# Treatment Strategies in Neutrophil Dermatoses: A Comprehensive Review
## 4 Hidradenitis Suppurativa
### Biological Treatment  
In recent years, the use of biological therapy has increased. Immunomodulation is essential in refractory or severe cases. Treatments are based on IL-1 (anakinra), IL-12/23 (ustekinumab), IL-17 (secukinumab), and the TNF-alpha (infliximab, adalimumab) blockade. To date, only adalimumab has been approved for first-line therapy, and infliximab for the second line [66].  
TNF-\(\alpha\) inhibitors  
**Adalimumab**  
Adalimumab is a recombinant human monoclonal antibody against TNF-\(\alpha\) effective for moderate and severe cases. The most relevant clinical trials in relation to its effectiveness are PIONEER I and II [71], which included a total of 633 patients who were randomized to receive placebo or adalimumab. The design was similar in both trials, the difference being that in the second trial, concomitant treatment with oral tetracyclines was allowed. The primary endpoint was clinical response, defined as a greater than 50% reduction in lesions, this being significantly greater in adalimumab-treated patients compared with placebo (41.8 vs. 26% in PIONEER I and 58.9 vs. 27.6% in PIONEER II). Based on these results, adalimumab was approved by the FDA for moderate to severe HS.  
**Infliximab**  
Infliximab is a monoclonal chimeric antibody against TNF-\(\alpha\), indicated as the second-line treatment in moderate-severe cases refractory to adalimumab. Its use in HS has not been specifically approved in this entity; despite this, the European guidelines recommend a dose of 5 mg/kg body weight administered on weeks 0, 2 and 6, and then regularly every 8 weeks [68].  
IL-1 inhibitors  
**Anakinra**  
Anakinra is a recombinant human IL-1 receptor antagonist that blocks the inflammatory effects of IL-1. Its efficacy has been demonstrated in two clinical trials. The first was a randomized clinical trial in 20 patients with Hurley stage II/II, in which the group randomized to receive anakinra presented clinically significant responses of 78%, while in the placebo group, this was 30% [72]. Similarly, [PERSON] et al. carried out an open clinical trial with five patients diagnosed with HS in the moderate-severe phase who received treatment with anakinra for 16 weeks, with an objective decrease in activity. The dose usually administered is 100 mg/day subcutaneously [73]. The HS ALLIANCE group currently recommends it as a third-line therapy in cases of the failure of TNF-alpha inhibitors [74].  
IL-23 inhibitors  
**Ustekinumab**  
Ustekinumab is a human IgG1 class monoclonal antibody that modulates IL-12 and IL-23 signaling. Regarding evidence of its use, a cohort of 17 patients with Hurley stage II-III HS received 45 mg s.c. at weeks 0, 4, 16, and 28. Of the subjects included, 82% presented a great clinical improvement [75]. The North American and European guidelines consider it in cases of refractoriness to previous lines [68; 76].  
L-23 inhibitors  
**Secukinumab**  
Secukinumab is a human monoclonal antibody directed against IL-17A. There seems to be an increase in IL-17A in the blood of patients with HS, related to the severity of the disease. Current clinical guidelines have not mentioned the use of secukinumab in this entity. However, there are several trials that have reported its use [77; 78], including SUNSHINE and SUNRISE, phase 3 multicenter randomized clinical trials with a total of 541 and 543 patients, respectively. The included cases were patients with moderate-severe HS who were randomized to receive secukinumab 300 mg s.c. every 2 weeks or every 4 weeks, or a placebo. The primary endpoint was clinically significant improvement, defined as a more than 50% improvement in lesions. Of the patients randomized to secukinumab, it was verified in both trials that the most effective regimen was every 2 weeks. Despite this, it is necessary to continue investigating the indication in this entity [78]. See Table 3.  
Regarding immunosuppressive treatment, the following drugs are distinguished.