Topical Conversations

In this episode of Topical Conversations, Dawn Merritt, DO, and Neal Bhatia, MD, discuss the management of patients with psoriasis who benefit from a higher-touch approach to care. Their conversation extends beyond selecting an effective biologic to examine how ongoing clinical engagement can support adherence, identify barriers to treatment, and provide opportunities to address the broader health concerns. The speakers also explore how health care professional (HCP)-administered biologics can facilitate regular patient contact and reinforce long-term treatment success.Identifying patients who benefit from closer follow-upDr Bhatia describes the "higher-touch patient" as someone who requires more frequent engagement to remain connected to treatment and achieve the best possible long-term outcomes. Rather than focusing solely on prescribing therapy, he emphasizes understanding where patients are in their treatment journey, discussing their goals, and helping them navigate the lifestyle changes that often accompany psoriasis management.These patients are not defined solely by disease severity. As clinicians develop long-term relationships with their patients, they often recognize social or logistical challenges that can interfere with treatment adherence. Dr Merritt describes a college student whose living situation made storing and self-administering a biologic both impractical and uncomfortable. Transitioning to an in-office administered biologic provided structured follow-up visits that helped keep the patient engaged with treatment.Dr Bhatia highlights similar situations among military personnel, who may face practical barriers to storing injectable medications or concerns about administering injections in shared living environments. For these patients, in-office administration can improve adherence while giving clinicians greater confidence that treatment is being received as intended.Regular touchpoints create opportunities beyond skin clearanceBoth speakers emphasize that scheduled office visits provide opportunities to evaluate much more than psoriasis severity. Dr Bhatia explains that seeing patients regularly allows clinicians to identify factors that may be limiting treatment response, including smoking, obesity, or other lifestyle influences that may not be apparent during less frequent follow-up.These visits also create opportunities to manage persistent symptoms while patients are working toward maximal biologic efficacy. Ongoing assessment of itch, scalp involvement, nail disease, joint symptoms, and oral manifestations allows clinicians to address residual disease, optimize supportive therapies, and better understand how psoriasis is affecting patients' daily lives, including their ability to exercise, work, and maintain overall health.Seeing the whole patientDr Merritt highlights the unique value of regular office visits among Medicare patients, many of whom appreciate returning every 12 weeks for treatment and develop strong relationships with the clinical staff. These encounters often reveal important health or social concerns that might otherwise go unnoticed.She recalls caring for an older patient whose psoriasis remained well controlled but who appeared withdrawn following the recent loss of his wife. During his treatment visit, she recognized signs that he was struggling with nutrition and self-care, ultimately reaching out to family members to help ensure he received additional support beyond dermatologic treatment.Dr Bhatia agrees that subtle changes in a patient's appearance, behavior, or overall well-being are often easier to recognize during in-person visits. He also notes that the broader clinical team can play an important role in identifying concerns that warrant further attention. For patients with metabolic syndrome or elevated cardiovascular risk, these regular encounters provide additional opportunities to remain engaged with their overall health, not just their skin disease.Persistence and adherence with HCP-administered biologicsDr Merritt also discusses real-world evidence suggesting strong treatment persistence with IL-23 inhibitors.While persistence is influenced by multiple factors, both speakers suggest that HCP-administered biologics may contribute by reducing some of the logistical barriers associated with self-administration. For patients who struggle with medication storage, scheduling doses, or treatment adherence, regular in-office administration provides consistent accountability while allowing clinicians to monitor progress throughout therapy.Integrating higher-touch care into a busy practiceProviding individualized care does not necessarily require disrupting clinic efficiency. Dr Bhatia explains that thoughtful scheduling can help match visit length to patient needs. Patients who are stable and doing well may be scheduled early in the day for streamlined appointments, while retirees or patients requiring more extensive discussion may benefit from appointment times that allow for greater flexibility.He also encourages practices to consider travel time, work schedules, and other patient commitments when coordinating visits. These logistical considerations can improve patient satisfaction while maintaining efficient clinic flow.Dr Merritt adds that patients with a history of poor adherence may particularly benefit from the structure provided by regular office visits. For individuals who struggle with remembering to obtain, store, or administer medications, closer clinical follow-up can reduce treatment interruptions and improve long-term disease control.Dr Bhatia concludes by noting that many dermatologists have experienced the frustration of seeing patients return after prolonged gaps in care with uncontrolled psoriasis because treatment was never initiated or maintained. Incorporating office-based therapies when appropriate allows clinicians to maintain closer engagement with selected patients and may improve both adherence and overall outcomes.

