Six advanced systemic treatments are licensed in the UK for moderate-to-severe atopic eczema: the injected antibodies dupilumab, tralokinumab and lebrikizumab, and the oral JAK inhibitors abrocitinib, baricitinib and upadacitinib (British Association of Dermatologists, Atopic eczema). They are for disease topical treatment has not controlled. In the pivotal monotherapy trials SOLO 1 and SOLO 2, a 75% improvement in eczema severity at sixteen weeks was reached by 51.3% and 44.2% of patients, against 14.7% and 11.9% on placebo (ClinicalTrials.gov, NCT02277743 and NCT02277769).
What dupilumab does, and how tralokinumab and lebrikizumab differ
Dupilumab is a recombinant human IgG4 monoclonal antibody that binds the IL-4 receptor alpha subunit. That subunit appears in two different receptor complexes, so blocking it stops IL-4 signalling through the type I receptor and both IL-4 and IL-13 signalling through the type II receptor (Dupixent SmPC). IL-4 and IL-13 are the cytokines driving the Th2-polarised inflammation behind barrier dysfunction, itch and the flare-and-settle cycle. Adults inject it under the skin every two weeks, usually themselves (BAD, Dupilumab).
The two newer antibodies are narrower. Tralokinumab binds IL-13 itself and neutralises it by blocking its interaction with the IL-13 receptor alpha 1 and IL-4 receptor alpha complex (Adtralza SmPC). Lebrikizumab binds IL-13 with high affinity and selectively inhibits its signalling through that same receptor pair, with maintenance dosing every four weeks once a response is reached (Ebglyss SmPC). Neither touches IL-4 signalling at all.
How the JAK inhibitors work differently
Abrocitinib, baricitinib and upadacitinib are tablets, and they act inside the cell rather than on the receptor surface. Janus kinases are the enzymes that relay signals from cytokine receptors to the nucleus, so inhibiting JAK1 prevents the phosphorylation and activation of STATs and damps a wide range of cytokine signalling at once. Serum IL-31, the cytokine acting on nerve endings, fell dose-dependently on abrocitinib (Cibinqo SmPC). The breadth is both the advantage and the cost.
The MHRA's 2023 Drug Safety Update advises that JAK inhibitors be used in people aged 65 or over, current or long-term past smokers, and those with other risk factors for cardiovascular disease or malignancy only when no suitable alternative exists. The named risks are major adverse cardiovascular events, malignancy, venous thromboembolism, serious infections and increased mortality (MHRA, 2023).
What the trials of each drug showed
The first two trials to put a JAK inhibitor directly against dupilumab were JADE COMPARE and Heads Up.
JADE COMPARE randomised 838 adults on background topical therapy to abrocitinib 200 mg, abrocitinib 100 mg, dupilumab 300 mg every two weeks, or placebo (Bieber et al, 2021). At week 12, EASI-75 was reached by 70.3% on abrocitinib 200 mg, 58.7% on abrocitinib 100 mg, 58.1% on dupilumab and 27.1% on placebo. On the stricter Investigator's Global Assessment endpoint the figures were 48.4%, 36.6%, 36.5% and 14.0%. The 100 mg dose was not separable from dupilumab. The 200 mg dose beat it on itch at week 2 but not on skin severity at week 16.
Heads Up randomised 673 adults to oral upadacitinib 30 mg daily or dupilumab 300 mg every two weeks (Blauvelt et al, 2021). That figure is 342 on upadacitinib plus 331 on dupilumab, out of 924 screened, and it is the number the trial registry records as actual enrolment. At week 16, 72.4% on upadacitinib and 62.6% on dupilumab reached EASI-75, and mean improvement in worst itch was 67.8% against 49.6%.
Pooled evidence is a better guide than any single pair. A living network meta-analysis covering 60 trials and 16,579 patients found that abrocitinib 200 mg and upadacitinib 30 mg reduced EASI slightly more than dupilumab, by 2.2 and 2.7 points, while tralokinumab and baricitinib 4 mg reduced it slightly less, by 3.5 and 3.2 points, all at high certainty (Drucker et al, 2022). Those are small gaps on a 72-point scale, so route, monitoring burden and side effects carry as much weight as efficacy. The appraisal criteria, licensed age bands and pricing rules that settle which agent is offered first are set out in which biologic for eczema.
