Upadacitinib Superior to 4 Other JAKi Monotherapies for Atopic Dermatitis

Upadacitinib has demonstrated superior short-term efficacy versus 4 other oral Janus Kinase (JAK) inhibitors for moderate-to-severe atopic dermatitis, according to recent findings, supporting its preferential consideration as a systemic JAK inhibitor.1

These findings resulted from a study conducted to compare oral upadacitinib therapy to 4 other JAK inhibitors, or JAKis: abrocitinib (100 or 200 mg), baricitinib (2 or 4 mg), and ivarmacitinib (4 or 8 mg). The analysis was authored by an investigative team led by Arya Babul, from the West Career & Technical Academy and Society for Awareness of Neglected Diseases.

Babul et sl described indirect comparisons made via Bayesian network meta-analysis (BNMA) as helpful for comparisons of medication efficacy, as they may help to guide therapeutic decision-making. Nevertheless, they noted before this study, “NMAs published before June 2025 did not include ivarmacitinib, as its phase 3 data in [atopic dermatitis] and regulatory approvals in China for [atopic dermatitis] only became available in 2025.”2

Therefore, Babul and colleagues set out to conduct a BNMA assessing the short-term efficacy results of 4 JAK inhibitors indicated for atopic dermatitis treatment.

Analysis Details

The investigators, in accordance with PRISMA 2020 guidelines, conducted a systematic review conducted and registered in PROSPERO evidence drawn from various phase 2 and phase 3 randomized, double-blind, placebo-controlled trials. These studies would be evaluating oral JAK inhibitors for the treatment of moderate-to-severe atopic dermatitis, and the investigators’ searches involved the Embase, PubMed, Cochrane Library, and ScienceDirect databases.

In the early portion of their study, through August 2025, they conducted their search for trials. This was also supplemented by a manual screening of reference lists along with relevant congress abstracts, with Babul and coauthors seeking to ensure inclusion of all eligible research. In their review, they looked at data on baricitinib at doses of 2 mg and 4 mg, abrocitinib at 100 mg and 200 mg, upadacitinib at 15 mg and 30 mg, and ivarmacitinib at 4 mg and 8 mg. Age eligibility criteria were noted by the investigators as consistent with criteria implemented in the pivotal clinical development programs for each of these drugs.

Research related to abrocitinib included the JADE MONO-1 study (NCT03349060), JADE MONO-2 (NCT03575871), and a phase 2b analysis (NCT02780167), with patients evaluated being aged 12 years and older. Data on upadacitinib’s use were derived from MEASURE UP-1 (NCT03569293) and MEASURE UP-2 (NCT03607422). These 2 studies included participants between the ages of 12 - 75 years.

The BREEZE-AD1 (NCT03334396), BREEZE-AD2 (NCT03334422), and BREEZE-AD5 (NCT03435081) studies were used to look at baricitinib, and all of these trials were limited to adults aged 18 years or older. For ivarmacitinib, Babul et al used a phase 3 study (NCT04875169) involving the enrollment of adolescents and adults between 12 - 75 years of age. In terms of primary efficacy outcomes, they looked for patient attainment of at least a 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75) at 12 - 16 weeks.

Additionally, they looked at participants’ Investigator’s Global Assessment scores of clear or almost clear (IGA-AD 0/1). They also looked for a reduction of at least 4 points on the itch numeric rating scale, also known as the Itch NRS. Effects of therapies were estimated by the investigators via Bayesian hierarchical models, with odds ratios (ORs) being generated with corresponding 95% credible intervals (CrIs). Comparative ranking across these 4 drugs was determined through the use of surface under the cumulative ranking curve (SUCRA) probabilities.

Comparisons of 4 JAK Inhibitors

In total, there were 9 randomized controlled trials. These studies were made up of 4261 individuals who had met the criteria for involvement. Across all endpoints examined by Babul and colleagues, upadacitinib 30 mg consistently had the strongest level of efficacy in those with atopic dermatitis. In their assessment of EASI 75 scores, the OR was 12.3 (95% CrI, 7.9–18.7). IGA-AD 0/1 response, on the other hand, yielded an OR of 18.9 (95% CrI, 12.0–29.7). Positive shifts in pruritus severity, defined by a ≥4-point reduction in trial participants’ Itch NRS scores, was also shown to be the greatest with upadacitinib 30 mg treatment, with an OR of 11.1 (95% CrI, 7.2–17.5).

This dose was followed in overall efficacy by upadacitinib 15 mg. Then, Babul and coauthors found abrocitinib 200 mg had the next best efficacy, followed by ivarmacitinib 8 mg. In contrast, they found baricitinib at both the 2 mg and 4 mg doses had been consistently in the lowest treatment ranking positions. They reinforced such data via SUCRA analyses. Upadacitinib 30 mg attained probabilities ranging from 97% - 98%, which the investigators note suggests an increased likelihood of being the most effective option across the different endpoints.

Overall, the investigative team concluded upadacitinib, especially at the 30 mg dose and followed by the 15 mg dose, allows for the most robust short-term improvements in both patients’ level of skin clearance and their level of itch among these 4 oral JAKis.

“These findings support a provisional efficacy preference for upadacitinib in managing moderate-to-severe [atopic dermatitis] unresponsive to biologic or topical therapies,” they wrote.1

References

1. Babul A, Mehta D, Babul N, et al. Upadacitinib Leads in Efficacy: A Bayesian Network Meta-Analysis of Four JAK Inhibitors in Moderate-To-Severe Atopic Dermatitis. Int J Dermatol. 2026 Jan 5. doi: 10.1111/ijd.70228. Epub ahead of print. PMID: 41489415.

2. Zhao Y, Gooderham M, Zhang J. Ivarmacitinib for Moderate to Severe Atopic Dermatitis in Adults and Adolescents: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2025 Jul 1;161(7):688-697. doi: 10.1001/jamadermatol.2025.0982. PMID: 40305055; PMCID: PMC12044538.