Comparing lebrikizumab with other systemic immunomodulators for moderate to severe atopic dermatitis: An updated systematic review

Table 1 Summary of risk of bias assessment for randomized controlled trials (n = 25)

Risk of bias rating	n (%)	Specific trials
Low risk across all domains	22 (88)	20 original trials + Warren et al[2], 2025 + Tanaka et al[3], 2024
Some concerns	3 (12)	1 small phase 2 trial (randomization), 1 trial (missing data), Guttman-Yassky et al[1], 2025 (open-label extension)
High risk	0 (0)	None

Table 2 Risk of bias assessment for newly included observational studies (Newcastle-Ottawa Scale)

Ref.	Selection (★/4)	Comparability (★/2)	Outcome (★/3)	Total score (★/9)	Quality rating
Avallone et al[4], 2025 (Italy)	★★★	★	★★	6/9	Moderate quality
Abraheem et al[5], 2025 (United Kingdom)	★★★	★	★★	6/9	Moderate quality
Hagino et al[6], 2025 (Japan)	★★★	No star	★★	5/9	Moderate quality

Table 3 Grading of Recommendations Assessment, Development and Evaluation quality of evidence assessment for key comparisons

Comparison	Outcome	Initial quality	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Final quality	Comments
Lebrikizumab vs dupilumab	IGA 0/1 at week 16	High	No serious	No serious	Serious (-1)	No serious	Undetected	Moderate	Indirect comparison via NMA
Lebrikizumab vs dupilumab	EASI 75 at week 16	High	No serious	No serious	Serious (-1)	No serious	Undetected	Moderate	Indirect comparison via NMA
Lebrikizumab vs tralokinumab	IGA 0/1 at week 16	High	No serious	No serious	No serious to serious	No serious	Undetected	Moderate to high	Consistent superiority
Lebrikizumab vs tralokinumab	EASI 75 at week 16	High	No serious	No serious	No serious to serious	No serious	Undetected	Moderate to high	Consistent superiority
Lebrikizumab vs baricitinib	IGA 0/1 at week 16	High	No serious	No serious	Serious (-1)	No serious	Undetected	Moderate	Indirect comparison via NMA
Lebrikizumab vs abrocitinib	IGA 0/1 at week 12/16	High	No serious	No serious	Serious (-1)	No serious	Undetected	Moderate	Different timepoints
Lebrikizumab vs upadacitinib 30 mg	IGA 0/1 at week 16	High	No serious	No serious	Serious (-1)	No serious	Undetected	Moderate	Clear inferiority

EASI: Eczema Area and Severity Index; IGA: Investigator global assessment; NMA: Network meta-analysis.

Table 4 Summary of comparative efficacy: Lebrikizumab vs other systemic therapies at week 12/16

Comparison	IGA 0/1, ORs (95% CrIs)	EASI-75, ORs (95% CrIs)	Itch (week 12/16)	Overall interpretation
Lebrikizumab vs dupilumab	1.01 (0.64-1.54)	0.93 (0.65-1.33)	0.79 (0.48-1.24)	Comparable efficacy
Lebrikizumab vs tralokinumab	0.46 (0.31-0.68)	0.57 (0.40-0.81)	0.39 (0.23-0.63)	Lebrikizumab superior
Lebrikizumab vs baricitinib 2 mg	0.40 (0.23-0.66)	0.37 (0.23-0.59)	0.28 (0.15-0.51)	Lebrikizumab superior
Lebrikizumab vs baricitinib 4 mg	0.43 (0.23-0.80)	0.47 (0.28-0.78)	0.35 (0.18-0.68)	Lebrikizumab superior
Lebrikizumab vs abrocitinib 100 mg	0.70 (0.44-1.15)	0.88 (0.60-1.29)	0.78 (0.47-1.24)	Comparable efficacy
Lebrikizumab vs abrocitinib 200 mg	1.38 (0.88-2.23)	1.43 (0.99-2.10)	1.43 (0.86-2.28)	Comparable efficacy
Lebrikizumab vs upadacitinib 15 mg	1.52 (0.92-2.41)	1.38 (0.97-1.96)	1.19 (0.72-1.93)	Comparable efficacy
Lebrikizumab vs upadacitinib 30 mg	2.73 (1.67-4.32)	1.57 (1.10-2.25)	1.84 (1.08-2.93)	Upadacitinib superior

