Guselkumab for hidradenitis suppurativa: a phase II, open-label, mode-of-action study.

BACKGROUND: The effectiveness of available biologics for the treatment of hidradenitis suppurativa (HS) is limited. Additional therapeutic options are needed. OBJECTIVES: To investigate the efficacy and mode of action of guselkumab [an anti-interleukin (IL)-23p19 monoclonal antibody] 200 mg subcutaneously every 4 weeks for 16 weeks in patients with HS. METHODS: An open-label, multicentre, phase IIa trial in patients with moderate-to-severe HS was carried out (NCT04061395). The pharmacodynamic response in skin and blood was measured after 16 weeks of treatment. Clinical efficacy was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and the abscess and inflammatory nodule (AN) count. The protocol was reviewed and approved by the local institutional review board (METC 2018/694), and the study was conducted in accordance with good clinical practice guidelines and applicable regulatory requirements. RESULTS: Thirteen of 20 patients (65%) achieved HiSCR with a statistically significant decrease in median IHS4 score (from 8.5 to 5.0; P = 0.002) and median AN count (from 6.5 to 4.0; P = 0.002). The overall patient-reported outcomes did not show a similar trend. One serious adverse event, likely to be unrelated to guselkumab treatment, was observed. In lesional skin, transcriptomic analysis revealed the upregulation of various genes associated with inflammation, including immunoglobulins, S100, matrix metalloproteinases, keratin, B-cell and complement genes, which decreased in clinical responders after treatment. Immunohistochemistry revealed a marked decrease in inflammatory markers in clinical responders at week 16. CONCLUSIONS: Sixty-five per cent of patients with moderate-to-severe HS achieved HiSCR after 16 weeks of treatment with guselkumab. We could not demonstrate a consistent correlation between gene and protein expression and clinical responses. The main limitations of this study were the small sample size and absence of a placebo arm. The large placebo-controlled phase IIb NOVA trial for guselkumab in patients with HS reported a lower HiSCR response of 45.0-50.8% in the treatment group and 38.7% in the placebo group. Guselkumab seems only to be of benefit in a subgroup of patients with HS, indicating that the IL-23/T helper 17 axis is not central to the pathophysiology of HS.

New insights in hidradenitis suppurativa from a population-based Dutch cohort: prevalence, smoking behaviour, socioeconomic status and comorbidities.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin condition and is associated with several comorbidities. Previous studies report variable prevalence rates of HS, depending on the methodology. However, the exact prevalence remains unknown. OBJECTIVES: To estimate the prevalence of HS in a large population-based cohort in the Northern Netherlands, and to compare patients with HS to the general population, investigate characteristics and identify potential associated comorbidities. METHODS: Data were collected through a cross-sectional survey-based study within the Lifelines Cohort Study (n = 167 729), based on the general population located in the Northern Netherlands. A digital self-reported questionnaire was developed consisting of validated questions for determining HS. RESULTS: Among 56 084 respondents, the overall prevalence of HS was 2.1% [95% confidence interval (CI) 2.0-2.2]. The respondents with HS had lower socioeconomic status than the controls (P < 0.001) and more frequently currently smoked (P < 0.001). Several new significant associations in patients with HS were revealed, such as fibromyalgia (OR 2.26, 95% CI 1.64-3.11), irritable bowel syndrome (OR 1.63, 95% CI 1.18-2.26), chronic fatigue syndrome (OR 1.72, 95% CI 1.06-2.78) and migraine (OR 1.48, 95% CI 1.11-1.96). Fibromyalgia and chronic fatigue syndrome remained significantly associated with HS in the multivariate analysis after adjusting for age, sex, body mass index, smoking status and socioeconomic status. CONCLUSIONS: Our study showed a higher prevalence of HS in the Northern Netherlands compared with the overall estimated prevalence of 1% and identified several new associated comorbidities.

