Jeffrey Crowley, MD, MS

Integrating Comparative Evidence to Optimize Psoriasis Treatment Decisions

In the final episode, "Integrating Comparative Evidence to Optimize Psoriasis Treatment Decisions," the panelists explore how the full body of available evidence, including comparative analyses, long term extension studies, real world data, and clinical experience, can be integrated into practical treatment decision making for plaque psoriasis.

The panel opens by outlining the distinct role each type of evidence plays in clinical practice. Comparative studies including MAICs, network meta-analyses, and head to head trials are valued for helping clinicians identify which therapy is most likely to work best for a given patient when all else is equal. Long term extension studies are primarily used to provide patients with reassurance around safety, offering years of accumulated clinical trial safety data with no new emerging signals. Real world data is highlighted as particularly valuable for informing drug persistence and helping clinicians select a therapy that patients are likely to stay on long term, reducing the burden of frequent switching for both the patient and the clinical team. The panel also acknowledges the role of anecdotal clinical experience, noting that when personal observations align with what is seen across clinical trial and real world data, it creates a compelling and well supported basis for treatment recommendations.

The discussion then turns to how community practice dermatologists can apply comparative evidence in their daily practice, with the panel emphasizing the importance of understanding what MAICs are and how to interpret them in the absence of head to head trial data. The panel acknowledges that real world evidence takes time to generate, making other data sources particularly important when evaluating newer agents.

The episode concludes with a summary of the strengths of the IL-23 inhibitor class, including superior efficacy, infrequent dosing, and a strong safety profile, and reinforces that each piece of evidence, from phase three trials to real world analyses, contributes to a complete picture that enables truly holistic and patient centered treatment decisions.

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Evaluating IL-23 Inhibitors with Long-Term Data and Real-World Evidence

In this episode, "Evaluating IL-23 Inhibitors with Long-Term Data and Real-World Evidence," the expert dermatologists explore the distinct but complementary roles of long term extension studies and real world evidence in evaluating the durability and safety of biologic therapies for plaque psoriasis.

The panel opens by examining the value and limitations of long term extension studies. While these studies are considered valuable primarily for identifying emerging safety signals and assessing whether adverse events accumulate over time, the panel expresses some skepticism about their ability to accurately reflect long term durability of response. This is because patients who remain in long term extension studies tend to be those who are already responding well, creating an inherently enriched population that does not capture patients who may have struggled to respond early on.

The discussion then shifts to real world evidence, with the panel outlining the key sources of this data including patient registries such as CorEvitas and various country specific registries, as well as claims based data. Registries are noted as semi real world in nature given their lack of strict entry criteria compared to clinical trials, while claims based data offers insight into how long patients persist on a given therapy, though often without accompanying efficacy data unless linked to electronic medical records.

The panel emphasizes that real world data is critical because clinical trials represent a best case scenario, with carefully screened patients, controlled comorbidities, and a high level of clinical support including dedicated nursing staff, medication delivery, and appointment reminders that do not reflect everyday practice. In contrast, real world patients may have uncontrolled comorbidities, complex medication regimens, and limited support, making adherence more challenging. When comparing drug classes in real world analyses, IL-23 inhibitors are noted to generally outperform IL-17 inhibitors, TNF inhibitors, and newer oral agents in keeping patients on therapy over time.

The last episode in this series, "Integrating Comparative Evidence to Optimize Psoriasis Treatment Decisions," features the panelists advancing their conversation on psoriasis and focusing on how clinicians can synthesize MAIC analyses, long term extension studies, real world data, and anecdotal clinical experience into a holistic framework for making individualized treatment decisions and optimizing long term outcomes for patients with plaque psoriasis.

Exploring Network Meta-Analyses (NMA) in Psoriasis

This episode, titled "Continuing the Conversation on Treatments in Psoriasis," features panelists discussing the value and limitations of network meta-analyses as a tool for comparing multiple psoriasis therapies across different clinical trials simultaneously.

