Pharmacology News Round-Up: June 21st, 2018

This week’s clinical pharmacology highlights include advances in cancer therapy, long-term followup of the landmark PROACT trial comparing anticoagulation strategies after aortic replacement, and the finding that hydrocortisone may not reduce mortality in septic shock.

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Pharmacology News 

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Ketamine Guidelines for Acute Pain

  • June 7th:  For the first time, consensus guidelines for the treatment of acute pain with ketamine have been developed by leading pain medicine organizations, including the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists’ Committees on Pain Medicine.

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Cannabis-Related Policy Changes in Portugal & Canada

  • June 15-20th:  Portugal recently legalized the sale and production of medical cannabis products and Canada has decriminalized cannabis possession and recreational use.

 

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Clinical Trials – New Horizons 

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Trifluridine & Tipiracil – Gastric Cancer

  • June 21st, ESMO Conference: A phase III trial of Lonsurf® (trifluridine & tipiracil combination) for patients with treatment-refractory metastatic gastric cancer demonstrated a 31% mortality risk reduction during the study (median survival increased by 2 months) compared with placebo. Randomized-placebo controlled.

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Ramucirumab – Hepatocellular Carcinoma

  • June 21st, WCGC Conference: A pooled analysis of two phase III RCTs suggests that the new VEGF-2 inhibitor ramucirumab is effective in patients with high serum AFP (>400 ng/mL, associated with poor outcomes), extending median survival by 3 months compared with placebo.  Pooled RCTs.

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Tisagenlecleucel – Diffuse Large B-Cell Lymphoma

  • June 16th, EHA Conference: 14-month follow-up of the phase II JULIET study evaluating the efficacy of the CAR-T cell gene therapy tisagenlecleucel has demonstrated a durable treatment effect, with 83% of the patients who experienced a complete initial response remained in remission after 1 year (1 of 3 patients overall).  Tisagenlecleucel is FDA approved for refractory DLBCL and acute lymphoblastic leukemia.  Single-arm interventional, open-label.

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Obinutuzumab – Chronic Lymphocytic Leukemia

  • June 15th, EHA Conference: 5-year follow-up of a phase III RCT of 901 patients with CLL comparing anti-CD20 therapies obinutuzumab and rituximab in combination with the DNA cross-linking chemotherapeutic chlorambucil has found that 5-year survival in the obinutuzumab/chlorambucil group was significantly higher (66%) than in the rituximab/chlorambucil group (57%).  Randomized, open-label.

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Ibrutinib – Waldenström’s Macroglobulinemia

  • June 21st, NEJM: The phase III iNNOVATE clinical trial of the Bruton kinase inhibitor ibrutinib (+ rituximab) in the treatment of Waldenström’s Macroglobulinemia, a rare B-cell lymphoma, has found that the 30-month progression-free survival rate was 82% with ibrutinib–rituximab versus 28% with placebo–rituximab.  Randomized placebo-controlled.

 

 

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Clinical Pharmacology Research

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Rituximab – Nephrotic Syndrome

  • June 18th, JAMA Pediatrics:  A randomized, open-label clinical study of children with corticoid-dependent nephrotic syndrome (a severe chronic or relapsing form of idiopathic nephrotic syndrome) found that the 2nd-line anti-B cell therapy rituximab is more effective than the first-line calcineurin inhibitor tacrolimus in minimizing corticosteroid exposure and facilitating disease remission. Randomized controlled.

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Canagliflozin – Renoprotection in T2DM

  • June 21st, The Lancet: The CANVAS program, based on two randomized trials of the SGLT2 inhibitor canagliflozin in the treatment of 10,142 participants with type 2 diabetes, has found that canagliflozin is associated with slower decline of eGFR and a reduction in albuminuria, although the total number of major adverse kidney-related events was similar in treatment and placebo groups.  Randomized placebo-controlled.

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Tamsulosin – Nephrolithiasis

  • June 19th, JAMA Internal Medicine: A randomized-controlled study of 512 adults with symptomatic ureteral stones < 9mm on CT found that tamsulosin did not signifantly increase the stone passage rate relative to placebo, suggesting that guidelines for medical expulsive therapy may require revision.  Randomized-controlled.