In this episode of Topical Conversations, Tina Bhutani, MD, and Adrian Rodriguez, MD, discuss the growing role of precision medicine in psoriasis management and how predictive testing may help guide biologic selection earlier in the treatment journey. With an expanding range of biologic therapies available for psoriasis, clinicians now have more therapeutic flexibility than ever before. However, as Dr Bhutani notes, one of the persistent challenges in practice is determining which patient is most likely to respond to which therapy before treatment is initiated. The discussion centers on Mind.Px, a predictive test that uses a dermal biomarker patch to help identify the likelihood of response to biologic classes including TNF inhibitors, IL-17 inhibitors, and IL-23 inhibitors. Moving toward precision medicine in psoriasisDr Rodriguez frames Mind.Px within the broader evolution of precision medicine across medicine, noting that while other specialties have increasingly incorporated predictive tools into treatment decision-making, dermatology has historically lacked similar guidance for psoriasis biologic selection. He describes the test as a practical tool to help clinicians identify which biologic class may be the best fit for an individual patient, potentially reducing the need for therapeutic switching and minimizing delays associated with insurance approvals and treatment interruptions. They emphasize that this type of approach may be particularly valuable given the growing number of available biologics and the reality that not every therapy will be effective for every patient.Supporting patient confidence and treatment buy-inBeyond biologic selection itself, the conversation highlights how predictive testing may influence patient engagement and confidence in treatment decisions.Dr Bhutani shares that she often finds the test useful in patients who are hesitant to initiate biologic therapy, including individuals with needlephobia or concerns about long-term treatment commitment. Presenting patients with data suggesting a higher likelihood of response may help reinforce confidence in the treatment plan. Dr Rodriguez discusses a patient case involving a needlephobic frequent traveler who was concerned about treatment selection and dosing logistics. In that scenario, the test supported selection of an IL-23 inhibitor, which aligned both with predicted response and the patient’s lifestyle needs due to its dosing schedule. The speakers also note that the report format itself is intentionally straightforward, categorizing biologic classes as likely responder (R) or nonresponder (NR), making interpretation relatively simple for both clinicians and patients. Applications in biologic-experienced patientsThe conversation also explores how predictive testing may be useful in biologic-experienced patients, particularly in situations involving loss of coverage, waning efficacy, or declining patient confidence after prior treatment challenges. Dr Rodriguez notes that the test can help rebuild patient confidence when prior therapeutic choices have not produced satisfactory outcomes. Similarly, Dr Bhutani explains that she often finds the test especially valuable in experienced patients because she wants to avoid another unsuccessful treatment selection that could further reduce patient engagement. Operational and access considerationsThe discussion next shifts to practical considerations surrounding biologic access and office workflow.Dr Rodriguez highlights the administrative burden associated with biologic switching, including repeat prior authorizations, reassessments, and additional staff workload. Selecting the most appropriate therapy earlier in the process may help reduce some of these operational challenges while also potentially lowering costs associated with cycling through multiple biologics. From a workflow standpoint, Dr Rodriguez notes that implementation in clinic has been relatively streamlined. The test involves application of a dermal patch for several minutes, with a kit provided for return shipment and relatively quick turnaround times. Limitations and future directionsThe speakers also discuss several limitations of the current test.One limitation is the binary responder/nonresponder output. If a patient is predicted to respond to multiple biologic classes, the report does not currently rank therapies or indicate which option may provide the strongest response. Dr Rodriguez also notes that current response categorizations were based on PASI75 thresholds, whereas many clinicians now aim for PASI90-level outcomes in practice. He points to ongoing work evaluating PASI90 data as an important future development. Dr Bhutani further explains that earlier studies suggested stronger predictive performance in patients with more severe disease, although ongoing real-world analyses are evaluating performance in patients with lower disease severity. This may become increasingly relevant as dermatologists consider earlier biologic intervention for patients with lower BSA involvement but high-impact disease in special sites such as the scalp, hands, feet, and genital regions. Key takeawaysPredictive testing may help support biologic selection in psoriasis by identifying likely responders and nonresponders across biologic classes Mind.Px uses a dermal biomarker patch and provides a simplified responder/nonresponder report format for TNF, IL-17, and IL-23 inhibitor categories There are potential benefits for both biologic-naïve and biologic-experienced patients, including improved patient confidence and reduced therapeutic switching Practical advantages may include reduced administrative burden associated with repeated prior authorizations and treatment changes Current limitations include lack of ranked therapeutic recommendations and reliance on PASI75-based response thresholds Ongoing research is evaluating predictive performance in lower-severity psoriasis and incorporating PASI90-level outcomes into future analyses

In this episode of Topical Conversations, Bruce E. Strober, MD, PhD, joins April Armstrong, MD, MPH, to explore the origins and clinical relevance of the suicidal ideation and behavior (SI/B) warning in the bimekizumab label. With bimekizumab now approved in dermatology for adults with moderate to severe plaque psoriasis and moderate to severe hidradenitis suppurativa (HS), many clinicians are asking whether this warning reflects a meaningful safety signal or a cautious interpretation of tightly monitored trial data.Where did the SI/B language come from?Dr Armstrong explains that the warning appears in the “Warnings and Precautions” section, advising clinicians to weigh risks and benefits in patients with a history of severe depression or SI/B and to monitor for new or worsening symptoms. Importantly, the label states that a causal association has not been established.She explains the likely origin of the language: highly sensitive, prospective monitoring in the bimekizumab trials. Compared with older psoriasis studies, these trials used more rigorous tools, such as the Columbia Suicide Severity Rating Scale (C-SSRS), capturing even passive ideation. In psoriasis trials, SI/B rates were 1.8% for bimekizumab vs 0.6% for placebo, but with wide confidence intervals crossing 1, signaling no clear statistical difference.In HS trials, confidence intervals were again wide and without consistent patterns in suicidal behavior. Across psoriatic arthritis, ankylosing spondyloarthritis, and nonradiographic axial spondyloarthritis studies, short-term data did not show elevated SI/B rates with bimekizumab.Interpreting the findings: context is criticalDr Strober emphasizes that no suicides occurred in the trials; the flagged events involved passive ideation captured through structured questionnaires and not clinical suicide attempts or behaviors.To contextualize, Dr Armstrong reviews background SI/B rates in psoriasis. Patients with psoriasis exhibit roughly double the risk of suicidal ideation and elevated risk of attempts vs the general population, particularly in patients with moderate to severe disease. Across psoriasis studies, SI/B event rates range from 0.1%–0.5% per 100 patient-years.Bimekizumab’s aggregated phase 2/3 psoriasis data show an SI/B rate of ~0.13% per 100 patient-years, aligning with background disease rates.How does bimekizumab compare with other biologics?Notably, SI/B rates for bimekizumab appear comparable to, or lower than, rates reported in trials of IL-17 inhibitors (such as secukinumab and ixekizumab) and IL-23 inhibitors. Dr Strober highlights that nothing in the bimekizumab dataset distinguishes it from patterns seen with other biologics across clinical development programs.Insights from depression measures in the trialsDr Armstrong points out that depression severity, measured by PHQ-9, improved substantially with bimekizumab in clinical trials. Additional key details include no dose–response relationship for SI/B, no clustering shortly after dosing, and many events adjudicated as not drug-related.Long-term extension and emerging real-world data have not revealed a new or consistent SI/B signal.A clinician’s approach to counseling and monitoringDr. Armstrong closes by noting that depression severity improved, on average, for bimekizumab-treated patients as measured by PHQ-9 scores. Still, because the language appears in the label, she recommends dermatologists approach patient discussions with clarity: contextualize the data, acknowledge the broader mental health burden in psoriasis, and continue standard monitoring for mood changes as part of comprehensive care.Key takeawaysThe bimekizumab SI/B warning is precautionary, and a causal relationship has not been establishedEvent rates in bimekizumab trials align with background SI/B rates expected in moderate–severe psoriasis populationsNo completed suicides or clear dose-related patterns were identified across the clinical programComparable or lower SI/B rates have been observed relative to other IL-17 and IL-23 inhibitorsPHQ-9 scores improved with treatment, suggesting overall positive effects on patient well-beingClinicians should contextualize the label language when counseling patients, especially given psoriasis’ intrinsic psychiatric comorbidity burdenStandard monitoring for depression remains appropriate, but current evidence does not indicate a unique or elevated SI/B risk with bimekizumab

