Daily Respiratory Research Analysis
Three studies stand out today: an individual participant data meta-analysis of randomized trials shows JAK inhibitors reduce 28-day mortality in hospitalized COVID-19 patients across respiratory support levels; a large phase 3b trial confirms nirsevimab provides sustained 6‑month protection against infant RSV hospitalizations; and a double-blind phase 3 trial in China evaluates atezolizumab plus bevacizumab with chemotherapy for metastatic non-squamous NSCLC.
Summary
Three studies stand out today: an individual participant data meta-analysis of randomized trials shows JAK inhibitors reduce 28-day mortality in hospitalized COVID-19 patients across respiratory support levels; a large phase 3b trial confirms nirsevimab provides sustained 6‑month protection against infant RSV hospitalizations; and a double-blind phase 3 trial in China evaluates atezolizumab plus bevacizumab with chemotherapy for metastatic non-squamous NSCLC.
Research Themes
- Immunomodulators for severe viral respiratory illness
- Long-acting monoclonal prophylaxis against RSV in infants
- Chemo-immunotherapy combinations in metastatic lung cancer
Selected Articles
1. Effects of Janus kinase inhibitors in adults admitted to hospital due to COVID-19: a systematic review and individual participant data meta-analysis of randomised clinical trials.
Across 12 RCTs with 12,902 participants, JAK inhibitors reduced 28-day mortality versus no JAK inhibitor (adjusted OR 0.67), decreased the need for new mechanical ventilation/respiratory support, and shortened hospital stay by about one day. Serious and grade 3–4 adverse events were fewer with JAK inhibitors, with consistent benefits across ventilation strata and concomitant dexamethasone/tocilizumab use.
Impact: This IPD meta-analysis provides the most granular and robust evidence to date that JAK inhibitors improve survival in hospitalized COVID-19, informing guideline refinement beyond single-trial results.
Clinical Implications: JAK inhibitors (e.g., baricitinib, tofacitinib) can be considered across respiratory support levels in hospitalized COVID-19, independent of corticosteroid or IL-6 blockade, with acceptable safety. Hospitals should integrate JAK inhibitors into protocols while monitoring for evolving variants and standard-of-care changes.
Key Findings
- 28-day all-cause mortality reduced with JAK inhibitors vs. control (755/6465 vs. 805/6108; adjusted OR 0.67, 95% CI 0.55–0.82).
- Lower need for new mechanical ventilation/respiratory support and ~1 day faster hospital discharge with JAK inhibitors.
- Fewer grade 3–4 adverse events and serious adverse events in the JAK inhibitor group; similar rates of adverse events of special interest.
- No credible subgroup effect by ventilation status, comorbidities, timing, CRP, or concomitant dexamethasone/tocilizumab; age showed relative effect modification.
Methodological Strengths
- Individual participant data from 12 RCTs (12,902 patients) enabling harmonized adjustment and subgroup analyses.
- Predefined statistical approach with two-stage meta-analysis adjusting for age and respiratory support; comprehensive safety assessment.
Limitations
- Not all eligible trials provided IPD (12/16); heterogeneity in standard of care and pandemic waves.
- Study period (2020–2022) may limit applicability to future variants and evolving treatment backdrops.
Future Directions: Head-to-head comparisons among JAK inhibitors, optimal timing relative to steroids/IL-6 blockers, and evaluation in newer variant eras are needed, including cost-effectiveness analyses.
2. Atezolizumab plus bevacizumab and chemotherapy in metastatic nonsquamous NSCLC: the randomized double-blind phase 3 IMpower151 trial.
This double-blind, randomized phase 3 trial in China (N=305) compared atezolizumab+bevacizumab+chemotherapy versus bevacizumab+chemotherapy in metastatic non-squamous NSCLC, with investigator-assessed PFS as the primary endpoint. Most patients received pemetrexed (97%), and 53% had EGFR alterations; outcomes included PFS, OS, ORR, and DoR per RECIST v1.1.
Impact: Provides region-specific, double-blind phase 3 data for a globally used chemo-immunotherapy backbone in metastatic NSCLC, addressing pharmacogenomic and practice nuances in a Chinese population.
Clinical Implications: Results inform first-line regimen selection for metastatic non-squamous NSCLC in China, including in settings with a high prevalence of EGFR alterations, and support contextual adoption of atezolizumab+bevacizumab+chemotherapy.
Key Findings
- Randomized, double-blind phase 3 design with 305 chemotherapy-naive metastatic non-squamous NSCLC patients.
- Primary endpoint: investigator-assessed PFS; secondary endpoints included IRF PFS, OS, ORR, and DoR per RECIST v1.1.
- Treatment arms: ABCPem/Pac (atezolizumab+bevacizumab+carboplatin with paclitaxel or pemetrexed) vs. BCPem/Pac (placebo+bevacizumab+carboplatin with paclitaxel or pemetrexed).
- Population characteristics: 97% received pemetrexed; 53% had EGFR alterations (as reported).
Methodological Strengths
- Double-blind, randomized, controlled phase 3 design addressing a defined regional population.
- Pre-specified efficacy endpoints with independent review facility assessment.
Limitations
- Abstract provides limited efficacy results (no PFS/OS effect sizes reported in the provided text).
- Single-country population may limit global generalizability; high EGFR prevalence may influence treatment effects.
Future Directions: Full efficacy and biomarker subgroup results (e.g., EGFR status) and safety profile are needed to guide tailored first-line strategies; comparative effectiveness versus other immunotherapy combinations in Asian populations would be informative.
3. 180-day efficacy of nirsevimab against hospitalisation for respiratory syncytial virus lower respiratory tract infections in infants (HARMONIE): a randomised, controlled, phase 3b trial.
Among 8057 infants randomized, nirsevimab reduced RSV LRTI hospitalizations through 180 days (0.3% vs 1.7%; efficacy 82.7%, 95% CI 67.8–91.5; p<0.0001). Safety over 365 days showed no apparent concerns; most adverse events were grade 1–2 and similar to standard care.
Impact: Demonstrates sustained 6‑month protection from a single dose of nirsevimab, extending beyond a typical RSV season, and supporting flexible real-world implementation for infant RSV prevention.
Clinical Implications: Supports single-dose nirsevimab prophylaxis ahead of or during the first RSV season, with efficacy persisting to 180 days and a reassuring safety profile—informing national rollout timing and inventory planning.
Key Findings
- Randomized 1:1 open-label phase 3b design across France, Germany, and the UK (N=8057 infants).
- RSV LRTI hospitalization to 180 days: 0.3% (12/4038) with nirsevimab vs 1.7% (68/4019) with standard care; efficacy 82.7% (95% CI 67.8–91.5).
- Safety up to 365 days showed predominantly grade 1–2 adverse events with no apparent safety concerns.
Methodological Strengths
- Large, multicountry randomized controlled design with stratified randomization by country and age.
- Assessment of extended efficacy (180 days) and long-term safety (365 days).
Limitations
- Open-label design may introduce performance/ascertainment bias, though hospitalization is a hard endpoint.
- Generalizability to extremely preterm infants (<29 weeks GA) not addressed in this analysis.
Future Directions: Evaluate impact on RSV healthcare utilization beyond hospitalization (e.g., ED visits), effectiveness in subgroups (e.g., high-risk infants), and programmatic cost-effectiveness across seasons.