The edition · Top Clinical Updates
A biologic for COPD that does not ask about eosinophils
Two replicate phase 3 trials cut exacerbations by about 30% with no eosinophil entry criterion; a masked trial with sham incisions finds robotic knee replacement no better and more expensive; and half a million adults suggest the mortality floor for haemoglobin sits above the anaemia threshold, not at it.
The edition in brief
Four findings for every clinician. OBERON and TITANIA, two replicate phase 3 trials, randomised about 1,750 adults with COPD and an exacerbation in the previous year, despite stable inhaled maintenance therapy, to subcutaneous tozorakimab 300 mg or placebo every four weeks for 52 weeks. There were no eosinophil eligibility criteria. Annualised moderate or severe exacerbations in the overall population fell from 2.00 to 1.41 in OBERON (rate ratio 0.70, 95% CI 0.58 to 0.85) and from 2.03 to 1.44 in TITANIA (rate ratio 0.71, 95% CI 0.59 to 0.84). Adverse event rates were similar to placebo. RACER-Knee randomised 339 patients at ten British hospitals to robotic-arm-assisted or conventional total knee replacement, masking participants with sham incisions and additional draping and masking assessors and operation notes. The Forgotten Joint Score at 12 months was 49.2 against 50.2, an adjusted difference of -1.5 (95% CI -7.5 to 4.5) against a prespecified target difference of 12 points, and the robotic arm cost more. A systematic review of 69 studies published between August 2025 and June 2026 found influenza vaccine effectiveness against hospitalisation in older adults of 19% to 43%, against death of 29% to 66%, and 80% (95% CI 75 to 84) against laboratory-confirmed influenza deaths in those aged 6 months to 17 years. A self-controlled case series of 9,973,703 people found no increase in serious adverse events. In 477,876 UK adults followed a median 13.6 years, all-cause mortality was lowest at haemoglobin 1 to 3 g/dL above the WHO anaemia threshold, and was already raised 18% in those sitting 0 to 1 g/dL above it.
Tozorakimab cuts COPD exacerbations without selecting on eosinophils
In COPD with exacerbations despite inhaled therapy, tozorakimab cut moderate or severe exacerbations by around 30% in two replicate 52-week phase 3 trials that set no eosinophil threshold for entry.
Robotic knee replacement, masked with sham incisions, gives nothing back
Robotic-arm-assisted total knee replacement produced no better Forgotten Joint Score at 12 months than conventional instruments (adjusted difference -1.5, 95% CI -7.5 to 4.5) in a participant-masked trial, at higher cost.
The influenza vaccine evidence for this season, with numbers to quote
Influenza vaccine effectiveness is modest against hospitalisation in older adults (19-43%) but around 80% against influenza-associated death in children, and a case series of nearly ten million people found no safety signal, including with coadministration.
A pan-RAS inhibitor shows activity in the third of lung cancers nobody could target
Daraxonrasib produced objective responses in 31-37% of previously treated RAS-mutant non-small-cell lung cancer, with grade 3 or higher adverse events in 54% and no comparator group, so it is a promising agent awaiting randomised evidence.
Watch the inhaler being used before you add anything to it
Before escalating inhaled therapy, watch the patient use their own inhaler and check the breath, the seal and the timing, because a device used wrongly is not a failed drug.
The safest haemoglobin sits above the anaemia threshold, not at it
Mortality was lowest at haemoglobin 1 to 3 g/dL above the WHO anaemia threshold and already 18% higher in people sitting just above it, so investigate a borderline or falling haemoglobin rather than reporting it as normal.
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