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Methadone vs. Morphine – Neonatal Abstinence Syndrome

  • June 18th, JAMA Pediatrics:  A study comparing Q4h methadone to morphine for 117 patients experiencing neonatal abstinence syndrome found that methadone treatment was associated with a shorter hospital length of stay (effect size ~3 days).  Randomized controlled.

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Methadone, Naltrexone, Buprenorphine – Opioid Use Disorder

  • June 19th, Annals of Internal Medicine: A retrospective study of 17,568 patients who experienced opioid overdose found that fewer than 1 in 3 received medications for opioid use disorder (methadone, naltrexone, or buprenorphine).  Those who did receive these medications had a lower risk of mortality 12 months after their initial overdose.  Retrospective Cohort.

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Opioids vs. Non-Opioids – Osteoarthritis Pain

  • June 19th, Annals of Internal Medicine: A randomized-controlled study of 240 patients with chronic back, hip, or knee osteoarthritis pain found that opioids and non-opioids (acetaminophen/NSAIDs/topicals/tramadol/pregabalin/duloxetine) had similar efficacy in controlling pain levels over 12 months.  Opioids were associated with an increased rate of adverse effects.  Randomized-controlled.

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NSAIDs – Osteoarthritis & Ischemic Heart Disease

  • June 14th, EULAR Conference: A study of 7743 people with osteoarthritis and 23,229 people without osteoarthritis from administrative health records in Canada has found that NSAID use nearly doubled the risk of ischemic heart disease in patients with osteoarthritis compared to individuals without osteoarthritis who were not prescribed NSAIDs.  Retrospective Cohort.

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Dopamine Agonists – Parkinson’s Disease

  • June 20th, Neurology: A longitudinal cohort study of 411 patients found that use of dopamine agonists (DA) for the treatment of Parkinson’s Disease was associated with an increased risk of developing impulse control disorders (ICD).  Individuals who had been exposed to DA had a 51% likelihood of developing ICD, compared with 5% of DA never-users.  Observational, Prospective Cohort.

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Low-Dose Warfarin + Aspirin – Mechanical Heart Valve

  • June 19th, JACC: 9-year followup of the PROACT trial showed that stepping down warfarin dose (+aspirin) 90 days after aortic valve replacement with the On-X replacement system resulted in 50% fewer bleeding episodes – and comparable reduction in thromboembolism – as standard-dose warfarin (+aspirin) therapy.  Randomized active-controlled.

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Glucocorticoids – Asthma

  • June 19th, Annals of Internal Medicine: A randomized-controlled study of 1114 patients experiencing deteriorating asthma control who self-administered an increased bronchodilator dose and quadrupled the dose of inhaled glucocorticoid until symptom resolution were less likely to experience severe asthma exacerbations requiring systemic corticosteroids.

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Hydrocortisone – Septic Shock

  • June 19th, Annals of Internal Medicine: A randomized-controlled study of 3800 patients with suspected septic shock found that continuous IV hydrocortisone for up to 7 days did not reduce 90-day mortality.  Randomized-controlled.

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Vitamin D – Colorectal Cancer

  • June 14th, JNCI: A pooled cohort study of 5706 individuals with colorectal cancer  and 7107 control participants found that high levels (75-100 nmol/L)  of 25-(OH)-Vitamin D are associated with a decreased colorectal cancer risk in women.  Pooled prospective cohort.

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Sodium Thiosulfate – Cisplatin-Induced Hearing Loss

  • June 21st, NEJM: The SIOPAL-6 study of has found that children with hepatoblastoma treated with cisplatin were 46% less likely to develop hearing loss when treated with intravenous sodium thiosulfate, a hearing protectant, 6 hours after cisplatin infusion. Randomized-controlled.

 

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Reviews

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Donepezil – Alzheimer’s Disease

  • June 18th, Cochrane: A meta-analysis of 30 studies and 8257 participants has found moderate-quality evidence that 12-24 weeks of donepezil therapy in mild, moderate, and severe Alzheimer’s Disease (AD) results in some benefits in cognitive function and ADLs.  Cost estimates suggest that donepezil treatment does not increase overall healthcare costs in patients with AD.  Meta-Analysis.

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Anticoagulation – Cancer & VTE

  • June 18th, Cochrane: A review of 16 trials enrolling 5167 participants with cancer and evidence of venous thromboembolism has found that DOACs > LMWH > VKA in preventing future VTE, although DOACs were associated with an increased risk of major bleeding events.  Meta-Analysis.

 

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