Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterised by painful recurrent nodules, abscesses, pus-discharging sinus tracts/fistulas, and scarring.1 Patients are greatly affected by severe pain, movement restrictions, and the foul odour of secretions.1 Genetic and environmental factors drive immune activation and cell infiltration, resulting in excessive and protracted inflammation.1,2 To date, the management of HS relies on antibiotics or antiinflammatory treatment, though adalimumab is the only therapeutic agent approved for HS treatment by the European Medicines Agency (EMA).1,2 Adalimumab is a human anti-tumour necrosis factor antibody shown to achieve Hidradenitis Suppurativa Clinical Response (HiSCR), improve quality of life (QoL) and reduces the number and duration of flares, with a predictable tolerability profile.1,2 Considering the impact of HS upon patient life and the limited number of available treatments, there is an unmet need for efficacious and safe therapies for this disease.

HS skin lesions were shown to be infiltrated with macrophages expressing increased levels of interleukin (IL)-23, a major driver of chronic inflammation that governs the maturation of T-helper 17 (Th17) cells,1,3 which are known producers of cytokines that trigger massive inflammation and autoimmunity.4 The IL-23/Th17 axis is implicated in the pathogenesis of autoinflammatory disorders such as HS, psoriasis, and Crohn's disease.4,5 Guselkumab, an approved treatment for moderate to severe psoriasis, is a human immunoglobulin G1 λ monoclonal antibody that targets the p19 subunit of IL-23, preventing intracellular signalling with activation and production of cytokines.6 Considering the key role of the IL-23/Th17 signalling axis in HS, guselkumab might be an adequate treatment alternative for the disease, but evidence on its efficacy treating HS comes from single case reports or case series including less than ten patients.7–11 A randomised phase 2 study evaluating guselkumab in moderate–severe HS was terminated at week 16, as no statistically significant differences in efficacy were found versus placebo.12 Based on this, we assessed the effectiveness and safety of guselkumab in treating moderate–severe HS in patients in the context of compassionate use of the drug in Spain.

A total of 69 HS patients were included in the study. Table 1 shows the demographic and clinical characteristics of the patients at baseline. The mean age was 44 years, and 50.7% were male. Nearly 60% of the patients had been diagnosed with HS for over ten years. Most patients had severe HS (Hurley stage III, 84.1%), an inflammatory phenotype (61.8%), and a mean of 4.3 affected areas. Overall, 47.5% of the patients experienced more than 12 HS flare-ups yearly. They had been treated previously with an average of 1.8 biologics, mainly adalimumab (88.2%), ustekinumab (33.8%), and infliximab (29.4%). The patients had undergone an average of 3.4 surgeries.

Treatment with guselkumab and combined therapies are summarised in Table 2. Most patients received guselkumab 100mg (66.2%) at baseline, week 4, and then every eight weeks. Most (69%) patients also received other systemic therapies such as oral antibiotics, mainly doxycycline (42.9%), metformin (19.0%), and dapsone (10.5%).

A significant decrease in IHS4, HS-PGA, NPRS, and DLQI scores from baseline was observed at week 16 (all p<0.0001), at week 24 (all p<0.0001) and at week 48 (all p<0.0001) (Fig. 1a). The achievement of HiSCR, IHS4-55, MCID in DLQI (a reduction in DLQI≥4 points), and an NPRS score<3 was recorded in 58.3%, 50%, 62.5%, and 48.7% of the patients at week 16 week, and in 56.5%, 55.1%, 59.3%, and 51.4% at week 24, respectively (Fig. 1b). A statistically significant association was found between guselkumab dose of 100mg/4 weeks and HiSCR achievement (OR=0.15; 95% CI: 0.04–0.56; p=0.004) at week16 but not at week 24. The possibility of a decrease in DLQI≥4 points (MCDI) at week 16 was lower in male patients (OR=0.11; 95% CI: 0.02–0.58; p=0.009) and those who had received a higher number of biologics (OR=0.29; 95% CI: 0.09–0.88; p=0.029).With regards to the pain, NPRS<3 points was significantly more difficult to achieve in patients with a higher number of biological treatments administered (OR=0.34; 95% CI: 0.13–0.84; p=0.020) at 16 weeks and with the number of fistulas (OR=0.68; 95% CI: 0.74–0.99; p=0.046) at 24 weeks. A greater number of body areas affected was associated with less probability to obtain a NPRS<3 at both 16 (OR=0.65; 95% CI: 0.44–0.96; p=0.033) and 24 weeks (OR=0.67; 95% CI: 0.44–0.99; p=0.049) (Table 3).

Figure 1.

Efficacy of guselkumab treatment. (a) Changes in iHS4, PGA, NPRS and DLQI from baseline to treatment week 48. (b) Percentage of patients achieve HiSCR, a reduction of 55% in IHS4, MCID in DLQI (decrease of ≥4 points) and NPRS score<3 at weeks 16 and 24.

