HS (HS) is a persistent, relapsing, inflammatory dermatological condition originating from pilosebaceous units, predominantly impacting intertriginous regions, and frequently correlated with multiple systemic comorbidities.1 Due to its chronicity and recurrent episodes, HS significantly impacts the patients’ quality of life, profoundly affecting social, occupational, and psychological dimensions.2 In Europe, the reported prevalence of HS fluctuates from 1% to 4% across various studies, attributable to differences in study populations and methodologies3; while epidemiological data from American surveys report prevalences between 0.05% and 0.20%.4,5

HS is clinically marked by recurrent episodes of neutrophilic inflammation. The inflammation initiates in the hair follicles, leading to the formation of painful nodules and abscesses, which, in advanced stages, develop into pus-discharging tunnels and extensive scarring.1,3

Although the pathogenesis of HS has not been fully understood, it is a multifactorial disease resulting from a combination of genetic, environmental, and immunologic factors.1,3,6–8

The initial pathophysiological events in HS are thought to be driven by the release of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) following early follicular occlusion and bacterial overgrowth. These events activate the inflammasome, leading to the secretion of Interleukin (IL)-1β, primarily by tissue macrophages, and subsequent release of downstream cytokines, including IL-17 and TNFα (6-8). Altered Toll-like receptor (TLR) signaling in macrophages and dendritic cells (DCs), which are the predominant cells in HS lesions, results in the elevated production of these cytokines, which triggers the activation of DCs, which in turn secrete IL-23, promoting the polarization of Th17 cells. IL-17-producing T helper cells have been observed to infiltrate the dermis in chronic HS lesions.6–8

HS treatment depends on disease severity and individual impact, involving topical, systemic, surgical, and combined approaches.9 Topical therapy is preferred in early stages, while systemic therapies, such as antibiotics, anti-inflammatory agents, immunosuppressants, botulinum toxin, isotretinoin, and antiandrogens are used for more severe cases.6,10

The introduction of biologics has transformed the management of moderate-to-severe HS. For years, adalimumab (a TNF-α inhibitor) was the only approved biologic.11,12 Recently, anti-IL-17 biologics, such as secukinumab, ixekizumab, brodalumab have emerged as options for patients unresponsive to other therapies.13–15

Data from 2 double-blind, randomized phase III clinical trials (SUNSHINE and SUNRISE) have demonstrated the safety and efficacy profile of secukinumab for treating moderate-to-severe HS vs placebo, with 42–48% of patients achieving HS Clinical Response (HiSCR).16–18 Additionally, different clinical-practice studies have shown that secukinumab may be effective in treating HS, although the proportion of treatment-responders was variable.19–27

The current study aimed to assess the mid-term safety and efficacy profile of secukinumab in patients with moderate-to-severe HS.

According to the results of the current real-world study, we concluded that in clinical practice secukinumab demonstrates to be a safe and effective treatment for patients with HS refractory to conventional systemic therapy. Key highlights include the high proportion of patients who achieved an IHS4-55 and HiSCR at week-16 and week-24 of treatment, as well as the low rate of treatment discontinuation (12.6%).

The Sunny trials (Sunrise and Sunshine)16–18 were 2 randomized control trials that assessed the safety and efficacy profile of secukinumab in patients with moderated-to-severe HS over a period of 52 weeks. The primary endpoint was the proportion of patients achieving HiSCR50, which ranged from 42% (Sunrise) to 46% (Sunshine) in the treatment groups.

Although HiSCR is a tool widely used in clinical practice for assessing the reduction of inflammatory nodules and abscesses, it does not include the reduction of draining tunnels in its evaluation.11. Recently, the IHS4-55 tool has been introduced for evaluating the efficacy of HS treatments.28,31

At week 16, 57.4% of patients achieved HiSCR50. In the same line, at week 16 up to 52% of patients reached an IHS455 (Fig. 1B).

