Bruce Strober, MD, PhD, FAAD

PsO Sequencing and Future Research 

As the psoriasis (PsO) armamentarium has grown, the question of how to sequence therapies — both initially and following partial or inadequate response — has become increasingly consequential. A patient's response to an IL-23 directed therapy, whether injectable or oral, provides direct in vivo information about the contribution of the IL-23 pathway to their individual disease. Partial response — on the order of 50% to 60% skin improvement after an adequate trial of at least 3 months — indicates that IL-23 inhibition is producing meaningful benefit and supports escalation within the class to a more potent IL-23 monoclonal antibody. Absence of meaningful response after an adequate trial argues against remaining within the IL-23 class and supports a mechanism switch to an IL-17 inhibitor rather than substituting one IL-23 directed agent for another. This sequencing logic provides a more principled basis for sequential prescribing than trial-and-error substitution and is directly applicable whether the initial IL-23 directed therapy was injectable or oral. Clinicians should also account for the time course of IL-23 inhibition: these agents typically reach maximal effect beyond week 16, often requiring 24 to 36 weeks for full benefit, and patients and clinicians must align expectations accordingly to avoid premature switching based on an incomplete response assessment.

Several important clinical questions in PsO remain incompletely answered and are likely to shape the field's trajectory over the next several years. Whether early, aggressive treatment with biologic therapy — initiated before structural joint damage or significant comorbid disease burden has accumulated — improves long-term outcomes for both skin and musculoskeletal disease is an active area of investigation with direct implications for when clinicians should escalate from conventional to advanced therapy. The relationship between biologic treatment and cardiovascular risk represents a second major frontier: PsO is associated with elevated cardiovascular risk through shared inflammatory mechanisms, and the degree to which effective suppression of psoriatic inflammation modifies that risk over time remains incompletely characterized but is an area of growing evidence. Body weight intersects with both questions — lower body weight is associated with better biologic response rates and with improved cardiovascular outcomes in PsO patients — and understanding how weight modulates both efficacy and downstream health outcomes has meaningful implications for how clinicians counsel patients about lifestyle alongside pharmacologic management.

Special Report final segment, Bruce Strober, MD, PhD, Clinical Professor of Dermatology at Yale University School of Medicine, surveys the therapeutic developments most likely to alter practice patterns over the next 5 years. Biologics with substantially extended half-lives capable of supporting dosing intervals of every 6 to 12 months — rather than the current standard of every 8 to 12 weeks at maintenance — are in development and would fundamentally change the treatment experience for patients who are well-controlled but find even quarterly injections burdensome.

Next‑generation oral agents continue to progress through clinical development, contributing additional options to the psoriasis treatment landscape, though their ultimate role relative to injectable biologics remains to be defined. While some have shown promising efficacy signals and acceptable safety profiles in controlled trial settings, these agents have not yet demonstrated the consistency, durability, or depth of response that underpin long‑term confidence in established biologic therapies. As a result, competition with injectable biologics is likely to remain selective and patient‑specific rather than broadly transformative.

Strober suggests that the distinction between oral and injectable therapy may evolve over time, but injectable biologics continue to represent the standard for patients with more significant disease burden, particularly where sustained clearance and long‑term outcomes are key priorities. Effectively navigating this landscape requires clinicians to balance short‑term efficacy signals with mechanistic rationale, durability of evidence, comorbidity considerations, and patient expectations—recognizing that psoriasis management is fundamentally longitudinal and that early convenience advantages must be weighed against long‑term disease control in a lifelong condition.

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Bruce Strober, MD, PhD, details a principled approach to sequencing psoriasis therapies based on mechanism and response pattern.

Updates in PsO Sequencing and Future Research 

Risankizumab vs Icotrokinra for Psoriasis 

With multiple high-performing agents now available for moderate to severe psoriasis (PsO), clinicians increasingly face a decision not between effective and ineffective therapy but among options that differ in mechanism, route, dosing schedule, and depth of long-term evidence. Comparative effectiveness data — including indirect analyses presented at major dermatology meetings — can inform these distinctions, but their clinical utility depends on a working standard for when observed numerical differences in response rates are large enough to matter in practice. Across PASI 90 and PASI 100 endpoints, absolute differences of approximately 7% to 10% or greater typically correspond to advantages that are clinically discernible — representing a meaningful proportion of additional patients achieving the outcome that defines therapeutic success in PsO. Differences below approximately 5% are rarely distinguishable at the bedside and generally should not drive agent selection in isolation. This framework is most useful when applied alongside consideration of the methodological quality of the underlying analysis and its congruence with pivotal trial data and real-world clinical experience.

