D Supplementation Not Associated with Improved Infant Growth
August 9th, NEJM: Vitamin D supplementation starting in the last half of pregnancy and continued until 6 months post-partum was not associated with any improvement in infant growth compared with no Vitamin D supplementation. RCT (1164 infants).
1 Week Continuous Epidural Lidocaine Infusion Associated with Sustained Herpes Zoster Pain Relief
August 9th, Journal Medicine: 1 week of continuous 2% epidural lidocaine infusion was associated with greater sustained pain relief and quality of life than medical therapy (e.g. gabapentinoids, opioids, tramadol) for up to 3 months following onset of rash in patients with lumbar or thoracic herpes zoster. Observational retrospective (256 patients).
Phenylephrine Increases Bupivacaine Necessary In Spinal Anesthesia During C-Section
August 9th, Journal Medicine: Adjuvant phenylephrine increased the ED50 of intrathecal (spinal) bupivacaine by nearly 30% in women receiving mixed bupivacaine/sufentanil spinal anesthesia during C-section. Phenylephrine also significantly decreased the frequency of hypotension.
RCT (60 patients).
Glycopyrrolate Premedication Associated with Faster, Easier Intubations
August 9th, Journal Medicine: Intramuscular glycopyrrolate injection was associated with higher laryngeal view grades and shorter intubation times, compared with no glycopyrrolate injection, in patients undergoing rigid video-stylet endotracheal intubation. RCT (78 patients).
Anticoagulation of Subsegmental Pulmonary Embolism Associated with Adverse Events
July 30th, JAMA Internal Medicine: Patients with CT angiography results positive for subsegmental (distal & small) pulmonary embolism, were as likely to be anticoagulated as patients who had more proximal embolisms. In the three months after initiation of anticoagulation, 42% of patients with subsegmental pulmonary embolism were readmitted or visited the ED for reasons unrelated to venous thromboembolism (most often bleeding). Retrospective observational (222 patients).
Inhaled Ipratropium May Lower Risk of Acute Mountain Sickness
August 9th, Journal Medicine: Inhaled combination ipratropium bromide/salbutamol sulfate lowered the risk of acute mountain sickness by more than half and was superior to inhaled budesonide and inhaled salbutamol sulfate monotherapy in decreasing the incidence and severity of acute mountain sickness. RCT (122 participants).
Rituximab Provides Prolonged Response in Splenic Lymphoma
August 10th, Journal Blood: Maintenance treatment of splenic marginal zone lymphoma with rituximab, an anti-CD20 monoclonal antibody, resulted in an overall 10-year survival rate of 85%, with 64% experiencing freedom from progression. Not controlled, interventional (108 patients).
Tobacco Smoke Exposure Associated with Higher Risk of Urgent Care & Emergency Room Visits in Adolescents
August 8th, Pediatrics: Adolescents who were exposed to tobacco smoke (e.g., by living with someone who smokes in the home) were found to have higher rates of shortness of breath, finding it hard to exercise, wheezing during or after exercise, and dry cough at night and were approximately 14% more likely to have visited the emergency room or urgent care than adolescents who were not exposed to tobacco. Observational, survey (7,389 adolescents).
Cigarette, E-Cigarette, Hookah Associated with Later Marijuana Use Among Adolescents
August 8th, Pediatrics: Among adolescents who had who reported never having used marijuana, those who had used hookah, cigarettes, or e-cigarettes were significantly more likely to report marijuana 24 months later compared with adolescents who did not report use of these products. Observational, survey (2,668 participants).
Propranolol Associated with Improved Outcomes in Infantile Hemangioma
August 8th, Pediatrics: Twice-daily oral propranolol therapy for 6-12 months was associated improved lesion resolution and decreased functional impact in 76% of patients treated for infantile hemangiomas. Single-arm, interventional prospective (43 patients).
DPP-4 Inhibitors May Increase Risk of Bullous Pemphigoid
August 8th , JAMA Dermatology: Diabetic patients who used dipeptidyl-peptidase 4 (DPP-4) inhibitors vildagliptin and linagliptin appeared to have a higher risk of developing bullous pemphigoid than patients with diabetes who did not use DPP-4 inhibitors. Observational retrospective (82 patients).
Mirtazapine Not Better Than Placebo in Fibromyalgia
August 6th, Cochrane: 15 -45 mg of oral mirtazapine, an atypical antidepressant medication, did not substantially reduce pain in people with fibromyalgia compared with placebo. Systematic review and meta-analysis (3 studies, 606 participants).
