Digest 45: Not a BORE, at all

September 16, 2023 | By

The Curbsiders Digest

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Issue 45


Appetizers (to whet your appetite) 

Palate Cleanser (aka the melon part of the meal) 

The Main Course

A Digestif or two


Brought to you hot off the stove, from a variety of specialties. Delivered in super tasty, bite-sized morsels. 
Jen Desalvo MD; Beth Garbitelli MD; Alyssa Mancini MD

  • A new vaccine has joined the anti-pneumonia ranks, to prevent Respiratory Syncytial Virus (RSV) infections in adults >60.  The FDA recently granted approval for two vaccines to prevent RSV-associated lower respiratory tract disease in adults >60.  RENOIR, a multicenter, phase 3, double-blind study published in NEJM randomized >34,000 adults aged ≥60 (excluding the immunocompromised) to receive a single intramuscular injection of a bivalent RSV prefusion F protein-based vaccine (RSVpreF, by Pfizer) or placebo. Adults who received RSVpreF had significantly lower rates of RSV-associated lower respiratory illness with multiple symptoms, with a vaccine efficacy of 67-86% (higher efficacy for prevention of severe illness), with similar rates of adverse systemic events to placebo. The trial of RSVPreF3 (GSK) demonstrated similar efficacy. Both had very low rates (but several cases) of inflammatory neurologic events, with postmarketing surveillance to follow. The CDC has recommended that adults > 60 may receive a dose of either RSVpreF and RSVPreF3, using shared clinical decision-making. (JD) 
  • Another viral hit? The FDA just approved the RSVpreF vaccine prenatally, between 32 and 36 weeks gestation, to prevent RSV in infants.  MATISSE, a phase 3, multinational, double-blind trial published in NEJM investigated the efficacy of Pfizer’s bivalent RSVpreF vaccine in >7,000 pregnant women at 24-36 weeks gestational age (excluding high-risk pregnancies), randomizing women to receive the vaccine or placebo. Infants born to women who received the vaccine had lower incidence of severe medically attended lower respiratory tract illnesses after birth, with vaccine efficacy of 81.8% at 90 days and 69% at 180 days. There were similar rates of adverse events reported in both groups, though slightly higher preterm birth numbers with RSVpreF, leading to the recommendation for administration after 32 weeks, with postmarketing surveillance to come. (JD) 
  • That’s Heavy –  Recent evaluation from Environmental Health Perspectives funded by NIH offers a blunt assessment of heavy metal exposure risks associated with marijuana consumption. Researchers evaluated > 7000 participants of the National Health and Nutrition Examination Survey (2005-2018) and found that marijuana users had significantly higher lead and cadmium levels in both the blood and urine, compared to non-marijuana/non-tobacco users. Levels of both cadmium and lead were higher in those with more recent marijuana exposure. Cannabis plants are known hyperaccumulators of metals, fertilizers, and pesticides. Besides risks from unfiltered smoke and unregulated cannabis growth practices, the authors also highlighted concerns that vape devices have demonstrated metal leaching in some studies. (BG) 
  • Results are in–a REPRIEVE in CAD. We first reported on REPRIEVE in Digest #41, after a planned interim analysis demonstrated a lower risk of cardiovascular disease in individuals with HIV with pitavastatin than placebo.  NEJM has now published the phase 3 trial results, which included 7769 adults (median age 50) with HIV infection on antiretroviral therapy and a low-to-moderate risk of cardiovascular disease. Participants were randomized to pitavastatin 4 mg daily or placebo. The trial was stopped early for efficacy after 5.1 years median follow-up, with an incidence of major adverse cardiovascular events of 4.81 / 1000 person-years with pitavastatin and 7.32 / 1000 person-years with placebo (HR 0.65, 95% CI 0.48-0.90, p=0.002). There were similar rates of adverse events in both groups, with higher rates of myalgias with pitavastatin. (AM) 
  • Psychedelic psilocybin for Major Depressive Disorder (MDD)? JAMA recently published results of a phase 2 randomized control trial of 104 adults (mean age 41.1 years, 50% women) with a diagnosis of moderate-severity MDD, randomizing patients to receive a single 25 mg capsule of psilocybin or niacin placebo, plus psychological support. Psilocybin treatment was associated with significantly reduced Montgomery-Asberg Depression Rating Scale (MADRS) scores compared with placebo from baseline to day 43 (mean difference -12.3; 95% CI -17.5 to -7.2), with differences apparent by day 8 and numerically more sustained responses among those receiving psilocybin. Adverse events occurred more frequently with psilocybin, including illusion, headache, or panic attack/paranoia in 4/50 participants. (AM) 

Palate Cleanser

The melon part. To get rid of the taste of those pesky apps.  And to fill your brain with some fun facts.

