Linda Stein Gold, MD, is a dermatologist at Henry Ford Health. 

Linda Stein Gold, MD

Panelists discuss how second-generation PDE4 inhibitors, such as orismilast, aim to improve upon apremilast’s efficacy while maintaining safety, with phase 2 data showing PASI 75 rates up to 50%.

Expert Perspectives on Investigational PDE4 Inhibitors in Psoriasis

Patients currently benefit from apremilast as an established PDE4 inhibitor for psoriasis treatment across all severity levels, but newer agents aim to enhance efficacy while maintaining favorable safety profiles. Second-generation PDE4 inhibitors, such as orismilast, represent an advancement in oral treatment options for patients seeking improved therapeutic outcomes. These newer agents target the same trusted mechanism while striving to deliver enhanced clinical benefits for patients with moderate to severe disease.

Health care providers report comfort with the PDE4 inhibitor pathway based on extensive clinical experience and established safety data that patients can trust. The dermatology community recognizes PDE4 inhibition as a reliable therapeutic approach with well-characterized safety profiles that patients have used successfully for years. This familiarity provides confidence for both patients and providers when considering newer PDE4 inhibitor options as they become available.

Clinical trial data for orismilast demonstrate PASI 75 response rates reaching approximately 50% in phase 2 studies, representing meaningful improvement for patients compared with earlier PDE4 inhibitors. These enhanced efficacy rates suggest patients may achieve superior outcomes with next-generation PDE4 inhibitors while maintaining the safety and tolerability profiles they expect from this medication class. Patients seeking oral treatment options may benefit from these advances in PDE4 inhibitor development as new agents progress through clinical development.

Videos

Panelists discuss how emerging TYK2 inhibitors such as brepocitinib and ESK001 target the JAK/STAT pathway to block IL-23 and IL-17 signaling, showing promising phase 2 results with PASI 100 rates around 33% and PASI 75 rates of 64%.

Expert Perspectives on Investigational TYK2 Inhibitors in Psoriasis

Patients may soon benefit from next-generation TYK2 inhibitors that offer enhanced efficacy compared with current oral treatment options. Two promising molecules in late-phase development, deucravacitinib and ESK001, represent advances in targeting the JAK/STAT pathway’s inflammatory cascade central to psoriasis pathophysiology. These treatments work by blocking TYK2 through allosteric inhibition, providing high selectivity and specificity for patients seeking targeted oral therapy.

TYK2 inhibitors offer patients oral treatment that targets key inflammatory cytokines IL-23 and IL-17 through downstream signaling disruption. This mechanism allows patients to benefit from reduced signs and symptoms of psoriasis through highly selective pathway targeting. The allosteric inhibition approach provides patients with precise therapeutic intervention that minimizes off-target effects while maximizing treatment efficacy for psoriatic inflammation.

Clinical trial data demonstrate impressive efficacy rates for patients receiving investigational TYK2 inhibitors, with approximately one-third achieving complete skin clearance (PASI 100) at 12 weeks with deucravacitinib. ESK001 shows PASI 75 response rates of 64% vs 0% with placebo at week 12, representing significant advancement for patients seeking oral treatment options. These results suggest that patients may soon have access to oral medications delivering efficacy levels previously associated primarily with biologic treatments, thereby expanding convenient treatment options for moderate to severe psoriasis.

Panelists discuss how effective shared decision-making involves clinicians presenting 2 to 3 optimal treatment options based on patient-specific factors rather than overwhelming patients with all possibilities or making unilateral decisions, ultimately improving treatment adherence.

Shared Decision-making in Moderate to Severe Psoriasis

Patients benefit most from shared decision-making approaches that balance clinical expertise with individual preferences and circumstances. Effective shared decision-making avoids both extremes of presenting overwhelming treatment options without guidance or dictating single treatment choices without patient input. Health care providers should evaluate each patient’s disease severity, comorbidities, and lifestyle factors to identify appropriate treatment candidates before engaging in preference discussions.

Patients achieve better treatment outcomes when providers present a curated selection of suitable options rather than an exhaustive list of possibilities. The most effective approach involves identifying 2 or 3 treatments that can achieve clear or almost clear skin for the individual patient, then discussing administration preferences such as oral vs injectable options. Patients appreciate understanding treatment frequency, dosing schedules, and practical aspects of medication administration that affect their daily routines.

Patient adherence improves significantly when individuals participate actively in treatment selection and express their preferences regarding administration methods. Whether patients prefer once-daily oral medication or periodic injections every few weeks, involving them in the decision-making process leads to better long-term adherence and treatment success. Patients who feel heard and respected in their treatment preferences demonstrate greater commitment to their chosen therapy and achieve superior clinical outcomes through sustained adherence.

Panelists discuss how many eligible patients with psoriasis remain undertreated despite advanced therapy availability due to patient discontinuation from topical burden, injection anxiety, and the historical lack of effective oral options with good safety profiles.

Discussing the Gaps in Treatment Satisfaction in Psoriasis

Patients with psoriasis continue to experience significant gaps between treatment eligibility and actual access to advanced therapies, despite expanded treatment options. Research reveals that many patients who qualify for systemic treatments remain under-treated, leading to suboptimal disease control and reduced quality of life. These gaps persist even as the dermatology field has developed increasingly effective therapeutic options for patients with moderate to severe disease.

Patients discontinue treatments for various practical reasons that health care providers must address proactively. Many patients find topical treatments cumbersome and prefer not to apply creams daily, viewing the routine as a constant reminder of their condition. Some patients develop needle phobia with biologic treatments, experiencing increasing anxiety as injection times approach. Others worry about long-term safety implications of injectable medications.

The oral medication space represents the greatest unmet need for patients seeking convenient, effective treatment options. Many patients express a preference for oral therapies when given comparable efficacy, safety, and tolerability profiles. Patient surveys consistently demonstrate strong preferences for oral medications, highlighting the importance of developing advanced oral treatments that can deliver biologic-level efficacy while maintaining the convenience and acceptability that patients desire for long-term adherence.

Linda Stein Gold, MD

Articles