Lindsay S. Ackerman, MD, FAAD

What Is Next for OX40 Ligand Inhibition in Atopic Dermatitis?

 explored the future potential of amlitelimab in atopic dermatitis, with hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, emphasizing the importance of maintaining scientific curiosity and clinical perspective as more data emerge regarding OX40 ligand-targeted therapy.

The discussion centered on balancing enthusiasm for a novel therapeutic mechanism with the need for continued investigation into safety signals and patient selection. Bunick argued the field should remain optimistic about amlitelimab’s future, noting that a better understanding of patient-specific risk factors could ultimately help clinicians identify individuals most appropriate for treatment. He compared this approach to the risk stratification strategies dermatologists have already adopted for JAK inhibitors, where clinicians routinely evaluate patients for factors that may increase the likelihood of adverse events before initiating therapy.

Rather than viewing emerging questions about the therapy as a reason to abandon the pathway, Bunick suggested that dermatology should focus on generating more data and demanding greater scientific transparency. In his view, understanding the underlying biology behind observed safety findings will allow clinicians to make more informed, patient-centered decisions while preserving access to potentially valuable treatment options.

Ackerman agreed, describing the OX40-OX40 ligand pathway as an example of why dermatology remains one of the most rapidly evolving areas of medicine. She highlighted the complexity of inflammatory disease biology and suggested that upstream immune modulation may ultimately have implications extending beyond atopic dermatitis. According to Ackerman, the pathway’s broad immunologic relevance could make it important not only for eczema but also for other chronic inflammatory disorders that continue to present therapeutic challenges.

The hosts also discussed the ongoing unmet need in atopic dermatitis despite an expanding therapeutic landscape. Ackerman noted that the disease remains highly heterogeneous, with significant variability in clinical presentation and treatment response. As a result, she argued that continued investment in new mechanisms of action remains essential, even as effective therapies already exist. She pointed to the continued development of amlitelimab as evidence of an ongoing commitment to addressing gaps in care for patients whose disease remains difficult to control.

The conversation then shifted to Ackerman’s firsthand experience as a clinical trial investigator. Drawing on her participation in amlitelimab studies, Ackerman described seeing several patients achieve substantial improvements despite having previously failed multiple therapies. Although she acknowledged that these observations represent only a small number of patients, she noted that some individuals continued to do well even after completing the interventional portion of the study. Ackerman said she had anticipated needing to rapidly transition certain participants to additional treatments after trial completion because of the severity and recalcitrance of their disease, but some had yet to experience significant flares.

Bunick cautioned against drawing broad conclusions from individual cases but viewed those experiences as further reason to remain open-minded. Both hosts ultimately stressed that advancing patient care requires careful scientific investigation, patience, and a willingness to evaluate new therapeutic pathways on the basis of evolving evidence. They concluded that maintaining a patient-centered approach while pursuing deeper mechanistic understanding will be critical as the role of OX40 ligand inhibition continues to develop within atopic dermatitis and potentially other inflammatory diseases.

Editor’s note: This segment was summarized with the help of AI tools.

Relevant disclosures for Bunick include AbbVie, South Beach Symposium, Almirall, Apogee Therapeutics, Arcutis Biotherapeutics, Daiichi Sankyo, Eli Lilly, LEO Pharma, US, Novan, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Timber Pharmaceuticals, and UCB. Relevant disclosures for Ackerman include AbbVie, Alumis, Amgen, Arcutis, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, L'Oréal, Novartis, Sun Pharmaceutical, and UCB.

Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed June 1, 2026. 

https://www.sanofi.com/en/media-room/press-releases/2026/2026-03-28-15-00-00-3264184

Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed June 1, 2026. 

https://www.kyowakirin.com/media_center/news_releases/2026/e20260303_01.html

Videos

The latest ABCs of Dermatology explored the future potential of amlitelimab in atopic dermatitis and the potential of OX40 ligand-targeted therapy.

What Does New Phase 3 Amlitelimab Data Suggest for Atopic Dermatitis?

, hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, discussed why the phase 3 amlitelimab data in atopic dermatitis may be more clinically meaningful than headline efficacy numbers alone initially suggest.