In this Experiences episode of Topical Conversations, Mona Shahriari, MD, Associate Clinical Professor of Dermatology at Yale University, and Jason Hawkes, MD, Chief Scientific Officer and investigator at the Oregon Medical Research Center, explore the evolution of oral therapy in psoriasis care, from the early days of apremilast to the growing impact of selective TYK2 inhibition.Together, they trace how the field has moved from broad, nonspecific PDE4 blockade to the more targeted, allosteric TYK2 mechanism that bridges IL-23 and IL-17 signaling. Dr Hawkes outlines how TYK2 inhibition can influence downstream pathways, including IL-12 and type I interferons, potentially extending benefits beyond skin disease. The discussion also highlights recent data in psoriatic arthritis and real-world safety outcomes, with consistent tolerability and durable efficacy across challenging sites like scalp, nails, and palms.Both clinicians emphasize practical considerations—how to identify appropriate candidates for oral therapy, manage expectations around treatment onset, and communicate the distinct safety profile and monitoring needs of TYK2 inhibitors. They close by looking ahead to next-generation orals, including second-generation TYK2 inhibitors and oral IL-23 receptor blockers, which are narrowing the gap between biologic and oral efficacy.A grounded, forward-looking conversation on how oral innovation continues to reshape the psoriasis treatment landscape.

In this episode of Topical Conversations, E. James Song, MD, speaks with Tina Bhutani, MD, about bimekizumab and its growing list of indications, including psoriasis, psoriatic arthritis (PsA), axial spondyloarthropathies, and hidradenitis suppurativa (HS), highlighting how this therapy may help dermatologists address the multifaceted needs of patients.Why another biologic?Dr Song opens by noting that bimekizumab is now the twelfth biologic approved for psoriasis, prompting the question of why additional biologics are still needed. Dr Bhutani stresses that despite the abundance of options, many patients cycle through therapies due to inadequate response or secondary failure. Moreover, patients often present with comorbidities such as joint disease that require broader treatment coverage, demonstrating the value of having multiple biologics available to personalize care.Bimekizumab in psoriatic arthritisPsA presents unique challenges, with many patients responding inconsistently or slowly to traditional therapies. Dr Bhutani explains that even when skin clearance is achieved, joint symptoms often remain uncontrolled. They explain that bimekizumab provides another option for these patients, adding to the armamentarium for both dermatologists and rheumatologists managing PsA.Addressing axial spondyloarthropathiesThe conversation turns to axial disease, specifically radiographic axial spondyloarthritis (axSpA, also known as ankylosing spondylitis) and nonradiographic axSpA (nr-axSpA). Dr Bhutani explains that these conditions involve inflammation of the central joints, particularly the spine and sacroiliac joints. Historically, treatment was limited until radiographic changes became apparent.Dr Song highlights the significance of bimekizumab’s approval for nr-axSpA, which allows earlier intervention before structural damage occurs. He contrasts IL-23 inhibitors, which have limited efficacy in axial disease, with IL-17 inhibitors like bimekizumab, which demonstrate consistent benefit across both peripheral and axial domains. Together, Drs Song and Bhutani emphasize that bimekizumab covers nearly all GRAPPA domains (skin, nails, enthesitis, dactylitis, peripheral joints, and axial disease) making it a versatile option for patients with overlapping manifestations.Expanding to hidradenitis suppurativaThe discussion closes with a look at bimekizumab’s approval in HS, a often difficult condition to manage. Dr Bhutani shares her clinical experience, noting rapid improvements in pain and inflammatory lesions, with the potential to reduce long-term complications such as scarring and tunneling. She emphasizes that patients with HS stand to benefit greatly from having more therapeutic options in what remains an area of significant unmet need.Key takeawaysOngoing need for new biologics: Despite many approved options, patients often require alternative therapies due to nonresponse or secondary failurePsA management: Bimekizumab offers an additional option for patients with joint diseaseAxial disease coverage: Approval in nr-axSpA allows earlier intervention and highlights IL-17 inhibitors as more effective than IL-23 inhibitors in axial domainsComprehensive domain coverage: Bimekizumab has potential to address nearly all GRAPPA domains, offering broad utility in patients with overlapping manifestationsHS treatment: Bimekizumab provides meaningful benefit in a challenging disease, with potential to improve quality of life and prevent long-term complications

