The Great Atopic Dermatitis Treatment Debate: Biologics vs JAK Inhibitors

Why choose an oral JAK inhibitor for atopic dermatitis? “I can make my argument in 5 easy points, said Raj Chovatiya, MD, PhD, MSCI, as he began his half of the presentation Rash decisions: the great debate between biologic vs JAK inhibitor for atopic dermatitis at the 2025 Midwinter Clinical Hawaii Dermatology Conference being held in Hawaii, February 15-19. Chovatiya is clinical assistant professor medicine at Rosalind Franklin University Chicago Medical School and founder and director of the Center for Medical Dermatology and Immunology Research in Chicago, Illinois.

Raj Chovatiya, MD, PhD

Point #1 Oral JAK inhibitors open possibilities to treat the full heterogeneity of atopic dermatitis

Chovatiya presented 2 cases of difficult to treat AD, both of which had failed to respond to a variety of therapies. In the first case a 60 year old woman with adult-onset atopic dermatitis (AD) had been treated unsuccessfully with multiple rounds of topical corticosteroid (TCS), had not responded to oral antihistamines, and has had short term but inadequate improvement with oral steroids with rebound flares: “I’m constantly itchy,” “I can’t sleep” “My skin is bleeding from sores” were her laments. She was treated with abrocitinib 100 mg with and within 3 months, Chovatiya said referring to a photo, “you can see her just about completely clear,” and indeed, her scores on standard AD assessment tools reflected that vIGA-AD: 1 (almost clear) BSA: 2% EASI: 2.1 oSCORAD: 14.1 PtGA: 1 (almost clear) NRS worst itch: 2/10 NRS sleep quality: 8/10 POEM: 7 (mild) DLQI: 5 (small effect).

A second case was the story of a 56-year-old woman with AD primarily involving her hands and feet. The pruritic, painful eruptions were ongoing for 2 years with some extension to the wrists and ankles. She was treated previously for presumed psoriasis and had failed to respond to a litany of treatments: TCS, topical retinoids, coal tar, phototherapy, acitretin, methotrexate, apremilast, adalimumab, and guselkumab. “I can’t stand without pain” “I can’t work with my hands” “I’m itchy and in pain at the same time.” “She worked as a nurse, very uncomfortable to stand.” She was treated with upadacitinib 15 mg with rapid resolution of all symptoms as measured by the same instruments (0 on all), from her baseline: vIGA-AD: 3 (moderate). “You can't see a single speck of scale on that foot. Just that fast, just that strong, for somebody very site limited disease,” he said.

Point #2 JAK inhibitors take a precision approach to target a conserved signal transduction pathway that is broadly relevant

JAK proteins play distinct roles for cytokine and growth factors signaling across multiple disease states (Hu X, et al. Signal Transduct Target Ther. 2021 Nov 26;6(1):402. doi: 10.1038/s41392-021-00791-1) JAK inhibitors target conserved signal transduction pathways essential for inflammatory signaling. Cytokines implicated in AD—IL-4, IL-13, IL-31, IL-5, and TSLP—utilize the JAK-STAT pathway for intracellular communication, Chovatiya explained. By selectively inhibiting these pathways, JAK inhibitors modulate inflammatory responses at a molecular level, offering a precision approach to treatment. It’s true, however, that the broad inhibition poses a potential risk, and that makes careful patient selection essential.

Point #3 The yin and yang of JAKi boils down to basic biochemistry

Chovatiya described the opportunity of JAK inhibition noting that “each subsequent molecule has been developed to leverage structural differences for its target.” First generation JAKi, eg tofacitinib, baricitinib, ruxolitinib, were non-selective while selectivity was enhanced with development of second generation molecules (eg, abrocitinib, upadacitinib) which are more selective. JAKis also are reversible ATP-competitive inhibitors, offering broad potential for future development. Negatives he pointed out include the ubiquity of JAK signaling, which means there are off target effects, including immune response, hematopoiesis, anti-viral immunity, and impacts on metabolism, lack of selectivity, and the potential for drug resistance

Point #3 Abrocitinib and Upadacitinib are practical first-line agents for patients with moderate-severe AD that provide a key efficacy advantage over biologics

Chovatiya then talked specifically about head-to-head studies between JAKi and biologics, citing, among others, theJADE trials, which demonstrated superior itch relief and skin clearance early in treatment in participants treated with abrocitinib vs dupilimab. Patients on abrocitinib 200 mg achieved significant improvement in pruritus within days, outperforming dupilumab at weeks 2 and 16. In the Heads Up study, higher rates of EASI-75 and EASI-90 were seen with upadacitinib 30 mg versus dupilumab, with symptom improvement beginning at week 2. He also pointed to enhanced efficacy of JAKi in traditionally treatment resistant areas, such as head and neck AD.

