Iltefat Hamzavi, MD

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.

Videos

Panelists discuss how secukinumab’s long-term data show sustained efficacy over 2 to 4 years with low immunogenicity, allowing patients to stop and restart therapy without loss of response—unlike TNF inhibitors—and demonstrate that some initial nonresponders improve significantly with extended treatment duration.

Additional Long-Term Data on IL-17 Inhibitors in HS

Long-term secukinumab data extend to 4 years with a complex trial design involving treatment withdrawal periods that revealed important insights about disease behavior and drug properties. The study demonstrated that many patients who lost response during withdrawal or dose reduction could recapture therapeutic benefit when returned to more frequent dosing, with some nonresponders at earlier time points achieving significant improvement with continued treatment over extended periods. This pattern differs markedly from TNF inhibitor experience, where treatment interruption often leads to antibody development and loss of response upon reinitiation.

The low immunogenicity profile of IL-17 inhibitors represents a major clinical advantage, allowing patients who experience insurance lapses or other treatment interruptions to successfully restart therapy and regain disease control. This characteristic proves particularly valuable for patients in unstable employment situations or those experiencing life changes that temporarily interrupt access to medication. In clinical practice, patients who discontinue IL-17 inhibitors and subsequently flare can typically recapture their previous response level when treatment resumes, though the timeline for improvement follows the original 3- to 6-month pattern.

Patient counseling around long-term IL-17 inhibitor use acknowledges the chronic nature of hidradenitis suppurativa (HS) while emphasizing the flexibility these medications offer compared to TNF inhibitors. Practitioners frame treatment as likely lifelong but stress that if life circumstances necessitate breaks, the ability to regain response remains high, reducing anxiety about indefinite commitment to therapy. This message helps address common patient concerns about permanent medication dependence while maintaining realistic expectations about the chronic disease requiring ongoing management for sustained benefit.

Panelists discuss how cutaneous adverse effects from IL-17 inhibitors, including eczematous rashes and fissures occurring in about 10% of patients, can be effectively managed with topical immunomodulators, antifungal prophylaxis, and patient counseling to maintain treatment adherence and prevent discontinuation.

Clinician Perspectives on Managing Adverse Effects in HS

Cutaneous adverse effects occur in approximately 10% of patients treated with IL-17 inhibitors for hidradenitis suppurativa (HS), with higher risk among those with previous history of psoriasis or eczema and more severe baseline HS disease. These reactions manifest as eczematous or psoriasiform rashes, often in intertriginous distributions where they may overlap with HS lesions and can include concerning findings like fissuring in the retroauricular area, perianal region, and inguinal creases. Management approaches start with topical therapies similar to those used for mild atopic dermatitis or psoriasis, including newer brand-name medications that offer safer profiles for use in sensitive areas.

For patients with persistent or severe cutaneous reactions, particularly those with underlying severe HS, dual biologic therapy or combination treatment with Janus kinase (JAK) inhibitors may provide synergistic benefits addressing both the paradoxical skin reactions and residual HS inflammation. Class switching represents another viable strategy, as patients may tolerate different molecules within the IL-17 inhibitor class or achieve better outcomes with TNF inhibitors if cutaneous reactions prove unmanageable. Some practitioners employ prophylactic fluconazole before each dose, hypothesizing that treating yeast colonization may prevent some cutaneous reactions, particularly given their predilection for intertriginous locations.

Additional management strategies include early use of topical calcineurin inhibitors like tacrolimus and topical JAK inhibitors in areas prone to fissuring or dermatitis, along with preventive measures for oral candidiasis including topical antifungals and sugar-free xylitol gum. Comprehensive patient counseling before treatment initiation proves essential for maintaining adherence, with practitioners emphasizing that cutaneous adverse effects, while uncomfortable, remain manageable within dermatologic expertise. Depression monitoring represents another important safety consideration, with rare but significant cases requiring treatment discontinuation, alongside routine liver function testing as indicated by current labeling requirements.

Panelists discuss how 2-year bimekizumab data demonstrate that nearly half of patients achieve complete clearance (HiSCR100) with peak efficacy around 6 months, sustained improvement over time, and manageable safety concerns primarily involving cutaneous reactions like eczematous rashes that can be treated topically.

Long-Term Data on Bimekizumab in HS and Its Clinical Implications

Two-year efficacy data for bimekizumab demonstrate sustained and progressive improvement in hidradenitis suppurativa (HS) outcomes, with patients typically reaching peak response around 6 months of treatment. At the 2-year mark, approximately one-third to nearly half of patients achieve HiSCR100 (complete resolution of inflammatory lesions), while over two-thirds reach HiSCR75 (75% improvement), representing clinically meaningful disease control that significantly impacts patient satisfaction and treatment adherence. The data show progressive improvement in all lesion types, with particularly notable reductions in draining tunnel counts and associated pain scores.

Safety data through 2 years confirm manageable adverse event profiles, though cutaneous reactions emerged as a notable concern requiring clinical attention. These skin reactions, sometimes characterized as eczematous or psoriasiform, can occur in intertriginous areas including over HS lesions themselves, potentially causing itching and burning sensations that may initially be mistaken for disease worsening or contact dermatitis from bandages. The incidence of oral candidiasis, an anticipated adverse effect of IL-17 inhibition, tends to decrease over time with continued treatment.

Clinical management strategies based on long-term data emphasize patient counseling about the expected timeline for improvement, with 3-month follow-up appointments serving as critical assessment points for determining treatment response and optimization needs. Practitioners coach patients that meaningful improvement requires patience, typically 3 to 6 months, though they should report any concerning cutaneous reactions promptly for early intervention. The data support continuing therapy through initial months even without dramatic improvement, as many patients show progressive benefit extending well beyond the first assessment period.

Iltefat Hamzavi, MD

Articles