From Skin to Joints: Clinical Impact of a Dual-Targeted ApproachIn this episode of Topical Conversations, Erin Boh, MD, and Benjamin Lockshin, MD, discuss the role of bimekizumab (Bimzelx), the first dual IL-17A/F inhibitor, in the management of patients with psoriasis (PsO) and psoriatic arthritis (PsA). The conversation highlights how this mechanism of action has the potential to reshape treatment strategies, particularly for patients with both extensive skin involvement and active joint disease.Treatment considerations in PsO and PsADr Boh explains that her initial considerations include the extent of skin involvement and the presence of comorbidities such as joint disease. These parameters help guide whether therapy should be directed primarily toward skin, joints, or both. She emphasizes a patient-centered approach directed by understanding whether skin or joint symptoms are the main driver of discomfort.For patients with both extensive skin and joint disease, she typically favors IL-17 inhibitors or IL-23 inhibitors over TNF inhibitors, noting that TNFs may struggle to achieve high levels of skin clearance in such cases.Advances with bimekizumabDr Lockshin notes that while treatments over the past 2 decades have been highly effective for skin clearance, progress in joint clearance has been more limited. Bimekizumab introduces a new approach with its dual inhibition of IL-17A and IL-17F, demonstrating robust results in both skin and joints.He highlights that bimekizumab is the first drug to use an American College of Rheumatology criteria for 50% response (ACR50) score as a primary endpoint in PsA trials, providing a more meaningful measure of response compared to ACR20. Clinical trial data showed achievement of ACR20, ACR50, and ACR70 responses in some patients faster than in timelines observed with other agents.Dr Boh agrees, noting that while other IL-17 inhibitors are effective for joint disease, there are subsets of patients who respond incompletely. In her view, bimekizumab represents not only a new drug but a new therapeutic class, with the potential to maximize outcomes in patients who do not achieve adequate improvement with IL-17A inhibition alone.Practical implications and switching therapyBoth Dr Boh and Dr Lockshin emphasize the potential benefit of of switching therapy. Dr Lockshin states he has no reservations about moving patients from a TNF inhibitor to an IL-17, or from an IL-17A inhibitor to dual IL-17A/F blockade with bimekizumab.Dr Boh highlights the potential role of bimekizumab when combination therapy is otherwise limited by access or insurance barriers. For example, if a patient has partial response to an IL-17A, switching to bimekizumab may offer greater improvement without the need for additional agents.Patient-centered decision-makingThe discussion concludes with a reminder from Dr Boh that treatment decisions should be patient-first: the patient comes first, the disease second, and the drug third. With an expanding set of options, including bimekizumab, dermatologists are better positioned to tailor treatment to each patient’s unique presentation, balancing efficacy across both skin and joint disease while considering mechanisms of action and long-term outcomes.Key takeawaysInitial considerations: Treatment decisions in PsO and PsA begin with assessing the extent of skin involvement and the presence of joint diseaseDual inhibition: Bimekizumab targets both IL-17A and IL-17F, offering robust efficacy in skin and joint clearanceClinical trials: In bimekizumab trials for PsA, ACR50 was used as a primary endpoint, a more clinically meaningful measure than ACR20Therapeutic flexibility: Switching from TNF inhibitors or single-pathway IL-17 inhibitors to bimekizumab can maximize outcomes without requiring combination therapyPatient-centered care: The patient’s priorities drive treatment (skin versus joints), with bimekizumab representing an option that addresses both domains effectively

In this episode of Topical Conversations, Naiem Issa, MD, and Christopher Bunick, MD, discuss their publication in the Journal of Drugs in Dermatology that highlighted a remarkable case of rapid plaque psoriasis clearance with bimekizumab. They explore the patient case, the mechanism of action driving the rapid response, key clinical insights, and future applications of bimekizumab in psoriatic arthritis (PsA) and hidradenitis suppurativa (HS). Rapid clearance in a treatment-naïve patient Dr Issa describes a male patient in his 30s with over 50% body surface area involvement who had classic plaque psoriasis but had been treatment-naïve for several years after moving to the US. After starting bimekizumab, the patient returned 3 days later, reporting rapid improvement, with plaques melting away and pruritus significantly improved within 24 hours. By 72 hours, 90% of his body had cleared, and within a week, his skin was completely clear, with no residual itching. Dr Issa notes that such rapid improvement is rare with biologic therapies and highlights the potential for bimekizumab to dramatically alter disease progression and patient quality of life. Dr Bunick emphasizes the underrecognized burden of itch in psoriasis, often associated more with atopic dermatitis than psoriasis, reflecting that bimekizumab’s efficacy in reducing both plaques and pruritus so quickly suggests it is a powerful option for improving patient outcomes. Why does bimekizumab work so quickly? Dr Bunick attributes bimekizumab’s rapid and sustained clearance to its unique mechanism of action. Unlike other IL-17 inhibitors, bimekizumab targets both IL-17A and IL-17F. While IL-17A is more potent, IL-17F is more abundant in psoriatic plaques, and inhibiting both cytokines leads to a stronger anti-inflammatory effect. Dr Issa highlights head-to-head trials comparing bimekizumab to adalimumab, ustekinumab, and secukinumab, all of which demonstrated bimekizumab’s superior response rates at 4 weeks. Additionally, IL-17F inhibition has been linked to rapid transcriptional changes in psoriasis plaques, supporting the observed early clearance seen in clinical practice. This challenges the traditional dogma that skin takes time to recover after inflammation subsides. Dr Bunick suggests that some patients may be capable of achieving near-immediate clearance, a paradigm shift in how dermatologists approach biologic response timelines. Addressing safety concerns Mood and suicidal ideation and behavior While bimekizumab’s prescribing information includes a warning for suicidal ideation and behavior, Dr Issa notes that in pivotal trials, Patient Health Questionnaire-9 scores, which assess the degree of depression severity, tended to improve in patients treated with bimekizumab compared to placebo. Dr Bunick compares this to oral isotretinoin, where concerns about depression often contrast with real-world improvements in patient mood and quality of life. As psoriasis improves, sleep, confidence, and social interactions also improve, often leading to better overall mental well-being. Oral and corporal candidiasis Candidiasis is the most common side effect associated with IL-17 inhibitors, but Dr Issa reassures that it is manageable with fluconazole or topical ketoconazole and rarely leads to treatment discontinuation. Dr Bunick explains that oral candidiasis tends to occur once or twice in early treatment but does not persist in most patients. However, if candidiasis is recurrent, alternative treatments may be considered. Expanding beyond psoriasis: bimekizumab in PsA and HS With additional FDA approvals for PsA and HS, bimekizumab is positioned to expand its role in dermatology. Dr Issa highlights that IL-17A and IL-17F levels are significantly elevated in HS, making bimekizumab a logical therapeutic option. For PsA, Dr Bunick emphasizes the importance of dermatologists "owning" psoriatic arthritis—as experts in skin disease, dermatologists should be actively involved in joint disease management as well. Bimekizumab’s efficacy in both psoriasis and PsA provides an opportunity to optimize care for patients with both skin and joint involvement. Positioning bimekizumab in the treatment landscape With IL-23 inhibitors already used for PsA, dermatologists may be wondering how bimekizumab should be positioned within the treatment landscape. Dr Bunick points to the ongoing BE BOLD trial, a direct head-to-head comparison of bimekizumab vs risankizumab in PsA, which will provide valuable insights into IL-17 vs IL-23 inhibition in psoriatic arthritis. Key takeaways In a case study, bimekizumab demonstrated rapid plaque clearance, with a treatment-naïve patient achieving full clearance within a week Its dual inhibition of IL-17A and IL-17F differentiates bimekizumab from other IL-17 inhibitors Safety concerns such as suicidal ideation and behavior and candidiasis are manageable, with mood improvements observed in clinical trials Bimekizumab is now approved for PsA and HS, making it a promising option beyond psoriasis A head-to-head trial with an IL-23 inhibitor (BE BOLD trial) will provide critical insights for PsA management

