Navigating the Evolving Landscape of Biologic Agents in Plaque Psoriasis Treatment

AJMC: In your experience, how has the rise of biologic agents in plaque psoriasis really changed the treatment landscape?

LEBWOHL: The rise of biologic agents in plaque psoriasis treatment has transformed patient care significantly. I recall attending Psoriasis Foundation meetings where patients expressed frustration with previous treatment approaches. They underwent rigorous regimens involving frequent visits or costly home units, often with limited success. Methotrexate and cyclosporine were also risky options. This landscape shifted with the introduction of drugs like alefacept and efalizumab offering improved response rates and reduced treatment burden.^1,2

Subsequently, TNF-α blockers (including etanercept, adalimumab, certolizumab pegol, and infliximab) emerged with notable efficacy against psoriasis. Despite box warnings for infection and malignancy, their risks were manageable. IL-12/IL-23 blockers marked another advancement with increased efficacy. Their safety profile was reassuring.^3-6

IL-17 blockers offered even greater efficacy, and their [adverse] effects were predictable. [These were] primarily yeast infections, just as occur in patients born deficient in IL-17. When brodalumab (an IL-17 receptor blocker) arrived, it showcased unprecedented efficacy.^7,8 Though a signal for suicides impacted its market presence, I continue to use it successfully in challenging cases. Studies involving bimekizumab were marked by impressive results in phase 3 trials, with 59% of patients achieving PASI 100 at the end of the placebo-controlled period.⁹

IL-23 blockers, preceding IL-17 in the psoriasis cascade, offer lasting remission through infrequent dosing.¹⁰ Presently, IL-17 blockers and IL-23 blockers dominate our approach, with the addition of bimekizumab further enhancing our ability to achieve remarkable clearance, even in severe cases. Consequently, phototherapy utilization in our center has diminished significantly, highlighting the substantial impact of biologic agents on the treatment landscape.

AJMC: What are the important factors that clinicians should consider when selecting a biologic treatment for plaque psoriasis for their patients?

LEBWOHL: When selecting a biologic treatment for plaque psoriasis, several crucial factors come into play. I vividly recall a meeting where I addressed a sizable group of patients, navigating the complex array of available drugs. To guide decision-making, I referred to an article published in the Journal of The American Academy of Dermatology co-authored with Shivani Kaushik, MD, my resident at the time.

I posed a series of questions to the group, asking them all to stand up. After reading a list of conditions and symptoms that included psoriatic arthritis, joint pain, obesity, heart disease risk factors, (including history of heart attack, family history, smoking, hypertension, and diabetes), cancer history, inflammatory bowel disease, multiple sclerosis, and blood tests for hepatitis C, hepatitis B, and HIV, I asked anyone to sit down if I mentioned a condition that affected them. Only 1 patient remained standing.

No universal drug solution exists, and tailoring treatment relies on patients’ unique conditions. For example, patients with psoriatic arthritis generally benefit from TNF-α and IL-17 blockers. For patients with heart disease, we typically lean toward TNF-α blockers, and we tend to select TNF-α or IL-23 blockers for patients with Crohn disease. IL-17 blockers are preferred for patients with multiple sclerosis. For patients with obesity—since infliximab and ustekinumab are dosed according to body weight, those are actually pretty good drugs in that setting. Drugs like etanercept or adalimumab are less effective in patients with obesity, so you may want to use more effective IL-17 or IL-23 blockers.¹¹

Lifestyle considerations further influence decisions. For college-bound individuals seeking convenience, a drug with 3-month dosing gains prominence. Pregnancy planning necessitates drugs with favorable pregnancy profiles and extended response durations, like certolizumab pegol, which does not cross the placenta.¹² Personalized drug selection hinges on each patient’s unique circumstances and preferences.

AJMC: How do the biologic agents differ in terms of immunogenicity and the development of antidrug antibodies?

LEBWOHL: Differences in immunogenicity and the development of antidrug antibodies are notable among biologic agents, particularly with TNF-α blockers such as infliximab and adalimumab. To counteract this, these drugs are often coadministered with methotrexate. Infliximab, in particular, exhibits significant antibody formation leading to reduced efficacy and injection reactions.¹³

A significant observation is that starting and stopping a drug seems to trigger antibody development. This trend holds true across various drugs. For instance, secukinumab and tildrakizumab display impressive recapture rates of 95% and 96%, respectively, upon retreatment after cessation. For risankizumab and guselkumab, the recapture rates range from 84% to 88%, showing some efficacy loss. However, the current non–TNF-α-blocker drugs frequently employed in practice generally exhibit favorable immunogenicity profiles.¹⁴

AJMC: How do efficacy and safety comparisons between different biologics inform treatment selection? Do clinicians think about “classes” in this context, or is it a consideration of product vs product?

LEBWOHL: The targeted nature of biologics renders them notably safer than prior treatments like methotrexate, cyclosporine, and acitretin. Though JAK inhibitors carry box warnings and are not recommended as first-line, their adverse effect incidence remains remarkably low, bolstering their safety profile. Within the biologics realm, both IL-17 and IL-23 blockers emerge as exceptionally benign options.

IL-17 and IL-23 blockers lack box warnings and pose no contraindications for patients with malignancies. Monilial infections are uncommon and a mild concern with IL-17 blockers; IL-23 blockers present minimal worries. Previously, utilizing TNF-α blockers necessitated thorough warnings about infections and malignancies due to box warnings.

Treatment with deucravacitinib boasts gentle cautions without box warnings. Despite upadacitinib carrying various box warnings, its substantial effectiveness in psoriatic arthritis balances the low occurrence rate of these events. This context aids patients in making informed choices when weighing the low risk against the notable benefits of these treatments.^15,16

AJMC: How do personalized medicine approaches, disease severity and extent, and comorbidities and safety considerations factor into treatment selection for plaque psoriasis?

