Hadar Lev-Tov, MD, MAS 

Panelists discuss how key research gaps include pediatric studies, understanding disease progression to enable early intervention, managing acute flares, addressing cosmetic concerns from scarring and hyperpigmentation, and highlight educational resources available through the HS Foundation, medical conferences, and specialized training programs.

Exploring Research Needs and Resources in HS Care

Critical research gaps in hidradenitis suppurativa (HS) include the need for pediatric studies, as current approval for adalimumab in patients aged 14 years and above relied on pharmacokinetic modeling rather than dedicated pediatric trials. Understanding disease progression and identifying predictive biomarkers could enable earlier intervention in patients at high risk for severe disease development, potentially altering the natural history through timely therapeutic intervention. Management of acute flares represents another pressing need, as current biologics reduce flare frequency but don’t eliminate them, leaving patients and providers without evidence-based rescue strategies.

Emerging research questions include whether early disease control can prevent the metabolic and inflammatory comorbidities commonly associated with HS or whether some comorbidities actually contribute to disease initiation and could be targeted for prevention. The relationship between HS and conditions like arthritis, inflammatory bowel disease, and metabolic syndrome requires deeper investigation to optimize holistic patient care. Additionally, addressing the cosmetic impact of residual scarring and hyperpigmentation after achieving inflammatory control represents an important quality of life consideration, with preliminary work exploring ablative lasers, fractional treatments, and microneedling approaches adapted from acne scar management.

Educational resources for clinicians continue expanding through multiple channels including the annual HiSTORIC conference, resident symposia that have evolved from niche events to high-demand educational opportunities, and online learning platforms. The HS Foundation website provides practical tools including prior authorization resources, wound care guidance, and educational modules for emergency department physicians and other nondermatology providers. Academic supplements, surgical video libraries, journal clubs, and basic science seminars through professional organizations offer ongoing learning opportunities at various career stages, supporting the growing community of practitioners committed to advancing HS care and improving patient outcomes.

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Panelists discuss how the pipeline includes promising therapies like sonelokimab (an IL-17A/F nanobody with potential for better tissue penetration), various JAK inhibitors, IL-1α/β inhibitors, OX40 ligand blockers, and B-cell targeted therapies that may address disease heterogeneity and offer hope for patients with treatment-resistant disease. 

Emerging Therapies in HS

Sonelokimab represents the newest IL-17 pathway inhibitor in development, utilizing nanobody technology to target both IL-17A and IL-17F with potentially enhanced tissue penetration due to its smaller molecular size. Phase 2 data demonstrated that approximately half of patients achieved HiSCR75, marking the first hidradenitis suppurativa (HS) trial to use this more stringent end point that better reflects clinically meaningful improvement and patient satisfaction. The nanobody structure may offer advantages in tissue penetration and potentially improved safety profile, though larger phase 3 studies will be necessary to confirm whether the cutaneous adverse events observed with other IL-17A/F inhibitors occur at similar rates.

The broader pipeline includes diverse mechanisms targeting various aspects of HS pathophysiology, reflecting growing understanding of disease heterogeneity. Combination IL-1α/β inhibitors, OX40 ligand costimulatory molecule blockers, and B-cell targeted therapies represent promising approaches for patients with treatment-refractory disease. Janus kinase (JAK) inhibitors from multiple companies are progressing through development with various selectivity profiles, offering oral treatment options with extensive safety databases from use in other inflammatory conditions.

Ongoing basic science research continues uncovering the roles of different immune pathways including IL-1α/β, B-cell switching mechanisms, and various T-cell populations, potentially enabling future biomarker-driven treatment selection. This research may ultimately allow matching specific therapies to individual patient immune profiles or phenotypes, moving beyond trial-and-error approaches toward precision medicine. For the 10% to 15% of patients with most severe disease who remain refractory to current therapies, customized antibody approaches targeting their specific immune abnormalities represent hope for future breakthrough treatments.