Indirect comparison data presented at recent major dermatology meetings comparing risankizumab and icotrakinra across PASI response thresholds and time points have demonstrated consistently higher placebo-adjusted response rates for risankizumab. Applied against the clinical threshold framework above, this difference reflects a real efficacy advantage for risankizumab that is relevant in practice — particularly for patients in whom maximum achievable skin clearance is the primary goal. Icotrakinra's phase 3 data through 1 year are considered robust, and its PASI 90 response rates of approximately two-thirds of patients at week 24 represent a meaningful advance for the oral therapy category. However, multi-year durability data comparable to those now available for risankizumab and other established IL-23 biologics have not yet been generated for icotrakinra, and this evidence gap is a practical consideration when selecting between an established biologic with a decade of real-world experience and a newer oral agent whose long-term performance profile is still being characterized.

In this Special Report segment, Bruce Strober, MD, PhD, Clinical Professor of Dermatology at Yale University School of Medicine, contextualizes these comparative data within the broader framework of how clinicians should weigh efficacy differences against route-of-administration preferences and long-term durability when making individual prescribing decisions. He emphasizes that the goal of comparative effectiveness data is not to produce a single rank-ordered list of agents but to equip clinicians with a principled basis for matching the right therapy to the right patient — and that matching requires accounting for what is known and what remains unknown about each option's long-term performance. For patients who prioritize maximum skin clearance and value the extensive safety and durability record of an established biologic, the data support risankizumab as a well-characterized, high-performing choice. For patients who prioritize oral administration and for whom the efficacy ceiling of an oral agent is clinically acceptable, icotrakinra represents a genuine advance. The decision between them is not a question of one therapy being categorically superior but of which profile best aligns with an individual patient's disease characteristics, preferences, and tolerance for uncertainty about long-term outcomes.

Bruce Strober, MD, PhD, introduces a practical framework for determining when differences in efficacy between psoriasis treatments are clinically meaningful.

IL-23 Inhibition and Preventing Psoriasis Progression 

Within the IL-23 inhibitor class — which includes risankizumab, guselkumab, and tildrakizumab — headline efficacy for skin disease is broadly comparable across agents, and large differences in PASI 90 or PASI 100 response rates at the class level are not observed in clinical practice. The more clinically meaningful distinctions lie in maintenance dosing intervals, emerging data in psoriatic arthritis, and the depth of accumulated long-term experience. Risankizumab is administered every 12 weeks at maintenance, while guselkumab requires every-8-week dosing — a difference that carries practical significance for patients who highly value infrequent injections. For some patients, the difference between 4 and 6 maintenance injections per year is a material factor in long-term adherence and treatment satisfaction, and clinicians should address it explicitly rather than treating it as incidental to the prescribing decision. Tildrakizumab occupies a similar maintenance interval to guselkumab and represents an additional option within the class, though its use in psoriatic arthritis is more limited.

Psoriatic arthritis data are increasingly reviewed to understand nuance within the IL‑23 class; however, clear clinical differentiation between agents remains limited. In routine practice, treatment selection is guided by overall disease control, durability, safety profile, comorbidities, and patient‑reported outcomes rather than any single joint‑specific endpoint. Differences in available PsA data across IL‑23 therapies largely reflect variations in clinical development programs rather than established superiority.

For patients with concomitant skin and joint involvement, IL‑23 inhibitors are commonly selected based on their consistent skin efficacy and favorable long‑term profiles, with improvement in joint symptoms viewed as part of broader inflammatory control. Structural or imaging outcomes may provide supportive context but are generally interpreted alongside functional measures and symptomatic response. For axial disease, IL‑17 inhibitors continue to have the strongest supporting evidence, while IL‑23 therapies are primarily positioned for patients whose treatment priorities are centered on sustained skin clearance with acceptable joint outcomes.

