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-17

IL-17 and IL-17A levels, as well as mRNA expression of IL-17, are elevated in HS skin compared with healthy control skin.[2,18,75] Serum IL-17 levels are also higher in patients with HS compared with healthy controls and, further, serum IL-17 levels correlate to HS severity.[4]

Secukinumab

Secukinumab is an anti-IL-17A human monoclonal antibody that inhibits binding of IL-17A to its receptor.[88] Only case reports describing efficacy of secukinumab in HS are published in the literature.[89–92] Secukinumab in these reports is typically dosed according to the psoriasis dosing (300 mg subcutaneously weekly during weeks 0–4, then administered every 4 weeks).[89–91] Three clinical trials studying use of secukinumab in HS are currently ongoing (Table 3). One is an investigator-initiated exploratory phase I clinical trial of secukinumab dosed at 300 mg weekly for the first 5 weeks followed by every 4 weeks over 24 weeks.[93] The results have not been formally published. However, they were reported at the European Academy of Dermatology and Venereology congress and are available online; the online report details that 14 of the 18 patients achieved HiSCR.[94] Two additional studies, SUNSHINE and SUNRISE, are looking at two different dosing regimens of secukinumab, 300 mg every 2 weeks and 300 mg every 4 weeks, compared with placebo over 16 weeks, with a long-term efficacy period up to 1 year.[95,96]

Other Agents Targeting IL-17

Studies assessing the efficacy of other IL-17 agents, such as bimekizumab and CJM112, have been completed but the results are not published (Table 3). Additionally, a clinical trial studying brodalumab is underway. A phase II clinical trial has been completed on the efficacy, safety, and pharmacokinetics of bimekizumab use in HS. This trial studied bimekizumab at two different dosing regimens and included an active comparator to adalimumab as well as comparison with placebo. The results have not been published yet.[97] Bimekizumab is a human monoclonal antibody that targets two isoforms of IL-17, IL-17A and Il-17F, and has been studied in psoriasis previously.[98] CJM112 is another anti-IL-17 biologic that has been studied in HS.[40,41] A phase II, double-blind RCT to study the efficacy and safety of CJM112 is complete but the results are not yet publicly available.[40,41,99] Brodalumab is an antagonist against IL-17 receptor A.[100] A phase II clinical trial studying the use of brodalumab in HS is planned but not yet recruiting.[101]

Safety Concerns

Increased risk of infections, as in other biologics, is of concern in IL-17 inhibitors such as secukinumab.[88] In a meta-analysis of seven phase III clinical trials on use of secukinumab, the most common adverse event reported was respiratory infections.[102] Of interest, IL-17 plays a role in protection against candida infections, and a small increased risk of candida infections in patients treated with IL-17 inhibitors has been observed in clinical trials.[103] Neutropenia and leukopenia are also observed in treatment with secukinumab, given the role of IL-17 in neutrophil trafficking.[104] Some concern exists that IL-17 inhibition via biologic therapy may increase the risk of IBD; however, this association has been difficult to elucidate.[105] This type of risk would potentially limit use of IL-17 antagonists in the HS population, as IBD is frequently comorbid in HS.[106] Additionally, reports have described cases of oral ulcers associated with IL-17 initiation such as ulcerative lichenoid mucositis,[107] oral lichen planus,[108] and oral lichenoid reaction.[109] Some authors suggest that increased risk of candidiasis infection with use of anti-IL-17 biologics may promote the development of oral lichen planus.[108]

Interestingly, exacerbation of HS has been reported as an adverse event of anti-IL-17 therapy. Ixekizumab, an anti-IL17A monoclonal antibody, has been studied in psoriasis but not in HS. In a study of ixekizumab for chronic plaque psoriasis, exacerbation of HS was reported as three separate adverse events in one patient.[110]

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