Medication-Assisted Treatment for Opioid Use Disorder Decreases Mortality Post-Overdose
August 7th, Annals of Internal Medicine: Following non-fatal opioid overdose, patients who received medications for opioid use disorder had significantly lower 12-month mortality (37% lower all-cause mortality risk with buprenorphine, 53% on methadone management), compared with individuals who did not use medications for opioid use disorder. Retrospective observational (17,568 patients).
HIV Transmission Rates Low Among Serodiscordant Male Couples with Low Viral Loads
July 16th, The Lancet HIV: In male couples with HIV serodiscordance, adherence to antiretroviral therapy with viral loads <200 copies/mL was associated with very low HIV transmission rates even when the uninfected partner was not using pre-exposure prophylactic medications. Observational prospective (343 couples).
Tiotropium Associated with Higher Risk of Cardiovascular Events in Patients with COPD
August 10th, Mayo Proceedings: Newly added inhaled tiotropium (an antimuscarinic agent) to long-acting beta agonist & inhaled corticosteroid therapy in patients with COPD was associated with a 88% higher risk of severe cardiovascular events compared with patients who did not intitiate tiotropium add-on therapy. Observational retrospective (65,966 patients).
~ Reviews ~
Tranexamic Acid Decreases Intraoperative Bleeding During Rhinoplasty
August 9th, JAMA Otolaryngology: Tranexamic acid was associated with lower volumes of intraoperative bleeding and decreased eyelid edema and ecchymosis compared with no tranexamic administration in patients undergoing rhinoplasty. Systematic review and meta-analysis (5 RCTs, 276 patients).
Lenalidomide Maintenance Therapy Associated with Highest Survival in Multiple Myeloma
August 9th, JAMA Oncology: Lenalidomide monotherapy was associated with higher overall survival and progression free survival than thalidomide-bortezomib and bortezomib-prednisone, lenalidomide-prednisone, and other agents in patients receiving maintenance therapy following newly diagnosed multiple myeloma. Systematic review and meta-analysis (11 trials, 5073 patients).
Tacrolimus, Infliximab Similarly Effective in Ulcerative Colitis Maintenance Therapy
August 9th, Journal Medicine: In patients with moderate-severe steroid refractory ulcerative colitis, tacrolimus (a calcineurin inhibitor) and infliximab (an anti-TNF-alpha monoclonal antibody) were found to have similar short-term clinical response rates, clinical remission rates, and three month colectomy rates when used as maintenance therapy. Systematic review and meta-analysis (1 RCT, 5 retrospective obseravational, 438 cases).
Antenatal Corticosteroids Associated with Lower Risk of Respiratory Distress Following Term C-Sections
August 3rd, Cochrane: Infant born to women undergoing elective C-sections at term who received antenatal maternal betamethasone or dexamethasone were found to have an approximately 50% lower risk of neonatal respiratory distress syndrome compared with infants whose mothers did not receive antenatal corticosteroids. Systematic review and meta-analysis (4 RCTs, 3956 women and 3893 babies).
Weight Loss, Vitamin D Supplementation May Decrease Psoriasis Severity
August 9th, JAMA Dermatology: Weight loss and vitamin D supplementation were weakly associated with a reduction in disease severity in patients with psoriasis and psoriatic arthritis. Systematic review and meta-analysis (55 trials, primarily observational, 77,557 participants, 4,534 with psoriasis).
Methylphenidate Most Effective For ADHD in Children, Amphetamines Best Choice in Adults
August 7th, The Lancet Psychiatry: Methylphenidate appears to be the most effective medication (compared with atomoxetine, bupropion, clonidine, guanfacine, and modafinil) for reducing ADHD symptoms in children when evaluated by both clinicians and teachers. In adults with ADHD, amphetamines were found have superior efficacy to methylphenidate, bupropion, atomoxetine, and placebo. Systematic review and meta-analysis (133 RCTs, 10,068 children & 8,131 adults).
Progestogens May Decrease Spontaneous Miscarriage
August 6th, Cochrane: Treatment with progestogens, medications that mimic the action of the sex hormone progesterone, was associated with lower rates of spontaneous miscarriage in women with threatened miscarriage, but may not decrease the overall number of pre-term deliveries. Systematic review and meta-analysis (7 RCTs, 696 women).