The results of our study suggested slightly improved outcomes vs those reported by the “Sunny trials.” Specifically, the proportion of patients achieving HiSCR50 was 57.4% at week 16 (vs 42% in the Sunrise and 46% in the Sunshine) and 63.6% at week 24 (vs 56% in the Sunny).16,17

The slightly better outcomes observed in our study may be attributed to the fact that 69.9% of the sample received combination therapy. Clinical trials on HS typically exclude treatments aimed at managing comorbidities that could potentially influence patient outcomes.16–18 In contrast, daily clinical practice and current clinical guidelines underscore the importance of addressing comorbidities, as their effective management positively impacts the control of HS.32–34

Although randomized clinical trials (RCTs) represent the highest level of clinical evidence,35 they have limitations that may reduce their clinical validity and applicability to certain population groups. Clinical-practice data can offer valuable insights into treatment efficacy across diverse patient subgroups in clinical practice.36,37

Other studies, conducted on daily clinical-practice conditions, have assessed the effectiveness of secukinumab in HS, predominantly using HiSCR as the primary outcome measure, with HiSCR rates ranging from 46% to 83.6% at 16–52-week follow-ups.19–27 However, these studies often involved limited samples (Table 2).

Casseres et al.21 found that 65% (13/20) of patients achieved HiSCR at week 12. Similarly, Melgosa et al.24 followed 23 patients and reported that 73.9% (17/23) achieved HiSCR at week 16, with sustained results of 71.4% (15/21) at week 24, 71.4% (10/14) at week 36, and 83.3% (10/12) at week 52 of secukinumab treatment. Fernandez-Crehuet et al.25 reported that 48.9% of patients achieved HiSCR at week 16, while Martora et al.26 found that 57.1% (8/14) of patients achieved HiSCR at week 16, with 71.4% (10/14) reaching HiSCR by week 52.

There is ongoing debate regarding the optimal time point for assessing therapeutic response to biologic agents, with week 24 generally considered the most informative in clinical practice. In our study, we observed an increased response at this time point, with 63.6% of patients achieving HiSCR50 and up to 56% achieving IHS4-55. These findings contrast with those reported by Haselgruber et al.,27 in a retrospective study of 67 patients, where 41.79% (28/67) achieved HiSCR and 44.78% (30/67) achieved IHS4-55 at week 24.

To the best of our knowledge, the current study, which includes 263 patients, is the largest clinical-practice analysis of secukinumab for HS conducted thus far.

Compared with published evidence, both clinical trials and clinical-practice studies, the HiSCR rate in our study is in the upper range of these studies. Nevertheless, it must be considered that the sample of this study presented a high proportion of patients at the Hurley III stage (indeed 97% of patients were either stage II or III), a long disease duration (15.4±9.2 years), and that patients presented previous exposure to biologic drugs (mean, 1.8±0.9 drugs).

This study has limitations that should be considered when evaluating its results. Firs, its retrospective design introduces potential confounding variables and inherent biases. Nevertheless, a key strength of this study is its execution within clinical settings, allowing for the inclusion and analysis of patient scenarios that extend beyond those typically assessed in controlled clinical trials. Secondly, its limited follow-up duration. A longer follow-up period might provide more comprehensive insights. Important strengths of this study include its multicenter design and the high number of patients included in it.

The results of this multicenter real-world study indicate that secukinumab can be considered a safe and effective treatment option for patients with moderate-to-severe HS who have failed other therapies, even with higher results vs the previous data published in the literature from the Sunny clinical trials. Special consideration would be made in the best moment to evaluate the response to medical therapy due to the differences between week 16 and 24.

Medical writing service has been supported by the AEDV Spanish Group of Psoriasis.

Antonio Martorell declared to have received honoraria and/or travel grants and/or acted as an advisory board member for Novartis, AbbVie, Janssen Cilag, UCB, Lilly, LEO Pharma, L’Oreal, Sanofi, Boehringer Ingelheim, Almirall, Bristol Myers Squib and Amgen. Moreover, he has worked as a principal investigator in clinical trials supported by AbbVie, UCB, Jansen, Bristol Myers Squibb, Lilly, Galderma, Sanofi, and Novartis.

Francisco Javier Melgosa Ramos declared to have received honoraria and/or travel grants and/or acted as an advisory board member for Novartis, Abbvie, Janssen Cilag, UCB, Lilly, LEO Pharma, L’Oreal, Sanofi, Almirall and Amgen. The remaining authors declared no conflicts of interest whatsoever.