IHS4 better suited as an outcome measure in HS trials?

The International Hidradenitis Suppurativa Severity Score System (IHS4) includes and accentuates draining tunnels. Compared with the currently most often used Hidradenitis Suppurativa Clinical Response (HiSCR) score, IHS4 shows advantages in illustrating study outcomes.

Unlike in psoriasis and atopic dermatitis, the inflammatory element of hidradenitis suppurativa (HS) advances [1]. “We have a disease that progresses from an inflammatory component to a scarring component if the inflammatory part is not treated well and early enough,” Prof. Thrasyvoulos Tzellos (Nordland Hospital Trust, Norway) stated. Up to now, adalimumab is the only approved biological treatment, thus, there is still a high unmet need. Still, there is somewhat unimpressive data on drug survival rates of adalimumab in HS (56.3% at 1 year and 30.5% at 2 years), with ineffectiveness being the main reason for discontinuation.  [2]. Currently, the common treatment goal is a 50% reduction in the HiSCR score [1]. “Do we need higher threshold outcomes in order to depict higher inflammatory effects?” Prof. Tzellos asked. As phase 2 data from bimekizumab (NCT03248531) showed that the use of higher HiSCR thresholds was able to demonstrate drug efficiency and simultaneously reduce the rate of placebo response (see Figure), his answer was ‘yes’ [1,3].

Figure: Is there a potential to aim for more ambitious HiSCR thresholds? [3]

HiSCR, Hidradenitis Suppurativa Clinical Response.

Prof. Tzellos continued that using HiSCR involves an inherent problem, as it only measures a reduction in the total count of abscesses and nodules but disregards draining tunnels. This may lead to study results in which participants who reach HiSCR100 still have actively draining tunnels. A validated score that captures all the components is the IHS4 score [4]. It includes draining tunnels and assigns different weights to the different types of lesions: nodules are multiplied by 1, abscesses by 2, and draining tunnels by 4. A post-hoc analysis of individual patient data from the PIONEER 1 and 2 trials (NCT02906930 and NCT01468233) that used the IHS4 score led to decreased placebo response rates between 4.5% and 12% [1,5]. “Actually, it reduced it to the rates we are familiar with in psoriasis and atopic dermatitis,” Prof. Tzellos commented. Further analysis of PIONEER 1 and 2 data by the Hidradenitis Suppurativa Foundation identified and externally validated IHS4-55 as an important dichotomous outcome [1]. “IHS4-55 will replace HiSCR because it has the same abilities when it comes to discriminating treatment groups, but it does not have the same drawbacks HiSCR has, as it includes dynamically draining tunnels in a validated manner,” Prof. Tzellos summarised.

1. Tzellos T. Hidradenitis Suppurativa: Pipeline and new concepts. FS4, SPIN 2022 Congress, 06–08 July, Paris, France.
2. Prens LM, et al. Br J Dermatol. 2021;185:177-84.
3. Glatt S, et al. JAMA Dermatol. 2021;157:1279-88.
4. Zouboulis CC, et al. Br J Dermatol. 2017;177:1401-09.
5. Frew JW, et al. J Am Acad Dermatol. 2020;82:1150-57.

 

Copyright ©2022 Medicom Medical Publishers

Posted on 26 August, 202226 August, 2022