Highlights from

WCD 2019

World Congress of Dermatology

Milan 10-15 June 2019

Biologicals beyond TNF blockade

Tumour necrosis factor (TNF) blockers are currently recommended in existing guidelines. Recent trials strive to find other targets for treatment as numerous immunological events are involved in hidradenitis suppurativa (HS).

“Looking at biologics beyond TNF blockade, I will concentrate on IL-1α, ß and the possible role of IL-17 and IL-23,” said Prof. Brian Kirby (St. Vincent’s University Hospital, Ireland) [1]. He emphasised that unlike in psoriasis, clinical trials will mostly show very high placebo response rates; one of the reasons that HS studies can be more difficult to interpret. In a not yet published phase 2 study without a placebo control group, bermekimab targeting IL-1α led to a positive Hidradenitis Suppurativa Clinical Response (HiSCR) at week 12 in 61% of the TNF-naïve patients [1,2]. A placebo-controlled phase 2 study of anakinra, an IL-1 receptor antagonist showed 78% HiSCR response at week 12 for the anakinra group vs 30% for placebo (P=0.04).

Focusing on the Th17-pathway, a phase 3 study is already planned for secukinumab; although the results of the phase 2 study have not yet been published. A small case series showed improvement with secukinumab and 4 individual case reports stated successful treatment with this agent [1,3-7]. “The first real evidence that we have seen to date that suggested that IL-17 blockade may be useful, comes from an RCT testing the new molecule CMJ112,” said Prof. Kirby. 66 patients of Hurley stage 2 or 3 were randomised to receive either CJM112 300 mg subcutaneously or placebo [8]. Primary endpoint was a decrease in HS physician global assessment (PGA) at week 16. It was met by 32% with CMJ112 and 13% with placebo (see Figure). There was a decrease in inflammatory lesions of 56% vs 30%. For IL-23 inhibition with guselkumab a phase 2 study is ongoing. Furthermore, IFX-1, an anti-complement factor C5a antibody, achieved HiSCR in 83% at day 50, but the study only comprised 12 adults and there was a significant number of adverse events [1,9]. “There are multiple potential targets for biological therapy of HS, but RCTs seem to be difficult and this may have to do with the disease itself,” told Prof. Kirby. “Until now there is a paucity of good evidence, but several phase 2 trials are still ongoing,” he concluded.

Figure: HS-PGA responder rate (primary endpoint) by treatment group up to week 16 [8]

Figure HS-PGA responder rate

  1. Kirby B. 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
  2. XBiotech. Press release: Friday, May 31, 2019.
  3. Prussick L, et al. Br J Dermatol. 2019 Feb 22.[Epub ahead of print]
  4. Giuseppe P, et al. Ann Dermatol. 2018;30:462-464.
  5. Jørgensen AR, et al. Case Rep Dermatol Med. 2018;2018:8685136.
  6. Schuch A, et al. Acta Derm Venereol. 2018;98:151-152.
  7. Thorlacius L, et al. Br J Dermatol. 2018;179:182-185.
  8. Kimball AB, et al. ePoster 24th World Congress of Dermatology, 10-15 June 2019, Milan, Italy.
  9. Argyropoulou M, et al. P0043 presented at EADV 2017, Geneva, Switzerland.

Top image: @ iStockPhoto: AzmanL

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