Bunick emphasized that understanding the study population is critical when interpreting the results from the COAST 1, COAST 2, and SHORE trials. Across the studies, each enrolled roughly 600 patients with moderate-to-severe atopic dermatitis, representing a sizable late-stage clinical program. He highlighted the diversity of the enrolled population, noting relatively strong representation of Black patients compared with many dermatology trials, alongside a notably large proportion of Asian participants, reflecting a broader global patient population.

The hosts also underscored the substantial disease burden among trial participants. According to Bunick, patients had lived with atopic dermatitis for nearly two decades on average, and many entered the studies with extensive body surface area involvement and high baseline disease severity. A large percentage had also previously received systemic therapies, including biologics, JAK inhibitors, and traditional immunosuppressive agents, suggesting investigators were studying a particularly treatment-resistant population rather than patients with milder disease.

Another point Bunick stressed was the rigor of the statistical analysis. The trials used nonresponder imputation methodology, meaning any participant who discontinued treatment, deviated from protocol, or required rescue therapy was automatically counted as a treatment failure. He argued that this conservative approach makes the efficacy findings more impressive when viewed in context.

Ackerman expanded on the significance of the long-term response patterns seen with amlitelimab, particularly the durability of efficacy through 52 weeks and the similarity between dosing every 4 weeks and every 12 weeks. She contrasted this upstream immune modulation strategy with more downstream approaches such as cytokine blockade or JAK inhibition, suggesting that targeting the OX40 ligand pathway may allow for broader recalibration of immune activity rather than suppression of isolated inflammatory signals.

She also noted that responses appeared to deepen over time, with later efficacy outcomes surpassing those seen at earlier time points despite the increasingly stringent nature of long-term analyses. Ackerman suggested this pattern could reflect gradual restoration of immune balance through preservation of regulatory T-cell function and normalization of aberrant T-cell memory responses, raising the possibility that upstream pathway modulation may eventually reshape how chronic inflammatory diseases such as atopic dermatitis are treated.

Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed May 28, 2026. 

Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed May 28, 2026. 

Amlitelimab was discussed in the ABCs in Dermatology podcast, with the hosts highlighting atopic dermatitis patient demographics and high disease burden.

Hosts breakdown news and updates related to the atopic dermatitis pipeline, specifically examining news surrounding a pair of agents targeting OX40 and OX40 ligand as therapeutic pathways.

ABCs in Dermatology: Understanding OX40L in Atopic Dermatitis

000:00 - Introduction: Why OX40/OX40L Matters in Atopic Dermatitis and Chronic Inflammation

08:37 - Ligand vs Receptor Targeting: Mechanistic Differences and the Role 

26:39 - Phase 2/3 Data for Amlitelimab: Efficacy, Dosing Frequency, and Disease Modification Signals

41:58 - Safety Profile, Patient Selection, and Future Directions for OX40L Inhibition

 is emerging as a central focus of therapeutic development, with OX40–OX40 ligand signaling offering a potential pathway for more durable disease control beyond downstream cytokine blockade. 

, co-hosts Christopher Bunick, MD, PhD, and Lindsay Ackerman, MD, examine the evolving science behind OX40 and OX40 ligand inhibition, with particular focus on how this pathway may alter T-cell activation, memory T-cell formation, and immune homeostasis in chronic inflammatory skin disease. 

The episode, which is supported by Sanofi with independently developed content, frames the pathway as one of the most closely watched areas in atopic dermatitis drug development, particularly as phase 3 data begin to clarify both the promise and remaining questions around upstream immune modulation. Bunick explains that OX40 ligand, expressed on antigen-presenting cells and other cell types such as dermal fibroblasts, interacts with OX40 on activated T cells as a costimulatory signal. 

By targeting this upstream interaction, investigational agents may reduce multiple downstream inflammatory pathways, including TH1, TH2, TH17, and TH22 signaling, while preserving or restoring regulatory T-cell activity. Ackerman emphasizes that this mechanism raises the possibility of disease modification, though both hosts note that the field still needs clearer definitions around what that term means clinically, whether durable remission, reduced treatment frequency, or true off-drug control.

