Biologic Treatment for Hidradenitis Suppurativa

Kelsey S. Flood; Martina L. Porter; Alexa B. Kimball

Disclosures

Am J Clin Dermatol. 2019;20(5):625-638. 

In This Article

Biologics Targeting IL-1

In a study of HS skin, IL-1β levels were increased 54-fold compared with healthy control skin. Further, in this study treatment with adalimumab was shown to decrease the levels of IL-1β.[2] Bechara et al. also reported that IL-1 mRNA levels were elevated in lesional as compared with nonlesional skin.[22] Another study demonstrated that keratinocytes from the hair follicles of patients with HS secreted higher levels of IL-1β compared with healthy donors.[111] Recently, IL-1α was also reported to be elevated in lesional HS skin as compared with control skin.[18]

Anakinra

Anakinra is an IL-1α receptor antagonist. Via competitive inhibition, anakinra binds to the IL-1 receptor, thereby preventing both IL-1α and IL-1β from binding.[17,112,113] Anakinra dosing starts at 1–2 mg/kg and can be up-titrated to 8 mg/kg.[114]Two clinical trials utilized a dosing regimen of anakinra 100 mg subcutaneously daily in HS.[17,115] Other authors have reported using up to 200 mg daily[112] (Table 1).

In an open-label clinical trial, treatment with anakinra for 8 weeks led to a significant improvement in Sartorius score, physician and patient global assessment, and DLQI in six patients, of whom five completed the study. These patients were subsequently followed for eight additional weeks after finishing treatment, during which time disease activity increased to levels similar to those seen prior to treatment.[115] In a later study, 20 patients (of whom 19 completed the study) were treated with anakinra in a double-blind RCT. A significantly greater improvement in disease activity score was seen in those patients treated with anakinra at the end of 12 weeks. In this study, patients treated with anakinra were also more likely to achieve HiSCR at week 12 but the change in HiSCR was not statistically significant at 24 weeks. Moreover, there was no significant difference in VAS score, DLQI, or Sartorius score between the placebo and treatment groups. Disease activity scores increased after stopping treatment; however, time until HS exacerbation was significantly longer in patients treated with anakinra.[17] Other literature describing use of anakinra in HS has been largely limited to case reports in both HS exclusively[112] and in PASH (pyoderma gangrenosum, acne and HS) syndrome.[114] Case reports have reported that efficacy may be seen as early as 1 month.[112] Alternatively, some case reports have reported a lack of efficacy and even worsening of HS with anakinra.[50,116]

Other Agents Targeting IL-1

Bermekimab (also known as MABp1) is another biologic with activity against IL-1α.[117–119] In a double-blind RCT of 20 patients with moderate-to-severe HS randomized to treatment with MABp1 versus placebo, 60% of subjects treated with MABp1 reached the primary endpoint (positive HiSCR) compared with 10% of subjects receiving placebo (odds ratio 13.5, 95% CI 1.19–152.51; p = 0.035). MABp1 was dosed at 7.5 mg/kg every 14 days; patients were treated with up to a maximum of seven infusions[117] (Table 1). Additionally, a phase II clinical trial studying MABp1, dosed at 400 mg subcutaneously weekly in two cohorts (one cohort with prior anti-TNF exposure and the other consisting of TNF-naïve subjects) to assess its safety and efficacy in HS, is currently recruiting.[120] A clinical trial studying use of MEDI8968, a subcutaneous biologic that binds to IL-1R1, thereby inhibiting the activity of IL-1α and IL-1β, in HS was stopped prematurely as, compared with placebo, MEDI8968 was found to not be efficacious in reducing pain or HS severity at an interim analysis.[41,121]

Safety Concerns

Information regarding the long-term safety of IL-1 antagonists is less readily available compared to other biologics. The FDA labeling for anakinra states that the impact of the drug on rate of malignancy and infections is unknown.[113] In part, the limited safety data regarding anakinra may be secondary to its limited use by rheumatologists for RA as it is less effective than other biologics.[122] Common adverse reactions include injection site reactions, infections, and immunogenicity.[122] In a retrospective study of 475 patients treated with IL-1 inhibitors, anakinra (421 treatment courses) and canakinumab (105 treatment courses), four infections, four anaphylactic reactions, and one neoplasm were observed.[123] In a meta-analysis of ten studies on use of anakinra in rheumatoid arthritis, the pooled relative risk of infections in patients treated with anakinra was not statistically significant (1.06, 95% CI 0.94–1.20).[124] Additional information on adverse events included on the FDA labeling of anakinra can be found in Table 1. Further investigation on the long-term safety of IL-1 antagonists is warranted.

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