Assessment tools and phenotype classification for hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a heterogeneous chronic relapsing skin disease. Several assessment tools are used to assess disease severity and to classify disease phenotype; however, no consensus exists. This review evaluates the various assessment tools and phenotypes, assessing their validity and reliability. Numerous assessment tools and phenotype classifications have been proposed for identifying various subtypes within the hidradenitis suppurativa disease spectrum. Each has a different purpose, such as use in daily practice or in clinical trial settings. Several assessment tools and phenotype classifications have been validated but not always with satisfactory results and often with studies showing divergent intra-rater reliability results. A consensus is needed for a validated, easy-to-use, and timesaving assessment tool for routine daily practice. For clinical trials, a validated and extensive assessment tool that also measures response to treatment is also needed.

Drug Survival of Oral Retinoids in Hidradenitis Suppurativa: A Real-Life Cohort Study.

INTRODUCTION: Cohort studies on the use of retinoids for hidradenitis suppurativa (HS) have yielded contradicting results. As the clinical presentation of HS is heterogeneous, with different predilection sites and hallmark features, it can be hypothesized that HS phenotypes are associated with the effectiveness of specific retinoid treatments. OBJECTIVES: The aim of this study was to evaluate the drug survival of oral retinoids in the treatment of HS and to establish predictors for longer treatment duration. METHODS: A retrospective, dual-center study was conducted in the Netherlands in adult HS patients treated with oral retinoids between 2011 and 2021. Drug survival analyses were performed through Kaplan-Meier survival curves. Additionally, Cox regression models were used to determine predictors for a longer drug survival. RESULTS: In total, 102 patients were included. Overall drug survival of (low-dose) isotretinoin (n = 66) at 12 and 24 months was 44.2% and 15.5%, respectively. Termination of treatment was mostly due to ineffectiveness (26%). Presence of widespread comedones (p = 0.03) and the use of concomitant systemic medication (p = 0.04) were associated with a prolonged treatment duration. For acitretin (n = 36), the overall drug survival was 42.0% at 12 months and 37.4% at 24 months, and was also predominantly determined by ineffectiveness (28%). Interestingly, the scarring folliculitis phenotype (p < 0.05) was associated with prolonged drug survival time for acitretin treatment relative to the regular phenotype. CONCLUSION: Comparable drug survival rates at 12 months for isotretinoin and acitretin were found. HS patients with widespread comedones and the scarring folliculitis phenotype could benefit from treatment with isotretinoin or acitretin, respectively.

Adverse Reactions to Biologics in Psoriasis.

Psoriasis is a chronic autoimmune disease which affects millions of people worldwide. Not only can psoriasis itself be debilitating and significantly reduce an individual's quality of life, but it is also a risk factor for other systemic disorders, such as metabolic syndrome, cardiovascular disease, and malignancy. Tremendous strides were made in the treatment of psoriasis during the mid-to-late-20th century, including the emergence of topical corticosteroids and vitamin D analogs, methotrexate, systemic retinoids, and phototherapy. However, it was not until 2004 with the advent of systemic biologic agents, which precisely target components of the immune system involved in the pathophysiological process of psoriasis, that the primary treatment benchmark increased from 50% improvement in the Psoriasis Area and Severity Index (PASI 50) to PASI 75, PASI 90, and even PASI 100, or complete resolution of cutaneous disease. Today, many patients receiving biologic therapy routinely experience greater than 75% or 90% reduction in cutaneous disease burden and a significant improvement in overall quality of life. These biologic agents are generally well-tolerated and safe but, like any medication, have associated adverse effects, some of which are predictable based on the effects of immune modulation, animal model studies, and human populations with known cytokine deficiencies. Going forward, it will be important to carefully monitor the safety profiles of these agents in both clinical trials and post-marketing surveillance registries to ensure long-term safety. It is reassuring that large safety registries are consistent in demonstrating an improved safety profile with newer and emerging biologic therapies.