Evaluating the Evidence for Emerging Oral Therapies in Psoriasis

In this Expert Perspectives video, Andrew Blauvelt, MD, MBA, discusses emerging efficacy data for targeted oral psoriasis therapies and how clinicians can interpret head-to-head trials, indirect comparisons, long-term outcomes, and difficult-to-treat disease when making treatment decisions.

The expanding psoriasis treatment landscape offers clinicians increasingly effective oral and injectable options, but determining how new therapies compare requires careful interpretation of clinical trial evidence. In this Dermatology Times Expert Perspectives video, Andrew Blauvelt, MD, MBA, dermatologist at Blauvelt Consulting in Annapolis, Maryland, and adjunct professor at the University of Maryland School of Medicine, discusses how clinicians can critically evaluate emerging data and translate efficacy findings into individualized treatment decisions.

Interpreting Head-to-Head Evidence

Blauvelt highlighted the value of head-to-head trials for understanding where emerging therapies may fit within an increasingly crowded treatment landscape. He discussed phase 3 findings for icotrokinra, an investigational targeted oral peptide designed to block the IL-23 receptor, including results from the ICONIC clinical development program.

In ICONIC-LEAD, 65% of patients receiving icotrokinra achieved an Investigator's Global Assessment (IGA) score of 0 or 1 at week 16 compared with 8% receiving placebo, while PASI 90 responses were achieved by 50% and 4%, respectively. In the ICONIC-ADVANCE 1 and 2 trials, approximately 68% to 70% of patients receiving icotrokinra achieved IGA 0/1 at week 16, with PASI 90 responses ranging from 55% to 57%. The studies also demonstrated superiority to deucravacitinib at weeks 16 and 24. Andrew Blauvelt Expert Perspect…

For Blauvelt, however, efficacy percentages need to be interpreted within the design of the study. The comparator selected for a trial helps determine the clinical question that the results can answer. An active-comparator trial can provide clinicians with more practical information than a placebo-controlled study alone, but the strength of the conclusion also depends on how effective that comparator is relative to other available therapies.

That distinction is increasingly important as newer oral therapies seek to narrow the historical efficacy gap between oral systemic agents and injectable biologics.

Putting Indirect Comparisons Into Context

Direct randomized comparisons between every psoriasis therapy are not feasible, making network meta-analyses and matching-adjusted indirect comparisons useful tools for estimating how treatments may perform relative to one another.

Blauvelt discussed emerging analyses comparing icotrokinra with injectable IL-23 inhibitors, as well as a matching-adjusted indirect comparison involving risankizumab and icotrokinra. The discussion guide also points toward ongoing head-to-head studies, including ICONIC-ASCEND, as an opportunity to strengthen the evidence available for direct treatment comparisons. Andrew Blauvelt Expert Perspect…

Although indirect comparisons can help clinicians contextualize efficacy when direct evidence is unavailable, Blauvelt cautioned against treating them as interchangeable with randomized head-to-head trials. Differences in patient populations, study design, baseline disease characteristics, outcome definitions, and timing of assessments can complicate comparisons across separate clinical programs.

For clinicians, the value of these analyses lies less in creating a rigid ranking of therapies and more in understanding the approximate efficacy range in which an emerging treatment may fall.

The Comparator Matters

Blauvelt also emphasized that clinicians should pay attention to what a new therapy was compared against when interpreting claims of superiority.

This becomes particularly relevant when looking across different targeted oral development programs. The pivotal trials of zasocitinib, for example, included apremilast as an active comparator. According to the episode discussion guide, approximately 69% to 71% of patients receiving zasocitinib achieved an sPGA score of 0 or 1 at week 16, with PASI 100 responses ranging from 25% to 33%. Andrew Blauvelt Expert Perspect…

A successful comparison against an established oral therapy provides clinically meaningful information, but it does not necessarily answer how that agent would compare with a highly efficacious biologic or another emerging targeted oral treatment. Understanding the comparator therefore helps clinicians avoid drawing conclusions beyond what a particular trial was designed to establish.

Looking Beyond Week 16

Blauvelt encouraged clinicians to look beyond primary end points when evaluating psoriasis therapies. Week 16 is a common landmark in clinical trials, but it does not necessarily represent the maximum response a patient will achieve.

Longer-term ICONIC data demonstrate this distinction. Among patients who achieved IGA 0/1 at week 16, 87% maintained that response through week 52. Across the broader population, IGA 0/1 responses remained between 67% and 70% from weeks 24 through 52, while complete clearance continued to improve over time. In ICONIC-ADVANCE, PASI 100 responses increased from 41% to 49% in one study and from 33% to 48% in the other between weeks 24 and 52. Andrew Blauvelt Expert Perspect…

These longer-term findings can change the conversation clinicians have with patients. A patient who has experienced meaningful improvement after several months but has not yet achieved complete clearance may still have the potential for additional benefit with continued treatment.

Setting Expectations for Difficult-to-Treat Areas

The same principle becomes particularly relevant when evaluating psoriasis in high-impact or difficult-to-treat areas. Blauvelt discussed the importance of considering disease involving areas such as the scalp, face, palms and soles, nails, and genital region, where even relatively limited involvement can substantially affect quality of life.

Response in these areas may also develop differently from overall skin clearance. Nail psoriasis, in particular, requires patience because improvement depends partly on the time required for healthy nail growth.

The long-term data discussed in the episode illustrate why clinicians should avoid judging treatment success too early. For hand and foot psoriasis, 42% of patients achieved an hf-PGA score of 0 or 1 at week 16, increasing to 62% by week 52. Mean improvement in modified Nail Psoriasis Severity Index scores increased from 33% at week 16 to 62% at week 52, with more than one-third of patients achieving completely clear nails. Andrew Blauvelt Expert Perspect…

These findings reinforce the importance of setting expectations before treatment begins, particularly for patients whose primary concern involves nails or other areas that may require longer treatment durations before the full effect becomes apparent.

Translating Trial Data Into Treatment Decisions

Ultimately, Blauvelt emphasized that clinical trial efficacy is only one component of treatment selection. Route of administration, safety, comorbid disease, patient preference, and access can all influence which therapy is most appropriate for an individual patient.

The growth of highly targeted oral therapies is particularly notable because it may give patients who prefer pills an opportunity to achieve levels of disease control that historically have been more closely associated with injectable therapies. At the same time, clinicians need to distinguish direct evidence from indirect comparisons and short-term end points from sustained long-term outcomes when discussing these options.

Rather than focusing on a single PASI or IGA percentage, Blauvelt's discussion underscores the importance of examining the totality of the evidence: how a study was designed, which comparator was used, how responses evolved over time, and whether the available data reflect the outcomes that matter most to the individual patient.

References

1. Johnson & Johnson. Icotrokinra shows superiority to deucravacitinib in first reported head-to-head trials reinforcing promise of investigational targeted oral peptide for treatment of plaque psoriasis. Published September 17, 2025. Accessed October 6, 2026. JNJ.com
2. Johnson & Johnson. ICOTYDE (icotrokinra) one-year results confirm lasting skin clearance and favorable safety profile in once-daily pill for plaque psoriasis. Published March 28, 2026. Accessed October 6, 2026. Johnson & Johnson Investor Relations