Prolonged drug survival of adalimumab in hidradenitis suppurativa: The importance of early intervention

Abstract

PIONEER I and II trials proved the efficacy and safety of adalimumab for moderate-to-severe hidradenitis suppurativa (HS).¹ When stringent eligibility criteria are applied in randomized trials, the extrapolation of research findings can become problematic, as studied populations lack heterogeneity. The PIONEER trials excluded Hurley stage 1 and ‘difficult’ patients with more than 20 fistulas and those requiring analgesics for HS-related pain.¹ Upon its approval, however, and as the only available drug in this indication, adalimumab was prescribed to an unselected, sometimes difficult-to-treat population.

Drug survival is an established endpoint of treatment success in real-world settings, encompassing drug efficacy and safety, cost, convenience, patient satisfaction, disparities in refund policies between countries, and access to care. In this issue, Garbayo-Salmons et al.² present a retrospective, multicentre study with real-world survival data from 539 patients who received at least one dose of adalimumab from May 2015 to December 2022. A pre-pandemic and post-pandemic treatment group were compared, using March 2020 as a time point. The median overall survival of adalimumab was 56.2 (95% CI 51.2 to 80.3) months, which is longer than previous reports.^{3, 4} The drug survival of adalimumab at 12 and 48 months was 82.95% and 58%, respectively, comparable to other indications like psoriasis. The reasons for discontinuation were loss of efficacy (51.69%) and adverse events (21.35%).

Long-term data from the Open-Label Extension of PIONEER studies showed that 52.3% of HS patients maintained a HiSCR response through Week 168.¹ Real-life studies have failed, however, until now to reproduce these results.^{3, 4} In 2021, a Dutch dual-center study of 104 patients calculated the median overall survival of adalimumab at 18.1 months [95% CI 11.4–24.8].³ In a 2024 Danish nationwide cohort, the median survival of adalimumab barely exceeded 8 months [33 weeks (IQR 16–63)].⁴ Male sex and being bio-naïve predicted prolonged survival.⁴

It can be difficult to compare drug survival studies. From the authors' standpoint, the longer survival of adalimumab can be attributed to the favourable refund policies of biologics in Spain and to low switching rates due to limited alternatives.² The study by Garbayo-Salmons et al. is the largest to date drug survival study in HS. Studying large, heterogeneous groups of prescribers and patients have been shown to better capture drug interruption thresholds and to provide a more robust representation of real-world practices. The study consisted mainly of bio-naïve patients (95.29%) who are known to better respond to adalimumab.⁴

In univariate analyses, a higher baseline IHS4 score and past experience with biologics predicted poor survival.² Soon after adalimumab's approval, it became apparent that early intervention, within a ‘window of opportunity’, when the inflammatory load is low and before severe scarring develops, improves adalimumab response rates.⁵ The younger age and the decreased severity at baseline in the post-pandemic group reflect the gradual implementation of this strategy by physicians.

The authors fail to clarify if patients received surgery during follow-up. This is an important limitation of the study. Surgery has been shown to prolong biologics' survival.³ In daily practice, adding surgery to adalimumab reduces disease burden, allows clinical remission, and improves patients' quality of life.

Secukinumab received approval in 2023, bimekizumab is expected to gain approval in 2024, and with numerous drugs advancing to Phase 3 trials (Table 1), the landscape of moderate-to-severe HS treatment is expected to evolve, forecasting a more treat-to-target approach in the following years. This large-scale study adds to the body of knowledge on the efficacy of adalimumab in daily practice and highlights the need for early intervention with disease-modifying agents to improve outcomes in HS.

There is no funding received for this commentary.

Maria Polina Konstantinou has received travel support and honoraria from Abbvie, Jannsen, Eli Lilly, LEO Pharma and Novartis and has participated on Advisory Boards for UCB. Konstantinos Krasagakis has received grants from Eli Lilly and Leo Pharma, travel support from AbbVie, Eli Lilly, Janssen, LEO Pharma, UCB, honoraria from UCB and Eli Lilly, and has participated on Advisory Boards for Eli Lilly, Boehringer Ingelheim, Sanofi and UCB.