Defining the oral advantage in psoriasis treatment In this episode of Topical Conversations, Dr Shahriari and Dr Bunick explore the evolving oral treatment landscape for plaque psoriasis, focusing on head-to-head comparisons between apremilast, a phosphodiesterase 4 (PDE4) inhibitor, and deucravacitinib, a selective tyrosine kinase 2 (TYK2) inhibitor. The discussion provides practical guidance for clinicians navigating therapeutic choices based on long-term efficacy, tolerability, and patient preference.Efficacy and tolerability Deucravacitinib demonstrated superior efficacy compared with apremilast in 2 phase 3 trials (POETYK PSO-1 and PSO-2). At week 16, Psoriasis Area and Severity Index (PASI) 90 response rates were 36% vs 20% in PSO-1 and 27% vs 18% in PSO-2, respectively. At week 52, 19% of patients receiving deucravacitinib achieved PASI 100.Regarding tolerability, common adverse events associated with apremilast (eg, nausea, diarrhea, headache) remain frequent. In contrast, deucravacitinib’s adverse event profile was comparable to or lower than placebo across clinical trials.Molecular mechanisms: explaining the difference Dr Bunick explains how apremilast’s chemical structure limits its mimicry of cyclic adenosine monophosphate (cAMP), potentially reducing potency. Deucravacitinib, by contrast, exerts selective allosteric inhibition of TYK2. Dr Bunick references his recent laboratory findings, which show TYK2 contains more phosphotyrosine sites than other Janus kinase (JAK) family members, enabling high STAT phosphorylation activity and robust cytokine suppression.Oral vs injectable Although biologic agents remain widely used, oral therapies play a growing role in psoriasis management, particularly for patients seeking noninjectable options or those already managing multiple conditions with injectable drugs. Dr Shahriari and Dr Bunick stress the importance of shared decision-making in determining patient preference.Sustained effects after discontinuation A notable finding: following discontinuation of deucravacitinib, patients maintained a PASI 75 response for a median of 12 weeks. This contrasts with JAK inhibitors used in atopic dermatitis, where symptom recurrence often occurs within 1 week of withdrawal. The speakers attribute this durability to TYK2’s upstream modulation of the Th17 axis and inflammatory cytokines.Key takeawaysDeucravacitinib demonstrated superior efficacy over apremilast in PASI 90 rates at week 16, with 19% of patients on deucravacitinib achieving PASI 100 by week 52Deucravacitinib is well tolerated, with adverse event rates similar to placeboSome patients prefer oral therapy due to convenience, control, or injection fatigueDiscontinuation of deucravacitinib does not lead to immediate loss of efficacy, supporting its role in long-term disease control

From Newcomer to Cornerstone: The Rise of Deucravacitinib In this episode of Topical Conversations, Dr Shahriari and Dr Bunick examine the long-term safety and efficacy data for deucravacitinib, a selective tyrosine kinase 2 (TYK2) inhibitor, in the treatment of plaque psoriasis. Once a novel oral agent, deucravacitinib is now supported by 5-year data that position it as a durable, patient-friendly alternative to injectable therapies. An Oral Option That Holds Its Ground Deucravacitinib has shown sustained efficacy over time, with Psoriasis Area and Severity Index (PASI) 75 response rates nearing 70% at 1 year and remaining above 65% at year 5. PASI 90 scores also held steady or improved modestly over time. More than 50% of patients achieved “clear” or “almost clear” skin by physician global assessment, making deucravacitinib a meaningful option for patients seeking long-term skin clearance with oral therapy. Safety in Focus: Addressing the JAK Association Drs Shahriari and Bunick clarify the distinction between TYK2 inhibition and Janus kinase (JAK) inhibition. Deucravacitinib targets the TYK2 pseudokinase domain selectively, avoiding signal transduction through JAK1, JAK2, and JAK3. This specificity contributes to its favorable safety profile. Over 5000 patient-years of exposure yielded low incidence rates of major adverse cardiovascular events (MACEs), venous thromboembolism (VTE), and malignancy. Understanding the Data: Durability and Rigor The 5-year data are based on modified nonresponder imputation, a conservative analytical method that accounts for dropouts and strengthens the robustness of results. The consistent performance across both safety and efficacy endpoints provides long-term validation for clinicians hesitant to adopt oral therapies without durability data. The Science of Selectivity: Why TYK2 Matters Dr Bunick explains the mechanistic rationale for TYK2 inhibition in psoriasis. By blocking TYK2, deucravacitinib disrupts IL-12, IL-23, and type I interferon signaling—key upstream mediators in the pathogenesis of plaque psoriasis. Genetic studies showing anti-inflammatory effects in individuals with TYK2 inactivation lend further biologic support to this therapeutic strategy. Real-World Practice Considerations The conversation closes with discussion of herpes zoster vaccination, particularly for patients aged ≥50 years initiating therapy. Key Takeaways Deucravacitinib provides sustained PASI 75 and PASI 90 responses, with >50% of patients achieving clear or almost clear skin at 5 yearsLong-term safety data demonstrate low rates of MACEs, VTE, and malignancyDeucravacitinib selectively inhibits TYK2, minimizing off-target effects seen with broader JAK inhibitorsUse of modified nonresponder imputation supports data durability and clinical reliabilityHerpes zoster vaccination is recommended in patients aged ≥50 years prior to therapy initiation

