Trial reportThe European respiratory journal2025
A phase 2a trial of the IL-33 monoclonal antibody tozorakimab in patients with COPD: FRONTIER-4.
Trial report in The European respiratory journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04631016 (A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of MEDI3506 in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis), which is not on this map. Cited by 48 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety and Tolerability of MEDI3506 in Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis (FRONTIER 4)
Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Biologic therapies targeting type 2 inflammation in chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomised controlled trials.BMJ open respiratory research · 2026Pooled it
- Efficacy of Biologics in Patients with Moderate to Very Severe COPD: A Systematic Review.International journal of chronic obstructive pulmonary disease · 2026Pooled it
- Article
- Antibodies to watch in 2026.mAbs · 2026Review
- Interleukin-33 and its receptor: multifaceted roles and emerging therapeutic potential.Nature reviews. Immunology · 2026Review
- COPD Biologics: Right Patient, Right Pathway, Right Time.Pulmonary therapy · 2026Review
- Advances in the treatment of eosinophilic granulomatosis with polyangiitis.Nature reviews. Rheumatology · 2026Review
- Airway mucus plugs in asthma and chronic obstructive pulmonary disease: pathobiology, imaging, and implications for clinical trials.American journal of respiratory and critical care medicine · 2026Review
- Association of Airway Mucus Plugs and Physical Activity, Exercise Tolerance, Sarcopenia, and Frailty in Patients With COPD and Pre-COPD.Respirology (Carlton, Vic.) · 2026Observational
- Biologics in Older Adults with Chronic Obstructive Pulmonary Disease: A Narrative Review.Journal of clinical medicine · 2026Review
- Imaging endpoints for biologic therapy in chronic obstructive pulmonary disease.The British journal of radiology · 2026Review
- Review
- Advances in targeting IL-1 family cytokines for the treatment of inflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Phase III LUNA clinical programme: design of four randomised, double-blind, placebo-controlled studies assessing the efficacy and safety of tozorakimab in patients with symptomatic COPD and a high risk of exacerbations.BMJ open respiratory research · 2026Article
- Targeting IL-33 in COPD: mechanistic lessons from clinical trials and the path forward.Respiratory research · 2026Review
- Beyond Triple Therapy: Anti-Type 2 Biologic Therapies for Eosinophilic COPD and Respiratory Comorbidities - a Review of Clinical Evidence.Current allergy and asthma reports · 2026Review
- Imaging in Chronic Obstructive Pulmonary Disease: Ready for Prime Time?Tuberculosis and respiratory diseases · 2026Article
- Biologics in Chronic Obstructive Pulmonary Disease: Current Status and Future Prospects.Tuberculosis and respiratory diseases · 2026Article
- Mucus Plugs and Eosinophilic Inflammation: Expanding the Paradigm to COPD.The journal of allergy and clinical immunology. In practice · 2026Review
- Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities.Nature reviews. Drug discovery · 2026Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInterleukin-33 may have a role in COPD pathobiology. FRONTIER-4 (NCT04631016) investigated tozorakimab (an anti-interleukin-33 monoclonal antibody) in patients with moderate-to-severe COPD with chronic bronchitis receiving dual or triple inhaled therapy.
methodsFRONTIER-4 was a phase 2a, randomised, double-blind, placebo-controlled study. Patients received tozorakimab 600 mg or placebo subcutaneously every 4 weeks for 24 weeks. The primary end‑point was change in pre-bronchodilator forced expiratory volume in 1 s (FEV
resultsThe intent-to-treat population included 135 patients (tozorakimab, n=67; placebo, n=68). At week 12 in the intent-to-treat population, tozorakimab showed a greater increase, although nonsignificant, from baseline in pre-bronchodilator FEV
conclusionAlthough the primary end-point was not met in the intent-to-treat population, tozorakimab showed positive efficacy signals
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.