A major portion of the discussion centers on distinguishing OX40 ligand blockade from OX40 receptor inhibition, particularly the implications of T-cell–depleting versus nondepleting antibody designs. That distinction has become increasingly relevant following Kyowa Kirin’s March 3, 2026, announcement that all ongoing rocatinlimab trials would be discontinued after a planned safety update identified emerging malignancy concerns with possible viral or immune-related links, including 1 new confirmed case and 1 suspected case of Kaposi sarcoma in addition to a previously confirmed case. 

Kyowa Kirin noted the overall malignancy rate remained below expected background rates but said the characteristics of the cases raised a plausible biological concern that could not be excluded. Against that backdrop, the hosts review safety considerations in the OX40 pathway more broadly, including pyrexia, chills, headache, and malignancy surveillance. In Sanofi’s phase 3 amlitelimab program, the company reported no Kaposi sarcoma events across COAST 1, COAST 2, or SHORE, with malignancy rates low, below 1%, and generally similar between amlitelimab and placebo groups. 

Sanofi also reported 2 cumulative Kaposi sarcoma cases among 3778 patients exposed to amlitelimab across all indications, both in patients with known risk factors, and no additional cases across an estimated 4630 patients in the full development program, including blinded studies. 

The episode also reviews phase 3 data for amlitelimab, a fully human, non–T-cell-depleting monoclonal antibody targeting OX40 ligand, across COAST 1, COAST 2, and SHORE. The studies enrolled patients aged 12 years and older with moderate-to-severe atopic dermatitis and evaluated amlitelimab given every 4 weeks or every 12 weeks, with both regimens following a loading dose. COAST 1 and COAST 2 evaluated amlitelimab as monotherapy in 601 and 589 participants, respectively, while SHORE evaluated amlitelimab with topical corticosteroids, with or without topical calcineurin inhibitors, in 643 participants. 

Bunick and Ackerman highlight that the amlitelimab data showed progressively increasing efficacy through Week 24, with Sanofi reporting no evidence of plateau across endpoints. In COAST 1, vIGA-AD 0/1 responses were 21.1% with every-4-week dosing and 22.5% with every-12-week dosing, compared with 9.2% for placebo; EASI-75 responses were 35.9% and 39.1%, respectively, compared with 19.1% for placebo. 

In SHORE, where amlitelimab was studied with topical therapy, vIGA-AD 0/1 responses reached 28.7% and 32.3% with every-4-week and every-12-week dosing, compared with 16.8% for placebo, while EASI-75 responses were 48.1% and 46.8%, compared with 32.3%. 

The hosts note that these later-improving response curves are particularly relevant when considering the potential for extended dosing intervals and long-term immune recalibration. They also emphasize the clinical importance of less frequent dosing, given Sanofi’s statement that the data reinforce the potential for every-12-week dosing from the start, while underscoring that amlitelimab remains investigational and has not been evaluated by any regulatory authority.

Sanofi. Press Release: AAD: new results from Sanofi’s amlitelimab phase 3 studies in atopic dermatitis presented in late-breaking research session. Sanofi.com. Published March 28, 2026. Accessed May 27, 2026. 

Kyowa Kirin. Kyowa Kirin Announces Discontinuation of Rocatinlimab Clinical Trials - Kyowa Kirin. Kyowakirin.com. Published March 3, 2026. Accessed May 27, 2026. 

Podcasts

Explore OX40/OX40L inhibition in atopic dermatitis: phase 3 amlitelimab efficacy, safety signals, and what upstream immune control could mean.

AAD 2026: Owning Psoriatic Disease, With Lindsay Ackerman, MD

From the first United States Food and Drug Administration (US FDA)-approved oral IL-23 receptor antagonist to new data suggesting that biologics may delay the onset of psoriatic arthritis (PsA), the 

2026 American Academy of Dermatology (AAD) Annual Meeting

During the meeting held in Denver, Colorado, from March 27-31, 

spoke with Lindsay Ackerman, MD, FAAD, who came away from Denver more convinced than ever that dermatologists should be taking ownership of the full psoriatic disease burden in their patients.