This issue, we’re highlighting The Retrievals, the remarkably disturbing exposé of a fertility clinic where patients underwent egg retrievals with little to no pain control. Yes, you read that right. Fentanyl, illegally swapped for saline, for women undergoing invasive fertility procedures. The story involves drug diversion by a staff member, healthcare workers and institutions that failed to protect or listen to their patients, and most importantly, patient stories. It’s heartbreaking and riveting, fascinating and horrifying, especially but not only if you work in healthcare–and only 5 episodes long. 

– Nora Taranto MD

The Main Course

Cyrus Askin MD

COPD & Dupilumab:

A “New Hope” in Patients with Peripheral Eosinophilia?
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Standard treatments include bronchodilators – primarily for symptom relief – along with other interventions such as supplemental oxygen, pulmonary physical therapy, and airway anti-inflammatories such as roflumilast and azithromycin. In certain cases, corticosteroids – both inhaled and systemic – demonstrate efficacy. The patients who benefit from steroids often fall closer to asthma on the “asthma-COPD spectrum” than your classic COPD patient who does not have a significant symptomatic response to steroids. 

Recent translational studies have tested physiologic hypotheses to account for the differences in steroid responsiveness in patients with COPD, including quantification of airway smooth muscle in the HISTORIC trial and assessment of different inflammatory mediators (such as IL-4, IL-5, IL-13) present in type 2 inflammation that cause increases in eosinophils and overactivation of the immune system, and which may be present in a substantial proportion of patients with COPD.  These inflammatory mediators have been found to be useful targets in allergic-type asthma with overactive Type 2 Inflammation. But up until now, there has been little data supporting the use of biologics targeting inflammatory mediators to augment traditional COPD therapy. This may finally be changing in the face of the BOREAS Trial.   

 Breaking it Down 

The BOREAS randomized clinical trial evaluated the efficacy of dupilumab – a monoclonal antibody that blocks Type-2 inflammation by blocking a shared receptor component of IL-4 and IL-13 – in COPD patients with persistent airway inflammation despite triple inhaler therapy (LABA, LAMA, ICS). This blinded, multi-center RCT included nearly 1000 symptomatic patients with COPD who had multiple moderate exacerbations over the prior year requiring systemic steroids, and who had a blood eosinophil count > 300/microliter at screening. Patients were randomized to receive subcutaneous dupilumab 300 mg or placebo every 2 weeks, in addition to current COPD therapies. The primary endpoint in this study was the annualized rate of moderate exacerbations (requiring glucocorticoids, antibiotics, or both) and severe exacerbations (requiring emergency visit or hospitalization). Patients treated with dupilumab were significantly less likely to have a moderate or severe exacerbation than those treated with placebo (rate ratio 0.7, CI 0.58 – 0.86, p<0.001). Secondary endpoints, such as objective improvements in lung function and patient reported symptom improvement, were also significantly better in those treated with dupilumab than those given placebo – all without an increase in adverse events. The authors also looked at a subgroup of patients with elevated FeNO levels suggesting active airway-specific inflammation and saw an even more significant improvement in lung function in that subpopulation. 

What does it mean? 

The BOREAS trial was a well-powered and elegantly designed study, providing a new hope in the battle against COPD. Traditionally, clinicians have been relegated primarily to corticosteroids to mitigate inflammation in COPD with eosinophilia, which can be challenging in multi-morbid patients. It is worth noting the significant underrepresentation of Black individuals in the trial, and the overall lower than anticipated incidence of exacerbations in the trial (perhaps in the setting of the trial occuring during the pandemic). But overall, this phase-3 clinical trial may very well change practice. It provides an evidence-based, anti-inflammatory biologic agent to turn to in at least some COPD subtypes, with a favorable side effect profile and demonstrable efficacy–both in terms of lung function and patient-centered outcomes that often fail to achieve significance. 

Read The Trial Results HERE


Before you go….
we’ve got a few nibbles!

Consolidate your learning with a Quiz!  

This week on The Curbsiders: This week, check out the DIGEST episode debut! Episode #407 covered content from our two prior digests in even more juicy detail. We’ve got Zuraonlone, alpha-gal, orforgliipron, bempedoic acid, and kiwis–all you could want and more. 

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The Curbsiders Digest

Issue 45

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures: Cyrus Askin, Beth Garbitelli,  Alyssa Mancini, Jennifer Desalvo, and Nora Taranto report no disclosures. 

Kate Grant reports no disclosures 


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Episode Credits

The Curbsiders Digest

Issue 45

Editor in Chief: Nora Taranto MD

Banner: Kate Grant  MBChB, DipGUMed

Disclosures: Cyrus Askin, Beth Garbitelli,  Alyssa Mancini, Jennifer Desalvo, and Nora Taranto report no disclosures. 

Kate Grant reports no disclosures

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