In this episode of Topical Conversations, Michael Cameron, MD, and James Allred, MD, explore the intersection of GIP and GLP-1 receptor agonists, such as tirzepatide and semaglutide, and inflammatory skin diseases like psoriasis, hidradenitis suppurativa (HS), and atopic dermatitis (AD). They discuss how these medications, originally developed for diabetes and weight management, are emerging as potential tools in dermatology, impacting the way clinicians can approach inflammatory conditions. GLP-1 receptor agonists: a game-changer for inflammation Dr Allred highlights how GLP-1 receptor agonists have shown significant anti-inflammatory effects, even before substantial weight loss occurs. Historically, weight reduction has been associated with improvements in inflammatory skin diseases but achieving it through diet and exercise alone is often challenging for many patients. GLP-1 receptor agonists provide a new avenue, reducing systemic inflammation and complementing existing therapies for psoriasis and other conditions. Dr Cameron adds that anecdotal evidence shows improvements in psoriasis, HS, and AD when these medications are used, often alongside biologics. He emphasizes that GLP-1 receptor agonists are becoming more accessible and commonly prescribed, making it crucial for dermatologists to understand their potential benefits. The role of visceral fat in inflammation Dr Allred explains the pathophysiology of visceral fat and its role in systemic inflammation. Unlike subcutaneous fat, visceral fat is hormonally active, releasing cytokines like IL-6 and TNF-alpha that exacerbate inflammatory diseases. He notes that GLP-1 receptor agonists reduce the inflammatory burden by targeting these fat cells, which are highly metabolically active and prone to cellular damage. Dr Cameron points out that some patients on GLP-1 receptor agonists experience marked improvements in their psoriasis even without concomitant biologics, suggesting the reduction in proinflammatory mediators from fat cells plays a significant role in disease improvement. Practical considerations for dermatologists Understanding the therapy: Dermatologists should familiarize themselves with the prescribing process for GLP-1 receptor agonists, including contraindications such as a history of medullary thyroid cancer or diabetes-related gastroparesis. These medications are relatively easy to initiate, requiring no specific lab monitoring. Holistic patient care: Dr Allred underscores the importance of screening patients with psoriasis for comorbidities such as obesity, lipid abnormalities, and metabolic syndrome. Addressing these factors can improve overall outcomes and complement traditional therapies. Expanding the scope of care: GLP-1 receptor agonists have often been considered the domain of endocrinologists and primary care providers, but Dr Allred advocates for dermatologists to take ownership of treating inflammation as part of managing inflammatory skin diseases. Future directions in research Dr Cameron concludes by previewing ongoing research comparing outcomes for patients on ixekizumab alone versus ixekizumab combined with GLP-1 receptor agonists. Early evidence suggests that this combination may amplify disease improvement in conditions like psoriasis and psoriatic arthritis. Dr Allred believes GLP-1 receptor agonists represent the next major evolution in psoriasis treatment, likening their impact to the revolutionary introduction of biologics. He encourages dermatologists to embrace this innovation to maximize the care they provide for their patients. Takeaways for Dermatologists GIP and GLP-1 receptor agonists like tirzepatide and semaglutide offer promising anti-inflammatory benefits, particularly for overweight patients with psoriasis, HS, and AD Understanding the role of visceral fat in systemic inflammation can help dermatologists appreciate the broader impact of weight management on skin health Dermatologists should consider integrating GLP-1 receptor agonists into treatment plans where appropriate Ongoing research will further elucidate the role of GLP-1 receptor agonists in dermatology, potentially paving the way for new treatment paradigms.

In this episode of Topical Conversations, Brad Glick, DO, and Jason Hawkes, MD, discuss the use of IL-17 inhibitors in managing psoriasis and psoriatic arthritis, with a focus on ixekizumab. Their conversation highlights the immunologic basis of IL-17, the safety and efficacy of ixekizumab, and its role in addressing the complex interplay of skin and joint symptoms in psoriatic disease. The role of IL-17 in psoriasis They begin by explaining that IL-17 plays a dual role in skin health. It provides natural protection against infections like candidiasis; however, excessive levels of IL-17 can drive keratinocyte hyperproliferation, leading to the scaling and plaque formation characteristic of psoriasis. Ixekizumab, by targeting IL-17A, helps normalize keratinocyte activity and significantly improves psoriasis symptoms. This mechanism of action also explains why some patients develop candidiasis during treatment, as blocking IL-17 reduces natural defenses against infections like candidiasis. Managing safety concerns While ixekizumab does not cause inflammatory bowel disease (IBD), it can exacerbate symptoms in patients with preexisting IBD. For patients who present with both psoriasis and IBD, clinicians need to carefully weigh the benefits of improved skin symptoms against the potential for worsening gastrointestinal issues. Monitoring and patient education are essential to ensure that risks are understood and managed effectively. Candidiasis, a known side effect of IL-17 inhibition, also requires consideration. By understanding the underlying immunologic mechanisms, dermatologists can counsel patients appropriately and address concerns about this potential complication. Efficacy of ixekizumab in psoriasis Clinical trials, including the UNCOVER studies, have demonstrated ixekizumab’s high efficacy in psoriasis treatment. The trials revealed significant rates of disease clearance, with about half of patients achieving PASI 100. These outcomes represent a substantial improvement over earlier treatments like methotrexate and TNF inhibitors. However, patient characteristics such as body weight can influence outcomes. For patients with higher body weights, efficacy may decrease, potentially due to the pro-inflammatory effects of adipose tissue. These findings highlight the importance of tailoring treatment approaches to individual patient profiles. Ixekizumab and psoriatic arthritis Psoriatic arthritis (PsA), a common comorbidity of psoriasis, remains challenging to treat. While ixekizumab and other IL-17 inhibitors have shown moderate efficacy in managing joint symptoms, they are highly effective for skin improvement. Dermatologists must set realistic expectations with patients, explaining that while dramatic skin improvements are likely, joint symptoms may respond more slowly or to a lesser degree. Exploring future approaches Emerging research is investigating the potential synergy of IL-17 inhibitors with GLP-1 receptor agonists. This approach aims to address systemic inflammation associated with obesity, which is linked to higher risks of diabetes, cardiovascular disease, and poorer psoriasis outcomes. By targeting both psoriasis and metabolic health, this strategy could offer comprehensive benefits, though further studies are needed to clarify its impact. Key takeaways for dermatologists Ixekizumab represents a significant advancement in psoriasis treatment, due to its high efficacy and targeted action. While considerations such as candidiasis risk and IBD management are important, this IL-17 inhibitor remains a strong option for dermatologists, with its potential for future innovations further underscoring its value in advancing patient care.