In this Special Report segment, Bruce Strober, MD, PhD, Clinical Professor of Dermatology at Yale University School of Medicine, identifies long-term drug survival as perhaps the most underappreciated factor in biologic selection. Registry and real-world data consistently demonstrate that IL-23 inhibitors exhibit superior drug survival compared with other biologic classes — patients are more likely to remain on an IL-23 inhibitor without loss of response, switching, or discontinuation over a 3- to 5-year horizon. This durability has direct practical consequences: each therapy switch in psoriasis carries administrative burden through prior authorization requirements, potential coverage gaps, and patient disruption — all of which add friction and can compromise disease control during transitions. A therapy that a patient can remain on effectively for 5 or more years avoids that friction entirely. Strober's real-world experience with risankizumab across approximately 800 treated patients reflects this durability in practice — he characterizes it as a mature agent whose performance is predictable, producing responses that deepen over the first 24 to 36 weeks and are sustained reliably over years in the majority of patients who respond initially. Patients on risankizumab frequently describe their outcomes in strongly positive terms, a pattern he attributes to the combination of deep skin clearance, infrequent dosing burden, and a tolerability profile that imposes no meaningful limitations on daily life.

Bruce Strober, MD, PhD, compares agents within the IL-23 inhibitor class on dosing schedule and joint outcome data, and explains why long-term drug survival has become a central consideration in biologic selection for psoriasis.

Comparing IL-23 Inhibitors — Dosing Intervals, Radiographic Data, and Long-Term Drug Survival

Patient-Level Treatment Drivers in Psoriasis

Effective psoriasis (PsO) management increasingly depends on a treatment selection framework that extends beyond skin severity to encompass the full clinical and contextual profile of the individual patient. Route of administration is among the most practically influential of these factors. Some patients may express an instinctive preference for oral medications, but that preference is rarely fixed and often shifts when clinicians provide the comparative context needed to make a genuinely informed choice — including how often injections actually occur at maintenance and how that burden compares with the commitment of daily oral dosing. For a patient on a biologic with every-12-week maintenance dosing, the annual injection burden is 4 administrations; for a once-daily oral agent it is 365. Surfacing this distinction explicitly, rather than assuming patients have already weighed it, is an important part of the prescribing conversation in PsO. Patients who value minimal day-to-day treatment interaction once disease is controlled may find that a long-interval injectable biologic ultimately imposes less lifestyle burden than they anticipated.

The presence, severity, and anatomical pattern of psoriatic arthritis are among the most consequential determinants of mechanism selection in patients with psoriatic disease. IL-17 inhibitors carry the most robust data across the full spectrum of psoriatic arthritis domains — peripheral joint disease, distal interphalangeal involvement, dactylitis, enthesitis, and axial disease — and have demonstrated inhibition of radiographic progression. For patients with prominent axial psoriatic arthritis in particular, IL-17 blockade remains the preferred mechanism, supported by an evidence base that other classes have not yet matched for this specific manifestation. Within the IL-23 class, guselkumab has recently demonstrated radiographic benefit in psoriatic arthritis, meaningfully narrowing the differentiation between IL-17 and IL-23 agents for patients with distal joint involvement, though axial disease continues to favor IL-17 inhibition. Conversely, IL-17 inhibitors carry an important contraindication in patients with inflammatory bowel disease — a comorbidity not uncommon in PsO — whereas IL-23 inhibitors can be used across a considerably broader comorbidity range without meaningful restriction.

In this Special Report segment, Bruce Strober, MD, PhD, Clinical Professor of Dermatology at Yale University School of Medicine, describes the practical decision framework he applies at the point of prescribing. IL-23 inhibitors occupy a favored default position for most patients with skin-predominant disease: they offer infrequent maintenance dosing, an essentially unrestricted comorbidity profile outside of active infection, and long-term durability data that compare favorably with other biologic classes. IL-17 inhibitors are reserved primarily for patients with significant psoriatic arthritis — particularly axial disease — where the evidence for superior joint outcomes justifies accepting a more restrictive contraindication profile. Oral agents are positioned for patients who prioritize the oral route and can accept a somewhat lower efficacy ceiling than the most potent injectable biologics. This mechanism-first framework, calibrated by comorbidity and arthritis pattern before patient preference is layered on, reflects how substantively PsO treatment selection has evolved from stepwise escalation into a nuanced, multidimensional clinical decision.

Bruce Strober, MD, PhD, examines patient preference for oral versus injectable therapy.

Bruce Strober, MD, PhD, FAAD

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