The panel opens by introducing a network meta-analysis presented at a 2026 meeting that evaluated icotrokinra against multiple biologic and oral therapies. The panel explains that while NMAs allow for a broader range of comparisons than a single MAIC, the data they generate provides a range of where a drug's efficacy is likely to fall rather than a definitive declaration of superiority over any individual comparator. In this particular analysis, icotrokinra demonstrated superiority over placebo, deucravacitinib, adalimumab, apremilast, and ustekinumab. It showed comparable performance to secukinumab, guselkumab, risankizumab, and ixekizumab, while bimekizumab and brodalumab outperformed icotrokinra in this analysis.

The panel then outlines the key methodological limitations of NMAs compared to MAICs. Unlike MAICs, NMAs do not adjust for differences in patient population demographics across studies, relying instead on assumptions that treatment effects would have behaved similarly across different trial populations. The panel cautions that higher placebo response rates in one study can make a drug appear less effective, and that overlapping confidence intervals in an NMA do not necessarily mean two drugs are equivalent, citing examples where head to head trials have subsequently demonstrated clear superiority of one agent over another despite NMA results suggesting comparability.

The panel concludes by acknowledging that both MAICs and NMAs have inherent limitations including known and unknown demographic confounders, and that head to head trials remain the gold standard for drug comparisons. However, given the significant resources required to power head to head trials sufficiently, particularly in a field where leading therapies perform at very high levels, these indirect comparison tools remain important and valuable pieces of the overall evidence puzzle.

In the next episode, "Evaluating IL-23 Inhibitors with Long-Term Data and Real-World Evidence," panelists will continue their discussion on psoriasis and highlight the complementary roles of long term extension studies and real world evidence in assessing the durability and safety of IL-23 inhibitors, and why real world data is critical for understanding how these therapies perform outside of the controlled clinical trial setting.

This episode, titled "Continuing the Conversation  on Treatments in Psoriasis," features panelists discussing the value and limitations of network meta-analyses as a tool for comparing multiple psoriasis therapies across different clinical trials simultaneously.

Continuing the Conversation  on Treatments in Psoriasis

Evaluating Psoriasis Therapies using MAICs

In "Evaluating Psoriasis Therapies using MAICs," our panel delves into several recent and clinically meaningful MAIC analyses comparing biologic therapies for plaque psoriasis, examining what the data reveals about relative efficacy across treatment classes and how these analyses have been validated over time.

The panel opens by discussing a recently presented anchored MAIC comparing risankizumab to icotrokinra, an oral IL-23 receptor blocker not yet approved for psoriasis. Using risankizumab patient level data matched to icotrokinra's aggregate demographic data and adjusted for placebo response, the analysis demonstrated statistically significant superiority for risankizumab across PASI 75, 90, and 100 endpoints at weeks 4, 8, 12, and 16. The panel is careful to note that icotrokinra performed well overall, and that the superiority observed reflects the rigor of the adjusted analysis rather than a dismissal of the comparator drug.

The discussion then broadens to cover three additional MAICs conducted across different biologic classes. The first compared risankizumab to deucravacitinib, a TYK2 inhibitor, showing risankizumab superiority with a 32 to 40% delta across PASI 75, 90, and 100 endpoints. The second compared deucravacitinib to adalimumab using long term extension data rather than a placebo controlled period, demonstrating a 10 to 13% delta favoring deucravacitinib at approximately two years. The third compared guselkumab to ixekizumab over three years, finding that while the IL-17 inhibitor ixekizumab performed faster initially, guselkumab not only caught up but appeared to outperform it in the long run.

The panel highlights that the true validation of the MAIC methodology lies in the fact that dedicated head to head trials subsequently conducted for both risankizumab versus deucravacitinib and guselkumab versus ixekizumab confirmed the findings predicted by the earlier MAIC analyses. The panel also acknowledges important methodological considerations for long term MAICs, including the absence of a placebo group, population enrichment over time, and the challenge of handling missing data, while noting that certain study designs used multiple statistical analyses and placebo crossover patients to strengthen the robustness of their conclusions.

Our next episode, "Exploring Network Meta-Analyses (NMA) in Psoriasis," further explores psoriasis highlighting the utility and limitations of network meta-analyses as a complementary statistical tool for comparing multiple biologic and oral therapies simultaneously, and how findings from a recent NMA evaluating icotrokinra against several available treatments help contextualize its place within the broader IL-23 treatment landscape.

Jeffrey Crowley, MD, MS

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