Ackerman serves as Chief of Dermatology at Banner University Medical Center, Clinical Associate Professor at the University of Arizona, Medical Director of the US Dermatology Partners Clinical Research Institute, and President of Medical Dermatology Specialists in Phoenix. The conversation ranged across the evolving oral treatment landscape, new data on PsA prevention, the late-breaking TOGETHER-PsA incretin combination results, and what Ackerman described as an exciting but still-early reckoning with how obesity management intersects with chronic inflammatory disease. 

Roughly 30% or more of psoriasis patients are likely to develop PsA at some point, and with emerging data showing that both risankizumab and guselkumab are demonstrating delay-to-onset and risk-reduction signals for PsA, Ackerman argued that dermatologists who are already managing these patients' skin disease have both the opportunity and the responsibility to engage with the joint disease — not to displace rheumatology colleagues, but to recognize that the majority of this patient population will be seen first and most frequently in the derm chair.

On the IL-23 front, the headline development for Ackerman was the FDA approval of icotrokinra (ICOTYDE) — the first oral IL-23 receptor antagonist, approved for adults and pediatric patients 12 and older weighing at least 40 kg, dosed once daily — which she characterized as a genuinely new lane for a psoriasis oral market that has historically underperformed relative to biologics. She highlighted the head-to-head data versus deucravacitinib as an important differentiator, and noted that the dosing logistics are manageable: once-daily on waking, with 30 minutes before food, compatible with morning coffee.

 Looking further ahead, she noted that Apogee Therapeutics and Takeda are both advancing oral agents targeting IL-23 or its receptor in phase 2a and phase 3 trials respectively — a pipeline that signals the field is serious about giving patients who prefer oral therapy a genuinely competitive option. The TOGETHER-PsA data showing superior ACR50 plus ≥10% weight loss outcomes with ixekizumab plus tirzepatide versus ixekizumab alone also caught Ackerman's attention — not as a settled paradigm, but as the first controlled signal that pharmacologic co-management of obesity in psoriatic disease may amplify inflammatory disease outcomes in ways anecdotal reports and meta-analyses had only suggested. The 52-week data and companion TOGETHER-PsO results are still to come, and Ackerman was careful to frame the obesity-inflammation intersection as a frontier the field is only beginning to quantify — but one she finds genuinely compelling.

“Medical dermatology has been evolving for the past 2 decades in ways that have escalated and escalated and escalated what our treatment options look like. We're now looking at patients with a different set of eyes, a different lens, into what we can therapeutically achieve. And to me, it's just a brilliant moment,” Ackerman said.

Relevant disclosures for Ackerman include AbbVie, Alumis, Amgen, Arcutis, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, L'Oréal, Novartis, Sun Pharmaceutical, and UCB.

Johnson & Johnson. FDA approval of ICOTYDE™ (icotrokinra) ushers in new era for first-line systemic treatment of plaque psoriasis with a targeted oral peptide. Press release. March 18, 2026. 

https://www.jnj.com/media-center/press-releases/fda-approval-of-icotyde-icotrokinra-ushers-in-new-era-for-first-line-systemic-treatment-of-plaque-psoriasis-with-a-targeted-oral-peptide

Merola JF, et al. Ixekizumab with tirzepatide achieved greater disease control than ixekizumab alone in adults with psoriatic arthritis and overweight or obesity: results from a randomized clinical trial. 

Eli Lilly and Company. Phase 3b data presented at AAD Annual Meeting show Lilly's Taltz (ixekizumab) plus Zepbound (tirzepatide) delivered superior efficacy for adults with psoriatic arthritis and obesity. Press release. March 28, 2026. 

https://investor.lilly.com/news-releases/news-release-details/phase-3b-data-presented-aad-annual-meeting-show-lillys-taltz

Ackerman offers a broad perspective on how psoriatic treatment is shifting, from oral IL-23 inhibitors to the emerging role of incretin therapy in psoriatic disease.

Lindsay S. Ackerman, MD, FAAD

Articles