Point #4 On balance, oral JAK inhibitors are quite safe for the treatment of AD when armed with the right information

There’s a lot more balanced safety data than you think , Chovatiya said. He referred to 6-year safety data for upadacitinib with continuous exposure and consistent safety with abrocitinib with up to 4.5 years of continuous exposure. He also emphasized that safety data need to be contextualized appropriately and cited epidemiologic research that suggests the risk of specific events may depend in part on patient factors, such as age, infection, and smoking. He also pointed out that the clearest dose-dependent signals in recent studies continue to be infections.

Point #5 Innovative data analyses show that you can do some pretty cool things with JAK inhibitors

• Abrocitinib is an effective option for AD in the head and neck region
• Abrocitinib efficacy at 4 weeks can serve as a helpful predictor of response
• Abrocitinib can capture response in dupilumab non-responders
• Upadacitinib increases the number of days spent high level efficacy thresholds
• padacitinib can achieve “minimal disease activity” outcomes based on clinician and patient targets
• Upadacitinib outperforms dupilumab in the simultaneous achievement of high-level skin + itch outcomes )

Neal D Bhatia, MD

The Other Side

“So, who qualifies for biologic therapy? Beyond infants, anyone requiring topical steroids or systemic treatments who is not responding adequately should be considered,” was Neal Bhatia, MD’s opening comment when he traded places with Chovatiya to support the use of biologics for treatment of AD. “While JAK inhibitors offer a ‘sprint’ in treatment, biologics are in it for the ‘marathon.’” And while concerns exist regarding boxed warnings, with biologics, these risks are more akin to ‘carry-on luggage’ than significant baggage. Bhatia is director of Clinical Dermatology Therapeutics Clinical Research, in San Diego, CA.

Bhatia pointed to the continued evolution of the field and stressed the need for informed discussion with patients and caregivers—do they prefer injections or oral therapies? “[Dr Chovatiya] made an excellent point: pills have a role, often providing that initial sprint that enables long-term success with biologics.” When selecting an AD treatment, compliance should be factored in, Bhatia said. Some patients benefit from a 4-week dosing schedule rather than every 2 weeks, which is a bit less burdensome. “Treatment flexibility—starting high and tapering—offers a personalized approach.”

He referred to new data that highlight potential for periods of remission with biologic therapy, with some studies suggesting an 18-week treatment window, “allowing for a temporary drug holiday before resuming therapy at the first sign of relapse.” Disease control is maintained while offering patients what is sometimes a needed break. Oral therapies, he continued, “often see patients discontinuing once they feel better, potentially leading to relapse.” The fatigue factor with the injectable biologics can’t be ignored, but Bhatia pointed to rotating injection sites and reaffirming the safety of the class for a patient who is concerned and plugged the every other week administration vs daily dosing of JAKs.

Bhatia moved quickly through slides demonstrating the efficacy of the 4 biologics with FDA approval for treatment of AD:

• Dupilumab: Moderate-to-severe AD in adults and children aged 6 months and older.
• Lebrikizumab: Moderate-to-severe AD in adults and children aged 12 years and older.
• Nemolizumab: Moderate-to-severe AD in patients aged 12 years and older, in combination with topical corticosteroids and/or calcineurin inhibitors.
• Tralokinumab: Moderate-to-severe AD in patients 12 years and older; can be used with or without topical corticosteroids.

He referenced the importance and utility of patient reported outcome measures, such as the Dermatology Life Quality Index and the Patient Oriented Eczema Measure, results of which are not only helpful to evaluate progress and disease management but could be included in EHR notes to support prior authorization requisites for some of the biologics.

At the end of the so-called debate, which was not as heated as might have been anticipated, Bhatia and Chovatiya did agree that patient characteristics and preferences, as well as those of caregivers involved, will determine the most appropriate choice of treatment for AD.