What NICE requires in England
NICE technology appraisals cover all six. Dupilumab is available on the NHS for moderate-to-severe atopic eczema in adults and children aged 6 and over whose disease has not improved on at least one systemic tablet treatment, such as ciclosporin, methotrexate, azathioprine or mycophenolate, or for whom those treatments cannot be used (BAD, Dupilumab). The adult appraisal is TA534.
Severity is scored with EASI for the skin and the Dermatology Life Quality Index for daily life. Continued funding then depends on measured response: NICE counts a 50% reduction in EASI plus a 4-point reduction in DLQI at sixteen weeks as an adequate response (STRIVE AD, 2026). Both scores are recorded before the first dose.
Side effects and monitoring
Conjunctivitis is the characteristic dupilumab effect. In Heads Up it affected 8.8% of the dupilumab group against 1.5% on upadacitinib. The Dupixent SmPC lists it as common, and more frequent in atopic dermatitis than in the drug's other licensed indications.
The JAK column of the same trial looks different: acne in 16.1% on upadacitinib against 2.7% on dupilumab, herpes zoster in 2.0% against 0.9%, and serious infection in 1.1% against 0.6%. Tablets also bring blood tests before treatment and again at four weeks, covering lipids and a full blood count with platelets, lymphocytes, neutrophils and haemoglobin (Cibinqo SmPC), on top of the prescribing restrictions the MHRA set out.
Where this sits in the NHS sequence
The appraisals assume the earlier steps have happened. That means an optimised emollient and topical steroid routine, wet wrapping for flares a cream alone does not settle, removal of identified triggers such as dust mites, hard water and detergents, and then at least one systemic tablet or a documented reason it cannot be used.
The path runs GP, dermatology referral, severity scoring, systemic trial, advanced therapy. It takes months. Structured trigger identification and a 45-day protocol establish how much inflammation is being fed by inputs you control, and the reasons standard treatment stalls explain what "optimised" means in practice. None of that substitutes for a drug in disease that needs one. It changes how much is left for the drug to do.
References
- British Association of Dermatologists. Atopic eczema, patient information leaflet. https://www.bad.org.uk/pils/atopic-eczema/
- British Association of Dermatologists. Dupilumab, patient information leaflet. https://www.bad.org.uk/pils/dupilumab/
- Electronic Medicines Compendium. Dupixent, summary of product characteristics. https://www.medicines.org.uk/emc/product/8553/smpc
- Electronic Medicines Compendium. Adtralza 300 mg, summary of product characteristics. https://www.medicines.org.uk/emc/product/15142/smpc
- Electronic Medicines Compendium. Ebglyss 250 mg, summary of product characteristics. https://www.medicines.org.uk/emc/product/15366/smpc
- Electronic Medicines Compendium. Cibinqo 200 mg, summary of product characteristics. https://www.medicines.org.uk/emc/product/12874/smpc
- MHRA. Janus kinase (JAK) inhibitors: new measures to reduce risks, 2023. https://www.gov.uk/drug-safety-update/janus-kinase-jak-inhibitors-new-measures-to-reduce-risks-of-major-cardiovascular-events-malignancy-venous-thromboembolism-serious-infections-and-increased-mortality
- Bieber T et al. Abrocitinib versus placebo or dupilumab for atopic dermatitis. New England Journal of Medicine, 2021. https://doi.org/10.1056/NEJMoa2019380
- ClinicalTrials.gov. JADE COMPARE results, NCT03720470. https://clinicaltrials.gov/study/NCT03720470
- Blauvelt A et al. Efficacy and safety of upadacitinib vs dupilumab in adults with moderate-to-severe atopic dermatitis, Heads Up. JAMA Dermatology, 2021. https://pmc.ncbi.nlm.nih.gov/articles/PMC8340015/
- ClinicalTrials.gov. Heads Up results, NCT03738397. https://clinicaltrials.gov/study/NCT03738397
- ClinicalTrials.gov. SOLO 1 results, NCT02277743. https://clinicaltrials.gov/study/NCT02277743
- ClinicalTrials.gov. SOLO 2 results, NCT02277769. https://clinicaltrials.gov/study/NCT02277769
- Drucker AM et al. Systemic immunomodulatory treatments for atopic dermatitis: update of a living systematic review and network meta-analysis. JAMA Dermatology, 2022. https://pmc.ncbi.nlm.nih.gov/articles/PMC8928094/
- STRIVE AD. Set targets, assess response, intervene early to achieve minimal disease activity in atopic dermatitis. JAAD International, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC12873730/