LEBWOHL: In personalized treatment approaches for plaque psoriasis, various factors influence selection to cater to patients’ unique needs. Disease severity plays a pivotal role. If patients are severely affected, IL-17 blockers are preferred for their rapid effectiveness.While IL-23 blockers might be suitable for certain patients due to their longer onset, the psychological burden can drive the choice toward faster-acting options.

Addressing comorbidities, safety concerns and patient preferences is integral. For instance, patients might lean toward IL-23 blockers for their longer dosing intervals. However, the efficacy of IL-17 blockers might lead these patients to consider this option, with bimekizumab’s possible upcoming every-2-month regimen providing further ease. Patient perception shifts once they experience injections, as they find them painless and life-changing.¹⁷

The personalized approach to plaque psoriasis treatment encompasses disease severity, psychological impact, comorbidities, and safety considerations, ensuring that the most suitable biologic agent is chosen for each patient’s unique circumstances.

AJMC: How do sequencing of treatment and switching of strategies influence the selection of options and optimize outcomes for nonresponders or inadequate responders?

LEBWOHL: Treatment sequencing and switching strategies play a pivotal role in optimizing outcomes for nonresponders or inadequate responders. When a patient fails to respond, the focus shifts to more effective alternatives within or across drug classes. Augmentation options like topical creams or adding oral agents can also be considered.

For patients who do not achieve desired results on IL-23 and IL-17 blockers, our recent study explored deucravacitinib as a promising solution. Historically, apremilast served a similar role, albeit with modest effectiveness. Addition of deucravacitinib displayed robust skin nonresponse improvement, albeit with slightly less efficacy for joint nonresponse. This reinforces the importance of evolving strategies to cater to individual patient needs.

It is important to note that the efficacy variation might not be a class-wide effect. Patients who did not respond to 1 IL-23 blocker could find success with another agent within the same class. This individualized approach ensures the optimization of treatment outcomes for patients who initially had inadequate responses.

AJMC: What are some of the things that you consider if it is a patient’s financial toxicity perspective that they need to be on a different agent?

LEBWOHL: Navigating the financial toxicity aspect for patients requires careful consideration. Challenges often arise when dealing with Medicare, a recurring issue throughout my career. The reality is that patients might need to transition from an effective drug to a more affordable option due to financial constraints. This is a common occurrence in my practice.

A noteworthy opportunity is tildrakizumab, which, interestingly, was not tested for at-home use during trials. Consequently, the FDA does not label it for home use, Medicare cannot mandate it either, and, therefore, tildrakizumab is predominantly used in office and hospital settings.¹⁸ Although it boasts a commendable response rate, there are instances in which patients originally responding well to a potent drug have to shift to tildrakizumab. However, this transition does not always yield the desired results, especially in the most challenging cases.

These financial considerations underscore the complexities clinicians face when balancing treatment effectiveness with patient affordability.

AJMC: How long do you typically give a patient on that initial biologic therapy to determine whether or not they’re a nonresponder or an inadequate responder? What optimization strategies do you use for nonresponders or inadequate responders to biologic agents in plaque psoriasis treatment?

LEBWOHL: Determining a patient’s response to initial biologic therapy involves a comprehensive approach. Our drug registry, CorEvitas, aids in tracking patient adherence. Remarkably, patients are highly compliant, as evidenced by cases in which tildrakizumab maintained a patient’s clearance for over 2 years, demonstrating the drug’s durable nature.

Occasionally, unique situations arise, like during the COVID-19 pandemic, in which misinformation led patients to halt treatment due to perceived immunosuppression. However, these drugs, specifically IL-23 blockers, are highly targeted and not broadly immunosuppressive. In fact, data suggests that patients on certain biologics fare better against COVID-19.

Precision in dosing timing is not pivotal, as these drugs exhibit consistent efficacy. For instance, in cases involving secukinumab, flexible dosing schedules—like multiple injections over a short span—yielded favorable results without causing adverse events.¹⁹

Our experience underscores the drugs’ safety and efficacy, even in unconventional dosing scenarios. For instance, over 100 cases demonstrated successful results when patients inadvertently received multiple injections in a week. In essence, these instances reinforce the drugs’ robust safety profiles and consistent outcomes.

AJMC: What are the key takeaways and practical considerations for clinicians when comparing and contrasting different biologic agents in the treatment of plaque psoriasis?

LEBWOHL: Key takeaways from comparing biologic agents for plaque psoriasis emphasize the unique advantage of targeted therapies. By precisely targeting specific molecules, biologics spare patients from collateral damage often associated with oral medications. Although administered through injection, biologics’ high level of targeting translates into remarkable safety.

Dermatology has pioneered this approach, swiftly embracing biologics and subsequently influencing various medical fields. Our breakthroughs have led to advancements in treating inflammatory conditions and cancers originating from our innovative strides in psoriasis management.

Current developments also present promising avenues. Janssen, for instance, has crafted oral small-molecule agents designed to specifically target the IL-23 receptor. This approach marries the targeting precision of biologics with the convenience of oral medication. An analogous strategy involving oral IL-17 molecules also holds potential.

Moreover, the progress extends to severe conditions like pustular psoriasis. The advent of a biologic targeting the IL-36 receptor has revolutionized treatment, offering patients newfound safety and exceptional efficacy.

In essence, dermatology’s proactive adoption of biologics has catalyzed breakthroughs across medical disciplines, setting the stage for future advancements that marry precision targeting and safety.

References

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