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Guselkumab was discontinued in 16 patients (23.2%), following a mean treatment time of 7.81 months (SD±5.06). The most common cause of discontinuation was inefficacy or loss of efficacy (62.5%). Only 39 patients (56.5%) reached 48 weeks of treatment with guselkumab. No serious AEs were observed (Table 4).

Our study suggests that the treatment of moderate to severe HS with guselkumab leads to significant reductions in HS severity (IHS4, HiSCR) and pain (NPRS), with an improvement of patient QoL (DLQI). Although patient characteristics and disease severity did not appear to be associated with the attainment of IHS4-55, an association was found between a larger number of fistulas and affected areas and failure to achieve a reduction of ≥4 points in DLQI (MCID) at 16 weeks and the attainment of NPRS<3 at 16 and 24 weeks. Males and those who had previously received more biologics also appeared less likely to reach MCID in DLQI (decrease of ≥4 points) at 16 weeks. Patients treated with guselkumab 100mg every four weeks had less chances of attaining HiSCR at 16 weeks but not at 24 weeks. These patients might have had more severe HS, requiring adjustments of the treatment regimen and length, though this was not evaluated.

Data on the effectiveness of guselkumab in treating HS is scarce and based on a small number of reports involving few or single patients. In a Spanish study, four HS patients that failed to respond to other biologics were treated with guselkumab 100mg every four weeks, showing improvement of the disease at 12 weeks in two cases, with moderate reduction of the IHS4, NPRS, and DLQI scores, and with no changes in HS-PGA or significant AEs.11 Guselkumab 100mg at baseline, week 4, and then every eight weeks (the most common regimen used in our series) also led to HS improvement in 5/8 patients in another study. However, three patients showed no improvement in the first 2–4 months, suggesting that more time might be needed to reach maximum efficacy.8

Guselkumab has been shown to be effective in treating HS patients with other comorbidities such as Crohn's disease.7,14 Interestingly, guselkumab was also reported to reduce HS lesions and resolve a paradoxical psoriasiform reaction and sacroiliitis following adalimumab treatment for HS in a patient who experienced a decrease in the Psoriasis Area and Severity Index and, in whom a further decrease in HS lesions was observed over ten months of follow-up.15 Together with these results, our findings suggest that guselkumab may be an effective and safe therapeutic option for moderate–severe HS, ameliorating other concomitant conditions and providing an alternative treatment for patients failing to respond to adalimumab. This is the first study to report a large series of HS patients treated with guselkumab.

Our study has limitations, including its retrospective nature. Despite a large number of enrolled individuals, only 39 patients remained on treatment after 48 weeks. Improvements in the therapeutic scheme and patient follow-up might be needed to further mitigate lesions, especially in severe cases; additional studies are needed to address this issue.

In conclusion, our results suggest that guselkumab may be a safe and effective therapeutic alternative for patients with moderate–severe HS failing to respond to other therapies.

The authors meet the authorship criteria recommended by the International Committee of Medical Journal Editors (ICMJE) and did not receive payment related to the development of this article.

R. Rivera-Díaz has the following conflict of interests: received honoraria for participating in advisory boards and clinical trials from Abbvie, Boehringer-Ingelheim, Janssen, Leo Pharma, Eli Lilly, Novartis, and UCB; received support for attending meetings and/or travel from Almirall, Janssen, Novartis, and Eli Lilly; and her institution received an ultrasonography from Abbvie. B. Díaz Ley received payment or honoraria for lectures and educational events from Abbvie, Almirall, Amgen, Boehringer-Ingelheim, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer Sandoz, and UCB; received support for attending meetings and/or travel from Abbvie, Almirall, Cantabria Labs, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB; and participated as member of Advisory Boards for Abbvie, Almirall, Amgen, Boehringer-Ingelheim, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB. E. Vilarrasa received payment or honoraria for lectures and educational events from Abbvie, Almirall, Amgen, Boehringer-Ingelheim, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer Sandoz, and UCB; received support for attending meetings and/or travel from Abbvie, Almirall, Cantabria Labs, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB; and participated as member of Advisory Boards for Abbvie, Almirall, Amgen, Boehringer-Ingelheim, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB. A. Martorell received payment or honoraria for lectures and educational events from Abbvie, Almirall, Amgen, Boehringer-Ingelheim, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB; received support for attending meetings and/or travel from Abbvie, Almirall, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB; and participated as member of Advisory Boards for Abbvie, Almirall, Amgen, Boehringer-Ingelheim, Janssen-Cilag, Leo Pharma, Lilly, Novartis, Pfizer, and UCB. The rest of the authors report no conflict of interest.