In this episode of Topical Conversations, pediatric dermatologists Lisa Swanson, MD, and Karan Lal, DO, discuss managing psoriasis in pediatric patients and the advantages of ixekizumab and other biologics, providing insights into optimal treatment choices and addressing challenges unique to treating pediatric psoriasis. Psoriasis in pediatric patients is becoming more common, necessitating effective treatment options tailored to the specific needs of young patients. Recognizing psoriasis as more than just a skin condition—as a chronic, systemic inflammatory disease—is essential when considering therapeutic strategies, particularly systemic treatments. Pediatric psoriasis: a systemic disease requiring systemic treatments Psoriasis in children has significant impacts beyond the skin, affecting overall health and increasing the risk of comorbidities, including arthritis and metabolic conditions. Acknowledging this systemic nature makes systemic treatments, such as biologics, a vital part of comprehensive care for many pediatric patients. Dr. Swanson notes that 5 systemic treatments are approved for pediatric use, including 4 injectable options (etanercept, ixekizumab, secukinumab, and ustekinumab) and one oral option (apremilast). While effective, the usage of apremilast is often limited in younger children due to side effects like nausea and diarrhea and the common difficulty of swallowing pills. Ixekizumab: a preferred biologic for pediatric psoriasis For Dr. Lal, ixekizumab is often the first choice for treating pediatric psoriasis, and he has observed strong results in adults that translate well to younger patients. Ixekizumab’s once-monthly dosing is particularly beneficial for children and their families due to the simplified dosing regimen, which can help improve adherence and reduce the burden of frequent injections. Moreover, ixekizumab acts rapidly, which is a boon for both patients and their caregivers. Addressing psoriatic arthritis in pediatric patients Psoriatic arthritis may go undetected in patients with pediatric psoriasis, particularly before treatment begins. Dr. Lal shares that increased activity levels post-treatment sometimes reveal undiagnosed joint inflammation. Dr. Swanson also emphasizes the importance of examining nail health in pediatric patients with psoriasis, as nail psoriasis is associated with an increased risk of psoriatic arthritis. Ixekizumab’s efficacy in managing nail psoriasis offers an added advantage in this context, helping dermatologists improve overall patient outcomes. Citrate-free ixekizumab for pediatric patients The original formulation of ixekizumab was painful, which often posed a challenge in younger patients. However, a citrate-free formulation now available improves comfort for pediatric patients, making the injections more tolerable. Dr. Lal notes his strategy of using EMLA cream under a bandage prior to injection to ease discomfort for children, who often become accustomed to injections over time. Moving beyond topicals: a comprehensive approach to psoriasis Many children and families express frustration with topical treatments, particularly the “whack-a-mole” effect, where plaques reappear in new locations despite regular topical application. Ixekizumab helps to address the underlying systemic inflammation, allowing for better control over psoriasis with a simpler regimen. As Dr. Lal highlights, biologics like ixekizumab not only reduce dependence on topicals but also work well alongside other therapies, such as phototherapy, offering a versatile, multimodal approach that reduces the overall burden on patients and caregivers. Safety considerations: screening for inflammatory bowel disease One concern with IL-17 inhibitors such as ixekizumab is the potential activation of inflammatory bowel disease (IBD) in patients predisposed to it. While IL-17 inhibitors don’t cause IBD directly, they may unmask it in genetically susceptible patients. Dr. Swanson and Dr. Lal emphasize the importance of screening for IBD in pediatric patients with psoriasis before initiating an IL-17 therapy. To address this, Dr. Swanson collaborated with pediatric gastroenterologists and developed a set of screening questions and labs. She makes sure to question patients and caregivers on the following key areas: Family history of IBD Growth issues, as growth delays can indicate Crohn’s disease Nocturnal diarrhea or frequent bowel movements at night Pain during bowel movements, including rectal pain or fissures In addition to these questions, she considers 3 laboratory tests: CBC to check for anemia CRP, which is usually normal in psoriasis but may be elevated in IBD or psoriatic arthritis Fecal calprotectin, a noninvasive test with high sensitivity and specificity for intestinal inflammation Dr. Lal concurs, noting that the fecal calprotectin test, while sometimes challenging to obtain from pediatric patients, is a critical tool for assessing IBD risk, especially in younger children for whom biologics may be considered. Ixekizumab’s role in evolving pediatric psoriasis care As pediatric psoriasis rates rise, so does the need for safe, effective treatments that address the full spectrum of the disease’s impact. Ixekizumab’s rapid efficacy, once-monthly dosing, and now pain-free formulation make it a valuable option in pediatric dermatology. By considering both the physical and psychological needs of young patients, and carefully screening for potential complications like IBD, dermatologists can leverage ixekizumab to improve outcomes for children with psoriasis.

