Off-Label Ixekizumab is Effective for HS After Treatment Failure with Adalimumab

Image Credit: © Евгений Вершинин - stock.adobe.com

Patients with hidradenitis suppurativa who have become resistant to adalimumab found clinical response with ixekizumab, according to a new trial.¹ Current approved therapies for hidradenitis suppurativa include adalimumab, secukinumab, and bimekizumab. Adalimumab is a TNF-α inhibitor that is typically administered subcutaneously; either 40 mg per week or 80 mg every other week.² Ixekixumab, an IL-17A inhibitor, has only been evaluated in a few cases thus far for off-label hidradenitis suppurativa treatment

This retrospective analysis of a case series involved 10 patients with hidradenitis suppurativa in Germany. The group was mostly female, with a mean age of 39.7. The median age of HS diagnosis was 34. Each experienced a secondary loss of effectiveness to treatment with adalimumab over time. This was clinically defined by a recurrence of at least 1 fistula or at least 75% worsening of response after 16 weeks.

The participants were treated with off-label ixekizumab in 2019 when adalimumab was the only approved biologic for hidradenitis suppurativa at the time. The drug was taken at a dose of 80 mg every 2 weeks for 3 months, then every 4 weeks. Clinical outcomes were measured using the International Hidradenitis Suppurativa Severity Score System (IHS4), in which severe disease is indicated by a score > 11. Quality of life was evaluated via the 10-question Dermatology Life Quality Index (DLQI). These measurements took place at baseline and 16 weeks after treatment began.

The average IHS4 score decreased from 13.6 at baseline to 9.6 at week 16. Seven patients saw a significant reduction in inflammatory lesions throughout the treatment period. However, 3 participants did develop new lesions during the trial. At week 16, 5 patients reached the IHS4-55 score, which corresponded to a 55% reduction of the IHS4 score versus baseline.

Three patients did not respond to the therapy, while 1 individual observed a worsening in symptoms at week 16, even though initial improvement was seen at week 4. Mean DLQI scores dropped by almost 4 points from 11.7 to 7.8. In fact, 2 patients saw a DLQI reduction of more than 10 points.

Although prior research is limited, the few existing cases support the findings demonstrated in this study. Patients in Wu et al. and Iannone et al. experienced a decrease in active lesion swelling with few flare-ups and no adverse events.^3,4 These results are promising, “displaying a trend toward effectiveness and safety of ixekizumab,” according to the authors.

However, the retrospective design, short study period, and small, homogeneous sample size are limitations of the current trial. Additionally, the use of the IHS4 score assessment can be subjective. Future open-label, placebo-controlled studies with larger sample sizes are necessary to assess the long-term effectiveness and safety of ixekizumab in patients with hidradenitis suppurativa, especially those who have become resistant to adalimumab. With further research, ixekizumab can become a strong hidradenitis suppurativa therapy option, alongside secukinumab and bimekizumab.

“From the experience with psoriasis and other chronic inflammatory diseases, a larger selection of targeted therapies is desirable, especially with regard to the possibility of a secondary loss of effectiveness or a primary nonresponse,” the authors concluded.

References

1. Hilbring C, Augustin M, Girbig G, et al. Ixekizumab Restores Clinical Response in Patients With Hidradenitis Suppurativa After Secondary Loss of Effectiveness From Adalimumab: Results From a Retrospective Analysis of a Case Series, Dermatol Ther, 2025, 5597039, 7 pages, 2025. https://doi.org/10.1155/dth/5597039

2. van der Zee HH, Laman JD, de Ruiter L, Dik WA, Prens EP. Adalimumab (antitumour necrosis factor-α) treatment of hidradenitis suppurativa ameliorates skin inflammation: an in situ and ex vivo study. Br J Dermatol. 2012;166(2):298-305. doi:10.1111/j.1365-2133.2011.10698.x

3. Wu KK, Dao H Jr. Off-label dermatologic uses of IL-17 inhibitors. J Dermatolog Treat. 2022;33(1):41-47. doi:10.1080/09546634.2020.1737638

4. Iannone M, Janowska A, Tonini G, Davini G, Dini V. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine during Ixekizumab treatment for hidradenitis suppurativa. Clin Dermatol. 2021;39(4):701-702. doi:10.1016/j.clindermatol.2021.05.026