Panelists discuss how they monitor patients through early follow-up visits at 1 to 3 months to assess medication access, manage cutaneous adverse effects, check liver function tests, and use educational handouts and pharmacy support to counsel patients on expected benefits vs risks while maintaining treatment adherence.

Monitoring Adverse Effects and Treatment Response of IL-17 Inhibitors in HS

Clinical monitoring protocols for IL-17 inhibitors involve early follow-up visits at 1 to 2 months primarily to confirm medication access, address initial cutaneous adverse effects that may impact adherence, and provide reassurance during the period before therapeutic benefit becomes apparent. The critical 3-month assessment point allows determination of treatment response and need for optimization, whether through dose escalation (for secukinumab from every 4 weeks to every 2 weeks) or consideration of alternative therapies if patients show worsening or inadequate improvement.

Safety monitoring includes liver function testing at 3 months based on current labeling requirements for bimekizumab, with ongoing monitoring until sufficient long-term safety data accumulate. Mental health assessment remains important given rare but significant cases of depression or suicidal ideation, though practitioners emphasize that mental health support benefits all patients with hidradenitis suppurativa (HS) regardless of treatment given the high baseline prevalence of psychological distress. Tuberculosis (TB) screening follows traditional protocols before initiating therapy, though the TB reactivation signal for IL-17 inhibitors appears minimal compared with TNF inhibitors.

Patient education tools include comprehensive handouts covering expected benefits, potential adverse effects, and when to seek medical attention, with modern digital formats using QR codes providing easy access to regularly updated resources with hyperlinks to additional support services. Counseling emphasizes that the most common “side effect” patients will experience is disease improvement, helping to balance safety information with realistic expectations about benefit. Many practices employ pharmacists or pharmacy technicians to conduct standardized counseling, reserving physician time for addressing patient-specific concerns and nuanced clinical decision-making while ensuring consistent, thorough safety education.

Panelists discuss how JAK inhibitors show promise for specific HS phenotypes, including patients with milder disease with inflammatory nodules, those with severe trunk/buttock disease, and systemically ill patients, and may work synergistically with IL-17 inhibitors in combination therapy for the most severe cases without additive infection risk.

Exploring the Role of JAK Inhibitors in HS

Janus kinase (JAK) inhibitors represent an emerging therapeutic class for hidradenitis suppurativa (HS), with phase 3 trials showing approximately 50% of patients achieving HiSCR75, positioning these oral medications as valuable additions to the treatment armamentarium. Clinical experience suggests JAK inhibitors may excel in specific patient subpopulations, including those with predominantly inflammatory nodular disease without extensive tunneling, and men with severe trunk and buttock involvement resembling a Crohn-like phenotype with multiple fistulas. Patients with significant systemic symptoms including weight loss, elevated metabolic activity, and persistent feverlike symptoms may benefit from JAK inhibitors’ broader immunologic effects.

The most exciting application of JAK inhibitors involves combination therapy with IL-17 inhibitors for patients with the most severe disease that fails monotherapy with any single agent. Early clinical experience suggests this combination maintains favorable safety profiles similar to those of the individual agents without the exponentially increased infection risk observed when combining TNF inhibitors with JAK inhibitors. This synergistic approach addresses the reality that trial exclusion criteria limiting draining tunnel counts mean many patients with the most severe disease never qualified for pivotal studies, yet they represent the population with greatest unmet need.

Multiple JAK inhibitors with varying selectivity profiles are in development for HS, offering potential advantages in terms of established safety databases from use in other indications and broad availability across multiple inflammatory conditions. The oral administration route provides practical advantages for some patients, though the classwide safety considerations familiar to dermatologists from use in other conditions require careful patient selection and monitoring. As more data emerge, JAK inhibitors may find specific niches based on patient phenotype, disease pattern, and treatment history.

Hadar Lev-Tov, MD, MAS

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