Odds ratios (ORs) (comparator vs lebrikizumab) and 95% credible intervals derived from Bayesian network meta-analysis; OR < 1 favors lebrikizumab and OR > 1 favors comparator. ORs: Odds ratios; CrIs: Credible intervals; IGA: Investigator global assessment; EASI: Eczema Area and Severity Index.

Table 5 Summary of efficacy outcomes from newly included studies

Ref.	Time point	EASI 75 (%)	IGA 0/1 (%)	Itch NRS ≥ 4-point (%)	Key findings
Warren et al[2], 2025 (ADvantage)	Week 16	52.1 vs 22.0 (placebo)a	32.5 vs 11.4 (placebo)a	Not reported	Efficacy in ciclosporin-inadequate population
Guttman-Yassky et al[1], 2025 (ADjoin)	Week 104	Maintained in 84.3% (Q2W) and 82.9% (Q4W)	Maintained in 76.5% (Q2W) and 74.8% (Q4W)	Not reported	Durable long-term response
Tanaka et al[3], 2024	Week 52	Not reported	Not reported	Significant improvement	Improved quality of life and PROs
Avallone et al[4], 2025 (Italy RWE)	Week 16	65.2	58.4	72.3	Real-world effectiveness confirmed
Avallone et al[4], 2025 (Italy RWE)	Week 24	71.6	64.1	78.5	Continued improvement over time
Abraheem et al[5], 2025 (United Kingdom RWE)	Week 16	72.7	66.4	Median -5 points	Effective in biologic-experienced patients
Hagino et al[6], 2025 (Japan RWE)	Week 24 (bio-naive)	78.3	Not reported	Not reported	Highest response in treatment-naive
Hagino et al[6], 2025 (Japan RWE)	Week 24 (prior JAKi)	69.8	Not reported	Not reported	Maintained efficacy after JAKi
Hagino et al[6], 2025 (Japan RWE)	Week 24 (prior biologic)	66.2	Not reported	Not reported	Maintained efficacy after biologic

^aP < 0.001 for lebrikizumab vs placebo.

EASI: Eczema Area and Severity Index; IGA: Investigator global assessment; JAKi: Janus kinase inhibitor; NRS: Numeric rating scale; PROs: Patient-reported outcomes; Q2W: Every 2 weeks; Q4W: Every 4 weeks; RWE: Real-world evidence.

Table 6 Summary of safety outcomes from newly included studies

Ref.	Total patients	Follow-up duration	Any AE (%)	Serious AE (%)	Discontinuation due to AE (%)	Most common AEs
Warren et al[2], 2025 (ADvantage)	237 (lebrikizumab arm)	16 weeks	42.6	2.5	3.4	Injection site reactions, nasopharyngitis
Guttman-Yassky et al[1], 2025 (ADjoin)	463	104 weeks	78.4	4.8	5.2	Nasopharyngitis, injection site reactions, conjunctivitis
Tanaka et al[3], 2024	156	52 weeks	Not reported	Not reported	4.5	Nasopharyngitis, injection site reactions
Avallone et al[4], 2025 (Italy RWE)	394	16-24 weeks	18.3	1.5	8.1	Injection site reactions (6.9%), URTI (4.6%)
Abraheem et al[5], 2025 (United Kingdom RWE)	128	16 weeks	15.6	0.8	6.3	Injection site reactions, conjunctivitis
Hagino et al[6], 2025 (Japan RWE)	938	24 weeks	12.8	1.2	4.9	Nasopharyngitis, injection site reactions

AE: Adverse event; RWE: Real-world evidence; URTI: Upper respiratory tract infection.