Welcome to Topical Conversations: Bright Spots, an illuminating 3-part series shedding light on tapinarof, a pioneering nonsteroidal topical treatment for plaque psoriasis. In Part 3, G Michael Lewitt, MD, is joined by Neal Bhatia, MD, to discuss the evolving landscape of psoriasis treatment, particularly the role of nonsteroidal therapies like tapinarof. Paradigm shift: embracing nonsteroidal therapies They begin by highlighting the significant paradigm shift towards nonsteroidal options in psoriasis treatment in recent years. Previously, alternatives to steroids were limited to calcineurin inhibitors. However, with the advent of nonsteroidal molecules, dermatologists now have access to treatments that offer rapid anti-inflammatory action, improved delivery mechanisms, and strong safety profiles. These alternatives provide patients with long-term solutions without the concerns of steroid atrophy or risks associated with facial application, marking them a welcomed advancement in dermatologic care. The continued relevance of topicals Despite the proliferation of small molecules and biologics for psoriatic disease, topicals remain a viable option in many scenarios. Dr Bhatia emphasizes the foundational role of topicals in dermatologic practice, rooted in the principle of working both outside in and inside out. Patients sometimes prefer topicals for their hands-on approach to managing trouble areas, and the trend toward creams and foams reflects a desire for tolerable formulations that offer once-daily application. While topical steroids continue to hold a place for their rapid efficacy, the emergence of new molecules offers a promising alternative for long-term management without the adverse effects associated with prolonged steroid use. The evolving landscape of psoriasis treatment There remains an enduring popularity of topical steroids among prescribers. While these medications continue to play a significant role in dermatologic care, there's a growing recognition of the limitations and potential risks associated with prolonged use. Topical steroids can be rapidly efficacious in extinguishing inflammatory flares, providing a "sprint effect" in managing skin conditions. However, frequent prescription and refill practices can inadvertently contribute to overuse and dependency, leading to adverse effects such as tachyphylaxis and straie. To address these concerns, dermatologists are increasingly exploring alternative treatment options that offer sustained benefits without the drawbacks associated with steroids. New molecules, such as tapinarof cream, are emerging as promising alternatives due to their reliable long-term efficacy, reduced risk of adverse effects, and patient-friendly formulation. Tapinarof: a small molecule topical therapeutic with a patient-friendly formulation Dr Bhatia further discusses tapinarof, an aryl hydrocarbon receptor agonist with a unique vehicle that distinguishes it from traditional formulations. Tapinarof's spreadability and nongreasy texture make it well-suited for application on hair-bearing areas, scalp, and intertriginous regions, addressing patient concerns about discomfort and visibility. Tailored treatment approaches: harnessing tapinarof's versatility Tapinarof's versatility extends to its application in challenging areas such as the scalp and intertriginous regions. Dr Bhatia discusses the transformative impact of tapinarof in these areas, offering patients greater control and efficacy in managing their psoriatic disease. Whether used as monotherapy or in conjunction with biologics, tapinarof presents a valuable addition to the psoriasis treatment armamentarium. Missed Parts 1 and 2?  Watch Part 1 to learn about tapinarof's mechanism of action and the phase 4 results from the open-label trial for treatment in the head and neck region. Watch Part 2 to learn more about tapinarof's remittive effect and its impact on real-world clinical practice.

Welcome to Topical Conversations: Bright Spots, an illuminating 3-part series shedding light on tapinarof, a pioneering nonsteroidal topical treatment for plaque psoriasis. In Part 2, G Michael Lewitt, MD, is joined by Lauren Miller, PA-C, to discuss the unique features of tapinarof, a nonsteroidal topical treatment option for plaque psoriasis in adult patients. A unique remittive effect The pair discusses a unique differentiator of tapinarof, with evidence suggesting that patients may encounter a remittive effect upon discontinuation. In the PSOARING 3 trial, a 40-week, open-label, long-term extension study, patients (n=73) who entered the trial with clear skin maintained clear or almost clear skin for an average of 114 days before returning to a state of mild disease. A versatile alternative to steroidal therapies They also discuss the versatility of tapinarof, which can be used on any body part, including the scalp and intertriginous areas, and its minimal systemic absorption with no evidence of straie, tachyphylaxis, skin atrophy, or hypopigmentation. They underscore the advantages of tapinarof over traditional steroidal treatments, highlighting its safety and the potential to reduce the burden of polypharmacy. Real-world impact They conclude their conversation by sharing an overview of a real-world patient case, that of a 23-year-old student with psoriasis in the genital area. They detail the significant improvement in both symptoms and emotional well-being seen in the patient after 4 weeks of treatment with tapinarof, highlighting it as a unique and innovative addition to the psoriasis topical treatment landscape.Missed Part 1? Check it out here to learn about tapinarof's mechanism of action and the phase 4 results from the open-label trial for treatment in the head and neck region.

Welcome to Topical Conversations: Bright Spots, an illuminating 3-part series shedding light on tapinarof, a pioneering nonsteroidal topical treatment for plaque psoriasis. In Part 1, Bright Spots host G. Michael Lewitt, MD, sits down with James Q Del Rosso, DO, to discuss the unique mechanism of action of tapinarof, its remittive effect, and results from the phase 4 open-label trial for treatment in the head and neck region. A unique mechanism of action Tapinarof is the first topical treatment of its kind, a naturally derived aryl hydrocarbon receptor (AhR) agonist. It binds to and activates AhR, which restores the skin barrier function by inducing expression of skin barrier proteins. It downregulates proinflammatory cytokines, including IL-17 and IL-22, with AhR playing an important role in maintaining skin homeostasis in an overzealous disease state like psoriasis. Duration of treatment and a remittive effect For patients on tapinarof, there is evidence that some may experience a remittive effect after stopping treatment. In the PSOARING 3 trial, a 40-week, open-label, long-term extension study, patients (n=73) who entered the trial with clear skin maintained clear or almost clear skin for around 4 months after stopping treatment. Of the patients who entered the trial with a PGA≥2 (n=519), 58.2% achieved PGA=0 or 1 at least once during the study. Head and neck phase 4 results In a phase 4 open-label trial focusing on the head and neck region, tapinarof demonstrated impressive efficacy. At Week 12, 88.5% of patients achieved a target lesion Physician Global Assessment (tPGA) score of 0 or 1 with a ≥2-grade improvement from baseline. Moreover, 80.8% achieved a tPGA score of 0 (clear) for the target plaque psoriasis lesion in the head and neck region, and 96.2% achieved PASI75 of the head and neck region at Week 12. The trial reported no new safety signals, with common adverse reactions being folliculitis, contact dermatitis, sinusitis, and seborrheic keratosis. Versatility and real-world impact A cosmetically elegant and well-tolerated therapeutic option, tapinarof shows promise as a versatile, nonsteroidal therapy for adults with mild, moderate, or severe psoriasis, specifically for the head and neck and intertriginous regions. With about 80% of patients with psoriasis experiencing scalp involvement, the efficacy demonstrated in these challenging areas highlights the significance of tapinarof in clinical practice.Check out Part 2 here to learn more about tapinarof's remittive effect and its impact on real-world clinical practice.