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Biologics in HS – a growing armamentarium

Presented By
Prof. Joslyn Kirby, Penn State University, USA
AAD 2020

There are more and more agents to consider for hidradenitis suppurativa (HS). Thus, choices can now be made based on the individual needs of the patient [1]. A few questions need to be answered when treating HS patients with biologics: who should receive them, what drug to choose, and how to switch drugs in case of treatment failure?

“How does your HS impact you?” This is an essential question that Prof. Joslyn Kirby (Penn State University, USA) asks her patients before deciding about treatment, since objective severity should not be the only determining variable. Factors that can influence objective severity include flare frequency and scarring. Scarring is usually observed in Hurley stages II or III with tunnels but can also be seen in patients without tunnels; in these cases, biologics may be an additional option. Indeed, the patient has to be willing to take a biologic and might need some education about the disease, as many of them still believe in the misconception that HS is caused by immunodeficiency.

HS act on a multitude of inflammatory pathways. HS can be influenced by genetics, certain exposures like smoking or body weight, or a change in microbiome. It can also be impacted by the innate immune system (i.e. neutrophils and complement) and the adapted immune system (i.e. T cells and B cells). This means that many possible targets for treatments exist. Moreover, comorbidities including a history of malignancy, inflammatory bowel disease, or psoriasis have to be taken into account. These additional conditions may open the door to drugs currently not approved for HS.

Currently, adalimumab is the only approved biologic for HS patients. A dosing of 160 mg (day 1), followed by 80 mg (day 15), and maintenance of 40 mg weekly as of day 29 induced a clinical response in about 40% to 60% of patients (see Figure) [2] and significantly reduced the number and duration of flares [3]. However, if the drug does not show the anticipated results, when is it time to switch? According to Prof. Kirby, one should wait between 3 and 4 but not longer than 6 months for a typical response to treatment. The new drug should be started at the same point when the old agent would have been given because then overlap risk is considered low.

Figure: Adalimumab results in the PIONEER I and II trials [2]

Day 1, 160 mg, day 15, 80 mg, from day 29, 40 mg weekly. Clinical response was defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts at week 12.

Infliximab with a dosing of 7.5 mg/kg every 4 weeks resulted in a Physician Global Assessment of clear, minimal, or mild (score of 0-2) response in 70.8% of HS patients [4]. In terms of other possible therapeutics, the interest in anakinra has subsided because it requires a daily dosing.

In a phase 2 trial, the IL-1α inhibitor bermekimab (400 mg weekly) showed great promise: 61% of HS patients naïve to TNF blockers and 63% of patients that failed prior anti-TNF therapy achieved an HS clinical response at week 12 [5]. Further, in an open-label trial, ustekinumab led to 47% of patients with a clinical response (≥50% reduction in total abscess and nodule count) and secukinumab had impressive results with about 70% reaching clinical response [6,7].

“These interesting results will have us optimistic that we will have more treatment options in the future,” according to Prof. Kirby.

  1. Kirby J. AAD Virtual Meeting Experience, 12-14 June 2020.
  2. Kimball A, et al. N Engl J Med. 2016;375:422-434.
  3. Van der Zee HH, et al. J Eur Acad Dermatol Venereol. 2020;34:1050-1056.
  4. Ghias MH, et al. J Am Acad Dermatol. 2020;82:1094-1101.
  5. Gottlieb A, et al. J Invest Dermatol. 2020 Jan 29;S0022-202X(20)30071-3.
  6. Blok JL, et al. Br J Dermatol. 2016 Apr;174:839-846.
  7. Casseres RG, et al. J Am Acad Dermatol. 2020;82:1524-1526.

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